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Sample records for gene dosage compensation

  1. Gene dosage compensation calibrates four regulatory RNAs to control Vibrio cholerae quorum sensing

    DEFF Research Database (Denmark)

    Svenningsen, Sine L; Tu, Kimberly C; Bassler, Bonnie L

    2009-01-01

    the quorum regulatory RNAs 1-4 (Qrr1-4). The four Qrr sRNAs are functionally redundant. That is, expression of any one of them is sufficient for wild-type quorum-sensing behaviour. Here, we show that the combined action of two feedback loops, one involving the sRNA-activator LuxO and one involving the sRNA......Quorum sensing is a mechanism of cell-to-cell communication that allows bacteria to coordinately regulate gene expression in response to changes in cell-population density. At the core of the Vibrio cholerae quorum-sensing signal transduction pathway reside four homologous small RNAs (sRNAs), named......-target HapR, promotes gene dosage compensation between the four qrr genes. Gene dosage compensation adjusts the total Qrr1-4 sRNA pool and provides the molecular mechanism underlying sRNA redundancy. The dosage compensation mechanism is exquisitely sensitive to small perturbations in Qrr levels. Precisely...

  2. Dosage compensation and demasculinization of X chromosomes in Drosophila.

    Science.gov (United States)

    Bachtrog, Doris; Toda, Nicholas R T; Lockton, Steven

    2010-08-24

    The X chromosome of Drosophila shows a deficiency of genes with male-biased expression, whereas mammalian X chromosomes are enriched for spermatogenesis genes expressed premeiosis and multicopy testis genes. Meiotic X-inactivation and sexual antagonism can only partly account for these patterns. Here, we show that dosage compensation (DC) in Drosophila may contribute substantially to the depletion of male genes on the X. To equalize expression between X-linked and autosomal genes in the two sexes, male Drosophila hypertranscribe their single X, whereas female mammals silence one of their two X chromosomes. We combine fine-scale mapping data of dosage compensated regions with genome-wide expression profiles and show that most male-biased genes on the D. melanogaster X are located outside dosage compensated regions. Additionally, X-linked genes that have newly acquired male-biased expression in D. melanogaster are less likely to be dosage compensated, and parental X-linked genes that gave rise to an autosomal male-biased retrocopy are more likely located within compensated regions. This suggests that DC contributes to the observed demasculinization of X chromosomes in Drosophila, both by limiting the emergence of male-biased expression patterns of existing X genes, and by contributing to gene trafficking of male genes off the X. Copyright 2010 Elsevier Ltd. All rights reserved.

  3. Evolution of vertebrate sex chromosomes and dosage compensation.

    Science.gov (United States)

    Graves, Jennifer A Marshall

    2016-01-01

    Differentiated sex chromosomes in mammals and other vertebrates evolved independently but in strikingly similar ways. Vertebrates with differentiated sex chromosomes share the problems of the unequal expression of the genes borne on sex chromosomes, both between the sexes and with respect to autosomes. Dosage compensation of genes on sex chromosomes is surprisingly variable - and can even be absent - in different vertebrate groups. Systems that compensate for different gene dosages include a wide range of global, regional and gene-by-gene processes that differ in their extent and their molecular mechanisms. However, many elements of these control systems are similar across distant phylogenetic divisions and show parallels to other gene silencing systems. These dosage systems cannot be identical by descent but were probably constructed from elements of ancient silencing mechanisms that are ubiquitous among vertebrates and shared throughout eukaryotes.

  4. X chromosome dosage compensation via enhanced transcriptional elongation in Drosophila.

    Science.gov (United States)

    Larschan, Erica; Bishop, Eric P; Kharchenko, Peter V; Core, Leighton J; Lis, John T; Park, Peter J; Kuroda, Mitzi I

    2011-03-03

    The evolution of sex chromosomes has resulted in numerous species in which females inherit two X chromosomes but males have a single X, thus requiring dosage compensation. MSL (Male-specific lethal) complex increases transcription on the single X chromosome of Drosophila males to equalize expression of X-linked genes between the sexes. The biochemical mechanisms used for dosage compensation must function over a wide dynamic range of transcription levels and differential expression patterns. It has been proposed that the MSL complex regulates transcriptional elongation to control dosage compensation, a model subsequently supported by mapping of the MSL complex and MSL-dependent histone 4 lysine 16 acetylation to the bodies of X-linked genes in males, with a bias towards 3' ends. However, experimental analysis of MSL function at the mechanistic level has been challenging owing to the small magnitude of the chromosome-wide effect and the lack of an in vitro system for biochemical analysis. Here we use global run-on sequencing (GRO-seq) to examine the specific effect of the MSL complex on RNA Polymerase II (RNAP II) on a genome-wide level. Results indicate that the MSL complex enhances transcription by facilitating the progression of RNAP II across the bodies of active X-linked genes. Improving transcriptional output downstream of typical gene-specific controls may explain how dosage compensation can be imposed on the diverse set of genes along an entire chromosome.

  5. A brief history of dosage compensation

    Indian Academy of Sciences (India)

    depression of X-linked gene activity in the female, as well as by hyperexpression of the ... to the Harvey lecture, Muller had presented important ideas relative to dosage ... at Columbia. I do recall a talk by the popular physical anthro- pologist ...

  6. Tissue- and stage-dependent dosage compensation on the Neo-X chromosome in drosophila pseudoobscura

    KAUST Repository

    Nozawa, Masafumi; Fukuda, Nana; Ikeo, Kazuho; Gojobori, Takashi

    2013-01-01

    Sex chromosome dosage compensation (DC) is widely accepted in various organisms. This concept is mostly supported by comparisons of gene expression between chromosomes and between sexes. However, genes on the X chromosome and autosomes are mostly

  7. Feedback Control of Sex Determination by Dosage Compensation Revealed through Caenorhabditis Elegans Sdc-3 Mutations

    OpenAIRE

    DeLong, L.; Plenefisch, J. D.; Klein, R. D.; Meyer, B. J.

    1993-01-01

    In Caenorhabditis elegans, sex determination and dosage compensation are coordinately controlled through a group of genes that respond to the primary sex determination signal. Here we describe a new gene, sdc-3, that also controls these processes. In contrast to previously described genes, the sex determination and dosage compensation activities of sdc-3 are separately mutable, indicating that they function independently. Paradoxically, the sdc-3 null phenotype fails to reveal the role of sdc...

  8. Mechanisms and evolutionary patterns of mammalian and avian dosage compensation.

    Directory of Open Access Journals (Sweden)

    Philippe Julien

    Full Text Available As a result of sex chromosome differentiation from ancestral autosomes, male mammalian cells only contain one X chromosome. It has long been hypothesized that X-linked gene expression levels have become doubled in males to restore the original transcriptional output, and that the resulting X overexpression in females then drove the evolution of X inactivation (XCI. However, this model has never been directly tested and patterns and mechanisms of dosage compensation across different mammals and birds generally remain little understood. Here we trace the evolution of dosage compensation using extensive transcriptome data from males and females representing all major mammalian lineages and birds. Our analyses suggest that the X has become globally upregulated in marsupials, whereas we do not detect a global upregulation of this chromosome in placental mammals. However, we find that a subset of autosomal genes interacting with X-linked genes have become downregulated in placentals upon the emergence of sex chromosomes. Thus, different driving forces may underlie the evolution of XCI and the highly efficient equilibration of X expression levels between the sexes observed for both of these lineages. In the egg-laying monotremes and birds, which have partially homologous sex chromosome systems, partial upregulation of the X (Z in birds evolved but is largely restricted to the heterogametic sex, which provides an explanation for the partially sex-biased X (Z expression and lack of global inactivation mechanisms in these lineages. Our findings suggest that dosage reductions imposed by sex chromosome differentiation events in amniotes were resolved in strikingly different ways.

  9. Dosage compensation of serine-4 transfer RNA in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Birchler, J.A.; Owenby, R.K.; Jacobson, K.B.

    1982-01-01

    A dosage series of the X chromosome site for serine-4 transfer RNA consisting of one of three copies in females and one to two in males was constructed to test whether transfer RNA expression is governed by dosage compensation. A dosage effect on the level of the serine-4 isoacceptor was observed in both females and males when the structural locus was varied. However, in males, each dose had a relatively greater expression so the normal one dose was slightly greater than the total female value and the duplicated male had the highest relative expression of all the types examined. Serine-4 levels in males and females from an isogenic Oregon-R stock were similar. Thus the transfer RNA levels conform to the expectations of dosage compensation

  10. Identification of chromatin-associated regulators of MSL complex targeting in Drosophila dosage compensation.

    Directory of Open Access Journals (Sweden)

    Erica Larschan

    Full Text Available Sex chromosome dosage compensation in Drosophila provides a model for understanding how chromatin organization can modulate coordinate gene regulation. Male Drosophila increase the transcript levels of genes on the single male X approximately two-fold to equal the gene expression in females, which have two X-chromosomes. Dosage compensation is mediated by the Male-Specific Lethal (MSL histone acetyltransferase complex. Five core components of the MSL complex were identified by genetic screens for genes that are specifically required for male viability and are dispensable for females. However, because dosage compensation must interface with the general transcriptional machinery, it is likely that identifying additional regulators that are not strictly male-specific will be key to understanding the process at a mechanistic level. Such regulators would not have been recovered from previous male-specific lethal screening strategies. Therefore, we have performed a cell culture-based, genome-wide RNAi screen to search for factors required for MSL targeting or function. Here we focus on the discovery of proteins that function to promote MSL complex recruitment to "chromatin entry sites," which are proposed to be the initial sites of MSL targeting. We find that components of the NSL (Non-specific lethal complex, and a previously unstudied zinc-finger protein, facilitate MSL targeting and display a striking enrichment at MSL entry sites. Identification of these factors provides new insight into how MSL complex establishes the specialized hyperactive chromatin required for dosage compensation in Drosophila.

  11. Incomplete sex chromosome dosage compensation in the Indian meal moth, Plodia interpunctella, based on de novo transcriptome assembly.

    Science.gov (United States)

    Harrison, Peter W; Mank, Judith E; Wedell, Nina

    2012-01-01

    Males and females experience differences in gene dose for loci in the nonrecombining region of heteromorphic sex chromosomes. If not compensated, this leads to expression imbalances, with the homogametic sex on average exhibiting greater expression due to the doubled gene dose. Many organisms with heteromorphic sex chromosomes display global dosage compensation mechanisms, which equalize gene expression levels between the sexes. However, birds and Schistosoma have been previously shown to lack chromosome-wide dosage compensation mechanisms, and the status in other female heterogametic taxa including Lepidoptera remains unresolved. To further our understanding of dosage compensation in female heterogametic taxa and to resolve its status in the lepidopterans, we assessed the Indian meal moth, Plodia interpunctella. As P. interpunctella lacks a complete reference genome, we conducted de novo transcriptome assembly combined with orthologous genomic location prediction from the related silkworm genome, Bombyx mori, to compare Z-linked and autosomal gene expression levels for each sex. We demonstrate that P. interpunctella lacks complete Z chromosome dosage compensation, female Z-linked genes having just over half the expression level of males and autosomal genes. This finding suggests that the Lepidoptera and possibly all female heterogametic taxa lack global dosage compensation, although more species will need to be sampled to confirm this assertion.

  12. Dosage Compensation of an Aneuploid Genome in Mouse Spermatogenic Cells

    Czech Academy of Sciences Publication Activity Database

    Jansa, Petr; Homolka, David; Blatný, Radek; Mistrik, M.; Bartek, Jiří; Forejt, Jiří

    2014-01-01

    Roč. 90, č. 6 (2014), 124/1-124/9 ISSN 0006-3363 R&D Projects: GA ČR GA13-08078S Institutional support: RVO:68378050 Keywords : gene dosage * male sterility * segmental trisomy * meiotic silencing of unsynapsed chromatin * DOWN-SYNDROME * MAMMALIAN MEIOSIS Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.318, year: 2014

  13. Dosage Compensation of an Aneuploid Genome in Mouse Spermatogenic Cells

    Czech Academy of Sciences Publication Activity Database

    Jansa, Petr; Homolka, David; Blatný, Radek; Mistrik, M.; Bartek, Jiří; Forejt, Jiří

    2014-01-01

    Roč. 90, č. 6 (2014), 124/1-124/9 ISSN 0006-3363 R&D Projects: GA ČR GA13-08078S Institutional support: RVO:68378050 Keywords : gene dosage * male sterility * segmental trisomy * meiotic silencing of unsynapsed chromatin * DOWN - SYNDROME * MAMMALIAN MEIOSIS Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.318, year: 2014

  14. Analysis of the dosage compensation of a specific transcript in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Breen, T.R.

    1985-01-01

    The basic tenet of dosage compensation is that males, which normally have one X-chromosome that contains half the amount of DNA as the two X-chromosomes in females, produce a relatively equivalent amount of X-encoded gene products compared to females. Quantitative analyses were performed to ascertain the amount of transcripts synthesized from the X-linked salivary gland secretion protein gene, Sgs-4, in larval third instar males and females which had a variety of genetic backgrounds. Two types of analyses were performed. In one, RNA from male and female late third instar salivary glands was isolated and quantitatively blotted to replica nitrocellulose filters. The replicas were hybridized with 32 P-labeled probes specific for either Sgs-4 or Sgs-3 RNA. The radioactive hybrids were quantitated by scintillation counting. In the other, male and female third instar salivary glands were incubated for 12.5 minutes with 3 H-uridine. The labelled, nascent RNAs were hybridized to dot blots of Sgs-4 and Sgs-3 DNA, and were scintillation counted. 3 H-uridine incorporation analysis showed that male Sgs-4 genes were transcribed at twice the rate of the female genes. These findings indicated that steady-state Sgs-4 RNA levels directly reflect the rate of their transcription. These results are important in that they demonstrate that dosage compensation operates at the level of the rate of transcription of a specific gene. They also dissolve ambiguities associated with results obtained in past dosage compensation experiments

  15. beta. -Amyloid gene dosage in Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Murdoch, G H; Manuelidis, L; Kim, J H; Manuelidis, E E

    1988-01-11

    The 4-5 kd amyloid ..beta..-peptide is a major constituent of the characteristic amyloid plaque of Alzheimer's disease. It has been reported that some cases of sporatic Alzheimer's disease are associated with at least a partial duplication of chromosome 21 containing the gene corresponding to the 695 residue precursor of this peptide. To contribute to an understanding of the frequency to such a duplication event in the overall Alzheimer's population, the authors have determined the gene dosage of the ..beta..-amyloid gene in this collection of cases. All cases had a clinical diagnosis of Alzheimer's confirmed neuropathologically. Each Alzheimer's case had an apparent normal diploid ..beta..-amyloid gene dosage, while control Down's cases had the expected triploid dosage. Thus partial duplication of chromosome 21 may be a rare finding in Alzheimer's disease. Similar conclusions were just reported in several studies of the Harvard Alzheimer collection.

  16. Dosage compensation in Drosophila melanogaster, a model for control in other insect species

    International Nuclear Information System (INIS)

    Hilfiker, A.; Hilfiker-Kleiner, D.; Lucchesi, J.C.

    1998-01-01

    In the animal kingdom, many species with euchromatic heteromorphic sex chromosomes have developed mechanisms for the equalization of gene products in the homo- and the heterogametic sex. This mechanism, called dosage compensation, is achieved in Drosophila by the doubling of the transcriptional activity of X-linked genes in the male, in comparison to the female. Any failure in achieving dosage compensation causes lethality: hapto-X male individuals that fail to hyperactivate their single X-chromosome as well as diplo-X female individuals that hyperactivate their X-chromosomes die. Five genes that are involved in the regulation of this process have been identified. in males, a group of four genes, the so called male-specific lethals (mle, msl-1, msl-2, msl-3), must be active in order for hypertranscription to occur, whereas in females the Sxl gene, the master key gene of sex determination, has to be active to prevent the msl genes from becoming active. However, XX individuals with mutations in Sxl cannot be rescued by mutations in the msl genes indicating that at least one member of this group is yet to be uncovered. Furthermore, the msl gene that is regulated in a sex-specific manner has not yet been identified. Given that msl-1 is transcribed in both sexes but its protein product is nearly absent in females, we have investigated whether this gene is the target of sex-specific regulation. We have also carried out extensive genetic screens for the purpose of identifying additional members of the msl group. These investigations are necessary prerequisites to the development of genetic sexing techniques based on the constitutive expression of msl genes in females causing female-specific lethality. (author)

  17. General lack of global dosage compensation in ZZ/ZW systems? Broadening the perspective with RNA-seq

    Directory of Open Access Journals (Sweden)

    Wolf Jochen BW

    2011-02-01

    Full Text Available Abstract Background Species with heteromorphic sex chromosomes face the challenge of large-scale imbalance in gene dose. Microarray-based studies in several independent male heterogametic XX/XY systems suggest that dosage compensation mechanisms are in place to mitigate the detrimental effects of gene dose differences. However, recent genomic research on female heterogametic ZZ/ZW systems has generated surprising results. In two bird species and one lepidopteran no evidence for a global dosage compensating mechanism has been found. The recent advent of massively parallel RNA sequencing now opens up the possibility to gauge the generality of this observation with a broader phylogenetic sampling. It further allows assessing the validity of microarray-based inference on dosage compensation with a novel technology. Results We here expemplify this approach using massively parallel sequencing on barcoded individuals of a bird species, the European crow (Corvus corone, where previously no genetic resources were available. Testing for Z-linkage with quantitative PCR (qPCR, we first establish that orthology with distantly related species (chicken, zebra finch can be used as a good predictor for chromosomal affiliation of a gene. We then use a digital measure of gene expression (RNA-seq on brain transcriptome and confirm a global lack of dosage compensation on the Z chromosome. RNA-seq estimates of male-to-female (m:f expression difference on the Z compare well to previous microarray-based estimates in birds and lepidopterans. The data further lends support that an up-regulation of female Z-linked genes conveys partial compensation and suggest a relationship between sex-bias and absolute expression level of a gene. Correlation of sex-biased gene expression on the Z chromosome across all three bird species further suggests that the degree of compensation has been partly conserved across 100 million years of avian evolution. Conclusions This work

  18. “Jump Start and Gain” Model for Dosage Compensation in Drosophila Based on Direct Sequencing of Nascent Transcripts

    Directory of Open Access Journals (Sweden)

    Francesco Ferrari

    2013-11-01

    Full Text Available Dosage compensation in Drosophila is mediated by the MSL complex, which increases male X-linked gene expression approximately 2-fold. The MSL complex preferentially binds the bodies of active genes on the male X, depositing H4K16ac with a 3′ bias. Two models have been proposed for the influence of the MSL complex on transcription: one based on promoter recruitment of RNA polymerase II (Pol II, and a second featuring enhanced transcriptional elongation. Here, we utilize nascent RNA sequencing to document dosage compensation during transcriptional elongation. We also compare X and autosomes from published data on paused and elongating polymerase in order to assess the role of Pol II recruitment. Our results support a model for differentially regulated elongation, starting with release from 5′ pausing and increasing through X-linked gene bodies. Our results highlight facilitated transcriptional elongation as a key mechanism for the coordinated regulation of a diverse set of genes.

  19. Condensin-driven remodelling of X chromosome topology during dosage compensation

    Science.gov (United States)

    Crane, Emily; Bian, Qian; McCord, Rachel Patton; Lajoie, Bryan R.; Wheeler, Bayly S.; Ralston, Edward J.; Uzawa, Satoru; Dekker, Job; Meyer, Barbara J.

    2015-07-01

    The three-dimensional organization of a genome plays a critical role in regulating gene expression, yet little is known about the machinery and mechanisms that determine higher-order chromosome structure. Here we perform genome-wide chromosome conformation capture analysis, fluorescent in situ hybridization (FISH), and RNA-seq to obtain comprehensive three-dimensional (3D) maps of the Caenorhabditis elegans genome and to dissect X chromosome dosage compensation, which balances gene expression between XX hermaphrodites and XO males. The dosage compensation complex (DCC), a condensin complex, binds to both hermaphrodite X chromosomes via sequence-specific recruitment elements on X (rex sites) to reduce chromosome-wide gene expression by half. Most DCC condensin subunits also act in other condensin complexes to control the compaction and resolution of all mitotic and meiotic chromosomes. By comparing chromosome structure in wild-type and DCC-defective embryos, we show that the DCC remodels hermaphrodite X chromosomes into a sex-specific spatial conformation distinct from autosomes. Dosage-compensated X chromosomes consist of self-interacting domains (~1 Mb) resembling mammalian topologically associating domains (TADs). TADs on X chromosomes have stronger boundaries and more regular spacing than on autosomes. Many TAD boundaries on X chromosomes coincide with the highest-affinity rex sites and become diminished or lost in DCC-defective mutants, thereby converting the topology of X to a conformation resembling autosomes. rex sites engage in DCC-dependent long-range interactions, with the most frequent interactions occurring between rex sites at DCC-dependent TAD boundaries. These results imply that the DCC reshapes the topology of X chromosomes by forming new TAD boundaries and reinforcing weak boundaries through interactions between its highest-affinity binding sites. As this model predicts, deletion of an endogenous rex site at a DCC-dependent TAD boundary using

  20. Expansion of GA Dinucleotide Repeats Increases the Density of CLAMP Binding Sites on the X-Chromosome to Promote Drosophila Dosage Compensation.

    Directory of Open Access Journals (Sweden)

    Guray Kuzu

    2016-07-01

    Full Text Available Dosage compensation is an essential process that equalizes transcript levels of X-linked genes between sexes by forming a domain of coordinated gene expression. Throughout the evolution of Diptera, many different X-chromosomes acquired the ability to be dosage compensated. Once each newly evolved X-chromosome is targeted for dosage compensation in XY males, its active genes are upregulated two-fold to equalize gene expression with XX females. In Drosophila melanogaster, the CLAMP zinc finger protein links the dosage compensation complex to the X-chromosome. However, the mechanism for X-chromosome identification has remained unknown. Here, we combine biochemical, genomic and evolutionary approaches to reveal that expansion of GA-dinucleotide repeats likely accumulated on the X-chromosome over evolutionary time to increase the density of CLAMP binding sites, thereby driving the evolution of dosage compensation. Overall, we present new insight into how subtle changes in genomic architecture, such as expansions of a simple sequence repeat, promote the evolution of coordinated gene expression.

  1. Weird mammals provide insights into the evolution of mammalian sex chromosomes and dosage compensation.

    Science.gov (United States)

    Graves, Jennifer A Marshall

    2015-12-01

    The deep divergence of mammalian groups 166 and 190 million years ago (MYA) provide genetic variation to explore the evolution of DNA sequence, gene arrangement and regulation of gene expression in mammals. With encouragement from the founder of the field, Mary Lyon, techniques in cytogenetics and molecular biology were progressively adapted to characterize the sex chromosomes of kangaroos and other marsupials, platypus and echidna-and weird rodent species. Comparative gene mapping reveals the process of sex chromosome evolution from their inception 190 MYA (they are autosomal in platypus) to their inevitable end (the Y has disappeared in two rodent lineages). Our X and Y are relatively young, getting their start with the evolution of the sex-determining SRY gene, which triggered progressive degradation of the Y chromosome. Even more recently, sex chromosomes of placental mammals fused with an autosomal region which now makes up most of the Y. Exploration of gene activity patterns over four decades showed that dosage compensation via X-chromosome inactivation is unique to therian mammals, and that this whole chromosome control process is different in marsupials and absent in monotremes and reptiles, and birds. These differences can be exploited to deduce how mammalian sex chromosomes and epigenetic silencing evolved.

  2. Untangling the Contributions of Sex-Specific Gene Regulation and X-Chromosome Dosage to Sex-Biased Gene Expression in Caenorhabditis elegans

    Science.gov (United States)

    Kramer, Maxwell; Rao, Prashant; Ercan, Sevinc

    2016-01-01

    Dosage compensation mechanisms equalize the level of X chromosome expression between sexes. Yet the X chromosome is often enriched for genes exhibiting sex-biased, i.e., imbalanced expression. The relationship between X chromosome dosage compensation and sex-biased gene expression remains largely unexplored. Most studies determine sex-biased gene expression without distinguishing between contributions from X chromosome copy number (dose) and the animal’s sex. Here, we uncoupled X chromosome dose from sex-specific gene regulation in Caenorhabditis elegans to determine the effect of each on X expression. In early embryogenesis, when dosage compensation is not yet fully active, X chromosome dose drives the hermaphrodite-biased expression of many X-linked genes, including several genes that were shown to be responsible for hermaphrodite fate. A similar effect is seen in the C. elegans germline, where X chromosome dose contributes to higher hermaphrodite X expression, suggesting that lack of dosage compensation in the germline may have a role in supporting higher expression of X chromosomal genes with female-biased functions in the gonad. In the soma, dosage compensation effectively balances X expression between the sexes. As a result, somatic sex-biased expression is almost entirely due to sex-specific gene regulation. These results suggest that lack of dosage compensation in different tissues and developmental stages allow X chromosome copy number to contribute to sex-biased gene expression and function. PMID:27356611

  3. Sex chromosome-specific regulation in the Drosophila male germline but little evidence for chromosomal dosage compensation or meiotic inactivation.

    Directory of Open Access Journals (Sweden)

    Colin D Meiklejohn

    2011-08-01

    Full Text Available The evolution of heteromorphic sex chromosomes (e.g., XY in males or ZW in females has repeatedly elicited the evolution of two kinds of chromosome-specific regulation: dosage compensation--the equalization of X chromosome gene expression in males and females--and meiotic sex chromosome inactivation (MSCI--the transcriptional silencing and heterochromatinization of the X during meiosis in the male (or Z in the female germline. How the X chromosome is regulated in the Drosophila melanogaster male germline is unclear. Here we report three new findings concerning gene expression from the X in Drosophila testes. First, X chromosome-wide dosage compensation appears to be absent from most of the Drosophila male germline. Second, microarray analysis provides no evidence for X chromosome-specific inactivation during meiosis. Third, we confirm the previous discovery that the expression of transgene reporters driven by autosomal spermatogenesis-specific promoters is strongly reduced when inserted on the X chromosome versus the autosomes; but we show that this chromosomal difference in expression is established in premeiotic cells and persists in meiotic cells. The magnitude of the X-autosome difference in transgene expression cannot be explained by the absence of dosage compensation, suggesting that a previously unrecognized mechanism limits expression from the X during spermatogenesis in Drosophila. These findings help to resolve several previously conflicting reports and have implications for patterns of genome evolution and speciation in Drosophila.

  4. Tissue- and stage-dependent dosage compensation on the Neo-X chromosome in drosophila pseudoobscura

    KAUST Repository

    Nozawa, Masafumi

    2013-12-03

    Sex chromosome dosage compensation (DC) is widely accepted in various organisms. This concept is mostly supported by comparisons of gene expression between chromosomes and between sexes. However, genes on the X chromosome and autosomes are mostly not homologous, and the average gene expression level on these chromosomes may not be the same even under DC, which complicates comparisons between chromosomes. Many genes with sex-biased expression also make comparisons between sexes difficult. To overcome these issues, we investigated DC by comparing the expression of neo-X-linked genes in Drosophila pseudoobscura with those of their autosomal orthologs in other Drosophila species. The ratio of the former to the latter in males would be 1 under DC, whereas it becomes 0.5 without DC. We found that the ratio was ∼0.85 for adult whole bodies, indicating that the DC is incomplete on the neo-X chromosome in adults as a whole. The ratio (∼0.90) was also significantly less than 1 for adult bodies without gonads, whereas it was ∼1.0 for adult heads. These results indicate that DC varies among tissues. Our sliding-window analysis of the ratio also revealed that the upregulation of neo-X-linked genes in males occurred chromosome wide in all tissues analyzed, indicating global upregulation mechanisms. However, we found that gene functions also affected the levels of DC. Furthermore, most of the genes recently moved to the X were already under DC at the larval stage but not at the adult stage. These results suggest that DC in Drosophila species operates in a tissue/stage-dependent manner. © 2013 The Author 2013. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved.

  5. Avian sex, sex chromosomes, and dosage compensation in the age of genomics.

    Science.gov (United States)

    Graves, Jennifer A Marshall

    2014-04-01

    Comparisons of the sex chromosome systems in birds and mammals are widening our view and deepening our understanding of vertebrate sex chromosome organization, function, and evolution. Birds have a very conserved ZW system of sex determination in which males have two copies of a large, gene-rich Z chromosome, and females have a single Z and a female-specific W chromosome. The avian ZW system is quite the reverse of the well-studied mammalian XY chromosome system, and evolved independently from different autosomal blocs. Despite the different gene content of mammal and bird sex chromosomes, there are many parallels. Genes on the bird Z and the mammal X have both undergone selection for male-advantage functions, and there has been amplification of male-advantage genes and accumulation of LINEs. The bird W and mammal Y have both undergone extensive degradation, but some birds retain early stages and some mammals terminal stages of the process, suggesting that the process is more advanced in mammals. Different sex-determining genes, DMRT1 and SRY, define the ZW and XY systems, but DMRT1 is involved in downstream events in mammals. Birds show strong cell autonomous specification of somatic sex differences in ZZ and ZW tissue, but there is growing evidence for direct X chromosome effects on sexual phenotype in mammals. Dosage compensation in birds appears to be phenotypically and molecularly quite different from X inactivation, being partial and gene-specific, but both systems use tools from the same molecular toolbox and there are some signs that galliform birds represent an early stage in the evolution of a coordinated system.

  6. Purifying Selection Maintains Dosage-Sensitive Genes during Degeneration of the Threespine Stickleback Y Chromosome

    Science.gov (United States)

    White, Michael A.; Kitano, Jun; Peichel, Catherine L.

    2015-01-01

    Sex chromosomes are subject to unique evolutionary forces that cause suppression of recombination, leading to sequence degeneration and the formation of heteromorphic chromosome pairs (i.e., XY or ZW). Although progress has been made in characterizing the outcomes of these evolutionary processes on vertebrate sex chromosomes, it is still unclear how recombination suppression and sequence divergence typically occur and how gene dosage imbalances are resolved in the heterogametic sex. The threespine stickleback fish (Gasterosteus aculeatus) is a powerful model system to explore vertebrate sex chromosome evolution, as it possesses an XY sex chromosome pair at relatively early stages of differentiation. Using a combination of whole-genome and transcriptome sequencing, we characterized sequence evolution and gene expression across the sex chromosomes. We uncovered two distinct evolutionary strata that correspond with known structural rearrangements on the Y chromosome. In the oldest stratum, only a handful of genes remain, and these genes are under strong purifying selection. By comparing sex-linked gene expression with expression of autosomal orthologs in an outgroup, we show that dosage compensation has not evolved in threespine sticklebacks through upregulation of the X chromosome in males. Instead, in the oldest stratum, the genes that still possess a Y chromosome allele are enriched for genes predicted to be dosage sensitive in mammals and yeast. Our results suggest that dosage imbalances may have been avoided at haploinsufficient genes by retaining function of the Y chromosome allele through strong purifying selection. PMID:25818858

  7. Sequence-specific targeting of dosage compensation in Drosophila favors an active chromatin context.

    Directory of Open Access Journals (Sweden)

    Artyom A Alekseyenko

    Full Text Available The Drosophila MSL complex mediates dosage compensation by increasing transcription of the single X chromosome in males approximately two-fold. This is accomplished through recognition of the X chromosome and subsequent acetylation of histone H4K16 on X-linked genes. Initial binding to the X is thought to occur at "entry sites" that contain a consensus sequence motif ("MSL recognition element" or MRE. However, this motif is only ∼2 fold enriched on X, and only a fraction of the motifs on X are initially targeted. Here we ask whether chromatin context could distinguish between utilized and non-utilized copies of the motif, by comparing their relative enrichment for histone modifications and chromosomal proteins mapped in the modENCODE project. Through a comparative analysis of the chromatin features in male S2 cells (which contain MSL complex and female Kc cells (which lack the complex, we find that the presence of active chromatin modifications, together with an elevated local GC content in the surrounding sequences, has strong predictive value for functional MSL entry sites, independent of MSL binding. We tested these sites for function in Kc cells by RNAi knockdown of Sxl, resulting in induction of MSL complex. We show that ectopic MSL expression in Kc cells leads to H4K16 acetylation around these sites and a relative increase in X chromosome transcription. Collectively, our results support a model in which a pre-existing active chromatin environment, coincident with H3K36me3, contributes to MSL entry site selection. The consequences of MSL targeting of the male X chromosome include increase in nucleosome lability, enrichment for H4K16 acetylation and JIL-1 kinase, and depletion of linker histone H1 on active X-linked genes. Our analysis can serve as a model for identifying chromatin and local sequence features that may contribute to selection of functional protein binding sites in the genome.

  8. Comparative Sex Chromosome Genomics in Snakes: Differentiation, Evolutionary Strata, and Lack of Global Dosage Compensation

    Science.gov (United States)

    Zektser, Yulia; Mahajan, Shivani; Bachtrog, Doris

    2013-01-01

    Snakes exhibit genetic sex determination, with female heterogametic sex chromosomes (ZZ males, ZW females). Extensive cytogenetic work has suggested that the level of sex chromosome heteromorphism varies among species, with Boidae having entirely homomorphic sex chromosomes, Viperidae having completely heteromorphic sex chromosomes, and Colubridae showing partial differentiation. Here, we take a genomic approach to compare sex chromosome differentiation in these three snake families. We identify homomorphic sex chromosomes in boas (Boidae), but completely heteromorphic sex chromosomes in both garter snakes (Colubridae) and pygmy rattlesnake (Viperidae). Detection of W-linked gametologs enables us to establish the presence of evolutionary strata on garter and pygmy rattlesnake sex chromosomes where recombination was abolished at different time points. Sequence analysis shows that all strata are shared between pygmy rattlesnake and garter snake, i.e., recombination was abolished between the sex chromosomes before the two lineages diverged. The sex-biased transmission of the Z and its hemizygosity in females can impact patterns of molecular evolution, and we show that rates of evolution for Z-linked genes are increased relative to their pseudoautosomal homologs, both at synonymous and amino acid sites (even after controlling for mutational biases). This demonstrates that mutation rates are male-biased in snakes (male-driven evolution), but also supports faster-Z evolution due to differential selective effects on the Z. Finally, we perform a transcriptome analysis in boa and pygmy rattlesnake to establish baseline levels of sex-biased expression in homomorphic sex chromosomes, and show that heteromorphic ZW chromosomes in rattlesnakes lack chromosome-wide dosage compensation. Our study provides the first full scale overview of the evolution of snake sex chromosomes at the genomic level, thus greatly expanding our knowledge of reptilian and vertebrate sex chromosomes

  9. Neural expression and post-transcriptional dosage compensation of the steroid metabolic enzyme 17β-HSD type 4

    Directory of Open Access Journals (Sweden)

    Wise Petra M

    2010-04-01

    Full Text Available Abstract Background Steroids affect many tissues, including the brain. In the zebra finch, the estrogenic steroid estradiol (E2 is especially effective at promoting growth of the neural circuit specialized for song. In this species, only the males sing and they have a much larger and more interconnected song circuit than females. Thus, it was surprising that the gene for 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4, an enzyme that converts E2 to a less potent estrogen, had been mapped to the Z sex chromosome. As a consequence, it was likely that HSD17B4 was differentially expressed in males (ZZ and females (ZW because dosage compensation of Z chromosome genes is incomplete in birds. If a higher abundance of HSD17B4 mRNA in males than females was translated into functional enzyme in the brain, then contrary to expectation, males could produce less E2 in their brains than females. Results Here, we used molecular and biochemical techniques to confirm the HSD17B4 Z chromosome location in the zebra finch and to determine that HSD17B4 mRNA and activity were detectable in the early developing and adult brain. As expected, HSD17B4 mRNA expression levels were higher in males compared to females. This provides further evidence of the incomplete Z chromosome inactivation mechanisms in birds. We detected HSD17B4 mRNA in regions that suggested a role for this enzyme in the early organization and adult function of song nuclei. We did not, however, detect significant sex differences in HSD17B4 activity levels in the adult brain. Conclusions Our results demonstrate that the HSD17B4 gene is expressed and active in the zebra finch brain as an E2 metabolizing enzyme, but that dosage compensation of this Z-linked gene may occur via post-transcriptional mechanisms.

  10. Maintenance and Loss of Duplicated Genes by Dosage Subfunctionalization.

    Science.gov (United States)

    Gout, Jean-Francois; Lynch, Michael

    2015-08-01

    Whole-genome duplications (WGDs) have contributed to gene-repertoire enrichment in many eukaryotic lineages. However, most duplicated genes are eventually lost and it is still unclear why some duplicated genes are evolutionary successful whereas others quickly turn to pseudogenes. Here, we show that dosage constraints are major factors opposing post-WGD gene loss in several Paramecium species that share a common ancestral WGD. We propose a model where a majority of WGD-derived duplicates preserve their ancestral function and are retained to produce enough of the proteins performing this same ancestral function. Under this model, the expression level of individual duplicated genes can evolve neutrally as long as they maintain a roughly constant summed expression, and this allows random genetic drift toward uneven contributions of the two copies to total expression. Our analysis suggests that once a high level of imbalance is reached, which can require substantial lengths of time, the copy with the lowest expression level contributes a small enough fraction of the total expression that selection no longer opposes its loss. Extension of our analysis to yeast species sharing a common ancestral WGD yields similar results, suggesting that duplicated-gene retention for dosage constraints followed by divergence in expression level and eventual deterministic gene loss might be a universal feature of post-WGD evolution. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. The relationship among gene expression, the evolution of gene dosage, and the rate of protein evolution.

    Directory of Open Access Journals (Sweden)

    Jean-François Gout

    2010-05-01

    Full Text Available The understanding of selective constraints affecting genes is a major issue in biology. It is well established that gene expression level is a major determinant of the rate of protein evolution, but the reasons for this relationship remain highly debated. Here we demonstrate that gene expression is also a major determinant of the evolution of gene dosage: the rate of gene losses after whole genome duplications in the Paramecium lineage is negatively correlated to the level of gene expression, and this relationship is not a byproduct of other factors known to affect the fate of gene duplicates. This indicates that changes in gene dosage are generally more deleterious for highly expressed genes. This rule also holds for other taxa: in yeast, we find a clear relationship between gene expression level and the fitness impact of reduction in gene dosage. To explain these observations, we propose a model based on the fact that the optimal expression level of a gene corresponds to a trade-off between the benefit and cost of its expression. This COSTEX model predicts that selective pressure against mutations changing gene expression level or affecting the encoded protein should on average be stronger in highly expressed genes and hence that both the frequency of gene loss and the rate of protein evolution should correlate negatively with gene expression. Thus, the COSTEX model provides a simple and common explanation for the general relationship observed between the level of gene expression and the different facets of gene evolution.

  12. Gene expression analysis identifies global gene dosage sensitivity in cancer

    DEFF Research Database (Denmark)

    Fehrmann, Rudolf S. N.; Karjalainen, Juha M.; Krajewska, Malgorzata

    2015-01-01

    Many cancer-associated somatic copy number alterations (SCNAs) are known. Currently, one of the challenges is to identify the molecular downstream effects of these variants. Although several SCNAs are known to change gene expression levels, it is not clear whether each individual SCNA affects gen...

  13. Chromosome X-wide association study identifies Loci for fasting insulin and height and evidence for incomplete dosage compensation.

    Science.gov (United States)

    Tukiainen, Taru; Pirinen, Matti; Sarin, Antti-Pekka; Ladenvall, Claes; Kettunen, Johannes; Lehtimäki, Terho; Lokki, Marja-Liisa; Perola, Markus; Sinisalo, Juha; Vlachopoulou, Efthymia; Eriksson, Johan G; Groop, Leif; Jula, Antti; Järvelin, Marjo-Riitta; Raitakari, Olli T; Salomaa, Veikko; Ripatti, Samuli

    2014-02-01

    The X chromosome (chrX) represents one potential source for the "missing heritability" for complex phenotypes, which thus far has remained underanalyzed in genome-wide association studies (GWAS). Here we demonstrate the benefits of including chrX in GWAS by assessing the contribution of 404,862 chrX SNPs to levels of twelve commonly studied cardiometabolic and anthropometric traits in 19,697 Finnish and Swedish individuals with replication data on 5,032 additional Finns. By using a linear mixed model, we estimate that on average 2.6% of the additive genetic variance in these twelve traits is attributable to chrX, this being in proportion to the number of SNPs in the chromosome. In a chrX-wide association analysis, we identify three novel loci: two for height (rs182838724 near FGF16/ATRX/MAGT1, joint P-value = 2.71×10(-9), and rs1751138 near ITM2A, P-value = 3.03×10(-10)) and one for fasting insulin (rs139163435 in Xq23, P-value = 5.18×10(-9)). Further, we find that effect sizes for variants near ITM2A, a gene implicated in cartilage development, show evidence for a lack of dosage compensation. This observation is further supported by a sex-difference in ITM2A expression in whole blood (P-value = 0.00251), and is also in agreement with a previous report showing ITM2A escapes from X chromosome inactivation (XCI) in the majority of women. Hence, our results show one of the first links between phenotypic variation in a population sample and an XCI-escaping locus and pinpoint ITM2A as a potential contributor to the sexual dimorphism in height. In conclusion, our study provides a clear motivation for including chrX in large-scale genetic studies of complex diseases and traits.

  14. Chromosome X-wide association study identifies Loci for fasting insulin and height and evidence for incomplete dosage compensation.

    Directory of Open Access Journals (Sweden)

    Taru Tukiainen

    2014-02-01

    Full Text Available The X chromosome (chrX represents one potential source for the "missing heritability" for complex phenotypes, which thus far has remained underanalyzed in genome-wide association studies (GWAS. Here we demonstrate the benefits of including chrX in GWAS by assessing the contribution of 404,862 chrX SNPs to levels of twelve commonly studied cardiometabolic and anthropometric traits in 19,697 Finnish and Swedish individuals with replication data on 5,032 additional Finns. By using a linear mixed model, we estimate that on average 2.6% of the additive genetic variance in these twelve traits is attributable to chrX, this being in proportion to the number of SNPs in the chromosome. In a chrX-wide association analysis, we identify three novel loci: two for height (rs182838724 near FGF16/ATRX/MAGT1, joint P-value = 2.71×10(-9, and rs1751138 near ITM2A, P-value = 3.03×10(-10 and one for fasting insulin (rs139163435 in Xq23, P-value = 5.18×10(-9. Further, we find that effect sizes for variants near ITM2A, a gene implicated in cartilage development, show evidence for a lack of dosage compensation. This observation is further supported by a sex-difference in ITM2A expression in whole blood (P-value = 0.00251, and is also in agreement with a previous report showing ITM2A escapes from X chromosome inactivation (XCI in the majority of women. Hence, our results show one of the first links between phenotypic variation in a population sample and an XCI-escaping locus and pinpoint ITM2A as a potential contributor to the sexual dimorphism in height. In conclusion, our study provides a clear motivation for including chrX in large-scale genetic studies of complex diseases and traits.

  15. Switch between life history strategies due to changes in glycolytic enzyme gene dosage in Saccharomyces cerevisiae.

    Science.gov (United States)

    Wang, Shaoxiao; Spor, Aymé; Nidelet, Thibault; Montalent, Pierre; Dillmann, Christine; de Vienne, Dominique; Sicard, Delphine

    2011-01-01

    Adaptation is the process whereby a population or species becomes better fitted to its habitat through modifications of various life history traits which can be positively or negatively correlated. The molecular factors underlying these covariations remain to be elucidated. Using Saccharomyces cerevisiae as a model system, we have investigated the effects on life history traits of varying the dosage of genes involved in the transformation of resources into energy. Changing gene dosage for each of three glycolytic enzyme genes (hexokinase 2, phosphoglucose isomerase, and fructose-1,6-bisphosphate aldolase) resulted in variation in enzyme activities, glucose consumption rate, and life history traits (growth rate, carrying capacity, and cell size). However, the range of effects depended on which enzyme was expressed differently. Most interestingly, these changes revealed a genetic trade-off between carrying capacity and cell size, supporting the discovery of two extreme life history strategies already described in yeast populations: the "ants," which have lower glycolytic gene dosage, take up glucose slowly, and have a small cell size but reach a high carrying capacity, and the "grasshoppers," which have higher glycolytic gene dosage, consume glucose more rapidly, and allocate it to a larger cell size but reach a lower carrying capacity. These results demonstrate antagonist pleiotropy for glycolytic genes and show that altered dosage of a single gene drives a switch between two life history strategies in yeast.

  16. ACE-it: a tool for genome-wide integration of gene dosage and RNA expression data

    NARCIS (Netherlands)

    van Wieringen, W.N.; Belien, J.A.M.; Vosse, S.; Achame, E.M.; Ylstra, B.

    2006-01-01

    Summary: We describe a tool, called ACE-it (Array CGH Expression integration tool). ACE-it links the chromosomal position of the gene dosage measured by array CGH to the genes measured by the expression array. ACE-it uses this link to statistically test whether gene dosage affects RNA expression. ©

  17. Gene dosage, expression, and ontology analysis identifies driver genes in the carcinogenesis and chemoradioresistance of cervical cancer.

    Directory of Open Access Journals (Sweden)

    Malin Lando

    2009-11-01

    Full Text Available Integrative analysis of gene dosage, expression, and ontology (GO data was performed to discover driver genes in the carcinogenesis and chemoradioresistance of cervical cancers. Gene dosage and expression profiles of 102 locally advanced cervical cancers were generated by microarray techniques. Fifty-two of these patients were also analyzed with the Illumina expression method to confirm the gene expression results. An independent cohort of 41 patients was used for validation of gene expressions associated with clinical outcome. Statistical analysis identified 29 recurrent gains and losses and 3 losses (on 3p, 13q, 21q associated with poor outcome after chemoradiotherapy. The intratumor heterogeneity, assessed from the gene dosage profiles, was low for these alterations, showing that they had emerged prior to many other alterations and probably were early events in carcinogenesis. Integration of the alterations with gene expression and GO data identified genes that were regulated by the alterations and revealed five biological processes that were significantly overrepresented among the affected genes: apoptosis, metabolism, macromolecule localization, translation, and transcription. Four genes on 3p (RYBP, GBE1 and 13q (FAM48A, MED4 correlated with outcome at both the gene dosage and expression level and were satisfactorily validated in the independent cohort. These integrated analyses yielded 57 candidate drivers of 24 genetic events, including novel loci responsible for chemoradioresistance. Further mapping of the connections among genetic events, drivers, and biological processes suggested that each individual event stimulates specific processes in carcinogenesis through the coordinated control of multiple genes. The present results may provide novel therapeutic opportunities of both early and advanced stage cervical cancers.

  18. Overexpression screens identify conserved dosage chromosome instability genes in yeast and human cancer

    Science.gov (United States)

    Duffy, Supipi; Fam, Hok Khim; Wang, Yi Kan; Styles, Erin B.; Kim, Jung-Hyun; Ang, J. Sidney; Singh, Tejomayee; Larionov, Vladimir; Shah, Sohrab P.; Andrews, Brenda; Boerkoel, Cornelius F.; Hieter, Philip

    2016-01-01

    Somatic copy number amplification and gene overexpression are common features of many cancers. To determine the role of gene overexpression on chromosome instability (CIN), we performed genome-wide screens in the budding yeast for yeast genes that cause CIN when overexpressed, a phenotype we refer to as dosage CIN (dCIN), and identified 245 dCIN genes. This catalog of genes reveals human orthologs known to be recurrently overexpressed and/or amplified in tumors. We show that two genes, TDP1, a tyrosyl-DNA-phosphdiesterase, and TAF12, an RNA polymerase II TATA-box binding factor, cause CIN when overexpressed in human cells. Rhabdomyosarcoma lines with elevated human Tdp1 levels also exhibit CIN that can be partially rescued by siRNA-mediated knockdown of TDP1. Overexpression of dCIN genes represents a genetic vulnerability that could be leveraged for selective killing of cancer cells through targeting of an unlinked synthetic dosage lethal (SDL) partner. Using SDL screens in yeast, we identified a set of genes that when deleted specifically kill cells with high levels of Tdp1. One gene was the histone deacetylase RPD3, for which there are known inhibitors. Both HT1080 cells overexpressing hTDP1 and rhabdomyosarcoma cells with elevated levels of hTdp1 were more sensitive to histone deacetylase inhibitors valproic acid (VPA) and trichostatin A (TSA), recapitulating the SDL interaction in human cells and suggesting VPA and TSA as potential therapeutic agents for tumors with elevated levels of hTdp1. The catalog of dCIN genes presented here provides a candidate list to identify genes that cause CIN when overexpressed in cancer, which can then be leveraged through SDL to selectively target tumors. PMID:27551064

  19. Mapping 22q11.2 Gene Dosage Effects on Brain Morphometry.

    Science.gov (United States)

    Lin, Amy; Ching, Christopher R K; Vajdi, Ariana; Sun, Daqiang; Jonas, Rachel K; Jalbrzikowski, Maria; Kushan-Wells, Leila; Pacheco Hansen, Laura; Krikorian, Emma; Gutman, Boris; Dokoru, Deepika; Helleman, Gerhard; Thompson, Paul M; Bearden, Carrie E

    2017-06-28

    Reciprocal chromosomal rearrangements at the 22q11.2 locus are associated with elevated risk of neurodevelopmental disorders. The 22q11.2 deletion confers the highest known genetic risk for schizophrenia, but a duplication in the same region is strongly associated with autism and is less common in schizophrenia cases than in the general population. Here we conducted the first study of 22q11.2 gene dosage effects on brain structure in a sample of 143 human subjects: 66 with 22q11.2 deletions (22q-del; 32 males), 21 with 22q11.2 duplications (22q-dup; 14 males), and 56 age- and sex-matched controls (31 males). 22q11.2 gene dosage varied positively with intracranial volume, gray and white matter volume, and cortical surface area (deletion control > duplication). Widespread differences were observed for cortical surface area with more localized effects on cortical thickness. These diametric patterns extended into subcortical regions: 22q-dup carriers had a significantly larger right hippocampus, on average, but lower right caudate and corpus callosum volume, relative to 22q-del carriers. Novel subcortical shape analysis revealed greater radial distance (thickness) of the right amygdala and left thalamus, and localized increases and decreases in subregions of the caudate, putamen, and hippocampus in 22q-dup relative to 22q-del carriers. This study provides the first evidence that 22q11.2 is a genomic region associated with gene-dose-dependent brain phenotypes. Pervasive effects on cortical surface area imply that this copy number variant affects brain structure early in the course of development. SIGNIFICANCE STATEMENT Probing naturally occurring reciprocal copy number variation in the genome may help us understand mechanisms underlying deviations from typical brain and cognitive development. The 22q11.2 genomic region is particularly susceptible to chromosomal rearrangements and contains many genes crucial for neuronal development and migration. Not surprisingly

  20. Gene Dosage Analysis in a Clinical Environment: Gene-Targeted Microarrays as the Platform-of-Choice

    Directory of Open Access Journals (Sweden)

    Donald R. Love

    2013-03-01

    Full Text Available The role of gene deletion and duplication in the aetiology of disease has become increasingly evident over the last decade. In addition to the classical deletion/duplication disorders diagnosed using molecular techniques, such as Duchenne Muscular Dystrophy and Charcot-Marie-Tooth Neuropathy Type 1A, the significance of partial or whole gene deletions in the pathogenesis of a large number single-gene disorders is becoming more apparent. A variety of dosage analysis methods are available to the diagnostic laboratory but the widespread application of many of these techniques is limited by the expense of the kits/reagents and restrictive targeting to a particular gene or portion of a gene. These limitations are particularly important in the context of a small diagnostic laboratory with modest sample throughput. We have developed a gene-targeted, custom-designed comparative genomic hybridisation (CGH array that allows twelve clinical samples to be interrogated simultaneously for exonic deletions/duplications within any gene (or panel of genes on the array. We report here on the use of the array in the analysis of a series of clinical samples processed by our laboratory over a twelve-month period. The array has proven itself to be robust, flexible and highly suited to the diagnostic environment.

  1. Feeding-Related Traits Are Affected by Dosage of the foraging Gene in Drosophila melanogaster.

    Science.gov (United States)

    Allen, Aaron M; Anreiter, Ina; Neville, Megan C; Sokolowski, Marla B

    2017-02-01

    Nutrient acquisition and energy storage are critical parts of achieving metabolic homeostasis. The foraging gene in Drosophila melanogaster has previously been implicated in multiple feeding-related and metabolic traits. Before foraging's functions can be further dissected, we need a precise genetic null mutant to definitively map its amorphic phenotypes. We used homologous recombination to precisely delete foraging, generating the for 0 null allele, and used recombineering to reintegrate a full copy of the gene, generating the {for BAC } rescue allele. We show that a total loss of foraging expression in larvae results in reduced larval path length and food intake behavior, while conversely showing an increase in triglyceride levels. Furthermore, varying foraging gene dosage demonstrates a linear dose-response on these phenotypes in relation to foraging gene expression levels. These experiments have unequivocally proven a causal, dose-dependent relationship between the foraging gene and its pleiotropic influence on these feeding-related traits. Our analysis of foraging's transcription start sites, termination sites, and splicing patterns using rapid amplification of cDNA ends (RACE) and full-length cDNA sequencing, revealed four independent promoters, pr1-4, that produce 21 transcripts with nine distinct open reading frames (ORFs). The use of alternative promoters and alternative splicing at the foraging locus creates diversity and flexibility in the regulation of gene expression, and ultimately function. Future studies will exploit these genetic tools to precisely dissect the isoform- and tissue-specific requirements of foraging's functions and shed light on the genetic control of feeding-related traits involved in energy homeostasis. Copyright © 2017 by the Genetics Society of America.

  2. Incorrect dosage of IQSEC2, a known intellectual disability and epilepsy gene, disrupts dendritic spine morphogenesis

    Science.gov (United States)

    Hinze, S J; Jackson, M R; Lie, S; Jolly, L; Field, M; Barry, S C; Harvey, R J; Shoubridge, C

    2017-01-01

    There is considerable genetic and phenotypic heterogeneity associated with intellectual disability (ID), specific learning disabilities, attention-deficit hyperactivity disorder, autism and epilepsy. The intelligence quotient (IQ) motif and SEC7 domain containing protein 2 gene (IQSEC2) is located on the X-chromosome and harbors mutations that contribute to non-syndromic ID with and without early-onset seizure phenotypes in both sexes. Although IQ and Sec7 domain mutations lead to partial loss of IQSEC2 enzymatic activity, the in vivo pathogenesis resulting from these mutations is not known. Here we reveal that IQSEC2 has a key role in dendritic spine morphology. Partial loss-of-function mutations were modeled using a lentiviral short hairpin RNA (shRNA) approach, which achieved a 57% knockdown of Iqsec2 expression in primary hippocampal cell cultures from mice. Investigating gross morphological parameters after 8 days of in vitro culture (8DIV) identified a 32% reduction in primary axon length, in contrast to a 27% and 31% increase in the number and complexity of dendrites protruding from the cell body, respectively. This increase in dendritic complexity and spread was carried through dendritic spine development, with a 34% increase in the number of protrusions per dendritic segment compared with controls at 15DIV. Although the number of dendritic spines had normalized by 21DIV, a reduction was noted in the number of immature spines. In contrast, when modeling increased dosage, overexpression of wild-type IQSEC2 led to neurons with shorter axons that were more compact and displayed simpler dendritic branching. Disturbances to dendritic morphology due to knockdown of Iqsec2 were recapitulated in neurons from Iqsec2 knockout mice generated in our laboratory using CRISPR/Cas9 technology. These observations provide evidence of dosage sensitivity for IQSEC2, which normally escapes X-inactivation in females, and links these disturbances in expression to alterations in

  3. The gene dosage effect of the rad52 mutation on X-ray survival curves of tetraploid yeast strains

    International Nuclear Information System (INIS)

    Ho, K.S.Y.

    1975-01-01

    The mutation rad52 in the yeast Saccharomyces cerevisiae confers sensitivity to X-rays. The gene dosage effect of this mutation on X-ray survival curves of tetraploid yeast strains is shown. With increasing number of rad52 alleles, both a decrease in the survival for a given dose and a decrease in the survival curve shoulder width are observed. The generation of such a family of survival curves using three different mathematical models is discussed

  4. GENE-dosage effects on fitness in recent adaptive duplications: ace-1 in the mosquito Culex pipiens.

    Science.gov (United States)

    Labbé, Pierrick; Milesi, Pascal; Yébakima, André; Pasteur, Nicole; Weill, Mylène; Lenormand, Thomas

    2014-07-01

    Gene duplications have long been advocated to contribute to the evolution of new functions. The role of selection in their early spread is more controversial. Unless duplications are favored for a direct benefit of increased expression, they are likely detrimental. In this article, we investigated the case of duplications favored because they combine already functionally divergent alleles. Their gene-dosage/fitness relations are poorly known because selection may operate on both overall expression and duplicates relative dosage. Using the well-documented case of Culex pipiens resistance to insecticides, we compared strains with various ace-1 allele combinations, including two duplicated alleles carrying both susceptible and resistant copies. The overall protein activity was nearly additive, but, surprisingly, fitness correlated better with the relative proportion of susceptible and resistant copies rather than any absolute measure of activity. Gene dosage is thus crucial, duplications stabilizing a "heterozygote" phenotype. It corroborates the view that these were favored because they fix a permanent heterosis, thereby solving the irreducible trade-off between resistance and synaptic transmission. Moreover, we showed that the contrasted successes of the two duplicated alleles in natural populations depend on genetic changes unrelated to ace-1, confirming the probable implication of recessive sublethal mutations linked to structural rearrangements in some duplications. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

  5. Gene dosage induction of silencing directed against an Arabidopsis Myb transgene in tobacco

    Science.gov (United States)

    An unexpected reduction in petal pigmentation on petunia plants genetically engineered for enhanced flower color was one of the first experimental demonstrations of the natural process of RNA-associated gene silencing. The obvious visual nature of such alterations to pigment patterns of transgenic ...

  6. Sprouty gene dosage influences temporal-spatial dynamics of primary enamel knot formation

    Czech Academy of Sciences Publication Activity Database

    Lochovská, Kateřina; Peterková, Renata; Pavlíková, Zuzana; Hovořáková, Mária

    2015-01-01

    Roč. 15, APR 22 (2015), s. 21 ISSN 1471-213X R&D Projects: GA ČR(CZ) GAP305/12/1766; GA ČR GB14-37368G Institutional support: RVO:68378041 Keywords : enamel knot * tooth development * mouse molar * sprouty genes * sonic hedgehog * cre-loxp system * supernumerary tooth Subject RIV: EA - Cell Biology Impact factor: 2.096, year: 2015

  7. Effects of starch synthase IIa gene dosage on grain, protein and starch in endosperm of wheat.

    Science.gov (United States)

    Konik-Rose, Christine; Thistleton, Jenny; Chanvrier, Helene; Tan, Ihwa; Halley, Peter; Gidley, Michael; Kosar-Hashemi, Behjat; Wang, Hong; Larroque, Oscar; Ikea, Joseph; McMaugh, Steve; Regina, Ahmed; Rahman, Sadequr; Morell, Matthew; Li, Zhongyi

    2007-11-01

    Starch synthases (SS) are responsible for elongating the alpha-1,4 glucan chains of starch. A doubled haploid population was generated by crossing a line of wheat, which lacks functional ssIIa genes on each genome (abd), and an Australian wheat cultivar, Sunco, with wild type ssIIa alleles on each genome (ABD). Evidence has been presented previously indicating that the SGP-1 (starch granule protein-1) proteins present in the starch granule in wheat are products of the ssIIa genes. Analysis of 100 progeny lines demonstrated co-segregation of the ssIIa alleles from the three genomes with the SGP-1 proteins, providing further evidence that the SGP-1 proteins are the products of the ssIIa genes. From the progeny lines, 40 doubled haploid lines representing the eight possible genotypes for SSIIa (ABD, aBD, AbD, ABd, abD, aBd, Abd, abd) were characterized for their grain weight, protein content, total starch content and starch properties. For some properties (chain length distribution, pasting properties, swelling power, and gelatinization properties), a progressive change was observed across the four classes of genotypes (wild type, single nulls, double nulls and triple nulls). However, for other grain properties (seed weight and protein content) and starch properties (total starch content, granule morphology and crystallinity, granule size distribution, amylose content, amylose-lipid dissociation properties), a statistically significant change only occurred for the triple nulls, indicating that all three genes had to be missing or inactive for a change to occur. These results illustrate the importance of SSIIa in controlling grain and starch properties and the importance of amylopectin fine structure in controlling starch granule properties in wheat.

  8. Patterns of evolutionary conservation of essential genes correlate with their compensability.

    Directory of Open Access Journals (Sweden)

    Tobias Bergmiller

    2012-06-01

    Full Text Available Essential genes code for fundamental cellular functions required for the viability of an organism. For this reason, essential genes are often highly conserved across organisms. However, this is not always the case: orthologues of genes that are essential in one organism are sometimes not essential in other organisms or are absent from their genomes. This suggests that, in the course of evolution, essential genes can be rendered nonessential. How can a gene become non-essential? Here we used genetic manipulation to deplete the products of 26 different essential genes in Escherichia coli. This depletion results in a lethal phenotype, which could often be rescued by the overexpression of a non-homologous, non-essential gene, most likely through replacement of the essential function. We also show that, in a smaller number of cases, the essential genes can be fully deleted from the genome, suggesting that complete functional replacement is possible. Finally, we show that essential genes whose function can be replaced in the laboratory are more likely to be non-essential or not present in other taxa. These results are consistent with the notion that patterns of evolutionary conservation of essential genes are influenced by their compensability-that is, by how easily they can be functionally replaced, for example through increased expression of other genes.

  9. Gene dosage effects of the imprinted delta-like homologue 1 (dlk1/pref1 in development: implications for the evolution of imprinting.

    Directory of Open Access Journals (Sweden)

    Simao Teixeira da Rocha

    2009-02-01

    Full Text Available Genomic imprinting is a normal process that causes genes to be expressed according to parental origin. The selective advantage conferred by imprinting is not understood but is hypothesised to act on dosage-critical genes. Here, we report a unique model in which the consequences of a single, double, and triple dosage of the imprinted Dlk1/Pref1, normally repressed on the maternally inherited chromosome, can be assessed in the growing embryo. BAC-transgenic mice were generated that over-express Dlk1 from endogenous regulators at all sites of embryonic activity. Triple dosage causes lethality associated with major organ abnormalities. Embryos expressing a double dose of Dlk1, recapitulating loss of imprinting, are growth enhanced but fail to thrive in early life, despite the early growth advantage. Thus, any benefit conferred by increased embryonic size is offset by postnatal lethality. We propose a negative correlation between gene dosage and survival that fixes an upper limit on growth promotion by Dlk1, and we hypothesize that trade-off between growth and lethality might have driven imprinting at this locus.

  10. X-chromosome gene dosage as a determinant of impaired pre and postnatal growth and adult height in Turner syndrome.

    Science.gov (United States)

    Fiot, Elodie; Zenaty, Delphine; Boizeau, Priscilla; Haigneré, Jeremy; Dos Santos, Sophie; Léger, Juliane

    2016-03-01

    Short stature is a key aspect of the phenotype of patients with Turner syndrome (TS). SHOX haploinsufficiency is responsible for about two-thirds of the height deficit. The aim was to investigate the effect of X-chromosome gene dosage on anthropometric parameters at birth, spontaneous height, and adult height (AH) after growth hormone (GH) treatment. We conducted a national observational multicenter study. Birth parameter SDS for gestational age, height, and AH before and after GH treatment respectively, and height deficit with respect to target height (SDS) were classified by karyotype subgroup in a cohort of 1501 patients with TS: 45,X (36%), isoXq (19%), 45,X/46,XX (15%), XrX (7%), presence of Y (6%), or other karyotypes (17%). Birth weight, length (P<0.0001), and head circumference (P<0.001), height and height deficit with respect to target height (SDS) before GH treatment, at a median age of 8.8 (5.3-11.8) years and after adjustment for age and correction for multiple testing (P<0.0001), and AH deficit with respect to target height at a median age of 19.3 (18.0-21.8) years and with additional adjustment for dose and duration of GH treatment (P=0.006), were significantly associated with karyotype subgroup. Growth retardation tended to be more severe in patients with XrX, isoXq, and, to a lesser extent, 45,X karyotypes than in patients with 45,X/46,XX karyotypes or a Y chromosome. These data suggest that haploinsufficiency for an unknown Xp gene increases the risk of fetal and postnatal growth deficit and short AH with respect to target height after GH therapy. © 2016 European Society of Endocrinology.

  11. C. elegans FOG-3/Tob can either promote or inhibit germline proliferation, depending on gene dosage and genetic context.

    Science.gov (United States)

    Snow, J J; Lee, M-H; Verheyden, J; Kroll-Conner, P L; Kimble, J

    2013-05-23

    Vertebrate Tob/BTG proteins inhibit cell proliferation when overexpressed in tissue-culture cells, and they can function as tumor suppressors in mice. The single Caenorhabditis elegans Tob/BTG ortholog, FOG-3, by contrast, was identified from its loss-of-function phenotype as a regulator of sperm fate specification. Here we report that FOG-3 also regulates proliferation in the germline tissue. We first demonstrate that FOG-3 is a positive regulator of germline proliferation. Thus, fog-3 null mutants possess fewer germ cells than normal, a modest but reproducible decrease observed for each of two distinct fog-3 null alleles. A similar decrease also occurred in fog-3/+ heterozygotes, again for both fog-3 alleles, revealing a haplo-insufficient effect on proliferation. Therefore, FOG-3 normally promotes proliferation, and two copies of the fog-3 gene are required for this function. We next overexpressed FOG-3 by removal of FBF, the collective term for FBF-1 and FBF-2, two nearly identical PUF RNA-binding proteins. We find that overexpressed FOG-3 blocks proliferation in fbf-1 fbf-2 mutants; whereas germ cells stop dividing and instead differentiate in fbf-1 fbf-2 double mutants, they continue to proliferate in fog-3; fbf-1 fbf-2 triple mutants. Therefore, like its vertebrate Tob/BTG cousins, overexpressed FOG-3 is 'antiproliferative'. Indeed, some fog-3; fbf-1 fbf-2 mutants possess small tumors, suggesting that FOG-3 can act as a tumor suppressor. Finally, we show that FOG-3 and FBF work together to promote tumor formation in animals carrying oncogenic Notch mutations. A similar effect was not observed when germline tumors were induced by manipulation of other regulators; therefore, this FOG-3 tumor-promoting effect is context dependent. We conclude that FOG-3 can either promote or inhibit proliferation in a manner that is sensitive to both genetic context and gene dosage. The discovery of these FOG-3 effects on proliferation has implications for our understanding of

  12. Radiation dosage

    Energy Technology Data Exchange (ETDEWEB)

    Finston, Roland [Health Physics, Stanford University, Stanford, CA (United States)

    1986-07-01

    Radiation dosage at Bikini Atoll is the result of current soil contamination, a relic of the nuclear weapons testing program of some 30 years ago. The principal contaminants today and some of their physical properties are listed: cesium-137, strontium-90, plutonium -239, 240 and americium-241. Cobalt-60 contributes less than 1 to the dose and is not considered significant. A resident of the atoll would accumulate radiation dose (rem) in two ways -- by exposure to radiation emanating from the ground and vegetation, and by exposure to radiation released in the spontaneous decay of radionuclides that have entered his body during the ingestion of locally grown foods. The latter process would account for some 90% of the dose; cesium-137 would be responsible for 0 90% of it. Since BARC's method of estimating dosage differs in some respects from that employed by the Lawrence Livermore National Laboratory (LLNL), (Ref.1, LLNL 1982) we are presenting our method in detail. The differences have two sources. First, the numbers used by BARC for the daily ingestion of radionuclides via the diet are higher than LLNL's. Second, BARC's calculation of dose from radionuclide intake utilizes the ICRP system. The net result is that BARC doses are consistently higher than LLNL doses, and in this respect are more conservative.

  13. Radiation dosage

    International Nuclear Information System (INIS)

    Finston, Roland

    1986-01-01

    Radiation dosage at Bikini Atoll is the result of current soil contamination, a relic of the nuclear weapons testing program of some 30 years ago. The principal contaminants today and some of their physical properties are listed: cesium-137, strontium-90, plutonium -239, 240 and americium-241. Cobalt-60 contributes less than 1 to the dose and is not considered significant. A resident of the atoll would accumulate radiation dose (rem) in two ways -- by exposure to radiation emanating from the ground and vegetation, and by exposure to radiation released in the spontaneous decay of radionuclides that have entered his body during the ingestion of locally grown foods. The latter process would account for some 90% of the dose; cesium-137 would be responsible for 0 90% of it. Since BARC's method of estimating dosage differs in some respects from that employed by the Lawrence Livermore National Laboratory (LLNL), (Ref.1, LLNL 1982) we are presenting our method in detail. The differences have two sources. First, the numbers used by BARC for the daily ingestion of radionuclides via the diet are higher than LLNL's. Second, BARC's calculation of dose from radionuclide intake utilizes the ICRP system. The net result is that BARC doses are consistently higher than LLNL doses, and in this respect are more conservative

  14. A TAD Closer to Understanding Dosage Compensation.

    Science.gov (United States)

    Wood, Andrew J; Bickmore, Wendy A

    2015-06-08

    Eukaryotic chromosomes are organized into topological domains, but how these are established and maintained is poorly understood. Writing in Nature, Crane et al. (2015) show that a specialized condensin complex enforces the domain boundaries along the C. elegans X chromosome to equalize transcription from the X between males and hermaphrodites. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Neurodevelopmental disorders associated with dosage imbalance of ZBTB20 correlate with the morbidity spectrum of ZBTB20 candidate target genes

    DEFF Research Database (Denmark)

    Rasmussen, Malene B; Nielsen, Jakob V; Lourenço, Charles M

    2014-01-01

    (SRO) involved five RefSeq genes, including the transcription factor gene ZBTB20 and the dopamine receptor gene DRD3, considered as candidate genes for the syndrome. METHODS AND RESULTS: We used array comparative genomic hybridization and next-generation mate-pair sequencing to identify key structural...... patient with developmental delay and autism, we detected the first microdeletion at 3q13.31, which truncated ZBTB20 but did not involve DRD3 or the other genes within the previously defined SRO. Zbtb20 directly represses 346 genes in the developing murine brain. Of the 342 human orthologous ZBTB20...

  16. Zebrafish homologs of genes within 16p11.2, a genomic region associated with brain disorders, are active during brain development, and include two deletion dosage sensor genes

    Directory of Open Access Journals (Sweden)

    Alicia Blaker-Lee

    2012-11-01

    Deletion or duplication of one copy of the human 16p11.2 interval is tightly associated with impaired brain function, including autism spectrum disorders (ASDs, intellectual disability disorder (IDD and other phenotypes, indicating the importance of gene dosage in this copy number variant region (CNV. The core of this CNV includes 25 genes; however, the number of genes that contribute to these phenotypes is not known. Furthermore, genes whose functional levels change with deletion or duplication (termed ‘dosage sensors’, which can associate the CNV with pathologies, have not been identified in this region. Using the zebrafish as a tool, a set of 16p11.2 homologs was identified, primarily on chromosomes 3 and 12. Use of 11 phenotypic assays, spanning the first 5 days of development, demonstrated that this set of genes is highly active, such that 21 out of the 22 homologs tested showed loss-of-function phenotypes. Most genes in this region were required for nervous system development – impacting brain morphology, eye development, axonal density or organization, and motor response. In general, human genes were able to substitute for the fish homolog, demonstrating orthology and suggesting conserved molecular pathways. In a screen for 16p11.2 genes whose function is sensitive to hemizygosity, the aldolase a (aldoaa and kinesin family member 22 (kif22 genes were identified as giving clear phenotypes when RNA levels were reduced by ∼50%, suggesting that these genes are deletion dosage sensors. This study leads to two major findings. The first is that the 16p11.2 region comprises a highly active set of genes, which could present a large genetic target and might explain why multiple brain function, and other, phenotypes are associated with this interval. The second major finding is that there are (at least two genes with deletion dosage sensor properties among the 16p11.2 set, and these could link this CNV to brain disorders such as ASD and IDD.

  17. Reciprocal Relationship between Head Size, an Autism Endophenotype, and Gene Dosage at 19p13.12 Points to AKAP8 and AKAP8L.

    Directory of Open Access Journals (Sweden)

    Rebecca A Nebel

    Full Text Available Microcephaly and macrocephaly are overrepresented in individuals with autism and are thought to be disease-related risk factors or endophenotypes. Analysis of DNA microarray results from a family with a low functioning autistic child determined that the proband and two additional unaffected family members who carry a rare inherited 760 kb duplication of unknown clinical significance at 19p13.12 are macrocephalic. Consideration alongside overlapping deletion and duplication events in the literature provides support for a strong relationship between gene dosage at this locus and head size, with losses and gains associated with microcephaly (p=1.11x10(-11 and macrocephaly (p=2.47x10(-11, respectively. Data support A kinase anchor protein 8 and 8-like (AKAP8 and AKAP8L as candidate genes involved in regulation of head growth, an interesting finding given previous work implicating the AKAP gene family in autism. Towards determination of which of AKAP8 and AKAP8L may be involved in the modulation of head size and risk for disease, we analyzed exome sequencing data for 693 autism families (2591 individuals where head circumference data were available. No predicted loss of function variants were observed, precluding insights into relationship to head size, but highlighting strong evolutionary conservation. Taken together, findings support the idea that gene dosage at 19p13.12, and AKAP8 and/or AKAP8L in particular, play an important role in modulation of head size and may contribute to autism risk. Exome sequencing of the family also identified a rare inherited variant predicted to disrupt splicing of TPTE / PTEN2, a PTEN homologue, which may likewise contribute to both macrocephaly and autism risk.

  18. Fear-Specific Amygdala Function in Children and Adolescents on the Fragile X Spectrum: A Dosage Response of the FMR1 Gene

    Science.gov (United States)

    Kim, So-Yeon; Burris, Jessica; Bassal, Frederick; Koldewyn, Kami; Chattarji, Sumantra; Tassone, Flora; Hessl, David; Rivera, Susan M.

    2014-01-01

    Mutations of the fragile X mental retardation 1 (FMR1) gene are the genetic cause of fragile X syndrome (FXS). The presence of significant socioemotional problems has been well documented in FXS although the brain basis of those deficits remains unspecified. Here, we investigated amygdala dysfunction and its relation to socioemotional deficits and FMR1 gene expression in children and adolescents on the FX spectrum (i.e., individuals whose trinucleotide CGG repeat expansion from 55 to over 200 places them somewhere within the fragile X diagnostic range from premutation to full mutation). Participants performed an fMRI task in which they viewed fearful, happy, and scrambled faces. Neuroimaging results demonstrated that FX participants revealed significantly attenuated amygdala activation in Fearful > Scrambled and Fearful > Happy contrasts compared with their neurotypical counterparts, while showing no differences in amygdala volume. Furthermore, we found significant relationships between FMR1 gene expression, anxiety/social dysfunction scores, and reduced amygdala activation in the FX group. In conclusion, we report novel evidence regarding a dosage response of the FMR1 gene on fear-specific functions of the amygdala, which is associated with socioemotional deficits in FXS. PMID:23146966

  19. [Gene polymorphism of CYP450 2C9 and VKORC1 in Chinese population and their relationships to the maintaining dosage of warfarin].

    Science.gov (United States)

    Zhang, Ya-nan; Cui, Wei; Han, Mei; Zheng, Bin; Liu, Fan; Xie, Rui-qin; Yang, Xiao-hong; Gu, Guo-qiang; Zheng, Hong-mei; Wen, Jin-kun

    2010-02-01

    To investigate the distribution of gene polymorphism of CYP450 2C9 and VKORC1-1639A/G in the Chinese population as well as the difference of genetic polymorphism between Chinese Han population and other ethnic populations. Contribution of CYP2C9 and VKORC1 genotype to the maintenance doses on warfarin was also studied. The genotype and allele frequencies were calculated and compared with those in other populations. One hundred and one patients with stable anticoagulation with warfarin under a target international normalized ratio (INR) of 2.0 to 3.0 were enrolled for studying the relationship between the CYP2C9 and VKORC1 gene polymorphism and the warfarin maintaining dosage. CYP450 2C9*3 + 1075C/A allele frequencies were:AA in 449 cases (92.2%), AC in 36 cases (7.4%) and CC in 2 cases (0.4%), respectively. VKORC1 -1639A/G allele frequencies were AA in 415 cases (85.2%), GA in 72 cases (14.8%), but GG in no case (0.0%), respectively. When linear stepwise regression analysis was used to identify factors contributing to warfarin stable dose, the final equation was: ln (D) = 0.346 + 0.017 (weight) - 0.376 (CYP450 2C9*3 + 1075C/A) + 0.148 (VKORC1-1639A/G) - 0.002 (age) (r = 0.827, P = 0.02). There existed significant gene polymorphism CYP450 2C9*3 + 1075C/A and VKORC1-1639A/G in the Chinese Han population. Both Gene polymorphisms of CYP450 2C9*3 + 1075C/A and VKORC1-1639A/G were significantly affecting the maintaining dose of warfarin in the Chinese population.

  20. Epilepsy caused by an abnormal alternative splicing with dosage effect of the SV2A gene in a chicken model.

    Directory of Open Access Journals (Sweden)

    Marine Douaud

    Full Text Available Photosensitive reflex epilepsy is caused by the combination of an individual's enhanced sensitivity with relevant light stimuli, such as stroboscopic lights or video games. This is the most common reflex epilepsy in humans; it is characterized by the photoparoxysmal response, which is an abnormal electroencephalographic reaction, and seizures triggered by intermittent light stimulation. Here, by using genetic mapping, sequencing and functional analyses, we report that a mutation in the acceptor site of the second intron of SV2A (the gene encoding synaptic vesicle glycoprotein 2A is causing photosensitive reflex epilepsy in a unique vertebrate model, the Fepi chicken strain, a spontaneous model where the neurological disorder is inherited as an autosomal recessive mutation. This mutation causes an aberrant splicing event and significantly reduces the level of SV2A mRNA in homozygous carriers. Levetiracetam, a second generation antiepileptic drug, is known to bind SV2A, and SV2A knock-out mice develop seizures soon after birth and usually die within three weeks. The Fepi chicken survives to adulthood and responds to levetiracetam, suggesting that the low-level expression of SV2A in these animals is sufficient to allow survival, but does not protect against seizures. Thus, the Fepi chicken model shows that the role of the SV2A pathway in the brain is conserved between birds and mammals, in spite of a large phylogenetic distance. The Fepi model appears particularly useful for further studies of physiopathology of reflex epilepsy, in comparison with induced models of epilepsy in rodents. Consequently, SV2A is a very attractive candidate gene for analysis in the context of both mono- and polygenic generalized epilepsies in humans.

  1. Knockout of the Gnrh genes in zebrafish: effects on reproduction and potential compensation by reproductive and feeding-related neuropeptides.

    Science.gov (United States)

    Marvel, Miranda; Spicer, Olivia Smith; Wong, Ten-Tsao; Zmora, Nilli; Zohar, Yonathan

    2018-04-04

    Gonadotropin-releasing hormone (GnRH) is known as a pivotal upstream regulator of reproduction in vertebrates. However, reproduction is not compromised in the hypophysiotropic Gnrh3 knockout line in zebrafish (gnrh3-/-). In order to determine if Gnrh2, the only other Gnrh isoform in zebrafish brains, is compensating for the loss of Gnrh3, we generated a double Gnrh knockout zebrafish line. Surprisingly, the loss of both Gnrh isoforms resulted in no major impact on reproduction, indicating that a compensatory response, outside of the Gnrh system, was evoked. A plethora of factors acting along the reproductive hypothalamus-pituitary axis were evaluated as possible compensators based on neuroanatomical and differential gene expression studies. In addition, we also examined the involvement of feeding factors in the brain as potential compensators for Gnrh2, which has known anorexigenic effects. We found that the double knockout fish exhibited upregulation of several genes in the brain, specifically gonadotropin-inhibitory hormone (gnih), secretogranin 2 (scg2), tachykinin 3a (tac3a), and pituitary adenylate cyclase-activating peptide 1 (pacap1), and downregulation of agouti-related peptide 1 (agrp1), indicating the compensation occurs outside of Gnrh cells and therefore is a non-cell autonomous response to the loss of Gnrh. While the differential expression of gnih and agrp1 in the double knockout line was confined to the periventricular nucleus and hypothalamus, respectively, the upregulation of scg2 corresponded with a broader neuronal redistribution in the lateral hypothalamus and hindbrain. In conclusion, our results demonstrate the existence of a redundant reproductive regulatory system that comes into play when Gnrh2 and Gnrh3 are lost.

  2. Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus

    Science.gov (United States)

    Jacquemont, Sébastien; Reymond, Alexandre; Zufferey, Flore; Harewood, Louise; Walters, Robin G.; Kutalik, Zoltán; Martinet, Danielle; Shen, Yiping; Valsesia, Armand; Beckmann, Noam D.; Thorleifsson, Gudmar; Belfiore, Marco; Bouquillon, Sonia; Campion, Dominique; De Leeuw, Nicole; De Vries, Bert B. A.; Esko, Tõnu; Fernandez, Bridget A.; Fernández-Aranda, Fernando; Fernández-Real, José Manuel; Gratacòs, Mònica; Guilmatre, Audrey; Hoyer, Juliane; Jarvelin, Marjo-Riitta; Kooy, Frank R.; Kurg, Ants; Le Caignec, Cédric; Männik, Katrin; Platt, Orah S.; Sanlaville, Damien; Van Haelst, Mieke M.; Villatoro Gomez, Sergi; Walha, Faida; Wu, Bai-Lin; Yu, Yongguo; Aboura, Azzedine; Addor, Marie-Claude; Alembik, Yves; Antonarakis, Stylianos E.; Arveiler, Benoît; Barth, Magalie; Bednarek, Nathalie; Béna, Frédérique; Bergmann, Sven; Beri, Mylène; Bernardini, Laura; Blaumeiser, Bettina; Bonneau, Dominique; Bottani, Armand; Boute, Odile; Brunner, Han G.; Cailley, Dorothée; Callier, Patrick; Chiesa, Jean; Chrast, Jacqueline; Coin, Lachlan; Coutton, Charles; Cuisset, Jean-Marie; Cuvellier, Jean-Christophe; David, Albert; De Freminville, Bénédicte; Delobel, Bruno; Delrue, Marie-Ange; Demeer, Bénédicte; Descamps, Dominique; Didelot, Gérard; Dieterich, Klaus; Disciglio, Vittoria; Doco-Fenzy, Martine; Drunat, Séverine; Duban-Bedu, Bénédicte; Dubourg, Christèle; El-Sayed Moustafa, Julia S.; Elliott, Paul; Faas, Brigitte H. W.; Faivre, Laurence; Faudet, Anne; Fellmann, Florence; Ferrarini, Alessandra; Fisher, Richard; Flori, Elisabeth; Forer, Lukas; Gaillard, Dominique; Gerard, Marion; Gieger, Christian; Gimelli, Stefania; Gimelli, Giorgio; Grabe, Hans J.; Guichet, Agnès; Guillin, Olivier; Hartikainen, Anna-Liisa; Heron, Délphine; Hippolyte, Loyse; Holder, Muriel; Homuth, Georg; Isidor, Bertrand; Jaillard, Sylvie; Jaros, Zdenek; Jiménez-Murcia, Susana; Joly Helas, Géraldine; Jonveaux, Philippe; Kaksonen, Satu; Keren, Boris; Kloss-Brandstätter, Anita; Knoers, Nine V. A. M.; Koolen, David A.; Kroisel, Peter M.; Kronenberg, Florian; Labalme, Audrey; Landais, Emilie; Lapi, Elisabetta; Layet, Valérie; Legallic, Solenn; Leheup, Bruno; Leube, Barbara; Lewis, Suzanne; Lucas, Josette; Macdermot, Kay D.; Magnusson, Pall; Marshall, Christian R.; Mathieu-Dramard, Michèle; Mccarthy, Mark I.; Meitinger, Thomas; Antonietta Mencarelli, Maria; Merla, Giuseppe; Moerman, Alexandre; Mooser, Vincent; Morice-Picard, Fanny; Mucciolo, Mafalda; Nauck, Matthias; Coumba Ndiaye, Ndeye; Nordgren, Ann; Pasquier, Laurent; Petit, Florence; Pfundt, Rolph; Plessis, Ghislaine; Rajcan-Separovic, Evica; Paolo Ramelli, Gian; Rauch, Anita; Ravazzolo, Roberto; Reis, Andre; Renieri, Alessandra; Richart, Cristobal; Ried, Janina S.; Rieubland, Claudine; Roberts, Wendy; Roetzer, Katharina M.; Rooryck, Caroline; Rossi, Massimiliano; Saemundsen, Evald; Satre, Véronique; Schurmann, Claudia; Sigurdsson, Engilbert; Stavropoulos, Dimitri J.; Stefansson, Hreinn; Tengström, Carola; Thorsteinsdóttir, Unnur; Tinahones, Francisco J.; Touraine, Renaud; Vallée, Louis; Van Binsbergen, Ellen; Van Der Aa, Nathalie; Vincent-Delorme, Catherine; Visvikis-Siest, Sophie; Vollenweider, Peter; Völzke, Henry; Vulto-Van Silfhout, Anneke T.; Waeber, Gérard; Wallgren-Pettersson, Carina; Witwicki, Robert M.; Zwolinksi, Simon; Andrieux, Joris; Estivill, Xavier; Gusella, James F.; Gustafsson, Omar; Metspalu, Andres; Scherer, Stephen W.; Stefansson, Kari; Blakemore, Alexandra I. F.; Beckmann, Jacques S.; Froguel, Philippe

    2011-01-01

    Both underweight and obesity have been associated with increased mortality1,2. Underweight, defined as body mass index (BMI) ≤ 18,5 kg/m2 in adults 3 and ≤ −2 standard deviations (SD) in children4,5, is the main sign of a series of heterogeneous clinical conditions such as failure to thrive (FTT) 6–8, feeding and eating disorder and/or anorexia nervosa9,10. In contrast to obesity, few genetic variants underlying these clinical conditions have been reported 11, 12. We previously demonstrated that hemizygosity of a ~600 kb region on the short arm of chromosome 16 (chr16:29.5–30.1Mb), causes a highly-penetrant form of obesity often associated with hyperphagia and intellectual disabilities13. Here we show that the corresponding reciprocal duplication is associated with underweight. We identified 138 (132 novel cases) duplication carriers (108 unrelated carriers) from over 95,000 individuals clinically-referred for developmental or intellectual disabilities (DD/ID), psychiatric disorders or recruited from population-based cohorts. These carriers show significantly reduced postnatal weight (mean Z-score −0.6; p=4.4×10−4) and BMI (mean Z-score −0.5; p=2.0×10−3). In particular, half of the boys younger than 5 years are underweight with a probable diagnosis of FTT, while adult duplication carriers have an 8.7-fold (p=5.9×10−11; CI_95=[4.5–16.6]) increased risk of being clinically underweight. We observe a significant trend towards increased severity in males, as well as a depletion of male carriers among non-medically ascertained cases. These features are associated with an unusually high frequency of selective and restrictive feeding behaviours and a significant reduction in head circumference (mean Z-score −0.9; p=7.8×10−6). Each of the observed phenotypes is the converse of one reported in carriers of deletions at this locus, correlating with changes in transcript levels for genes mapping within the duplication but not within flanking

  3. Integration of gene dosage and gene expression in non-small cell lung cancer, identification of HSP90 as potential target.

    Directory of Open Access Journals (Sweden)

    Mariëlle I Gallegos Ruiz

    Full Text Available BACKGROUND: Lung cancer causes approximately 1.2 million deaths per year worldwide, and non-small cell lung cancer (NSCLC represents 85% of all lung cancers. Understanding the molecular events in non-small cell lung cancer (NSCLC is essential to improve early diagnosis and treatment for this disease. METHODOLOGY AND PRINCIPAL FINDINGS: In an attempt to identify novel NSCLC related genes, we performed a genome-wide screening of chromosomal copy number changes affecting gene expression using microarray based comparative genomic hybridization and gene expression arrays on 32 radically resected tumor samples from stage I and II NSCLC patients. An integrative analysis tool was applied to determine whether chromosomal copy number affects gene expression. We identified a deletion on 14q32.2-33 as a common alteration in NSCLC (44%, which significantly influenced gene expression for HSP90, residing on 14q32. This deletion was correlated with better overall survival (P = 0.008, survival was also longer in patients whose tumors had low expression levels of HSP90. We extended the analysis to three independent validation sets of NSCLC patients, and confirmed low HSP90 expression to be related with longer overall survival (P = 0.003, P = 0.07 and P = 0.04. Furthermore, in vitro treatment with an HSP90 inhibitor had potent antiproliferative activity in NSCLC cell lines. CONCLUSIONS: We suggest that targeting HSP90 will have clinical impact for NSCLC patients.

  4. Possible gene dosage effect of glutathione-S-transferases on atopic asthma: using real-time PCR for quantification of GSTM1 and GSTT1 gene copy numbers

    DEFF Research Database (Denmark)

    Brasch-Andersen, Charlotte; Christiansen, L; Tan, Q

    2004-01-01

    -S-transferase (GST) involved in the antioxidant defense were tested for association to asthma using 246 Danish atopic families in a family-based transmission disequilibrium test (TDT) design. A real-time PCR assay for relative quantification of gene copy number of GSTM1 and GSTT1 was developed. The assay made......Asthma is a complex genetic disorder characterized by chronic inflammation in the airways. As oxidative stress is a key component of inflammation, variations in genes involved in antioxidant defense could therefore be likely candidates for asthma. Three enzymes from the superfamily glutathione...

  5. Intercavitary implants dosage calculation

    International Nuclear Information System (INIS)

    Rehder, B.P.

    The use of spacial geometry peculiar to each treatment for the attainment of intercavitary and intersticial implants dosage calculation is presented. The study is made in patients with intercavitary implants by applying a modified Manchester technique [pt

  6. Creative compensation

    International Nuclear Information System (INIS)

    Coll, D.

    1994-01-01

    A discussion is presented of executive compensation in Canada's petroleum industry. Mandatory disclosure of executive compensation and benefits is regulated by the Ontario Securities Commission. Examination of the compensation packages of 80 oilpatch CEOs shows a clear difference in philosophy between large and small companies. Larger companies pay larger salaries, offer pension plans, and reward long-term loyalty. Within smaller companies, compensation tends to be linked with stock performance. Trends in compensation are to lower base salaries with more variables such as bonuses, cash incentives and gain-sharing programs. Increasing shareholder scrutiny is prompting more stringent guidelines on stock option plans. Some companies place performance conditions on stock vesting. Another option is to grant premium priced options to executives, to increase the gains required for the executive to post a profit. Other comapanies are granting stock options to their field personnel, or are granting stock to all employees. Directors are playing an increasing role in executive compensation. 4 tabs

  7. Endotoxin dosage in sepsis

    Directory of Open Access Journals (Sweden)

    Vincenzo Rondinelli

    2012-03-01

    Full Text Available Introduction. Endotoxin, a component of the cell wall of Gram-negative bacteria is a major contributor to the pathogenesis of septic shock and multiple organ failure (MOF. Its entry into the bloodstream stimulates monocytes/macrophages which once activated produce and release cytokines, nitric oxide and other mediators that induce systemic inflammation, endothelial damage, organ dysfunction, hypotension (shock and MOF.The aim of this study is to evaluate the usefulness of a quantitative test for the dosage of endotoxin to determine the risk of severe Gram-negative sepsis. Materials and methods. In the period January 2009 - June 2011 we performed 897 tests for 765 patients, mostly coming from the emergency room and intensive care, of which 328 (43% women (mean age 53 and 437 (57% male (mean age 49. Fifty-nine patients, no statistically significant difference in sex, were monitored by an average of two determinations of EA.All patients had procalcitonin values significantly altered.The kit used was EAA (Endotoxin Activity Assay Estor Company, Milan, which has three ranges of endotoxin activity (EA: low risk of sepsis if <0.40 units, medium if between 0.40 and 0.59; high if 0.60. Results. 78 out of 765 patients (10% had a low risk, 447 (58% a medium risk and 240 (32% a high risk.The dosage of EA, combined with that of procalcitonin, has allowed a more targeted antibiotic therapy. Six patients in serious clinical conditions were treated by direct hemoperfusion with Toraymyxin, a device comprising a housing containing a fiber polypropylene and polystyrene with surface-bound polymyxin B, an antibiotic that removes bacterial endotoxins from the blood. Conclusions.The test is useful in risk stratification as well as Gram negative sepsis, to set and monitor targeted therapies, also based on the neutralization of endotoxin.

  8. Dosage changes of a segment at 17p13.1 lead to intellectual disability and microcephaly as a result of complex genetic interaction of multiple genes

    DEFF Research Database (Denmark)

    Carvalho, Claudia M B; Vasanth, Shivakumar; Shinawi, Marwan

    2014-01-01

    with copy-number variants (CNVs) on 17p13.1 for whom we performed detailed clinical and molecular studies. Breakpoint mapping and retrospective analysis of published cases refined the smallest region of overlap (SRO) for microcephaly to a genomic interval containing nine genes. Dissection of this phenotype...

  9. Genetic epidemiology of pharmacogenetic variations in CYP2C9, CYP4F2 and VKORC1 genes associated with warfarin dosage in the Indian population.

    Science.gov (United States)

    Giri, Anil K; Khan, Nazir M; Grover, Sandeep; Kaur, Ismeet; Basu, Analabha; Tandon, Nikhil; Scaria, Vinod; Kukreti, Ritushree; Brahmachari, Samir K; Bharadwaj, Dwaipayan

    2014-07-01

    study examining variants associated with warfarin that could potentially be valuable to clinicians in optimizing dosage strategies.

  10. Losses compensation; Compensation des pertes

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-07-01

    One mission of RTE (Electric Power Transportation), is to watch over the losses compensation resulting from the power transport on the electric power network. Since january 2001, RTE makes good the electric losses by the purchase of energy. To choose the marketers, a consultation has been realized by RTE. This document presents the rules concerning these losses compensation. (A.L.B.)

  11. Effects of Gene Dose, Chromatin, and Network Topology on Expression in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Hangnoh Lee

    2016-09-01

    Full Text Available Deletions, commonly referred to as deficiencies by Drosophila geneticists, are valuable tools for mapping genes and for genetic pathway discovery via dose-dependent suppressor and enhancer screens. More recently, it has become clear that deviations from normal gene dosage are associated with multiple disorders in a range of species including humans. While we are beginning to understand some of the transcriptional effects brought about by gene dosage changes and the chromosome rearrangement breakpoints associated with them, much of this work relies on isolated examples. We have systematically examined deficiencies of the left arm of chromosome 2 and characterize gene-by-gene dosage responses that vary from collapsed expression through modest partial dosage compensation to full or even over compensation. We found negligible long-range effects of creating novel chromosome domains at deletion breakpoints, suggesting that cases of gene regulation due to altered nuclear architecture are rare. These rare cases include trans de-repression when deficiencies delete chromatin characterized as repressive in other studies. Generally, effects of breakpoints on expression are promoter proximal (~100bp or in the gene body. Effects of deficiencies genome-wide are in genes with regulatory relationships to genes within the deleted segments, highlighting the subtle expression network defects in these sensitized genetic backgrounds.

  12. Effects of Gene Dose, Chromatin, and Network Topology on Expression in Drosophila melanogaster.

    Science.gov (United States)

    Lee, Hangnoh; Cho, Dong-Yeon; Whitworth, Cale; Eisman, Robert; Phelps, Melissa; Roote, John; Kaufman, Thomas; Cook, Kevin; Russell, Steven; Przytycka, Teresa; Oliver, Brian

    2016-09-01

    Deletions, commonly referred to as deficiencies by Drosophila geneticists, are valuable tools for mapping genes and for genetic pathway discovery via dose-dependent suppressor and enhancer screens. More recently, it has become clear that deviations from normal gene dosage are associated with multiple disorders in a range of species including humans. While we are beginning to understand some of the transcriptional effects brought about by gene dosage changes and the chromosome rearrangement breakpoints associated with them, much of this work relies on isolated examples. We have systematically examined deficiencies of the left arm of chromosome 2 and characterize gene-by-gene dosage responses that vary from collapsed expression through modest partial dosage compensation to full or even over compensation. We found negligible long-range effects of creating novel chromosome domains at deletion breakpoints, suggesting that cases of gene regulation due to altered nuclear architecture are rare. These rare cases include trans de-repression when deficiencies delete chromatin characterized as repressive in other studies. Generally, effects of breakpoints on expression are promoter proximal (~100bp) or in the gene body. Effects of deficiencies genome-wide are in genes with regulatory relationships to genes within the deleted segments, highlighting the subtle expression network defects in these sensitized genetic backgrounds.

  13. Creative compensation

    Energy Technology Data Exchange (ETDEWEB)

    Coll, D

    1994-09-19

    A discussion is presented of executive compensation in Canada's petroleum industry. Mandatory disclosure of executive compensation and benefits is regulated by the Ontario Securities Commission. Examination of the compensation packages of 80 oilpatch CEOs shows a clear difference in philosophy between large and small companies. Larger companies pay larger salaries, offer pension plans, and reward long-term loyalty. Within smaller companies, compensation tends to be linked with stock performance. Trends in compensation are to lower base salaries with more variables such as bonuses, cash incentives and gain-sharing programs. Increasing shareholder scrutiny is prompting more stringent guidelines on stock option plans. Some companies place performance conditions on stock vesting. Another option is to grant premium priced options to executives, to increase the gains required for the executive to post a profit. Other comapanies are granting stock options to their field personnel, or are granting stock to all employees. Directors are playing an increasing role in executive compensation. 4 tabs.

  14. DYRK1A (Dual-Specificity Tyrosine-Phosphorylated and -Regulated Kinase 1A: A Gene with Dosage Effect During Development and Neurogenesis

    Directory of Open Access Journals (Sweden)

    M. Dierssen

    2006-01-01

    Full Text Available DYRKs (dual-specificity tyrosine-regulated kinases are an emerging family of evolutionarily conserved dual-specificity kinases that play key roles in cell proliferation, survival, and development. The research in the last years suggests a relevant conserved function during neuronal development, related to proliferation and/or differentiation for DYRK1A. It is expressed in neural progenitor cells and has been proposed to participate in the signaling mechanisms that regulate dendrite differentiation. In Drosophila, disruption of the homolog minibrain gene results in flies with reduced neuroblast proliferation, decreased numbers of central brain neurons, and learning/memory deficits. Knockout DYRK1A mice are embryonic lethal, and heterozygotes show decreased viability and region-specific reductions in brain size. In humans, DYRK1A has been proposed to be involved in the neurodevelopmental alterations associated with Down syndrome. The large number of protein interaction and putative substrates described for DYRK1A suggest multiple pathways and functions to be involved in its developmental function. This review focuses on the functional role that DYRK1A plays in brain development.

  15. Graded Elevation of c-Jun in Schwann Cells In Vivo: Gene Dosage Determines Effects on Development, Remyelination, Tumorigenesis, and Hypomyelination.

    Science.gov (United States)

    Fazal, Shaline V; Gomez-Sanchez, Jose A; Wagstaff, Laura J; Musner, Nicolo; Otto, Georg; Janz, Martin; Mirsky, Rhona; Jessen, Kristján R

    2017-12-13

    Schwann cell c-Jun is implicated in adaptive and maladaptive functions in peripheral nerves. In injured nerves, this transcription factor promotes the repair Schwann cell phenotype and regeneration and promotes Schwann-cell-mediated neurotrophic support in models of peripheral neuropathies. However, c-Jun is associated with tumor formation in some systems, potentially suppresses myelin genes, and has been implicated in demyelinating neuropathies. To clarify these issues and to determine how c-Jun levels determine its function, we have generated c-Jun OE/+ and c-Jun OE/OE mice with graded expression of c-Jun in Schwann cells and examined these lines during development, in adulthood, and after injury using RNA sequencing analysis, quantitative electron microscopic morphometry, Western blotting, and functional tests. Schwann cells are remarkably tolerant of elevated c-Jun because the nerves of c-Jun OE/+ mice, in which c-Jun is elevated ∼6-fold, are normal with the exception of modestly reduced myelin thickness. The stronger elevation of c-Jun in c-Jun OE/OE mice is, however, sufficient to induce significant hypomyelination pathology, implicating c-Jun as a potential player in demyelinating neuropathies. The tumor suppressor P19 ARF is strongly activated in the nerves of these mice and, even in aged c-Jun OE/OE mice, there is no evidence of tumors. This is consistent with the fact that tumors do not form in injured nerves, although they contain proliferating Schwann cells with strikingly elevated c-Jun. Furthermore, in crushed nerves of c-Jun OE/+ mice, where c-Jun levels are overexpressed sufficiently to accelerate axonal regeneration, myelination and function are restored after injury. SIGNIFICANCE STATEMENT In injured and diseased nerves, the transcription factor c-Jun in Schwann cells is elevated and variously implicated in controlling beneficial or adverse functions, including trophic Schwann cell support for neurons, promotion of regeneration, tumorigenesis

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

    Science.gov (United States)

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

    2013-10-02

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

  17. NCKX3 was compensated by calcium transporting genes and bone resorption in a NCKX3 KO mouse model.

    Science.gov (United States)

    Yang, Hyun; Ahn, Changhwan; Shin, Eun-Kyeong; Lee, Ji-Sun; An, Beum-Soo; Jeung, Eui-Bae

    2017-10-15

    Gene knockout is the most powerful tool for determination of gene function or permanent modification of the phenotypic characteristics of an animal. Existing methods for gene disruption are limited by their efficiency, time required for completion and potential for confounding off-target effects. In this study, a rapid single-step approach to knockout of a targeted gene in mice using zinc-finger nucleases (ZFNs) was demonstrated for generation of mutant (knockout; KO) alleles. Specifically, ZFNs to target the sodium/calcium/potassium exchanger3 (NCKX3) gene in C57bl/6j were designed using the concept of this approach. NCKX3 KO mice were generated and the phenotypic characterization and molecular regulation of active calcium transporting genes was assessed when mice were fed different calcium diets during growth. General phenotypes such as body weight and plasma ion level showed no distinct abnormalities. Thus, the potassium/sodium/calcium exchanger of NCKX3 KO mice proceeded normally in this study. As a result, the compensatory molecular regulation of this mechanism was elucidated. Renal TRPV5 mRNA of NCKX3 KO mice increased in both male and female mice. Expression of TRPV6 mRNA was only down-regulated in the duodenum of male KO mice. Renal- and duodenal expression of PTHR and VDR were not changed; however, GR mRNA expression was increased in the kidney of NCKX3 KO mice. Depletion of the NCKX3 gene in a KO mouse model showed loss of bone mineral contents and increased plasma parathyroid hormone, suggesting that NCKX3 may play a role in regulating calcium homeostasis. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Parental genome dosage imbalance deregulates imprinting in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Pauline E Jullien

    2010-03-01

    Full Text Available In mammals and in plants, parental genome dosage imbalance deregulates embryo growth and might be involved in reproductive isolation between emerging new species. Increased dosage of maternal genomes represses growth while an increased dosage of paternal genomes has the opposite effect. These observations led to the discovery of imprinted genes, which are expressed by a single parental allele. It was further proposed in the frame of the parental conflict theory that parental genome imbalances are directly mirrored by antagonistic regulations of imprinted genes encoding maternal growth inhibitors and paternal growth enhancers. However these hypotheses were never tested directly. Here, we investigated the effect of parental genome imbalance on the expression of Arabidopsis imprinted genes FERTILIZATION INDEPENDENT SEED2 (FIS2 and FLOWERING WAGENINGEN (FWA controlled by DNA methylation, and MEDEA (MEA and PHERES1 (PHE1 controlled by histone methylation. Genome dosage imbalance deregulated the expression of FIS2 and PHE1 in an antagonistic manner. In addition increased dosage of inactive alleles caused a loss of imprinting of FIS2 and MEA. Although FIS2 controls histone methylation, which represses MEA and PHE1 expression, the changes of PHE1 and MEA expression could not be fully accounted for by the corresponding fluctuations of FIS2 expression. Our results show that parental genome dosage imbalance deregulates imprinting using mechanisms, which are independent from known regulators of imprinting. The complexity of the network of regulations between expressed and silenced alleles of imprinted genes activated in response to parental dosage imbalance does not support simple models derived from the parental conflict hypothesis.

  19. Dosage sensitivity shapes the evolution of copy-number varied regions.

    Directory of Open Access Journals (Sweden)

    Benjamin Schuster-Böckler

    2010-03-01

    Full Text Available Dosage sensitivity is an important evolutionary force which impacts on gene dispensability and duplicability. The newly available data on human copy-number variation (CNV allow an analysis of the most recent and ongoing evolution. Provided that heterozygous gene deletions and duplications actually change gene dosage, we expect to observe negative selection against CNVs encompassing dosage sensitive genes. In this study, we make use of several sources of population genetic data to identify selection on structural variations of dosage sensitive genes. We show that CNVs can directly affect expression levels of contained genes. We find that genes encoding members of protein complexes exhibit limited expression variation and overlap significantly with a manually derived set of dosage sensitive genes. We show that complexes and other dosage sensitive genes are underrepresented in CNV regions, with a particular bias against frequent variations and duplications. These results suggest that dosage sensitivity is a significant force of negative selection on regions of copy-number variation.

  20. [Vestibular compensation studies]. [Vestibular Compensation and Morphological Studies

    Science.gov (United States)

    Perachio, Adrian A. (Principal Investigator)

    1996-01-01

    The following topics are reported: neurophysiological studies on MVN neurons during vestibular compensation; effects of spinal cord lesions on VNC neurons during compensation; a closed-loop vestibular compensation model for horizontally canal-related MVN neurons; spatiotemporal convergence in VNC neurons; contributions of irregularly firing vestibular afferents to linear and angular VOR's; application to flight studies; metabolic measures in vestibular neurons; immediate early gene expression following vestibular stimulation; morphological studies on primary afferents, central vestibular pathways, vestibular efferent projection to the vestibular end organs, and three-dimensional morphometry and imaging.

  1. A mutation in the dynein heavy chain gene compensates for energy deficit of mutant SOD1 mice and increases potentially neuroprotective IGF-1

    Directory of Open Access Journals (Sweden)

    Larmet Yves

    2011-04-01

    Full Text Available Abstract Background Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons. ALS patients, as well as animal models such as mice overexpressing mutant SOD1s, are characterized by increased energy expenditure. In mice, this hypermetabolism leads to energy deficit and precipitates motor neuron degeneration. Recent studies have shown that mutations in the gene encoding the dynein heavy chain protein are able to extend lifespan of mutant SOD1 mice. It remains unknown whether the protection offered by these dynein mutations relies on a compensation of energy metabolism defects. Results SOD1(G93A mice were crossbred with mice harboring the dynein mutant Cramping allele (Cra/+ mice. Dynein mutation increased adipose stores in compound transgenic mice through increasing carbohydrate oxidation and sparing lipids. Metabolic changes that occurred in double transgenic mice were accompanied by the normalization of the expression of key mRNAs in the white adipose tissue and liver. Furthermore, Dynein Cra mutation rescued decreased post-prandial plasma triglycerides and decreased non esterified fatty acids upon fasting. In SOD1(G93A mice, the dynein Cra mutation led to increased expression of IGF-1 in the liver, increased systemic IGF-1 and, most importantly, to increased spinal IGF-1 levels that are potentially neuroprotective. Conclusions These findings suggest that the protection against SOD1(G93A offered by the Cramping mutation in the dynein gene is, at least partially, mediated by a reversal in energy deficit and increased IGF-1 availability to motor neurons.

  2. Reactive power compensating system

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Timothy J. (Redondo Beach, CA); El-Sharkawi, Mohamed A. (Renton, WA); Venkata, Subrahmanyam S. (Seattle, WA)

    1987-01-01

    The reactive power of an induction machine is compensated by providing fixed capacitors on each phase line for the minimum compensation required, sensing the current on one line at the time its voltage crosses zero to determine the actual compensation required for each phase, and selecting switched capacitors on each line to provide the balance of the compensation required.

  3. Hydraulic Modular Dosaging Systems for Machine Drives

    Directory of Open Access Journals (Sweden)

    A. J. Kotlobai

    2005-01-01

    Full Text Available The justified principle of making modular dosaging systems for positive-displacement multimotor hydraulic drives used in running gear and technological equipment of mobile construction, road and agricultural machines makes it possible to synchronize motion of running parts. The examples of the realization of modular dosaging systems and an algorithm of their operation are given in the paper.

  4. [Pharmaceutical advice concerning different pharmaceutical dosage forms].

    Science.gov (United States)

    Szakonyi, Gergely; Zelkó, Romána

    2010-01-01

    The present paper summarizes the commonly applied types of drug uptake and the pharmacists' advice concerning a certain dosage form. The manuscript also deals with the modified release dosage forms and their abbreviations in the name of the marketing authorized products.

  5. Genetic basis for dosage sensitivity in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Isabelle M Henry

    2007-04-01

    Full Text Available Aneuploidy, the relative excess or deficiency of specific chromosome types, results in gene dosage imbalance. Plants can produce viable and fertile aneuploid individuals, while most animal aneuploids are inviable or developmentally abnormal. The swarms of aneuploid progeny produced by Arabidopsis triploids constitute an excellent model to investigate the mechanisms governing dosage sensitivity and aneuploid syndromes. Indeed, genotype alters the frequency of aneuploid types within these swarms. Recombinant inbred lines that were derived from a triploid hybrid segregated into diploid and tetraploid individuals. In these recombinant inbred lines, a single locus, which we call SENSITIVE TO DOSAGE IMBALANCE (SDI, exhibited segregation distortion in the tetraploid subpopulation only. Recent progress in quantitative genotyping now allows molecular karyotyping and genetic analysis of aneuploid populations. In this study, we investigated the causes of the ploidy-specific distortion at SDI. Allele frequency was distorted in the aneuploid swarms produced by the triploid hybrid. We developed a simple quantitative measure for aneuploidy lethality and using this measure demonstrated that distortion was greatest in the aneuploids facing the strongest viability selection. When triploids were crossed to euploids, the progeny, which lack severe aneuploids, exhibited no distortion at SDI. Genetic characterization of SDI in the aneuploid swarm identified a mechanism governing aneuploid survival, perhaps by buffering the effects of dosage imbalance. As such, SDI could increase the likelihood of retaining genomic rearrangements such as segmental duplications. Additionally, in species where triploids are fertile, aneuploid survival would facilitate gene flow between diploid and tetraploid populations via a triploid bridge and prevent polyploid speciation. Our results demonstrate that positional cloning of loci affecting traits in populations containing ploidy and

  6. Essays in Executive Compensation

    NARCIS (Netherlands)

    D. Zhang (Dan)

    2012-01-01

    textabstractThis dissertation focuses on how executive compensation is designed and its implications for corporate finance and government regulations. Chapter 2 analyzes several proposals to restrict CEO compensation and calibrates two models of executive compensation that describe how firms would

  7. Advances in solid dosage form manufacturing technology.

    Science.gov (United States)

    Andrews, Gavin P

    2007-12-15

    Currently, the pharmaceutical and healthcare industries are moving through a period of unparalleled change. Major multinational pharmaceutical companies are restructuring, consolidating, merging and more importantly critically assessing their competitiveness to ensure constant growth in an ever-more demanding market where the cost of developing novel products is continuously increasing. The pharmaceutical manufacturing processes currently in existence for the production of solid oral dosage forms are associated with significant disadvantages and in many instances provide many processing problems. Therefore, it is well accepted that there is an increasing need for alternative processes to dramatically improve powder processing, and more importantly to ensure that acceptable, reproducible solid dosage forms can be manufactured. Consequently, pharmaceutical companies are beginning to invest in innovative processes capable of producing solid dosage forms that better meet the needs of the patient while providing efficient manufacturing operations. This article discusses two emerging solid dosage form manufacturing technologies, namely hot-melt extrusion and fluidized hot-melt granulation.

  8. Sex-biased gene expression during head development in a sexually dimorphic stalk-eyed fly.

    Directory of Open Access Journals (Sweden)

    Gerald S Wilkinson

    Full Text Available Stalk-eyed flies (family Diopsidae are a model system for studying sexual selection due to the elongated and sexually dimorphic eye-stalks found in many species. These flies are of additional interest because their X chromosome is derived largely from an autosomal arm in other flies. To identify candidate genes required for development of dimorphic eyestalks and investigate how sex-biased expression arose on the novel X, we compared gene expression between males and females using oligonucleotide microarrays and RNA from developing eyestalk tissue or adult heads in the dimorphic diopsid, Teleopsis dalmanni. Microarray analysis revealed sex-biased expression for 26% of 3,748 genes expressed in eye-antennal imaginal discs and concordant sex-biased expression for 86 genes in adult heads. Overall, 415 female-biased and 482 male-biased genes were associated with dimorphic eyestalk development but not differential expression in the adult head. Functional analysis revealed that male-biased genes are disproportionately associated with growth and mitochondrial function while female-biased genes are associated with cell differentiation and patterning or are novel transcripts. With regard to chromosomal effects, dosage compensation occurs by elevated expression of X-linked genes in males. Genes with female-biased expression were more common on the X and less common on autosomes than expected, while male-biased genes exhibited no chromosomal pattern. Rates of protein evolution were lower for female-biased genes but higher for genes that moved on or off the novel X chromosome. These findings cannot be due to meiotic sex chromosome inactivation or by constraints associated with dosage compensation. Instead, they could be consistent with sexual conflict in which female-biased genes on the novel X act primarily to reduce eyespan in females while other genes increase eyespan in both sexes. Additional information on sex-biased gene expression in other tissues and

  9. Developing fair compensation structures

    International Nuclear Information System (INIS)

    Trousdale, W.J.

    1998-01-01

    The issue of finding an effective way to incorporate Aboriginal values into the process of developing fair compensation structures was discussed. This paper discusses pricing intangible values using dollars, but it was emphasized that 'values' are whatever are important to us. Therefore, in order to achieve fair compensation, creative alternatives that are value-focused should be pursued. In addition to the more straight-forward monetary compensation, compensation could also be about avoiding losses, mitigating adverse impacts, achieving better communication, and promoting cultural understanding. 25 refs., 2 tabs

  10. The Endosymbiotic Bacterium Wolbachia Selectively Kills Male Hosts by Targeting the Masculinizing Gene.

    Directory of Open Access Journals (Sweden)

    Takahiro Fukui

    2015-07-01

    Full Text Available Pathogens are known to manipulate the reproduction and development of their hosts for their own benefit. Wolbachia is an endosymbiotic bacterium that infects a wide range of insect species. Wolbachia is known as an example of a parasite that manipulates the sex of its host's progeny. Infection of Ostrinia moths by Wolbachia causes the production of all-female progeny, however, the mechanism of how Wolbachia accomplishes this male-specific killing is unknown. Here we show for the first time that Wolbachia targets the host masculinizing gene of Ostrinia to accomplish male-killing. We found that Wolbachia-infected O. furnacalis embryos do not express the male-specific splice variant of doublesex, a gene which acts at the downstream end of the sex differentiation cascade, throughout embryonic development. Transcriptome analysis revealed that Wolbachia infection markedly reduces the mRNA level of Masc, a gene that encodes a protein required for both masculinization and dosage compensation in the silkworm Bombyx mori. Detailed bioinformatic analysis also elucidated that dosage compensation of Z-linked genes fails in Wolbachia-infected O. furnacalis embryos, a phenomenon that is extremely similar to that observed in Masc mRNA-depleted male embryos of B. mori. Finally, injection of in vitro transcribed Masc cRNA into Wolbachia-infected embryos rescued male progeny. Our results show that Wolbachia-induced male-killing is caused by a failure of dosage compensation via repression of the host masculinizing gene. Our study also shows a novel strategy by which a pathogen hijacks the host sex determination cascade.

  11. Cooperation, compensation and transition

    NARCIS (Netherlands)

    Ju, Y.

    2004-01-01

    Cooperation and compensation are two important and well-linked issues in economics. The central question in cooperation is how to share the joint gains among participating players. Compensation is a specific aspect of surplus sharing problems providing incentives for agents to sacrifice their own

  12. Options in Compensation

    DEFF Research Database (Denmark)

    Flor, Christian Riis; Frimor, Hans; Munk, Claus

    2014-01-01

    We derive the optimal compensation contract in a principal–agent setting in which outcome is used to provide incentives for both effort and risky investments. To motivate investment, optimal compensation entails rewards for high as well as low outcomes, and it is increasing at the mean outcome...

  13. Intelligent system for improving dosage control

    Directory of Open Access Journals (Sweden)

    Fabio Cosme Rodrigues dos Santos

    2017-02-01

    Full Text Available Coagulation is one of the most important processes in a drinking-water treatment plant, and it is applied to destabilize impurities in water for the subsequent flocculation stage. Several techniques are currently used in the water industry to determine the best dosage of the coagulant, such as the jar-test method, zeta potential measurements, artificial intelligence methods, comprising neural networks, fuzzy and expert systems, and the combination of the above-mentioned techniques to help operators and engineers in the water treatment process. Current paper presents an artificial neural network approach to evaluate optimum coagulant dosage for various scenarios in raw water quality, using parameters such as raw water color, raw water turbidity, clarified and filtered water turbidity and a calculated Dose Rate to provide the best performance in the filtration process. Another feature in current approach is the use of a backpropagation neural network method to estimate the best coagulant dosage simultaneously at two points of the water treatment plant. Simulation results were compared to the current dosage rate and showed that the proposed system may reduce costs of raw material in water treatment plant.

  14. Spectrophotometric Determination of Trimipramine in Tablet Dosage ...

    African Journals Online (AJOL)

    Purpose: To develop and validate simple, rapid and sensitive spectrophotometric procedures for determination of trimipramine in tablet dosage form. Methods: The methods were based on the interaction of trimipramine as n-electron donor with the ο-acceptor, iodine and various π-acceptors, namely: chloranil (CH), ...

  15. Reactive power compensator

    Science.gov (United States)

    El-Sharkawi, Mohamed A.; Venkata, Subrahmanyam S.; Chen, Mingliang; Andexler, George; Huang, Tony

    1992-01-01

    A system and method for determining and providing reactive power compensation for an inductive load. A reactive power compensator (50,50') monitors the voltage and current flowing through each of three distribution lines (52a, 52b, 52c), which are supplying three-phase power to one or more inductive loads. Using signals indicative of the current on each of these lines when the voltage waveform on the line crosses zero, the reactive power compensator determines a reactive power compensator capacitance that must be connected to the lines to maintain a desired VAR level, power factor, or line voltage. Alternatively, an operator can manually select a specific capacitance for connection to each line, or the capacitance can be selected based on a time schedule. The reactive power compensator produces control signals, which are coupled through optical fibers (102/106) to a switch driver (110, 110') to select specific compensation capacitors (112) for connections to each line. The switch driver develops triggering signals that are supplied to a plurality of series-connected solid state switches (350), which control charge current in one direction in respect to ground for each compensation capacitor. During each cycle, current flows from ground to charge the capacitors as the voltage on the line begins to go negative from its positive peak value. The triggering signals are applied to gate the solid state switches into a conducting state when the potential on the lines and on the capacitors reaches a negative peak value, thereby minimizing both the potential difference and across the charge current through the switches when they begin to conduct. Any harmonic distortion on the potential and current carried by the lines is filtered out from the current and potential signals used by the reactive power compensator so that it does not affect the determination of the required reactive compensation.

  16. Reactive power compensator

    Energy Technology Data Exchange (ETDEWEB)

    El-Sharkawi, Mohamed A. (Renton, WA); Venkata, Subrahmanyam S. (Woodinville, WA); Chen, Mingliang (Kirkland, WA); Andexler, George (Everett, WA); Huang, Tony (Seattle, WA)

    1992-01-01

    A system and method for determining and providing reactive power compensation for an inductive load. A reactive power compensator (50,50') monitors the voltage and current flowing through each of three distribution lines (52a, 52b, 52c), which are supplying three-phase power to one or more inductive loads. Using signals indicative of the current on each of these lines when the voltage waveform on the line crosses zero, the reactive power compensator determines a reactive power compensator capacitance that must be connected to the lines to maintain a desired VAR level, power factor, or line voltage. Alternatively, an operator can manually select a specific capacitance for connection to each line, or the capacitance can be selected based on a time schedule. The reactive power compensator produces control signals, which are coupled through optical fibers (102/106) to a switch driver (110, 110') to select specific compensation capacitors (112) for connections to each line. The switch driver develops triggering signals that are supplied to a plurality of series-connected solid state switches (350), which control charge current in one direction in respect to ground for each compensation capacitor. During each cycle, current flows from ground to charge the capacitors as the voltage on the line begins to go negative from its positive peak value. The triggering signals are applied to gate the solid state switches into a conducting state when the potential on the lines and on the capacitors reaches a negative peak value, thereby minimizing both the potential difference and across the charge current through the switches when they begin to conduct. Any harmonic distortion on the potential and current carried by the lines is filtered out from the current and potential signals used by the reactive power compensator so that it does not affect the determination of the required reactive compensation.

  17. Climate change and compensation

    DEFF Research Database (Denmark)

    Jensen, Karsten Klint; Flanagan, Tine Bech

    2013-01-01

    This paper presents a case for compensation of actual harm from climate change in the poorest countries. First, it is shown that climate change threatens to reverse the fight to eradicate poverty. Secondly, it is shown how the problems raised in the literature for compensation to some extent...... are based on misconceptions and do not apply to compensation of present actual harm. Finally, two arguments are presented to the effect that, in so far as developed countries accept a major commitment to mitigate climate change, they should also accept a commitment to address or compensate actual harm from...... climate change. The first argument appeals to the principle that if it is an injustice to cause risk of incurring harm in the future, then it is also an injustice to cause a similar harm now. The second argument appeals to the principle that if there is moral reason to reduce the risk of specific harms...

  18. Workers Compensation Claim Data -

    Data.gov (United States)

    Department of Transportation — This data set contains DOT employee workers compensation claim data for current and past DOT employees. Types of data include claim data consisting of PII data (SSN,...

  19. Exogenous GA3 application can compensate the morphogenetic effects of the GA-responsive dwarfing gene Rht12 in bread wheat.

    Directory of Open Access Journals (Sweden)

    Liang Chen

    Full Text Available The most common dwarfing genes in wheat, Rht-B1b and Rht-D1b, classified as gibberellin-insensitive (GAI dwarfing genes due to their reduced response to exogenous GA, have been verified as encoding negative regulators of gibberellin signaling. In contrast, the response of gibberellin-responsive (GAR dwarfing genes, such as Rht12, to exogenous GA is still unclear and the role of them, if any, in GA biosynthesis or signaling is unknown. The responses of Rht12 to exogenous GA3 were investigated on seedling vigour, spike phenological development, plant height and other agronomic traits, using F2 ∶ 3 and F3 ∶ 4 lines derived from a cross between Ningchun45 and Karcagi-12 in three experiments. The application of exogenous GA3 significantly increased coleoptile length and seedling leaf 1 length and area. While there was no significant difference between the dwarf and the tall lines at the seedling stage in the responsiveness to GA3, plant height was significantly increased, by 41 cm (53% averaged across the three experiments, in the GA3-treated Rht12 dwarf lines. Plant height of the tall lines was not affected significantly by GA3 treatment (<10 cm increased. Plant biomass and seed size of the GA3-treated dwarf lines was significantly increased compared with untreated dwarf plants while there was no such difference in the tall lines. GA3-treated Rht12 dwarf plants with the dominant Vrn-B1 developed faster than untreated plants and reached double ridge stage 57 days, 11 days and 50 days earlier and finally flowered earlier by almost 7 days while the GA3-treated tall lines flowering only 1-2 days earlier than the untreated tall lines. Thus, it is clear that exogenous GA3 can break the masking effect of Rht12 on Vrn-B1 and also restore other characters of Rht12 to normal. It suggested that Rht12 mutants may be deficient in GA biosynthesis rather than in GA signal transduction like the GA-insensitive dwarfs.

  20. Optimizing the dosage of stabilizing chemical

    OpenAIRE

    Harjula, Tomi

    2013-01-01

    A chemical company provides chemical treatment at customer mill in paper industry. This thesis work was done to determine the optimum dosage of stabilizing chemical. The theoretical framework explains the basics of paper brightness and bleaching and how these topics are connected to each other. The knowledge gained is very valuable and can possibly be used in the future in other similar applications as well. This thesis work contains confidential back ground information. Key ...

  1. Microbial quality of some herbal solid dosage forms

    African Journals Online (AJOL)

    STORAGESEVER

    2010-03-15

    Mar 15, 2010 ... Key words: Microbial quality, herbal, contamination, solid dosage form ... The type of dosage form, packaging, manufacturing and expiration dates of subject solid herbal .... According to WHO report (2002), Salmonella food.

  2. Aeromagnetic Compensation for UAVs

    Science.gov (United States)

    Naprstek, T.; Lee, M. D.

    2017-12-01

    Aeromagnetic data is one of the most widely collected types of data in exploration geophysics. With the continuing prevalence of unmanned air vehicles (UAVs) in everyday life there is a strong push for aeromagnetic data collection using UAVs. However, apart from the many political and legal barriers to overcome in the development of UAVs as aeromagnetic data collection platforms, there are also significant scientific hurdles, primary of which is magnetic compensation. This is a well-established process in manned aircraft achieved through a combination of platform magnetic de-noising and compensation routines. However, not all of this protocol can be directly applied to UAVs due to fundamental differences in the platforms, most notably the decrease in scale causing magnetometers to be significantly closer to the avionics. As such, the methodology must be suitably adjusted. The National Research Council of Canada has collaborated with Aeromagnetic Solutions Incorporated to develop a standardized approach to de-noising and compensating UAVs, which is accomplished through a series of static and dynamic experiments. On the ground, small static tests are conducted on individual components to determine their magnetization. If they are highly magnetic, they are removed, demagnetized, or characterized such that they can be accounted for in the compensation. Dynamic tests can include measuring specific components as they are powered on and off to assess their potential effect on airborne data. The UAV is then flown, and a modified compensation routine is applied. These modifications include utilizing onboard autopilot current sensors as additional terms in the compensation algorithm. This process has been applied with success to fixed-wing and rotary-wing platforms, with both a standard manned-aircraft magnetometer, as well as a new atomic magnetometer, much smaller in scale.

  3. Enthalpy–entropy compensation

    Indian Academy of Sciences (India)

    Enthalpy–entropy compensation is the name given to the correlation sometimes observed between the estimates of the enthalpy and entropy of a reaction obtained from temperature-dependence data. Although the mainly artefactual nature of this correlation has been known for many years, the subject enjoys periodical ...

  4. Motion compensated digital tomosynthesis

    NARCIS (Netherlands)

    van der Reijden, Anneke; van Herk, Marcel; Sonke, Jan-Jakob

    2013-01-01

    Digital tomosynthesis (DTS) is a limited angle image reconstruction method for cone beam projections that offers patient surveillance capabilities during VMAT based SBRT delivery. Motion compensation (MC) has the potential to mitigate motion artifacts caused by respiratory motion, such as blur. The

  5. Teacher Compensation and Organization.

    Science.gov (United States)

    Kelley, Carolyn

    1997-01-01

    Examines changes in the conceptualization of schooling over time from an organizational perspective. Explores how compensation systems might be better designed to match alternative organizational designs, considering scientific management, effective schools, content-driven schooling, and high standards/high involvement schools as organizational…

  6. (statcom) in synchronous compensator

    African Journals Online (AJOL)

    eobe

    with fast response and low cost for stabilizing electricity grid power and voltage. ... The conventional and modified Newton-Raphson-based power flow equations .... The control of the reactive power exchange between .... because of its faster rate of convergence and accuracy ..... compensator, North American Power System.

  7. Reactive Power Compensating System.

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Timothy J.; El-Sharkawi, Mohamed A.; Venkata, Subrahmanyam S.

    1985-01-04

    The circuit was designed for the specific application of wind-driven induction generators. It has great potential for application in any situation where a varying reactive power load is present, such as with induction motors or generators, or for transmission network compensation.

  8. Dosage of DTPA administration by inhalation

    International Nuclear Information System (INIS)

    Koizumi, Akira; Fukuda, Satoshi; Yamada, Yuji; Iida, Haruzo; Shimo, Michikuni

    2000-01-01

    The administration of DTPA by inhalation was examined as an emergency medical treatment. In order to estimate the practical dosage to the human, an accurate model of the human air way was connected to a anesthetizer and respiration was simulated. Ca-DTPA, aerosolized by an ultra-sonic nebulizer, was administered by inhalation to the model. For the experiments, the respiratory volume (tidal volume) and the respiration rate was 12 per minute. Irrigation water from the model of larynx and mouth, and the air filter were collected and measured by chelate titration in order to determine the quantity of aerosolized DTPA and the amount deposited on the trachea and lang. The results indicated that the quantity of aerosolized DTPA varied with dilution of the DTPA solution in a ample. It was found that a 3 time dilution was the most practical and that 73 mg of DTPA per minute could be aerosolized. Furthermore, the results indicated that 46% of the aerosolized DTPA was taken in through inhalation and that 26% of DTPA was deposited in the trachea and lung. These results suggest that in practical application in the emergency medical treatment, 15 minutes of inhalation could delivered to approximately 500 mg of DTPA, and 130 mg could be delivered to the trachea and lung. It is considered that these quantity are enough amount to increase the effects of radioactive nuclides from the body, comparing with the recommended dosage for injection administration. (author)

  9. The characteristics of novel dosage forms

    Directory of Open Access Journals (Sweden)

    Milić-Aškrabić Jela

    2003-01-01

    Full Text Available The objective of pharmaceutical-technological development is to find a procedure of transforming an active substance (a drug into a drug dosage form which is not only acceptable for application, but also enables the active substance to be released following administration, pursuant to therapy objectives. The aim is that the concentration of the active substance in the action location rapidly reaches a therapeutic level and maintains an approximately constant level in the course of a particular time, according to the established therapeutic goal. The primary objective is to present the active ingredient (drug in the form and concentration/quantity that enables the corresponding therapeutic response, i.e. to control the site and rate of medicinal substance release from the drug, as well as the rate at which it reaches the membranes and surfaces to which it is absorbed, while applying a common method of administration. The procedures used to achieve this goal are becoming highly complex and demanding and are aiming at sophisticated drug delivery systems and functional packaging material. Development from the existing drug molecule, through the conventional drug dosage form, to a new system of drug "delivery" (novel delivery system, can improve the drug (active substance characteristics significantly in view of compliance (acceptability by the patient, safety and efficiency. The paper presents an overview of the most important examples of pharmaceutical forms with controlled release and advanced drug "carriers".

  10. Center for Worker's Compensation Studies

    Data.gov (United States)

    Federal Laboratory Consortium — The mission of the NIOSH Center for Workers’ Compensation Studies (CWCS) is to use workers’ compensation data and systems to improve workplace safety and health....

  11. Addressing inadequate compensation | IDRC - International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2016-08-12

    Aug 12, 2016 ... The issue LSLAs raise a number of concerns regarding compensation, including ... at a meeting with traders in Lamu, Kenya, where a new port is planned. ... compensation and a fair share of benefits and risks in land deals.

  12. Structuring competitive physician compensation models.

    Science.gov (United States)

    Mobley, Kim; Turcotte, Claire

    2010-12-01

    When developing and reviewing their physician compensation programs, healthcare organizations should: Understand the market data. Test outcomes of incentive plans for fair market value. Check total compensation for fair market value and reasonableness.

  13. RELIABILITY OF LENTICULAR EXPANSION COMPENSATORS

    Directory of Open Access Journals (Sweden)

    Gabriel BURLACU,

    2011-11-01

    Full Text Available Axial lenticular compensators are made to take over the longitudinal heat expansion, shock , vibration and noise, made elastic connections for piping systems. In order to have a long life for installations it is necessary that all elements, including lenticular compensators, have a good reliability. This desire can be did by technology of manufactoring and assembly of compensators, the material for lenses and by maintenance.of compensator

  14. [Oral films as perspective dosage form].

    Science.gov (United States)

    Walicová, Veronika; Gajdziok, Jan

    Oral films, namely buccal mucoadhesive films and orodispersible films represent innovative formulations for administration of a wide range of drugs. Oral films show many advantageous properties and are intended for systemic drug delivery or for local treatment of the oral mucosa. In both cases, the film represents a thin layer, which could be intended to adhere to the oral mucosa by means of mucoadhesion; or to rapid dissolution and subsequent swallowing without the need of liquid intake, in the case of orodispersible films. Main constitutive excipients are film-forming polymers, which must in the case of mucoadhesive forms remain on the mucosa within the required time interval. Oral films are currently available on the pharmaceutical market and could compete with conventional oral dosage forms in the future. oral cavity oral films buccal mucoadhesive films orodispersible films film-forming polymers.

  15. Enalapril dosage in progressive chronic nephropathy

    DEFF Research Database (Denmark)

    Elung-Jensen, Thomas; Heisterberg, Jens; Sonne, Jesper

    2005-01-01

    OBJECTIVE: In chronic renal failure, clearance of enalapril is reduced. Hence, a renoprotective effect may be achieved with lower doses than conventionally used. Since marked inter-patient variation in concentrations of enalaprilat has been shown in patients with renal failure despite equivalent...... dosage of enalapril, a direct comparison of the effect of high versus low plasma concentrations of enalaprilat on the progression of renal failure was undertaken. METHODS: Forty patients with a median glomerular filtration rate (GFR) of 17 (6-35) ml/min/1.73 m2 were studied in an open-label, randomised...... intervals by the plasma clearance of 51Cr-EDTA, and the individual rates of progression of renal failure were calculated as the slope of GFR versus time plot. RESULTS: In the high-concentration group, the median enalaprilat trough concentration was 92.9 ng/ml (21.8-371.0 ng/ml) and in the low...

  16. Compensation Consultants and CEO Pay

    NARCIS (Netherlands)

    Kabir, Mohammed Rezaul; Minhat, Marizah

    2014-01-01

    The study examines the practice of employing multiple compensation consultants. Examining data of a sample of UK companies over the period 2003–2006 we find that CEOs receive higher equity-based pay when firms employ more than one compensation consultant. An increase in the number of compensation

  17. Compensability index for compensation radiotherapy after treatment interruptions

    International Nuclear Information System (INIS)

    Putora, Paul Martin; Schmuecking, Michael; Aebersold, Daniel; Plasswilm, Ludwig

    2012-01-01

    The goal of our work was to develop a simple method to evaluate a compensation treatment after unplanned treatment interruptions with respect to their tumour- and normal tissue effect. We developed a software tool in java programming language based on existing recommendations to compensate for treatment interruptions. In order to express and visualize the deviations from the originally planned tumour and normal tissue effects we defined the compensability index. The compensability index represents an evaluation of the suitability of compensatory radiotherapy in a single number based on the number of days used for compensation and the preference of preserving the originally planned tumour effect or not exceeding the originally planned normal tissue effect. An automated tool provides a method for quick evaluation of compensation treatments. The compensability index calculation may serve as a decision support system based on existing and established recommendations

  18. Compensability index for compensation radiotherapy after treatment interruptions

    Directory of Open Access Journals (Sweden)

    Putora Paul

    2012-12-01

    Full Text Available Abstract Background The goal of our work was to develop a simple method to evaluate a compensation treatment after unplanned treatment interruptions with respect to their tumour- and normal tissue effect. Methods We developed a software tool in java programming language based on existing recommendations to compensate for treatment interruptions. In order to express and visualize the deviations from the originally planned tumour and normal tissue effects we defined the compensability index. Results The compensability index represents an evaluation of the suitability of compensatory radiotherapy in a single number based on the number of days used for compensation and the preference of preserving the originally planned tumour effect or not exceeding the originally planned normal tissue effect. An automated tool provides a method for quick evaluation of compensation treatments. Conclusions The compensability index calculation may serve as a decision support system based on existing and established recommendations.

  19. Fukushima: liability and compensation

    International Nuclear Information System (INIS)

    Vasquez-Maignan, Ximena

    2012-01-01

    On 11 March 2011, Japan endured one of the worst natural disasters in its history when a massive earthquake struck the Pacific coast of the country and was followed by a tsunami which led to considerable loss of lives. It also led to a major accident at the Fukushima Daiichi nuclear power plant. Soon afterwards, the operator of the plant, Tokyo Electric Power Company (TEPCO), assumed responsibility and liability for the nuclear accident. On 28 April 2011, TEPCO established a dedicated contact line to provide consulting services for financial compensation related to the damage caused

  20. Whiplash and the compensation hypothesis.

    Science.gov (United States)

    Spearing, Natalie M; Connelly, Luke B

    2011-12-01

    Review article. To explain why the evidence that compensation-related factors lead to worse health outcomes is not compelling, either in general, or in the specific case of whiplash. There is a common view that compensation-related factors lead to worse health outcomes ("the compensation hypothesis"), despite the presence of important, and unresolved sources of bias. The empirical evidence on this question has ramifications for the design of compensation schemes. Using studies on whiplash, this article outlines the methodological problems that impede attempts to confirm or refute the compensation hypothesis. Compensation studies are prone to measurement bias, reverse causation bias, and selection bias. Errors in measurement are largely due to the latent nature of whiplash injuries and health itself, a lack of clarity over the unit of measurement (specific factors, or "compensation"), and a lack of appreciation for the heterogeneous qualities of compensation-related factors and schemes. There has been a failure to acknowledge and empirically address reverse causation bias, or the likelihood that poor health influences the decision to pursue compensation: it is unclear if compensation is a cause or a consequence of poor health, or both. Finally, unresolved selection bias (and hence, confounding) is evident in longitudinal studies and natural experiments. In both cases, between-group differences have not been addressed convincingly. The nature of the relationship between compensation-related factors and health is unclear. Current approaches to testing the compensation hypothesis are prone to several important sources of bias, which compromise the validity of their results. Methods that explicitly test the hypothesis and establish whether or not a causal relationship exists between compensation factors and prolonged whiplash symptoms are needed in future studies.

  1. 21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

  2. 21 CFR 520.1696 - Penicillin oral dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin oral dosage forms. 520.1696 Section 520.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696 Penicillin oral...

  3. 21 CFR 526.1696 - Penicillin intramammary dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS INTRAMAMMARY DOSAGE FORMS § 526.1696 Penicillin...

  4. 21 CFR 522.1660 - Oxytetracycline injectable dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline injectable dosage forms. 522.1660 Section 522.1660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 522.1660 Oxytetracycline injectable dosage forms. ...

  5. 21 CFR 520.905 - Fenbendazole oral dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Fenbendazole oral dosage forms. 520.905 Section 520.905 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Fenbendazole oral dosage forms. ...

  6. 21 CFR 520.45 - Albendazole oral dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Albendazole oral dosage forms. 520.45 Section 520.45 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.45 Albendazole oral...

  7. Histone dosage regulates DNA damage sensitivity in a checkpoint-independent manner by the homologous recombination pathway

    Science.gov (United States)

    Liang, Dun; Burkhart, Sarah Lyn; Singh, Rakesh Kumar; Kabbaj, Marie-Helene Miquel; Gunjan, Akash

    2012-01-01

    In eukaryotes, multiple genes encode histone proteins that package genomic deoxyribonucleic acid (DNA) and regulate its accessibility. Because of their positive charge, ‘free’ (non-chromatin associated) histones can bind non-specifically to the negatively charged DNA and affect its metabolism, including DNA repair. We have investigated the effect of altering histone dosage on DNA repair in budding yeast. An increase in histone gene dosage resulted in enhanced DNA damage sensitivity, whereas deletion of a H3–H4 gene pair resulted in reduced levels of free H3 and H4 concomitant with resistance to DNA damaging agents, even in mutants defective in the DNA damage checkpoint. Studies involving the repair of a HO endonuclease-mediated DNA double-strand break (DSB) at the MAT locus show enhanced repair efficiency by the homologous recombination (HR) pathway on a reduction in histone dosage. Cells with reduced histone dosage experience greater histone loss around a DSB, whereas the recruitment of HR factors is concomitantly enhanced. Further, free histones compete with the HR machinery for binding to DNA and associate with certain HR factors, potentially interfering with HR-mediated repair. Our findings may have important implications for DNA repair, genomic stability, carcinogenesis and aging in human cells that have dozens of histone genes. PMID:22850743

  8. Radiation dosage of various CT-methods in lung diagnostics

    International Nuclear Information System (INIS)

    Heinz-Peer, G.; Weninger, F.; Nowotny, R.; Herold, C.J.

    1996-01-01

    Introduction of the computed tomography index CTDI and the multiple scan average dose (MSAD) has led to standardization of the dose description in CT examinations. Despite the use of these dose parameters, many different dosages are reported in the literature for different CT methods. In addition, there is still a wide range of radiation dosimetry results reported for conventional CT, helical CT, and HRCT used in chest examinations. The variations in dosage are mainly due to difference in factors affecting the dose, i.e. beam geometry, beam quality, scanner geometry ('generation'), and operating parameters. In addition, CT dosimetry instrumentation and methodology make a contribution to dosages. Recent studies calculating differences in factors affecting dosage and CT dosimetry and using similar operating parameters, show similar results in CT dosimetry for conventional and helical CT. On the other hand, dosages for HRCT were greatly reduced. This was mainly caused by narrow beam collimation and increasing section spacing. (orig.) [de

  9. 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,...

  10. Temperature compensated photovoltaic array

    Science.gov (United States)

    Mosher, Dan Michael

    1997-11-18

    A temperature compensated photovoltaic module (20) comprised of a series of solar cells (22) having a thermally activated switch (24) connected in parallel with several of the cells (22). The photovoltaic module (20) is adapted to charge conventional batteries having a temperature coefficient (TC) differing from the temperature coefficient (TC) of the module (20). The calibration temperatures of the switches (24) are chosen whereby the colder the ambient temperature for the module (20), the more switches that are on and form a closed circuit to short the associated solar cells (22). By shorting some of the solar cells (22) as the ambient temperature decreases, the battery being charged by the module (20) is not excessively overcharged at lower temperatures. PV module (20) is an integrated solution that is reliable and inexpensive.

  11. Population and sex differences in Drosophila melanogaster brain gene expression

    Directory of Open Access Journals (Sweden)

    Catalán Ana

    2012-11-01

    Full Text Available Abstract Background Changes in gene regulation are thought to be crucial for the adaptation of organisms to their environment. Transcriptome analyses can be used to identify candidate genes for ecological adaptation, but can be complicated by variation in gene expression between tissues, sexes, or individuals. Here we use high-throughput RNA sequencing of a single Drosophila melanogaster tissue to detect brain-specific differences in gene expression between the sexes and between two populations, one from the ancestral species range in sub-Saharan Africa and one from the recently colonized species range in Europe. Results Relatively few genes (Cyp6g1 and CHKov1. Conclusions Analysis of the brain transcriptome revealed many genes differing in expression between populations that were not detected in previous studies using whole flies. There was little evidence for sex-specific regulatory adaptation in the brain, as most expression differences between populations were observed in both males and females. The enrichment of genes with sexually dimorphic expression on the X chromosome is consistent with dosage compensation mechanisms affecting sex-biased expression in somatic tissues.

  12. Determining S-1 dosage at hospitals prioritizing cancer chemotherapy

    International Nuclear Information System (INIS)

    Morimoto, Shigefumi; Kitada, Noriaki; Anami, Setsuko

    2008-01-01

    Although it is recommended that the standard S-1 dosage should be based on how large the body surface area is, an on-site setting of the appropriate dosage is often lower than the standard one, depending on the individual's condition and considering possible side effects and so, on. Here, we investigated usage conditions for S-1 as a part of field training for expert pharmacists at our hospital that performs total clinical treatments. Decreases in dosage per day for elderly patients were although the standard dosage is generally determined according to the amount of a patient's body surface. We conducted a retrospective survey with a total 90 patients by creating a tree-diagram to identify a reduction standard. It was found that the S-1 dosage was decreased when there were side effects, aggravation in performance status, decrease in kidney function, old age, combined injection chemotherapy, and a decrease in radiation therapy performance. The dosage decreases without such medical reasons were seen in only 4 of the 90 patients. At hospitals giving priority to chemotherapy, it became clear that appropriate treatment was promoted by decreasing. The individual target dosage on the basis of daily medical examination. (author)

  13. Takeovers and (Excess) CEO Compensation

    NARCIS (Netherlands)

    Feito Ruiz, Isabel; Renneboog, Luc

    2017-01-01

    We study if a CEO’s equity-based compensation affects the expected value generation in takeovers. When the objectives of management and shareholders are more aligned, as proxied by the use of equity-based compensation, more value-maximizing acquisitions are expected. Whereas in widely-held firms the

  14. Takeovers and (excess) CEO compensation

    NARCIS (Netherlands)

    Feito Ruiz, Isabel; Renneboog, Luc

    We study if a CEO’s equity-based compensation affects the expected value generation in takeovers. When the objectives of management and shareholders are more aligned, as proxied by the use of equity-based compensation, more value-maximizing acquisitions are expected. Whereas in widely-held firms the

  15. Changing Conceptions of Employee Compensation

    Science.gov (United States)

    Dixon, Mark R.; Hayes, Linda J.

    2004-01-01

    This paper reviews and discusses many differing forms of incentive compensation systems that are being used in today's organizations. The review traces the roots of bonus compensation from individual piece-work plans through the adoption of organization-wide gain sharing plans to the growing recognition of open-book management. Reasons for the…

  16. Compensated pulsed alternator

    International Nuclear Information System (INIS)

    Weldon, W.F.; Driga, M.D.; Woodson, H.H.

    1980-01-01

    This invention relates to an electromechanical energy converter with inertial energy storage. The device, a single phase, two or multi-pole alternator with stationary field coils, and a rotating armature is provided. The rotor itself may be of laminated steel for slower pulses or for faster pulses should be nonmagnetic and electrically nonconductive in order to allow rapid penetration of the field as the armature coil rotates. The armature coil comprises a plurality of power generating conductors mounted on the rotor. The alternator may also include a stationary or counterrotating compensating coil to increase the output voltage thereof and to reduce the internal impedance of the alternator at the moment of peak output. As the machine voltage rises sinusoidally, an external trigger switch is adapted to be closed at the appropriate time to create the desired output current from said alternator to an external load circuit, and as the output current passes through zero a self-commutating effect is provided to allow the switch to disconnect the generator from the external circuit

  17. Stabilized thermally compensated mirror

    International Nuclear Information System (INIS)

    Dunn, C. III; Tobin, R.D.; Bergstreser, N.E.; Heinz, T.A.

    1975-01-01

    A thermally compensated mirror is described that is formed by a laminated structure. The structure is comprised of a front plate having a reflective front surface and having a plurality of grooves formed in the rear surface for conducting coolant fluid in heat exchanging relation with said reflective surface, a rear plate having coolant inlet and coolant outlet openings extending therethrough, a minimum temperature plate interposed between said front and rear plates and formed with a plurality of coolant distribution passageways coupled to receive coolant fluid from said coolant inlet and oriented to distribute said coolant fluid in a manner to establish a minimum temperature plane parallel to said reflective surface, a temperature stabilization plate interposed between said front plate and said minimum temperature plate and formed with a plurality of coolant distribution channels coupled to receive said coolant fluid after said coolant fluid has passed in heat exchanging relation with said reflective surface and oriented to distribute said coolant fluid in a manner to establish a uniform temperature plane parallel to said reflective surface, and means for circulating said coolant fluid through said structure in a predetermined path. (U.S.)

  18. Automatic identification and normalization of dosage forms in drug monographs

    Science.gov (United States)

    2012-01-01

    Background Each day, millions of health consumers seek drug-related information on the Web. Despite some efforts in linking related resources, drug information is largely scattered in a wide variety of websites of different quality and credibility. Methods As a step toward providing users with integrated access to multiple trustworthy drug resources, we aim to develop a method capable of identifying drug's dosage form information in addition to drug name recognition. We developed rules and patterns for identifying dosage forms from different sections of full-text drug monographs, and subsequently normalized them to standardized RxNorm dosage forms. Results Our method represents a significant improvement compared with a baseline lookup approach, achieving overall macro-averaged Precision of 80%, Recall of 98%, and F-Measure of 85%. Conclusions We successfully developed an automatic approach for drug dosage form identification, which is critical for building links between different drug-related resources. PMID:22336431

  19. Fourteen days oral administration of therapeutic dosage of some ...

    African Journals Online (AJOL)

    Fourteen days oral administration of therapeutic dosage of some antibiotics reduced serum testosterone in male rats. FO Awobajo, Y Raji, II Olatunji-Bello, FT Kunle-Alabi, AO Adesanya, TO Awobajo ...

  20. Buccal Dosage Forms: General Considerations for Pediatric Patients.

    Science.gov (United States)

    Montero-Padilla, Soledad; Velaga, Sitaram; Morales, Javier O

    2017-02-01

    The development of an appropriate dosage form for pediatric patients needs to take into account several aspects, since adult drug biodistribution differs from that of pediatrics. In recent years, buccal administration has become an attractive route, having different dosage forms under development including tablets, lozenges, films, and solutions among others. Furthermore, the buccal epithelium can allow quick access to systemic circulation, which could be used for a rapid onset of action. For pediatric patients, dosage forms to be placed in the oral cavity have higher requirements for palatability to increase acceptance and therapy compliance. Therefore, an understanding of the excipients required and their functions and properties needs to be particularly addressed. This review is focused on the differences and requirements relevant to buccal administration for pediatric patients (compared to adults) and how novel dosage forms can be less invasive and more acceptable alternatives.

  1. Dosage of trace carbon in sodium (1963); Dosage de traces de carbone dans le sodium (1963)

    Energy Technology Data Exchange (ETDEWEB)

    Sannier, J; Vasseur, A [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1963-07-01

    A wet method for dosing carbon in sodium has been developed. The carbon is oxidised in a vacuum using Van SLYKE'S solution. The carbonic acid formed is measured volumetrically; its purity can be controlled by chromatographic analysis. The results obtained show that this method makes it possible to measure carbon in concentrations of about 10 ppm. (authors) [French] Une methode de dosage par voie humide du carbone dans le sodium a ete mise au point. L'oxydation du carbone par la solution de Van SLYKE est realisee sous vide. Le gaz carbonique forme est dose volumetriquement; sa purete peut etre controlee par analyse chromatographique. Les resultats obtenus montrent que cette methode permet de doser des teneurs en carbone de l'ordre de 10 ppm. (auteurs)

  2. Skew quad compensation at PEP

    International Nuclear Information System (INIS)

    Murray, J.J.

    1977-10-01

    Rotational and focal effects of solenoids used in PEP detectors will cause severe perturbations of machine beam optics and must be corrected. Ordinarily this would be accomplished by the addition of compensating solenoids and adjustment of insertion quadrupole strengths. It has been found that an arbitrary cross plane coupling representing the effects of solenoids and/or skew quads in any combination can be synthesized (or compensated) exactly using a quartet of skew quads combined with other erect transport elements in a wide variety of configurations. Specific skew quad compensating systems for PEP have been designed and are under study by PEP staff. So far no fundamental flaws have been discovered. In view of that, PEP management has tentatively authorized the use of such a system in the PEP-4, PEP-9 experiments and proposes to leave the question open ''without prejudice'' for other experiments. Use of skew quad compensation involves an imponderable risk, of course, simply because the method is new and untested. But in addition to providing the only known method for dealing with skew quad perturbations, skew quad compensation, as an alternate to compensating solenoids, promises to be much cheaper, to require much less power and to occupy much less space in the IR's. The purpose of this note is to inform potential users of the foregoing situation and to explain skew quad compensation more fully. 2 refs., 1 fig., 1 tab

  3. A primer for workers' compensation.

    Science.gov (United States)

    Bible, Jesse E; Spengler, Dan M; Mir, Hassan R

    2014-07-01

    A physician's role within a workers' compensation injury extends far beyond just evaluation and treatment with several socioeconomic and psychological factors at play compared with similar injuries occurring outside of the workplace. Although workers' compensation statutes vary among states, all have several basic features with the overall goal of returning the injured worker to maximal function in the shortest time period, with the least residual disability and shortest time away from work. To help physicians unfamiliar with the workers' compensation process accomplish these goals. Review. Educational review. The streamlined review addresses the topics of why is workers' compensation necessary; what does workers' compensation cover; progression after work injury; impairment and maximum medical improvement, including how to use the sixth edition of American Medical Association's (AMA) Guides to the evaluation of permanent impairment (Guides); completion of work injury claim after impairment rating; independent medical evaluation; and causation. In the "no-fault" workers' compensation system, physicians play a key role in progressing the claim along and, more importantly, getting the injured worker back to work as soon as safely possible. Physicians should remain familiar with the workers' compensation process, along with how to properly use the AMA Guides. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Altitude Compensating Nozzle

    Science.gov (United States)

    Ruf, Joseph H.; Jones, Daniel

    2015-01-01

    The dual-bell nozzle (fig. 1) is an altitude-compensating nozzle that has an inner contour consisting of two overlapped bells. At low altitudes, the dual-bell nozzle operates in mode 1, only utilizing the smaller, first bell of the nozzle. In mode 1, the nozzle flow separates from the wall at the inflection point between the two bell contours. As the vehicle reaches higher altitudes, the dual-bell nozzle flow transitions to mode 2, to flow full into the second, larger bell. This dual-mode operation allows near optimal expansion at two altitudes, enabling a higher mission average specific impulse (Isp) relative to that of a conventional, single-bell nozzle. Dual-bell nozzles have been studied analytically and subscale nozzle tests have been completed.1 This higher mission averaged Isp can provide up to a 5% increase2 in payload to orbit for existing launch vehicles. The next important step for the dual-bell nozzle is to confirm its potential in a relevant flight environment. Toward this end, NASA Marshall Space Flight Center (MSFC) and Armstrong Flight Research Center (AFRC) have been working to develop a subscale, hot-fire, dual-bell nozzle test article for flight testing on AFRC's F15-D flight test bed (figs. 2 and 3). Flight test data demonstrating a dual-bell ability to control the mode transition and result in a sufficient increase in a rocket's mission averaged Isp should help convince the launch service providers that the dual-bell nozzle would provide a return on the required investment to bring a dual-bell into flight operation. The Game Changing Department provided 0.2 FTE to ER42 for this effort in 2014.

  5. What Constitutes Fair Compensation for Unfair Dismissal

    African Journals Online (AJOL)

    user

    Generally the monetary compensation is perceived to be a solatium. 19 .... compensation for non-patrimonial loss in the context of an unfair labour practice. 41 .... awards of compensation where a person's dignity is impaired in the course of an.

  6. Genome-Wide Gene Expression Disturbance by Single A1/C1 Chromosome Substitution in Brassica rapa Restituted From Natural B. napus

    Directory of Open Access Journals (Sweden)

    Bin Zhu

    2018-03-01

    Full Text Available Alien chromosome substitution (CS lines are treated as vital germplasms for breeding and genetic mapping. Previously, a whole set of nine Brassica rapa-oleracea monosonic alien addition lines (MAALs, C1-C9 was established in the background of natural B. napus genotype “Oro,” after the restituted B. rapa (RBR for Oro was realized. Herein, a monosomic substitution line with one alien C1 chromosome (Cs1 in the RBR complement was selected in the progenies of MAAL C1 and RBR, by the PCR amplification of specific gene markers and fluorescence in situ hybridization. Cs1 exhibited the whole plant morphology similar to RBR except for the defective stamens without fertile pollen grains, but it produced some seeds and progeny plants carrying the C1 chromosome at high rate besides those without the alien chromosome after pollinated by RBR. The viability of the substitution and its progeny for the RBR diploid further elucidated the functional compensation between the chromosome pairs with high homoeology. To reveal the impact of such aneuploidy on genome-wide gene expression, the transcriptomes of MAAL C1, Cs1 and euploid RBR were analyzed. Compared to RBR, Cs1 had sharply reduced gene expression level across chromosome A1, demonstrating the loss of one copy of A1 chromosome. Both additional chromosome C1 in MAAL and substitutional chromosome C1 in Cs1 caused not only cis-effect but also prevalent trans-effect differentially expressed genes. A dominant gene dosage effects prevailed among low expressed genes across chromosome A1 in Cs1, and moreover, dosage effects for some genes potentially contributed to the phenotype deviations. Our results provided novel insights into the transcriptomic perturbation and gene dosage effects on phenotype in CS related to one naturally evolved allopolyploid.

  7. Evaluation of students' knowledge about paediatric dosage calculations.

    Science.gov (United States)

    Özyazıcıoğlu, Nurcan; Aydın, Ayla İrem; Sürenler, Semra; Çinar, Hava Gökdere; Yılmaz, Dilek; Arkan, Burcu; Tunç, Gülseren Çıtak

    2018-01-01

    Medication errors are common and may jeopardize the patient safety. As paediatric dosages are calculated based on the child's age and weight, risk of error in dosage calculations is increasing. In paediatric patients, overdose drug prescribed regardless of the child's weight, age and clinical picture may lead to excessive toxicity and mortalities while low doses may delay the treatment. This study was carried out to evaluate the knowledge of nursing students about paediatric dosage calculations. This research, which is of retrospective type, covers a population consisting of all the 3rd grade students at the bachelor's degree in May, 2015 (148 students). Drug dose calculation questions in exam papers including 3 open ended questions on dosage calculation problems, addressing 5 variables were distributed to the students and their responses were evaluated by the researchers. In the evaluation of the data, figures and percentage distribution were calculated and Spearman correlation analysis was applied. Exam question on the dosage calculation based on child's age, which is the most common method in paediatrics, and which ensures right dosages and drug dilution was answered correctly by 87.1% of the students while 9.5% answered it wrong and 3.4% left it blank. 69.6% of the students was successful in finding the safe dose range, and 79.1% in finding the right ratio/proportion. 65.5% of the answers with regard to Ml/dzy calculation were correct. Moreover, student's four operation skills were assessed and 68.2% of the students were determined to have found the correct answer. When the relation among the questions on medication was examined, a significant relation (correlation) was determined between them. It is seen that in dosage calculations, the students failed mostly in calculating ml/dzy (decimal). This result means that as dosage calculations are based on decimal values, calculations may be ten times erroneous when the decimal point is placed wrongly. Moreover, it

  8. A benefit/risk approach towards selecting appropriate pharmaceutical dosage forms - an application for paediatric dosage form selection.

    Science.gov (United States)

    Sam, Tom; Ernest, Terry B; Walsh, Jennifer; Williams, Julie L

    2012-10-05

    The design and selection of new pharmaceutical dosage forms involves the careful consideration and balancing of a quality target product profile against technical challenges and development feasibility. Paediatric dosage forms present particular complexity due to the diverse patient population, patient compliance challenges and safety considerations of this vulnerable population. This paper presents a structured framework for assessing the comparative benefits and risks of different pharmaceutical design options against pre-determined criteria relating to (1) efficacy, (2) safety and (3) patient access. This benefit/risk framework has then been applied to three hypothetical, but realistic, scenarios for paediatric dosage forms in order to explore its utility in guiding dosage form design and formulation selection. The approach allows a rigorous, systematic and qualitative assessment of the merits and disadvantages of each dosage form option and helps identify mitigating strategies to modify risk. The application of a weighting and scoring system to the criteria depending on the specific case could further refine the analysis and aid decision-making. In this paper, one case study is scored for illustrative purposes. However, it is acknowledged that in real development scenarios, the generation of actual data considering the very specific situation for the patient/product/developer would come into play to drive decisions on the most appropriate dosage form strategy. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Compensative hypertrophy of the kidney

    International Nuclear Information System (INIS)

    Raynaud, C.

    1976-01-01

    Several measurement methods are available to practitioners to reveal a compensative hypertrophy. Mensuration of the kidney has the advantage of simplicity but is in fact an unreliable and inaccurate method. Separate clearances in their traditional form have never entered into routine use because of the disadvantages of ureteral catheterism. The use of radioactive tracers avoids this drawback, but clearances calculated in this way are only valid in the absence of obstructive urinary disorders. Solutions have been proposed, but the values obtained are no longer identical with the clearances. The Hg uptake test quantifies quite accurately the function of each kidney. From the results obtained a complete compensative hypertrophy developed on a healthy kidney and an incomplete compensative hypertrophy developed on the diseased kidney have been described. In each of these situations the degree to which compensative hypertrophy develops seems to be fixed at a given level peculiar to each patient [fr

  10. CEO Compensation and Disclosure Policy

    OpenAIRE

    Zhang, Weijia; Zhang, Kun

    2016-01-01

    This paper examines the relationship between CEO compensation and disclosure policy related to corporate governance information within S&P 500 index. Our sample consists of 456 companies for the period from 2005 to 2015. Most previous researchers mainly put their attention on various corporate governance characteristics such as board size, board independence, and executive ownership when analysing CEO compensation. Our paper extends the previous study by dividing corporate governance into...

  11. Investigation of contrast agent dosage for perfusion-weighted MRI

    International Nuclear Information System (INIS)

    Erb, G.; Benner, T.; Heiland, S.; Reith, W.; Sartor, K.; Forsting, M.

    1997-01-01

    Purpose: In this study we investigated, whether increasing the dosage of a paramagnetic contrast agent results in a stronger signal decrease in T 2 *-weighted perfusion sequences and therefore more meaningful parameter maps. Material and methods: In a prospective study bolus injection of gadolinium-DTPA was performed at dosages of 0.1, 0.2, and 0.3 mmol/kg body weight (BW) in 10 patients each. Before, during and after bolus injection 40 T 2 *-weighted images of a reference brain slice were acquired within 65.6 seconds on a 1.0 T clinical scanner and perfusion parameters were calculated. Results: Due to the limited signal decrease during bolus passage and the resulting low signal-difference-to-noise ratio (ΔS/N) no reliable differentiation of gray and white matter was possible at a contrast agent dosage of 0.1 mmol/kg BW. Only at higher dosages, both, signal decrease and ΔS/N were strong enough to allow differentiation of gray and white matter and to yield reliable parameter maps. Conclusion: For meaningful MR perfusion imaging at 1.0 T and with the given sequence a contrast agent dosage of at least 0.2 mmol/kg BW is necessary, if a 0.5-molar contrast agent is used. (orig.) [de

  12. Doubled dosage of sofosbuviris expected for inhibiting Zika virus infection

    Institute of Scientific and Technical Information of China (English)

    Somsri Wiwanitkit; Viroj Wiwanitkit

    2017-01-01

    Sofosbuvir is a new antiviral drug that has been recommended for management of hepatitis C virus (HCV) for a few years. New researches support that sofosbuvir might be useful for the management of Zika virus infection. Based on the pharmacological activity, inhibiting the HCV RNA-dependent RNA polymerase (RdRp or NS5 protein), sofosbuvir is proposed for its effectiveness against Zika virus infection. Here, the authors used a mathematical modelling theoretical approach to predict the expected dosage of sofosbuvir for inhibiting Zika virus infection. Based on the modeling study, if sofosbuvir is assigned for management of Zika virus infection, doubled dosage of the present dosage for hepatitis C management is recommended.

  13. Dosage of boron traces in graphite, uranium and beryllium oxide

    International Nuclear Information System (INIS)

    Coursier, J.; Hure, J.; Platzer, R.

    1955-01-01

    The problem of the dosage of the boron in the materials serving to the construction of nuclear reactors arises of the following way: to determine to about 0,1 ppm close to the quantities of boron of the order of tenth ppm. We have chosen the colorimetric analysis with curcumin as method of dosage. To reach the indicated contents, it is necessary to do a previous separation of the boron and the materials of basis, either by extraction of tetraphenylarsonium fluoborate in the case of the boron dosage in uranium and the beryllium oxide, either by the use of a cations exchanger resin of in the case of graphite. (M.B.) [fr

  14. The NSL Complex Regulates Housekeeping Genes in Drosophila

    Science.gov (United States)

    Raja, Sunil Jayaramaiah; Holz, Herbert; Luscombe, Nicholas M.; Manke, Thomas; Akhtar, Asifa

    2012-01-01

    MOF is the major histone H4 lysine 16-specific (H4K16) acetyltransferase in mammals and Drosophila. In flies, it is involved in the regulation of X-chromosomal and autosomal genes as part of the MSL and the NSL complexes, respectively. While the function of the MSL complex as a dosage compensation regulator is fairly well understood, the role of the NSL complex in gene regulation is still poorly characterized. Here we report a comprehensive ChIP–seq analysis of four NSL complex members (NSL1, NSL3, MBD-R2, and MCRS2) throughout the Drosophila melanogaster genome. Strikingly, the majority (85.5%) of NSL-bound genes are constitutively expressed across different cell types. We find that an increased abundance of the histone modifications H4K16ac, H3K4me2, H3K4me3, and H3K9ac in gene promoter regions is characteristic of NSL-targeted genes. Furthermore, we show that these genes have a well-defined nucleosome free region and broad transcription initiation patterns. Finally, by performing ChIP–seq analyses of RNA polymerase II (Pol II) in NSL1- and NSL3-depleted cells, we demonstrate that both NSL proteins are required for efficient recruitment of Pol II to NSL target gene promoters. The observed Pol II reduction coincides with compromised binding of TBP and TFIIB to target promoters, indicating that the NSL complex is required for optimal recruitment of the pre-initiation complex on target genes. Moreover, genes that undergo the most dramatic loss of Pol II upon NSL knockdowns tend to be enriched in DNA Replication–related Element (DRE). Taken together, our findings show that the MOF-containing NSL complex acts as a major regulator of housekeeping genes in flies by modulating initiation of Pol II transcription. PMID:22723752

  15. Dosage effect of a Phex mutation in a murine model of X-linked hypophosphatemia

    Science.gov (United States)

    Ichikawa, Shoji; Gray, Amie K.; Bikorimana, Emmanuel; Econs, Michael J.

    2013-01-01

    X-linked hypophosphatemia (XLH) is caused by mutations in the PHEX gene, which increase circulating levels of the phosphaturic hormone, fibroblast growth factor 23 (FGF23). Since XLH is a dominant disease, one mutant allele is sufficient for manifestation of the disease. However, dosage effect of a PHEX mutation in XLH is not completely understood. To examine the effect of Phex genotypes, we compared serum biochemistries and skeletal measures between all five possible genotypes of a new murine model of XLH (PhexK496X or PhexJrt). Compared to sex-matched littermate controls, all Phex mutant mice had hypophosphatemia, mild hypocalcemia, and increased parathyroid hormone and alkaline phosphatase levels. Furthermore, mutant mice had markedly elevated serum Fgf23 levels due to increased Fgf23 expression and reduced cleavage of Fgf23. Although females with a homozygous Phex mutation were slightly more hypocalcemic and hypophosphatemic than heterozygous females, the two groups had comparable intact Fgf23 levels. Similarly, there was no difference in intact Fgf23 or phosphorus concentrations between hemizygous males and heterozygous females. Compared to heterozygous females, homozygous counterparts were significantly smaller and had shorter femurs with reduced bone mineral density, suggesting the existence of dosage effect in the skeletal phenotype of XLH. However, overall phenotypic trends in regards to mineral ion homeostasis were mostly unaffected by the presence of one or two mutant Phex allele(s). The lack of gene dosage effect on circulating Fgf23 (and thus, phosphorus) levels suggests that a Phex mutation may create the lower set point for extracellular phosphate concentrations. PMID:23700148

  16. Evaluation of the effect of torsemide on warfarin dosage requirements.

    Science.gov (United States)

    Lai, Sophia; Momper, Jeremiah D; Yam, Felix K

    2017-08-01

    Background According to drug interaction databases, torsemide may potentiate the effects of warfarin. Evidence for this drug-drug interaction, however, is conflicting and the clinical significance is unknown. Objective The aim of this study is to evaluate the impact of torsemide initiation on warfarin dosage requirements. Setting This study was conducted at the Veterans Affairs Healthcare System in San Diego, California. Method A retrospective cohort study was conducted using Veterans Affairs data from patients who were converted from bumetanide to torsemide between March 2014 and July 2014. Patients were also prescribed and taking warfarin during the observation period. Warfarin dosage requirements were evaluated to determine if any changes occurred within the first 3 months of starting torsemide. Main outcome measure The primary outcome was the average weekly warfarin dose before and after torsemide initiation. Results Eighteen patients met study inclusion criteria. The weekly warfarin dose before and after initiation of torsemide was not significantly different (34 ± 15 and 34 ± 13 mg, p > 0.05). Of those eighteen patients, only two experienced elevations in INR that required a decrease in warfarin dosage after torsemide initiation. Between those two patients, dosage reductions ranged from 5.3 to 18%. Conclusion These results indicated that most patients did not require any warfarin dosage adjustments after torsemide was initiated. The potential for interaction, however, still exists. While empiric warfarin dosage adjustments are not recommended when initiating torsemide, increased monitoring is warranted to minimize the risk of adverse effects.

  17. 29 CFR 525.6 - Compensable time.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Compensable time. 525.6 Section 525.6 Labor Regulations... WITH DISABILITIES UNDER SPECIAL CERTIFICATES § 525.6 Compensable time. Individuals employed subject to this part must be compensated for all hours worked. Compensable time includes not only those hours...

  18. 48 CFR 970.2270 - Unemployment compensation.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Unemployment compensation... Unemployment compensation. (a) Each state has its own unemployment compensation system to provide payments to... unemployment compensation benefits through a payroll tax on employers. Most DOE contractors are subject to the...

  19. Motion-compensated processing of image signals

    NARCIS (Netherlands)

    2010-01-01

    In a motion-compensated processing of images, input images are down-scaled (scl) to obtain down-scaled images, the down-scaled images are subjected to motion- compensated processing (ME UPC) to obtain motion-compensated images, the motion- compensated images are up-scaled (sc2) to obtain up-scaled

  20. Dosage-based parameters for characterization of puff dispersion results.

    Science.gov (United States)

    Berbekar, Eva; Harms, Frank; Leitl, Bernd

    2015-01-01

    A set of parameters is introduced to characterize the dispersion of puff releases based on the measured dosage. These parameters are the dosage, peak concentration, arrival time, peak time, leaving time, ascent time, descent time and duration. Dimensionless numbers for the scaling of the parameters are derived from dimensional analysis. The dimensionless numbers are tested and confirmed based on a statistically representative wind tunnel dataset. The measurements were carried out in a 1:300 scale model of the Central Business District in Oklahoma City. Additionally, the effect of the release duration on the puff parameters is investigated. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Crime victims‘ right to compensation

    Directory of Open Access Journals (Sweden)

    Mrvić-Petrović Nataša

    2012-01-01

    Full Text Available This paper analyzes the most important documents of the United Nations, Council of Europe and the European Union relating to rights to damage compensation (restitution from offender and state compensation. The analysis shows that there is a gradual move from the concept of exercising the rights of victims in favor of a solidaristic model that takes less into account the rights of victims, and more the need to satisfy their legitimate interests. The economic crisis that is undermining the foundations of the welfare state could jeopardize the realization of this concept, especially in those European countries where the criminal justice system focuses solely on the offender, as is the case in Serbia. In such circumstances, regulation which protects the right to compensation, other rights and interests of victims, shall apply only to the extent that serves crime prevention. So it happens that in spite of a suitable normative framework and developments regarding the protection of victims of domestic violence and trafficking, the right to compensation and other rights of the victims do not actually get actualized in practice. In order to overcome this, a systemic reform to the criminal justice system should be undertaken with the aim to redirect the system towards the victim of the offense. Within these reforms a public fund for compensation of the victims of violence should be established and the process of mediation between the victim and the offender with the goal to make a settlement should be regulated, because these mechanisms do not exist in Serbia.

  2. Preparation of Shrinkage Compensating Concrete with HCSA Expansive Agent

    Science.gov (United States)

    Li, Changcheng; Jia, Fujia

    2017-10-01

    Shrinkage compensating concrete (SCC) has become one of the best effective methods of preventing and reducing concrete cracking. SCC is prepared by HCSA high performance expansive agent for concrete which restrained expansion rate is optimized by 0.057%. Slump, compressive strength, restrained expansion rate and cracking resistance test were carried out on SCC. The results show that the initial slump of fresh SCC was about 220mm-230mm, while slump after 2 hours was 180mm-200mm. The restrained expansion rate of SCC increased with the mixing amount of expansive agent. After cured in water for 14 days, the restrained expansion rate of C35 and C40 SCC were 0.020%-0.032%. With the dosage of expansive agent increasing, restrained expansion rate of SCC increased, maximum compressive stress and cracking stress improved, cracking temperature fell, thus cracking resistance got effectively improvement.

  3. Adaptive Motion Compensation in Radiotherapy

    CERN Document Server

    Murphy, Martin J

    2011-01-01

    External-beam radiotherapy has long been challenged by the simple fact that patients can (and do) move during the delivery of radiation. Recent advances in imaging and beam delivery technologies have made the solution--adapting delivery to natural movement--a practical reality. Adaptive Motion Compensation in Radiotherapy provides the first detailed treatment of online interventional techniques for motion compensation radiotherapy. This authoritative book discusses: Each of the contributing elements of a motion-adaptive system, including target detection and tracking, beam adaptation, and pati

  4. Network compensation for missing sensors

    Science.gov (United States)

    Ahumada, Albert J., Jr.; Mulligan, Jeffrey B.

    1991-01-01

    A network learning translation invariance algorithm to compute interpolation functions is presented. This algorithm with one fixed receptive field can construct a linear transformation compensating for gain changes, sensor position jitter, and sensor loss when there are enough remaining sensors to adequately sample the input images. However, when the images are undersampled and complete compensation is not possible, the algorithm need to be modified. For moderate sensor losses, the algorithm works if the transformation weight adjustment is restricted to the weights to output units affected by the loss.

  5. Metabolic Compensation and Circadian Resilience in Prokaryotic Cyanobacteria

    Science.gov (United States)

    Johnson, Carl Hirschie; Egli, Martin

    2014-01-01

    For a biological oscillator to function as a circadian pacemaker that confers a fitness advantage, its timing functions must be stable in response to environmental and metabolic fluctuations. One such stability enhancer, temperature compensation, has long been a defining characteristic of these timekeepers. However, an accurate biological timekeeper must also resist changes in metabolism, and this review suggests that temperature compensation is actually a subset of a larger phenomenon, namely metabolic compensation, which maintains the frequency of circadian oscillators in response to a host of factors that impinge on metabolism and would otherwise destabilize these clocks. The circadian system of prokaryotic cyanobacteria is an illustrative model because it is composed of transcriptional and nontranscriptional oscillators that are coupled to promote resilience. Moreover, the cyanobacterial circadian program regulates gene activity and metabolic pathways, and it can be manipulated to improve the expression of bioproducts that have practical value. PMID:24905782

  6. 76 FR 59023 - Oral Dosage Form New Animal Drugs; Tylosin

    Science.gov (United States)

    2011-09-23

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Tylosin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  7. 77 FR 3927 - Oral Dosage Form New Animal Drugs; Deracoxib

    Science.gov (United States)

    2012-01-26

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Deracoxib AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  8. 76 FR 18648 - Oral Dosage Form New Animal Drugs; Robenacoxib

    Science.gov (United States)

    2011-04-05

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Robenacoxib AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  9. 76 FR 40808 - Oral Dosage Form New Animal Drugs; Amprolium

    Science.gov (United States)

    2011-07-12

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Amprolium AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  10. 77 FR 15960 - Oral Dosage Form New Animal Drugs; Pergolide

    Science.gov (United States)

    2012-03-19

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Pergolide AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  11. 75 FR 67031 - Oral Dosage Form New Animal Drugs; Domperidone

    Science.gov (United States)

    2010-11-01

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2010-N-0002] Oral Dosage Form New Animal Drugs; Domperidone AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  12. 76 FR 78149 - Oral Dosage Form New Animal Drugs; Estriol

    Science.gov (United States)

    2011-12-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Estriol AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  13. Pharmaceutical development of an intravenous dosage form of diacetylmorphine hydrochloride

    NARCIS (Netherlands)

    Klous, Marjolein G.; Nuijen, Bastiaan; van den Brink, Wim; van Ree, Jan M.; Beijnen, Jos H.

    2004-01-01

    A solid dosage form for multiple use was developed for parenteral administration of diacetylmorphine in a clinical trial on co-prescription of heroin to heroin addicts. A 300-mg/mL diacetylmorphine hydrochloride solution was lyophilised as 10-mL aliquots in 30-mL glass vials, to be reconstituted to

  14. Effect of lead acetate administered orally at different dosage levels ...

    African Journals Online (AJOL)

    The project was conducted to evaluate the effect of lead administered as lead acetate at different dosage levels via drinking water in broiler chicks. Thirty-five healthy chicks were divided into seven groups (five chicks each) and one group was kept as un-medicated control. Groups A, B, C, D, E and F were medicated with ...

  15. Quality of 'Climax' blueberries after low dosage electron beam irradiation

    International Nuclear Information System (INIS)

    Miller, W.R.; McDonald, R.E.; McCollum, T.G.; Smittle, B.J.

    1994-01-01

    Fruit of 'Climax' rabbiteye blueberries (Vaccinium ashei Reade) were irradiated by a linear accelerator at 0, 0.25, 0.5, 0.75, 1.0, and 1.25 kGy and evaluated for various quality attributes after storage for 1, 3, 7, or 14 days at 1C plus 2 days at 15C, respectively. Weight loss increased during storage and averaged 4.2% after the final inspection and was not affected by irradiation dosage. About 5% of total berries were decayed after 14 days at 1C, about 6% after the final inspection at 15C, but decay was not affected by the level of irradiation. Electrolyte leakage, skin color, total soluble solids, acidity, and pH were also not affected by irradiation dosage. There was a significant decline in berry firmness, flavor, and texture as dosage increased. Berries treated at 1.0 kGy or above were softer and had lower flavor and texture preference scores than berries treated at lower dosages or nontreated berries

  16. Dosage plasmatique et globulaire du magnesium dans l'exploration ...

    African Journals Online (AJOL)

    Objectives: The allergic rhinitis represents a real public health problem. The goal of this survey is to value the interest of the dosage plasmatical and globular of magnesium in the diagnosis of the allergic rhinitis. Materials and methods : Analytic and prospective survey of 80 files, on one period of 4 years and 5 months (from ...

  17. Determination of methadone hydrochloride in a maintenance dosage formulation.

    Science.gov (United States)

    Hoffmann, T J; Thompson, R D

    1975-07-01

    A colorimetric method for direct quantitative assay of methadone hydrochloride in liquid oral dosage forms is presented. The procedure involves the formation of a dye complex with bromothymol blue buffer solution. The resultant complex is extracted with benzene and measured spectrophotometrically. Duplicate tests on the formulation showed 99.2% of the labeled amount of methadone.

  18. 21 CFR 520.1448 - Monensin oral dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Monensin oral dosage forms. 520.1448 Section 520.1448 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... distance the spots travel from the starting line divided by the distance the solvent front travels from the...

  19. Gonadal dosage during hip dysplasia radiography in the dog.

    Science.gov (United States)

    Wood, A K; Reynolds, K M; Leith, I S; Burns, P A

    1977-01-01

    Thermoluminescent dosemeters were used to estimate gonadal dosage during hip dysplasia radiography of labrador retriever dogs. The mean radiation dose to the unshielded testes was 100 millirad (mrad) and the estimated dose to the shielded testes was 9 mrad. It was considered unnecessary to shield the ovaries.

  20. Fuzzy-based dosage model of aqueous decoction of Adansonia ...

    African Journals Online (AJOL)

    However, in the area of traditional medicine, no much attention has been given to its enhancement with the use of information technology especially in the area of herbal prescription. ... The mass of herb and volume of solvent were used as input parameters to design the dosage model, and simulated using MATLAB.

  1. Formulation of Croton penduliflorus seed into tablet dosage form ...

    African Journals Online (AJOL)

    Formulation of Croton penduliflorus seed into tablet dosage form. GC Onunkwo. Abstract. No Abstract. Global Journal of Medical Sciences Vol. 5(1) 2006: 29-33. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.4314/gjms.v5i1.10145.

  2. Formulation and evaluation of tablet dosage form of Hunteria ...

    African Journals Online (AJOL)

    The present study was aimed at formulating and evaluating tablet dosage form of Hunteria umbellata (HU) seed aqueous and purified extracts. HU seeds were dried, pulverized and the powder macerated in water to obtain aqueous extract, while alkaloidal extraction process was used to obtain purified extract. Extracts ...

  3. Biowaiver monographs for immediate release solid oral dosage forms: cimetidine.

    NARCIS (Netherlands)

    Jantratid, E; Prakongpan, S; Dressman, J B; Amidon, G L; Junginger, H E; Midha, K K; Barends, D M

    2006-01-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing cimetidine are reviewed. According to the current Biopharmaceutics Classification System (BCS), cimetidine would be assigned

  4. Spectrophotometric Determination of Cilostazol in Tablet Dosage Form

    African Journals Online (AJOL)

    Purpose: To develop simple, rapid and selective spectrophotometric methods for the determination of cilostazol in tablet dosage form. Methods: Cilostazol was dissolved in 50 % methanol and its absorbance was scanned by ultraviolet (UV) spectrophotometry. Both linear regression equation and standard absorptivity were ...

  5. Maths anxiety and medication dosage calculation errors: A scoping review.

    Science.gov (United States)

    Williams, Brett; Davis, Samantha

    2016-09-01

    A student's accuracy on drug calculation tests may be influenced by maths anxiety, which can impede one's ability to understand and complete mathematic problems. It is important for healthcare students to overcome this barrier when calculating drug dosages in order to avoid administering the incorrect dose to a patient when in the clinical setting. The aim of this study was to examine the effects of maths anxiety on healthcare students' ability to accurately calculate drug dosages by performing a scoping review of the existing literature. This review utilised a six-stage methodology using the following databases; CINAHL, Embase, Medline, Scopus, PsycINFO, Google Scholar, Trip database (http://www.tripdatabase.com/) and Grey Literature report (http://www.greylit.org/). After an initial title/abstract review of relevant papers, and then full text review of the remaining papers, six articles were selected for inclusion in this study. Of the six articles included, there were three experimental studies, two quantitative studies and one mixed method study. All studies addressed nursing students and the presence of maths anxiety. No relevant studies from other disciplines were identified in the existing literature. Three studies took place in the U.S, the remainder in Canada, Australia and United Kingdom. Upon analysis of these studies, four factors including maths anxiety were identified as having an influence on a student's drug dosage calculation abilities. Ultimately, the results from this review suggest more research is required in nursing and other relevant healthcare disciplines regarding the effects of maths anxiety on drug dosage calculations. This additional knowledge will be important to further inform development of strategies to decrease the potentially serious effects of errors in drug dosage calculation to patient safety. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Identification of imprinted genes subject to parent-of-origin specific expression in Arabidopsis thaliana seeds.

    NARCIS (Netherlands)

    Mckeown, P.C.; Laouielle-Duprat, S.; Prins, J.C.P.; Wolff, de P.; Schmid, M.W.; Donoghue, M.T.; Fort, A.; Duszynska, D.; Comte, A.; Lao, N.T.; Wennblom, T.J.; Smant, G.; Köhler, C.; Grossniklaus, U.; Spillane, C.

    2011-01-01

    Background: Epigenetic regulation of gene dosage by genomic imprinting of some autosomal genes facilitates normal reproductive development in both mammals and flowering plants. While many imprinted genes have been identified and intensively studied in mammals, smaller numbers have been characterized

  7. Psychology of Pay and Compensation

    NARCIS (Netherlands)

    Thierry, Hk.; Smelser, N.J.; Baltes, P.B.

    2002-01-01

    In most industrialized countries the compensation, of managers and employees is structured along quite comparable patterns. One part consists of base pay, a second part of results-oriented pay, and a third part of secondary labor conditions. In many instances part four is composed of perquisites:

  8. Ongoing transients in carbonate compensation

    NARCIS (Netherlands)

    Boudreau, B.P.; Middelburg, J.J.; Hofmann, A.F.; Meysman, F.J.R.

    2010-01-01

    Uptake of anthropogenic CO2 is acidifying the oceans. Over the next 2000 years, this will modify the dissolution and preservation of sedimentary carbonate. By coupling new formulas for the positions of the calcite saturation horizon, zsat, the compensation depth, zcc, and the snowline, zsnow, to a

  9. Strategic Design of Teacher Compensation

    Science.gov (United States)

    Shields, Regis

    2012-01-01

    Spurred by the national focus on revitalizing the teacher evaluation and support/development process, as well as the current economic downturn, many school districts are reviewing how teachers are compensated. While a few courageous districts have completely upended current structures, most districts are undertaking changes that leave the most…

  10. Optimal compensation for neuron loss

    Science.gov (United States)

    Barrett, David GT; Denève, Sophie; Machens, Christian K

    2016-01-01

    The brain has an impressive ability to withstand neural damage. Diseases that kill neurons can go unnoticed for years, and incomplete brain lesions or silencing of neurons often fail to produce any behavioral effect. How does the brain compensate for such damage, and what are the limits of this compensation? We propose that neural circuits instantly compensate for neuron loss, thereby preserving their function as much as possible. We show that this compensation can explain changes in tuning curves induced by neuron silencing across a variety of systems, including the primary visual cortex. We find that compensatory mechanisms can be implemented through the dynamics of networks with a tight balance of excitation and inhibition, without requiring synaptic plasticity. The limits of this compensatory mechanism are reached when excitation and inhibition become unbalanced, thereby demarcating a recovery boundary, where signal representation fails and where diseases may become symptomatic. DOI: http://dx.doi.org/10.7554/eLife.12454.001 PMID:27935480

  11. Synchrony - Cyberknife Respiratory Compensation Technology

    International Nuclear Information System (INIS)

    Ozhasoglu, Cihat; Saw, Cheng B.; Chen Hungcheng; Burton, Steven; Komanduri, Krishna; Yue, Ning J.; Huq, Saiful M.; Heron, Dwight E.

    2008-01-01

    Studies of organs in the thorax and abdomen have shown that these organs can move as much as 40 mm due to respiratory motion. Without compensation for this motion during the course of external beam radiation therapy, the dose coverage to target may be compromised. On the other hand, if compensation of this motion is by expansion of the margin around the target, a significant volume of normal tissue may be unnecessarily irradiated. In hypofractionated regimens, the issue of respiratory compensation becomes an important factor and is critical in single-fraction extracranial radiosurgery applications. CyberKnife is an image-guided radiosurgery system that consists of a 6-MV LINAC mounted to a robotic arm coupled through a control loop to a digital diagnostic x-ray imaging system. The robotic arm can point the beam anywhere in space with 6 degrees of freedom, without being constrained to a conventional isocenter. The CyberKnife has been recently upgraded with a real-time respiratory tracking and compensation system called Synchrony. Using external markers in conjunction with diagnostic x-ray images, Synchrony helps guide the robotic arm to move the radiation beam in real time such that the beam always remains aligned with the target. With the aid of Synchrony, the tumor motion can be tracked in three-dimensional space, and the motion-induced dosimetric change to target can be minimized with a limited margin. The working principles, advantages, limitations, and our clinical experience with this new technology will be discussed

  12. The association between GGCX, miR-133 genetic polymorphisms and warfarin stable dosage in Han Chinese patients with mechanical heart valve replacement.

    Science.gov (United States)

    Tang, X-Y; Zhang, J; Peng, J; Tan, S-L; Zhang, W; Song, G-B; Liu, L-M; Li, C-L; Ren, H; Zeng, L; Liu, Z-Q; Chen, X-P; Zhou, X-M; Zhou, H-H; Hu, J-X; Li, Z

    2017-08-01

    Warfarin is a widely used anticoagulant with a narrow therapeutic index. Polymorphisms in the VKORC1, CYP2C9 and CYP4F2 genes have been verified to correlate with warfarin stable dosage (WSD). Whether any other genes or variants affect the dosage is unknown. The aim of our study was to investigate the relationship between GGCX, miR-133 variants and the WSD in Han Chinese patients with mechanical heart valve replacement (MHVR). A total of 231 patients were enrolled in the study. Blood samples were collected for genotyping. The average WSD among subjects with different GGCX or miR-133 genotypes was compared. Regression analyses were performed to test for any association of genetic polymorphisms with WSD. The warfarin dosage in patients with the GGCX rs699664 TT and rs12714145 TT genotypes was 3.77±0.93 (95% CI: 3.35-4.19) mg/d and 3.70±1.00 (95% CI: 3.32-4.09) mg/d, respectively. The GGCX rs699664 and rs12714145 genotypes were significantly associated with WSD (Pwarfarin stable dosage between subjects with MIR133B rs142410335 wild-type and variant genotypes (P>.05). The genotypes of GGCX rs699644 and rs12714145 were significantly associated with WSD (Pwarfarin stable dosage in Han Chinese patients with MHVR neither in univariate regression nor in multivariate regression analyses. © 2017 John Wiley & Sons Ltd.

  13. 33 CFR 136.223 - Compensation allowable.

    Science.gov (United States)

    2010-07-01

    ...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND; CLAIMS... allowable under paragraph (a) of this section must be reduced by— (1) All compensation made available to the... under § 136.235. Government Revenues ...

  14. Nuclear damage compensation and energy reform

    International Nuclear Information System (INIS)

    Yokemoto, Masafumi

    2013-01-01

    Nuclear damage compensation and energy reform were closely related. Nuclear damage compensation cost should be part of generation cost of nuclear power. Extend of nuclear damage compensation was limited by compensation standard of Tokyo Electric Power Co. (TEPCO) following guidelines of Dispute Reconciliation Committee for Nuclear Damage Compensation. TEPCO had already paid compensation of about two trillion yen until now, which was only a part of total damage compensation cost. TEPCO had been provided more than 3.4 trillion yen by Nuclear Damage Liability Facilitation Cooperation, which would be put back by nuclear operators including TEPCO. TEPCO could obtain present raising funds and try to reconstruct business with restart of nuclear power, which might disturb energy reform. Present nuclear damage compensation scheme had better be reformed with learning more from Minamata disease case in Japan. (T. Tanaka)

  15. Digital and conventional radiology techniques: comparison of dosage and costs

    International Nuclear Information System (INIS)

    Arranza, L.; Albornoz, C. de

    1996-01-01

    To compare the radiation dosage and costs in conventional and digital technologies. The study dealt with transverse sections. The dosage applied with conventional technology was measured in 254 patients who intertwined 402 explorations of 6 anatomic regions in 4 Radiodiagnostic Services. The dosage applied with digital technology was measured in 57 patients who underwent 95 explorations of the same anatomic region in one Radiodiagnostic Service. The costs of the 6 types of conventional and digital explorations performed were calculated for two Radiodiagnostic Service. The doses administered (mGy) using convectional/digital technology were as follows: chest PA 0.2/0.1; chest LAT 0.7/0.3; breast CC 7.0/8.4; breast LAT 7.0/7.8; breast OB 7.0/10.5; cervical spine AP 9.6/9.0; cervical spine LAT 21.9/29.6; pelvis AP 7.3/7.1; plain abdominal 6.5/2.2. The costs incurred (1992 pesetas) with the convectional/digital technologies: chest AP and LAT 1,393/2,973; portable chest 2,027/3,714; mammography 2,357/3,486; phlebography 12,718/14,023; hysterosalpingography 4,876/6,701; bone scientigraphy 1,633/2,839. Compared with conventional technology, digital imaging reduces the radiation doses received by the patients, except in the case of mammography. The costs associated with the use of digital technology are greater than those incurred with conventional technology, mainly due to the costs of amortization. the use of digital technology is more justified when: 1) it is very necessary to reduce the dosage; 2) studies of chest and abdomen predominant; 3) the volume of utilization is high; 4) staff management is flexible , and 5) the cost of purchasing the equipment is lower. (Author) 10 refs

  16. Quantum electrodynamics with compensating current

    Energy Technology Data Exchange (ETDEWEB)

    Bechler, A [Warsaw Univ. (Poland). Instytut Fizyki Teoretycznej

    1974-01-01

    A formulation of quantum electrodynamics is proposed in which all the propagators and field operators are gauge invariant. It is based on an old idea of Heisenberg and Euler which consists in the introduction of the linear integrals of potentials as arguments of the exponential functions. This method is generalized by an introduction of the so-called ''compensating currents'', which ensure local, i.e. in every point of space-time, charge conservation. The linear integral method is a particular case of that proposed in this paper. As the starting point we use quantum electrodynamics with a non-zero, small photon mass (Proca theory). It is shown that, due to the presence of the compensating current, the theory is fully renormalizable in Hilbert space with positive definite scalar product. The problem of the definition of the current operator is also briefly discussed.

  17. Executive compensation: a calibration approach

    OpenAIRE

    Ivilina Popova; Joseph G. Haubrich

    1998-01-01

    We use a version of the Grossman and Hart principal-agent model with 10 actions and 10 states to produce quantitative predictions for executive compensation. Performance incentives derived from the model are compared with the performance incentives of 350 firms chosen from a survey by Michael Jensen and Kevin Murphy. The results suggest both that the model does a reasonable job of explaining the data and that actual incentives are close to the optimal incentives predicted by theory.

  18. Compensating Differentials for Sexual Harassment

    OpenAIRE

    Joni Hersch

    2011-01-01

    Workplace sexual harassment is illegal, but many workers report that they have been sexually harassed. Exposure to the risk of sexual harassment may decrease productivity, which would reduce wages. Alternatively, workers may receive a compensating differential for exposure to sexual harassment, which would increase wages. Data on claims of sexual harassment filed with the Equal Employment Opportunity Commission are used to calculate the first measures of sexual harassment risks by industry, a...

  19. QR encoded smart oral dosage forms by inkjet printing.

    Science.gov (United States)

    Edinger, Magnus; Bar-Shalom, Daniel; Sandler, Niklas; Rantanen, Jukka; Genina, Natalja

    2018-01-30

    The use of inkjet printing (IJP) technology enables the flexible manufacturing of personalized medicine with the doses tailored for each patient. In this study we demonstrate, for the first time, the applicability of IJP in the production of edible dosage forms in the pattern of a quick response (QR) code. This printed pattern contains the drug itself and encoded information relevant to the patient and/or healthcare professionals. IJP of the active pharmaceutical ingredient (API)-containing ink in the pattern of QR code was performed onto a newly developed porous and flexible, but mechanically stable substrate with a good absorption capacity. The printing did not affect the mechanical properties of the substrate. The actual drug content of the printed dosage forms was in accordance with the encoded drug content. The QR encoded dosage forms had a good print definition without significant edge bleeding. They were readable by a smartphone even after storage in harsh conditions. This approach of efficient data incorporation and data storage combined with the use of smart devices can lead to safer and more patient-friendly drug products in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Prevalence and trends of cellulosics in pharmaceutical dosage forms.

    Science.gov (United States)

    Mastropietro, David J; Omidian, Hossein

    2013-02-01

    Many studies have shown that cellulose derivatives (cellulosics) can provide various benefits when used in virtually all types of dosage forms. Nevertheless, the popularity of their use in approved drug products is rather unknown. This research reports the current prevalence and trends of use for 15 common cellulosics in prescription drug products. The cellulosics were powdered and microcrystalline cellulose (MCC), ethyl cellulose, hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), hypromellose (HPMC), HPMC phthalate, HPMC acetate succinate, cellulose acetate (CA), CA phthalate, sodium (Na) and calcium (Ca) carboxymethylcellulose (CMC), croscarmellose sodium (XCMCNa), methyl cellulose, and low substituted HPC. The number of brand drug products utilizing each cellulosics was determined using the online drug index Rxlist. A total of 607 brand products were identified having one or more of the cellulosics as an active or inactive ingredient. An array of various dosage forms was identified and revealed HPMC and MCC to be the most utilized cellulosics in all products followed by XCMCNa and HPC. Many products contained two or more cellulosics in the formulation (42% containing two, 23% containing three, and 4% containing 4-5). The largest combination occurrence was HPMC with MCC. The use of certain cellulosics within different dosage form types was found to contain specific trends. All injectables utilized only CMCNa, and the same with all ophthalmic solutions utilizing HPMC, and otic suspensions utilizing HEC. Popularity and trends regarding cellulosics use may occur based on many factors including functionality, safety, availability, stability, and ease of manufacturing.

  1. 23 CFR 751.15 - Just compensation.

    Science.gov (United States)

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Just compensation. 751.15 Section 751.15 Highways... AND ACQUISITION § 751.15 Just compensation. (a) Just compensation shall be paid the owner for the... nonconforming junkyard as provided in § 751.11 must pertain at the time of the taking or removal in order to...

  2. Dynamic Phase Compensation of wind turbines

    DEFF Research Database (Denmark)

    Soerensen, P.; Skaarup, J.; Iov, Florin

    2004-01-01

    This paper describes a dynamic phase compensation unit for a wind turbine with directly connected induction generators. The compensation unit is based on thyristor switched capacitors, where conventional wind turbine compensations use mechanical contactors to switch the capacitors. The unit modules...

  3. 33 CFR 136.217 - Compensation allowable.

    Science.gov (United States)

    2010-07-01

    ...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND; CLAIMS PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.217 Compensation... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Compensation allowable. 136.217...

  4. 33 CFR 136.205 - Compensation allowable.

    Science.gov (United States)

    2010-07-01

    ...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND; CLAIMS PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.205 Compensation... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Compensation allowable. 136.205...

  5. 33 CFR 136.113 - Other compensation.

    Science.gov (United States)

    2010-07-01

    ...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND; CLAIMS PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT General Procedure § 136.113 Other compensation. A... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Other compensation. 136.113...

  6. The battle over workers' compensation.

    Science.gov (United States)

    Ellenberger, J N

    2000-01-01

    Faced with lower profits and rapidly increasing premium costs in the 1980s, insurers and employer organizations cleverly parlayed the public perception of worker fraud and abuse in the workers' compensation system (that they helped to create) into massive legislative changes. Over the last decade, state legislators and governors, Republican and Democrat alike, have jumped on this bandwagon, one that workers and their allies have dubbed the workers' compensation "deform" movement. Alleging a "game plan" and a calculated campaign on the part of insurers and employers, the author looks at the major components of changes that were made, examines the elements of workers' compensation over which employers and insurers have gained control, and discusses Newt Gingrich's efforts to capitalize on employer and insurer fervor over the system. This campaign whistled through the country until it goaded the labor movement, injured workers, the trial bar, and others in Ohio in 1997 to organize themselves to stand up to employers by defeating the deform law through a ballot initiative. The article details that battle and suggests that similar voices can be achieved through a return to grassroots organizing and mobilization.

  7. Compensation Techniques in Accelerator Physics

    Energy Technology Data Exchange (ETDEWEB)

    Sayed, Hisham Kamal [Old Dominion Univ., Norfolk, VA (United States)

    2011-05-01

    Accelerator physics is one of the most diverse multidisciplinary fields of physics, wherein the dynamics of particle beams is studied. It takes more than the understanding of basic electromagnetic interactions to be able to predict the beam dynamics, and to be able to develop new techniques to produce, maintain, and deliver high quality beams for different applications. In this work, some basic theory regarding particle beam dynamics in accelerators will be presented. This basic theory, along with applying state of the art techniques in beam dynamics will be used in this dissertation to study and solve accelerator physics problems. Two problems involving compensation are studied in the context of the MEIC (Medium Energy Electron Ion Collider) project at Jefferson Laboratory. Several chromaticity (the energy dependence of the particle tune) compensation methods are evaluated numerically and deployed in a figure eight ring designed for the electrons in the collider. Furthermore, transverse coupling optics have been developed to compensate the coupling introduced by the spin rotators in the MEIC electron ring design.

  8. 38 CFR 21.3023 - Nonduplication; pension, compensation, and dependency and indemnity compensation.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Nonduplication; pension, compensation, and dependency and indemnity compensation. 21.3023 Section 21.3023 Pensions, Bonuses, and... Nonduplication; pension, compensation, and dependency and indemnity compensation. (a) Child; age 18. A child who...

  9. 21 CFR 330.3 - Imprinting of solid oral dosage form drug products.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Imprinting of solid oral dosage form drug products... AS SAFE AND EFFECTIVE AND NOT MISBRANDED General Provisions § 330.3 Imprinting of solid oral dosage form drug products. A requirement to imprint an identification code on solid oral dosage form drug...

  10. 21 CFR 522.1696 - Penicillin G procaine implantation and injectable dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin G procaine implantation and injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... DOSAGE FORM NEW ANIMAL DRUGS § 522.1696 Penicillin G procaine implantation and injectable dosage forms. ...

  11. 21 CFR 524.1662 - Oxytetracycline hydrochloride ophthalmic and topical dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride ophthalmic and topical dosage forms. 524.1662 Section 524.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... DOSAGE FORM NEW ANIMAL DRUGS § 524.1662 Oxytetracycline hydrochloride ophthalmic and topical dosage forms. ...

  12. Automatic error compensation in dc amplifiers

    International Nuclear Information System (INIS)

    Longden, L.L.

    1976-01-01

    When operational amplifiers are exposed to high levels of neutron fluence or total ionizing dose, significant changes may be observed in input voltages and currents. These changes may produce large errors at the output of direct-coupled amplifier stages. Therefore, the need exists for automatic compensation techniques. However, previously introduced techniques compensate only for errors in the main amplifier and neglect the errors induced by the compensating circuitry. In this paper, the techniques introduced compensate not only for errors in the main operational amplifier, but also for errors induced by the compensation circuitry. Included in the paper is a theoretical analysis of each compensation technique, along with advantages and disadvantages of each. Important design criteria and information necessary for proper selection of semiconductor switches will also be included. Introduced in this paper will be compensation circuitry for both resistive and capacitive feedback networks

  13. DC-Compensated Current Transformer.

    Science.gov (United States)

    Ripka, Pavel; Draxler, Karel; Styblíková, Renata

    2016-01-20

    Instrument current transformers (CTs) measure AC currents. The DC component in the measured current can saturate the transformer and cause gross error. We use fluxgate detection and digital feedback compensation of the DC flux to suppress the overall error to 0.15%. This concept can be used not only for high-end CTs with a nanocrystalline core, but it also works for low-cost CTs with FeSi cores. The method described here allows simultaneous measurements of the DC current component.

  14. Dependence of 'CT clearance' on dosage and time

    International Nuclear Information System (INIS)

    Kaltenborn, H.A.; Klose, K.J.; Dexheimer, C.; Steinijans, V.

    1989-01-01

    The contrast medium dose used in CT renal function analysis corresponds to about 1 ml/kg body weight at a measurement interval of 5 or 10 minutes. In the present study the dependence of 'CT clearance' on dosage and time was examined in 12 healthy subjects. The amount of clearance was directly proportional to the employed contrast medium dose and to the length of the measurement interval. On account of the superior signal-to-noise ratio, the higher dose (1 ml/kg body weight) will continue to be prefered in future. The measurement interval can be limited to 10 minutes. (orig.) [de

  15. Comprehensive review on additives of topical dosage forms for drug delivery.

    Science.gov (United States)

    Garg, Tarun; Rath, Goutam; Goyal, Amit K

    2015-12-01

    Skin is the largest organ of the human body and plays the most important role in protecting against pathogen and foreign matter. Three important modes such as topical, regional and transdermal are widely used for delivery of various dosage forms. Among these modes, the topical dosage forms are preferred because it provides local therapeutic activity when applied to the skin or mucous membranes. Additives or pharmaceutical excipients (non-drug component of dosage form) are used as inactive ingredients in dosage form or tools for structuring dosage forms. The main use of topical dosage form additives are controling the extent of absorption, maintaining the viscosity, improving the stability as well as organoleptic property and increasing the bulk of the formulation. The overall goal of this article is to provide the clinician with information related to the topical dosage form additives and their current major applications against various diseases.

  16. Gamma ray dosage and mutation breeding in St. Augustinegrass

    International Nuclear Information System (INIS)

    Busey, P.

    1980-01-01

    Stolon pieces of St. Augustinegrass [Stenotaphrum secundatum (Walt.) Kuntze] were irradiated with gamma rays in an attempt to cause mutations. A practical dosage for most genotypes was 4,500 rads. This dosage caused considerable (50%) growth retardation and a mean survival of about 40% of single-node cuttings. However, Bitterblue and another accession were entirely killed at 4,000 rads. At 4,500 rads, up to 7% recognizable mutants of accession FA-243 were obtained. This proportion resulted when irradiated cuttings were propagated clonally and observed for 1.5 years in replicated microplots. In addition to morphological variants, a chimeral anthocyanin change was noticed. From this chimera arose a stable genotype with green stolons and white stigmas, whereas the source genotype (FA-243) had red stolons and purple stigmas. Associated reduction in fertility from 56 to 0.6% suggested that the mutation arose as a small chromosome deletion. Mutation breeding is effective in improving St. Augustinegrass when easily recognizable variants are needed

  17. Biowaiver monographs for immediate release solid oral dosage forms: efavirenz.

    Science.gov (United States)

    Cristofoletti, Rodrigo; Nair, Anita; Abrahamsson, Bertil; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James E; Shah, Vinod P; Dressman, Jennifer B

    2013-02-01

    Literature data pertaining to the decision to allow a waiver of in vivo bioequivalence testing for the approval of immediate-release (IR) solid oral dosage forms containing efavirenz as the only active pharmaceutical ingredient (API) are reviewed. Because of lack of conclusive data about efavirenz's permeability and its failure to comply with the "high solubility" criteria according to the Biopharmaceutics Classification System (BCS), the API can be classified as BCS Class II/IV. In line with the solubility characteristics, the innovator product does not meet the dissolution criteria for a "rapidly dissolving product." Furthermore, product variations containing commonly used excipients or in the manufacturing process have been reported to impact the rate and extent of efavirenz absorption. Despite its wide therapeutic index, subtherapeutic levels of efavirenz can lead to treatment failure and also facilitate the emergence of efavirenz-resistant mutants. For all these reasons, a biowaiver for IR solid oral dosage forms containing efavirenz as the sole API is not scientifically justified for reformulated or multisource drug products. Copyright © 2012 Wiley Periodicals, Inc.

  18. Gamma scintigraphy in the evaluation of pharmaceutical dosage forms

    International Nuclear Information System (INIS)

    Davis, S.S.; Hardy, J.G.; Newman, S.P.; Wilding, I.R.

    1992-01-01

    Gamma-scintigraphy is applied extensively in the development and evaluation of pharmaceutical drug delivery systems. It is used particularly for monitoring formulations in the gastrointestinal and respiratory tracts. The radiolabelling is generally achieved by the incorporation of an appropriate technetium-99m or indium-111 labelled radiopharmaceutical into the formulation. In the case of complex dosage forms, such as enteric-coated tablets, labelling is best undertaken by the addition of a non-radioactive tracer such as samarium-152 or erbium-170 followed by neutron activation of the final product. Systems investigated include tablets and multiparticulates for oral administration, enemas and suppositories, metered dose inhalers and nebulisers, and nasal sprays and drops. Gamma-scintigraphy provides information on the deposition, dispersion and movement of the formulation. The combination of such studies with the assay of drug levels in blood or urine specimens, pharmacoscintigraphy, provides information concerning the sites of drug release and absorption. Data acquired from the scintigraphic evaluation of pharmaceutical dosage forms are now being used increasingly at all stages of product development, from the assessment of prototype delivery systems to supporting the product licence application. (orig.)

  19. Emergence of 3D Printed Dosage Forms: Opportunities and Challenges.

    Science.gov (United States)

    Alhnan, Mohamed A; Okwuosa, Tochukwu C; Sadia, Muzna; Wan, Ka-Wai; Ahmed, Waqar; Arafat, Basel

    2016-08-01

    The recent introduction of the first FDA approved 3D-printed drug has fuelled interest in 3D printing technology, which is set to revolutionize healthcare. Since its initial use, this rapid prototyping (RP) technology has evolved to such an extent that it is currently being used in a wide range of applications including in tissue engineering, dentistry, construction, automotive and aerospace. However, in the pharmaceutical industry this technology is still in its infancy and its potential yet to be fully explored. This paper presents various 3D printing technologies such as stereolithographic, powder based, selective laser sintering, fused deposition modelling and semi-solid extrusion 3D printing. It also provides a comprehensive review of previous attempts at using 3D printing technologies on the manufacturing dosage forms with a particular focus on oral tablets. Their advantages particularly with adaptability in the pharmaceutical field have been highlighted, which enables the preparation of dosage forms with complex designs and geometries, multiple actives and tailored release profiles. An insight into the technical challenges facing the different 3D printing technologies such as the formulation and processing parameters is provided. Light is also shed on the different regulatory challenges that need to be overcome for 3D printing to fulfil its real potential in the pharmaceutical industry.

  20. Gamma scintigraphy in the evaluation of pharmaceutical dosage forms

    Energy Technology Data Exchange (ETDEWEB)

    Davis, S.S.; Hardy, J.G.; Newman, S.P.; Wilding, I.R. (Pharmaceutical Profiles Ltd., Nottingham (United Kingdom))

    1992-11-01

    Gamma-scintigraphy is applied extensively in the development and evaluation of pharmaceutical drug delivery systems. It is used particularly for monitoring formulations in the gastrointestinal and respiratory tracts. The radiolabelling is generally achieved by the incorporation of an appropriate technetium-99m or indium-111 labelled radiopharmaceutical into the formulation. In the case of complex dosage forms, such as enteric-coated tablets, labelling is best undertaken by the addition of a non-radioactive tracer such as samarium-152 or erbium-170 followed by neutron activation of the final product. Systems investigated include tablets and multiparticulates for oral administration, enemas and suppositories, metered dose inhalers and nebulisers, and nasal sprays and drops. Gamma-scintigraphy provides information on the deposition, dispersion and movement of the formulation. The combination of such studies with the assay of drug levels in blood or urine specimens, pharmacoscintigraphy, provides information concerning the sites of drug release and absorption. Data acquired from the scintigraphic evaluation of pharmaceutical dosage forms are now being used increasingly at all stages of product development, from the assessment of prototype delivery systems to supporting the product licence application. (orig.).

  1. ORODISPERSIBLE TABLET: A Patient Friendly Dosage Form (a Review

    Directory of Open Access Journals (Sweden)

    C. K. Rameesa

    2015-03-01

    Full Text Available Background: The most common and preferred route of drug administration is through the oral route. Orodispersible tablets are gaining importance among novel oral drug delivery system as they have improved patient compliance and have some additional advantages compared to other formulation. They are also solid unit dosage forms, which disintegrate in the mouth within a minute in the presence of saliva due to superdisintegrants in the formulation. Thus this type of drug delivery helps a proper per oral administration in pediatric and geriatric population where swallowing is a matter of trouble. Various scientists have prepared orodispersible tablets by following various methods. However, the most common method is the direct compression method. Other special methods are Freeze Drying,Tablet Molding, Sublimation, Spray Drying, Mass extrusion, Phase transition process, etc. Since these tablets dissolve directly in the mouth, so, their taste is also an important factor. Various approaches have been taken in order to mask the bitter taste of the drug. A number of scientists have explored several drugs in this field. Like all other solid dosage forms, they are also evaluated in the field of hardness, friability, wetting time, moisture uptake, disintegration test and dissolution test.

  2. Stability of pharmaceutical salts in solid oral dosage forms.

    Science.gov (United States)

    Nie, Haichen; Byrn, Stephen R; Zhou, Qi Tony

    2017-08-01

    Using pharmaceutical salts in solid dosage forms can raise stability concerns, especially salt dissociation which can adversely affect the product performance. Therefore, a thorough understanding of the salt instability encountered in solid-state formulations is imperative to ensure the product quality. The present article uses the fundamental theory of acid base, ionic equilibrium, relationship of pH and solubility as a starting point to illustrate and interpret the salt formation and salt disproportionation in pharmaceutical systems. The criteria of selecting the optimal salt form and the underlying theory of salt formation and disproportionation are reviewed in detail. Factors influencing salt stability in solid dosage forms are scrutinized and discussed with the case studies. In addition, both commonly used and innovative strategies for preventing salt dissociations in formulation, on storage and during manufacturing will be suggested herein. This article will provide formulation scientists and manufacturing engineers an insight into the mechanisms of salt disproportionation and salt formation, which can help them to avoid and solve the instability issues of pharmaceutical salts in the product design.

  3. Vertical vibration analysis for elevator compensating sheave

    International Nuclear Information System (INIS)

    Watanabe, Seiji; Nakazawa, Daisuke; Fukui, Daiki; Okawa, Takeya

    2013-01-01

    Most elevators applied to tall buildings include compensating ropes to satisfy the balanced rope tension between the car and the counter weight. The compensating ropes receive tension by the compensating sheave, which is installed at the bottom space of the elevator shaft. The compensating sheave is only suspended by the compensating ropes, therefore, the sheave can move vertically while the car is traveling. This paper shows the elevator dynamic model to evaluate the vertical motion of the compensating sheave. Especially, behavior in emergency cases, such as brake activation and buffer strike, was investigated to evaluate the maximum upward motion of the sheave. The simulation results were validated by experiments and the most influenced factor for the sheave vertical motion was clarified

  4. How to avoid deferred-compensation troubles.

    Science.gov (United States)

    Freeman, Todd I

    2005-06-01

    Executive compensation packages have long included stock options and deferred compensation plans in order to compete for talent. Last year, Congress passed a law in response to the Enron debacle, in which executives were perceived to be protecting their deferred compensation at the expense of employees, creditors, and investors. The new law is designed to protect companies and their shareholders from being raided by the very executives that guided the company to financial ruin. Physicians who are part owners of medical practices need to know about the changes in the law regarding deferred compensation and how to avoid costly tax penalties. This article discusses how the changes affect medical practices as well as steps physician-owned clinics can take to avoid the risk of penalty, such as freezing deferred compensation and creating a new deferred compensation plan.

  5. Vertical vibration analysis for elevator compensating sheave

    Science.gov (United States)

    Watanabe, Seiji; Okawa, Takeya; Nakazawa, Daisuke; Fukui, Daiki

    2013-07-01

    Most elevators applied to tall buildings include compensating ropes to satisfy the balanced rope tension between the car and the counter weight. The compensating ropes receive tension by the compensating sheave, which is installed at the bottom space of the elevator shaft. The compensating sheave is only suspended by the compensating ropes, therefore, the sheave can move vertically while the car is traveling. This paper shows the elevator dynamic model to evaluate the vertical motion of the compensating sheave. Especially, behavior in emergency cases, such as brake activation and buffer strike, was investigated to evaluate the maximum upward motion of the sheave. The simulation results were validated by experiments and the most influenced factor for the sheave vertical motion was clarified.

  6. Enthalpy-entropy compensation in protein unfolding

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Enthalpy-entropy compensation was found to be a universal law in protein unfolding based on over 3 000 experimental data. Water molecular reorganization accompanying the protein unfolding was suggested as the origin of the enthalpy-entropy compensation in protein unfolding. It is indicated that the enthalpy-entropy compensation constitutes the physical foundation that satisfies the biological need of the small free energy changes in protein unfolding, without the sacrifice of the bio-diversity of proteins. The enthalpy-entropy compensation theory proposed herein also provides valuable insights into the Privalov's puzzle of enthalpy and entropy convergence in protein unfolding.

  7. Multi-qubit compensation sequences

    International Nuclear Information System (INIS)

    Tomita, Y; Merrill, J T; Brown, K R

    2010-01-01

    The Hamiltonian control of n qubits requires precision control of both the strength and timing of interactions. Compensation pulses relax the precision requirements by reducing unknown but systematic errors. Using composite pulse techniques designed for single qubits, we show that systematic errors for n-qubit systems can be corrected to arbitrary accuracy given either two non-commuting control Hamiltonians with identical systematic errors or one error-free control Hamiltonian. We also examine composite pulses in the context of quantum computers controlled by two-qubit interactions. For quantum computers based on the XY interaction, single-qubit composite pulse sequences naturally correct systematic errors. For quantum computers based on the Heisenberg or exchange interaction, the composite pulse sequences reduce the logical single-qubit gate errors but increase the errors for logical two-qubit gates.

  8. Compensation for incoherent ground motion

    International Nuclear Information System (INIS)

    Shigeru, Takeda; Hiroshi, Matsumoto; Masakazu, Yoshioka; Yasunori, Takeuchi; Kikuo, Kudo; Tsuneya, Tsubokawa; Mitsuaki, Nozaki; Kiyotomo, Kawagoe

    1999-01-01

    The power spectrum density and coherence function for ground motions are studied for the construction of the next generation electron-positron linear collider. It should provide a center of mass energy between 500 GeV-1 TeV with luminosity as high as 10 33 to 10 34 cm -2 sec -1 . Since the linear collider has a relatively slow repetition rate, large number of particles and small sizes of the beam should be generated and preserved in the machine to obtain the required high luminosity. One of the most critical parameters is the extremely small vertical beam size at the interaction point, thus a proper alignment system for the focusing and accelerating elements of the machine is necessary to achieve the luminosity. We describe recent observed incoherent ground motions and an alignment system to compensate the distortion by the ground motions. (authors)

  9. Self compensating fire detection device

    International Nuclear Information System (INIS)

    Cholin, J. M.

    1985-01-01

    A device employing ionization principles for fire detection disclosing a configuration which allows compensation for adverse effects due to the flow of the gas through the device or due to the accumulation of dust and dirt therein. The detecting device includes two ionization chambers, each having a first member, such as a cylindrically shaped cup, having first and second conductive surface portions. Each chamber also incudes a second member, such as a circular, electrode disc having two conductive surface portions. There is disposed in each chamber a radioactive source for ionizing the gas in the volumes intervening between respective pairs of surfaces. The area dimensions of the respective pairs of surfaces, the interventing volumes and the distances there between, and the relative orientation of the respective pairs are calculated and placed such that the ionization currents flowing between pairs of conductive surfaces are substantially equal and orthogonal to each other

  10. Reduced Erg Dosage Impairs Survival of Hematopoietic Stem and Progenitor Cells.

    Science.gov (United States)

    Xie, Ying; Koch, Mia Lee; Zhang, Xin; Hamblen, Melanie J; Godinho, Frank J; Fujiwara, Yuko; Xie, Huafeng; Klusmann, Jan-Henning; Orkin, Stuart H; Li, Zhe

    2017-07-01

    ERG, an ETS family transcription factor frequently overexpressed in human leukemia, has been implicated as a key regulator of hematopoietic stem cells. However, how ERG controls normal hematopoiesis, particularly at the stem and progenitor cell level, and how it contributes to leukemogenesis remain incompletely understood. Using homologous recombination, we generated an Erg knockdown allele (Erg kd ) in which Erg expression can be conditionally restored by Cre recombinase. Erg kd/kd animals die at E10.5-E11.5 due to defects in endothelial and hematopoietic cells, but can be completely rescued by Tie2-Cre-mediated restoration of Erg in these cells. In Erg kd/+ mice, ∼40% reduction in Erg dosage perturbs both fetal liver and bone marrow hematopoiesis by reducing the numbers of Lin - Sca-1 + c-Kit + (LSK) hematopoietic stem and progenitor cells (HSPCs) and megakaryocytic progenitors. By genetic mosaic analysis, we find that Erg-restored HSPCs outcompete Erg kd/+ HSPCs for contribution to adult hematopoiesis in vivo. This defect is in part due to increased apoptosis of HSPCs with reduced Erg dosage, a phenotype that becomes more drastic during 5-FU-induced stress hematopoiesis. Expression analysis reveals that reduced Erg expression leads to changes in expression of a subset of ERG target genes involved in regulating survival of HSPCs, including increased expression of a pro-apoptotic regulator Bcl2l11 (Bim) and reduced expression of Jun. Collectively, our data demonstrate that ERG controls survival of HSPCs, a property that may be used by leukemic cells. Stem Cells 2017;35:1773-1785. © 2017 AlphaMed Press.

  11. ABCB1 genetic variability and methadone dosage requirements in opioid-dependent individuals.

    Science.gov (United States)

    Coller, Janet K; Barratt, Daniel T; Dahlen, Karianne; Loennechen, Morten H; Somogyi, Andrew A

    2006-12-01

    The most common treatment for opioid dependence is substitution therapy with another opioid such as methadone. The methadone dosage is individualized but highly variable, and program retention rates are low due in part to nonoptimal dosing resulting in withdrawal symptoms and further heroin craving and use. Methadone is a substrate for the P-glycoprotein transporter, encoded by the ABCB1 gene, which regulates central nervous system exposure. This retrospective study aimed to investigate the influence of ABCB1 genetic variability on methadone dose requirements. Genomic deoxyribonucleic acid was isolated from opioid-dependent subjects (n = 60) and non-opioid-dependent control subjects (n = 60), and polymerase chain reaction-restriction fragment length polymorphism and allele-specific polymerase chain reaction were used to determine the presence of single nucleotide polymorphisms at positions 61, 1199, 1236, 2677, and 3435. ABCB1 haplotypes were inferred with PHASE software (version 2.1). There were no significant differences in the allele or genotype frequencies of the individual single nucleotide polymorphisms or haplotypes between the 2 populations. ABCB1 genetic variability influenced daily methadone dose requirements, such that subjects carrying 2 copies of the wild-type haplotype required higher doses compared with those with 1 copy and those with no copies (98.3 +/- 10.4, 58.6 +/- 20.9, and 55.4 +/- 26.1 mg/d, respectively; P = .029). In addition, carriers of the AGCTT haplotype required significantly lower doses than noncarriers (38.0 +/- 16.8 and 61.3 +/- 24.6 mg/d, respectively; P = .04). Although ABCB1 genetic variability is not related to the development of opioid dependence, identification of variant haplotypes may, after larger prospective studies have been performed, provide clinicians with a tool for methadone dosage individualization.

  12. 38 CFR 3.351 - Special monthly dependency and indemnity compensation, death compensation, pension and spouse's...

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Special monthly dependency and indemnity compensation, death compensation, pension and spouse's compensation ratings. 3.351 Section 3.351 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension...

  13. Oral Solid Dosage Form Disintegration Testing - The Forgotten Test.

    Science.gov (United States)

    Al-Gousous, Jozef; Langguth, Peter

    2015-09-01

    Since its inception in the 1930s, disintegration testing has become an important quality control (QC) test in pharmaceutical industry, and disintegration test procedures for various dosage forms have been described by the different pharmacopoeias, with harmonization among them still not quite complete. However, because of the fact that complete disintegration does not necessarily imply complete dissolution, much more research has been focused on dissolution rather than on disintegration testing. Nevertheless, owing to its simplicity, disintegration testing seems to be an attractive replacement to dissolution testing as recognized by the International Conference on Harmonization guidelines, in some cases. Therefore, with proper research being carried out to overcome the associated challenges, the full potential of disintegration testing could be tapped saving considerable efforts allocated to QC testing and quality assurance. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  14. Nanofibrous solid dosage form of living bacteria prepared by electrospinning

    Directory of Open Access Journals (Sweden)

    I. Wagner

    2014-05-01

    Full Text Available The aim of this work was to investigate the suitability of electrospinning for biodrug delivery and to develop an electrospinning-based method to produce vaginal drug delivery systems. Lactobacillus acidophilus bacteria were encapsulated into nanofibers of three different polymers (polyvinyl alcohol and polyvinylpyrrolidone with two different molar masses. Shelf life of the bacteria could be enhanced by the exclusion of water and by preparing a solid dosage form, which is an advantageous and patient-friendly way of administration. The formulations were stored at –20, 7 and 25°C, respectively. Viability testing showed that the nanofibers can provide long term stability for huge amounts of living bacteria if they are kept at (or below 7°C. Furthermore, all kinds of nanowebs prepared in this work dissolved instantly when they got in contact with water, thus the developed biohybrid nanowebs can provide new potential ways for curing bacterial vaginosis.

  15. Investigation of radiation exposure dosage in dental and panoramic radiography

    International Nuclear Information System (INIS)

    Ishii, Kenichi

    2005-01-01

    Dental radiography and a 10-sheet procedure were conducted at 10 sites in the maxillomandibular anterior teeth and at both sides of the premolar and molar teeth sections with and without a protective apron (total 22 patterns). Experiments, which included a total of five patterns, involving standard ortho-radiography were performed with and without a protective apron, positioning of an apron exclusively on the anterior or the posterior portion of the body and utility of an apron that covered the entire body. Results are as follows: In dental radiography, internal organs included in a bundle demonstrated high radiation exposure, whereas organs excluded from the bundle exhibited low radiation exposure. In organs situated below the thyroid gland, utilization of aprons resulted in lower radiation exposure. In ortho-radiography, radiation exposure was greatest in the parotid gland, followed by the mandibular, sublingual and thyroid glands, respectively. The protective apron resulted in lower radiation exposure at sites situated below the mammary glands; moreover, a protector covering the entire body led to lower radiation exposure in comparison to an apron worn exclusively on the anterior or the posterior aspect of the body. No significant difference was observed in terms of exposure between protective aprons worn on the anterior or the posterior aspect of the body. Furthermore, a protective collar resulted in nearly zero radiation exposure in the thyroid gland. However, a protective collar largely interferes with interpretation of the radiograph; thus, in order to produce interpretable radiographs, protection of the thyroid gland is not possible. In conclusion, radiation exposure dosage can be reduced via utilization of a protective apron positioned below the thyroid gland during dental radiography and below the mammary glands during ortho-radiography. We confirmed evidence indicating that application of a protective apron can reduce patient radiation exposure dosage

  16. Effects of maternal psychotropic drug dosage on birth outcomes

    Directory of Open Access Journals (Sweden)

    Michielsen LA

    2013-12-01

    Full Text Available Laura A Michielsen,1 Frank MMA van der Heijden,1 Paddy KC Janssen,2 Harold JH Kuijpers11Vincent van Gogh Institute for Psychiatry, Venlo, the Netherlands; 2Department of Pharmacy, VieCuri Medical Centre, Venlo, the NetherlandsBackground: The aim of this retrospective study was to explore the relationship between psychotropic medication dosage and birth outcomes.Methods: A total of 136 women were enrolled, who had an active mental disorder, were taking medication to prevent a relapse, or had a history of postpartum depression or psychosis. Medication use was evaluated for the three trimesters and during labor. Based on the defined daily dose, medication use was classified into three groups. Primary outcome variables included the infant gestational age at birth, birth weight, and Apgar scores at one and 5 minutes.Results: Our study showed a significantly higher incidence of Apgar score ≤7 at 5 minutes in women taking psychotropic drugs as compared with the group taking no medication, respectively (16.3% versus 0.0%, P=0.01. There was no significant difference between the two groups in Apgar score at one minute or in gestational age and birth weight. The results showed no significant differences in gestational age, birth weight, or Apgar scores for a low–intermediate or high dose of a selective serotonin reuptake inhibitor and for a low or intermediate dose of an antipsychotic.Conclusion: This study does not indicate a relationship between doses of selective serotonin reuptake inhibitors and antipsychotics and adverse neonatal outcomes.Keywords: pregnancy, psychotropic medication, dosage, birth outcomes

  17. Warfarin dosage response related pharmacogenetics in Chinese population.

    Directory of Open Access Journals (Sweden)

    Siyue Li

    Full Text Available As the most frequently prescribed anticoagulant, warfarin has large inter-individual variability in dosage. Genetic polymorphisms could largely explain the differences in dosage requirement. rs9923231 (VKORC1, rs7294 (VKORC1, rs1057910 (CYP2C9, rs2108622 (CYP4F2, and rs699664 (GGCX involved in the warfarin action mechanism and the circulatory vitamin K were selected to investigate their polymorphism characteristics and their effects on the pharmacodynamics and pharmacokinetics of warfarin in Chinese population.220 patients with cardiac valve replacement were recruited. International normalized ratio and plasma warfarin concentrations were determined. The five genetic polymorphisms were genotyping by pyro-sequencing. The relationships of maintenance dose, plasma warfarin concentration and INR were assessed among groups categorized by genotypes.rs9923231 and rs7294 in VKORC1 had the analogous genotype frequencies (D': 0.969. 158 of 220 recruited individuals had the target INR (1.5-2.5. Patients with AA of rs9923231 and CC of rs7294 required a significantly lower maintenance dose and plasma concentration than those with AG and TC, respectively. The mean weekly maintenance dose was also significantly lower in CYP2C9 rs1057910 mutated heterozygote than in patients with the wild homozygote. Eliminating the influence from environment factors (age, body weight and gender, rs9923231 and rs1057910 could explain about 32.0% of the variability in warfarin maintenance dose; rs7294 could explain 26.7% of the variability in plasma concentration. For patients with allele G of rs9923231 and allele T of rs7294, higher plasma concentration was needed to achieve the similar goal INR.A better understanding of the genetic variants in individuals can be the foundation of warfarin dosing algorithm and facilitate the reasonable and effective use of warfarin in Chinese.

  18. 77 FR 58469 - Plum Pox Compensation

    Science.gov (United States)

    2012-09-21

    .... APHIS-2011-0004] RIN 0579-AD58 Plum Pox Compensation AGENCY: Animal and Plant Health Inspection Service... interim rule that amended the plum pox regulations to provide for the payment of compensation to eligible... are required to be destroyed in order to prevent the spread of plum pox. The interim rule also...

  19. 33 CFR 136.211 - Compensation allowable.

    Science.gov (United States)

    2010-07-01

    ...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND; CLAIMS PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.211 Compensation... that amount required to accomplish the activities for which the claim was paid. Real or Personal...

  20. Multiple Compensation Consultants and CEO Pay

    NARCIS (Netherlands)

    Kabir, Mohammed Rezaul; Minhat, Marizah

    The study examines the practice of employing multiple compensation consultants. Data for a sample of UK companies over the period 2003-2006 are analyzed using a variety of econometric methods. We find that CEOs receive higher equity-based pay when firms employ more than one compensation consultant.

  1. Compensation of oscillation coupling induced by solenoids

    International Nuclear Information System (INIS)

    Zelinskij, A.Yu.; Karnaukhov, I.M.; Shcherbakov, A.A.

    1988-01-01

    Methods for construction of various schemes of oscillation coupling compensation, induced by solenoids in charged particle storage rings, are described. Peculiarities of magnetic structure, enabling to localize oscillation coupling in wide energy range are discussed. Results of calculation of compensation schemes for design of NR-2000 storage ring spin rotation are presented

  2. Individual Hearing Loss: Characterization, Modelling, Compensation Strategies

    DEFF Research Database (Denmark)

    Santurette, Sébastien; Dau, Torsten; Christensen-Dalsgaard, Jakob

    2016-01-01

    account for such individual differences, which make it challenging to find adequate compensation strategies in hearing devices. How to characterize, model, and compensate for individual hearing loss were the main topics of the fifth International Symposium on Auditory and Audiological Research (ISAAR...

  3. 75 FR 76079 - Sound Incentive Compensation Guidance

    Science.gov (United States)

    2010-12-07

    ... management; and Be supported by strong corporate governance, including active and effective oversight by the... Sound Compensation Practices adopted by the Financial Stability Board (FSB) in April 2009, as well as... will promote the prompt improvement of incentive compensation practices in the banking industry by...

  4. 75 FR 53023 - Sound Incentive Compensation Guidance

    Science.gov (United States)

    2010-08-30

    ... management; and Be supported by strong corporate governance, including active and effective oversight by the... Sound Compensation Practices adopted by the Financial Stability Board (FSB) in April 2009, as well as... will promote the prompt improvement of incentive compensation practices in the banking industry by...

  5. 75 FR 22679 - Sound Incentive Compensation Guidance

    Science.gov (United States)

    2010-04-29

    ... management; and Be supported by strong corporate governance, including active and effective oversight by the... Sound Compensation Practices adopted by the Financial Stability Board (FSB) in April 2009, as well as... will promote the prompt improvement of incentive compensation practices in the banking industry by...

  6. Dosage of strontium 90 in human bone ashes; Dosage du strontium 90 sans les cendres d'os humain

    Energy Technology Data Exchange (ETDEWEB)

    Patti, F; Jeanmaire, L [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

    1964-07-01

    The determination of {sup 90}Sr in bones by dosage of its daughter product {sup 90}Y is a 4-step process: 1) elimination of the phosphate ions by precipitation of the Ca and Sr as oxalate in the presence of acid; 2) reduction in the calcium concentration to a suitable level by the addition of a known volume of nitric acid (a single precipitation is sufficient), the precipitation yield of the strontium nitrate is checked by the measurement of the amount of {sup 85}Sr added as tracer; 3) purification by a yttrium hydroxide precipitation; 4) extraction at equilibrium of the {sup 90}Y which is counted to give the concentration. By using 50 gm of ash it is possible to detect about 0.1 pCi of {sup 90}Sr per gram of calcium. The advantages of this technique: -) treatment of a large quantity of bone ash -) the use of a small volume of nitric acid (less than 2 ml/g of ash, and -) the various operations present no difficulty. (authors) [French] Determination du Sr dans les os par dosage de son produit de filiation {sup 90}Y. Principe du dosage: 1 - Eliminer les ions phosphates par precipitation du calcium et du strontium sous forme d'oxalate en milieu acide. 2 - Reduire la concentration en calcium a un niveau convenable par addition d'un volume determine d'acide nitrique (une seule precipitation est necessaire). Le rendement de precipitation du nitrate de strontium est controle par la mesure de {sup 85}Sr ajoute comme traceur. 3 - Purifier par une precipitation d'hydroxyde d'yttrium. 4 - Extraire a l'equilibre l'{sup 90}Y qui eat compte pour determiner le {sup 90}Sr. En traitant 50 g de cendre, il est possible de deceler de l'ordre de 0,1 pCi de {sup 90}Sr par gramme de calcium. Les 3 avantages de cette technique: 1 - traitement d'une quantite importante de cendres d'os, 2 - emploi d'un faible volume d'acide nitrique (moins de 2 ml/g de cendres), et 3 - les diverses operations ne presentent aucune difficulte.

  7. A small molecule for a big transformation: Topical application of a 20-nucleotide-long antisense fragment of the DIAP-2 gene inhibits the development of Drosophila melanogaster female imagos

    Directory of Open Access Journals (Sweden)

    Nyadar Palmah M.

    2018-01-01

    Full Text Available Several genes have been identified to play important roles associated with sex selection in Drosophila melanogaster. An essential part is attributed to the sex-lethal gene that depends on the expression of the X:A (number of chromosomes to autosomes ratio signal controlling both sex selection and dosage compensation processes in D. melanogaster. Interestingly, for sex selection in D. melanogaster there are no documented data addressing the role of the inhibitor of apoptosis (IAP genes and their signaling influence on this biological process. In this study, we found that topical application of a 20-nucleotide-long antisense DNA fragment (oligoDIAP-2 from the death-associated inhibitor of apoptosis (DIAP-2 gene interferes with D. melanogaster development and significantly decreases the number of female imagos and their biomass. We show that the applied antisense oligoDIAP-2 fragment downregulates the target DIAP-2 gene whose normal concentration is necessary for the development of female D. melanogaster. These data correspond to the results on downregulation of the target host IAP-Z gene of Lymantria dispar L. female imagos after topical treatment with an 18-nucleotide-long antisense DNA fragment from the L. dispar multicapsid nuclear polyhedrosis virus IAP-3 gene at the larval stage. The observed novel phenomenon linking the downregulation of insect IAP genes and the low rate of female imago development could have practical application, especially in insect pest control and molecular pathology.

  8. TaS2 nanosheet-based room-temperature dosage meter for nitric oxide

    Directory of Open Access Journals (Sweden)

    Qiyuan He

    2014-09-01

    Full Text Available A miniature dosage meter for toxic gas is developed based on TaS2 nanosheets, which is capable of indicating the toxic dosage of trace level NO at room temperature. The TaS2 film-based chemiresistor shows an irreversible current response against the exposure of NO. The unique non-recovery characteristic makes the TaS2 film-based device an ideal indicator of total dosage of chronicle exposure.

  9. Compensation of Disadvantages in University Examination Procedures

    Directory of Open Access Journals (Sweden)

    Ulrike Quapp

    2016-08-01

    Full Text Available Active social participation of disabled people is one of the major tasks of modern society. That also includes access to the academic community by higher education. Universities all over the world work hard to give handicapped students a chance to graduate. In this context, compensation of disadvantages in examination procedures is an important matter. But, also chronic illness may impair the student's examination performance. To ensure equal examination opportunities for all students, responsible university officials must be creative to find individual compensation solutions. The paper analyzes examination regulations at universities in different countries and offers solutions to compensate disabled and chronic ill students' disadvantages. It discusses the necessity of compensation for different types of disability and chronic illness. Finally, an overview of current German case law and solutions for compensation problems are provided.

  10. Does CEO compensation impact patient satisfaction?

    Science.gov (United States)

    Akingbola, Kunle; van den Berg, Herman A

    2015-01-01

    This study examines the relationship between CEO compensation and patient satisfaction in Ontario, Canada. The purpose of this paper is to determine what impact hospital CEO compensation has on hospital patient satisfaction. The analyses in this study were based on data of 261 CEO-hospital-year observations in a sample of 103 nonprofit hospitals. A number of linear regressions were conducted, with patient satisfaction as the dependent variable and CEO compensation as the independent variable of interest. Controlling variables included hospital size, type of hospital, and frequency of adverse clinical outcomes. CEO compensation does not significantly influence hospital patient satisfaction. Both patient satisfaction and CEO compensation appear to be driven primarily by hospital size. Patient satisfaction decreases, while CEO compensation increases, with the number of acute care beds in a hospital. In addition, CEO compensation does not even appear to moderate the influence of hospital size on patient satisfaction. There are several limitations to this study. First, observations of CEO-hospital-years in which annual nominal CEO compensation was below $100,000 were excluded, as they were not publicly available. Second, this research was limited to a three-year range. Third, this study related the compensation of individual CEOs to a measure of performance based on a multitude of patient satisfaction surveys. Finally, this research is restricted to not-for-profit hospitals in Ontario, Canada. The findings seem to suggest that hospital directors seeking to improve patient satisfaction may find their efforts frustrated if they focus exclusively on the hospital CEO. The findings highlight the need for further research on how CEOs may, through leading and supporting those hospital clinicians and staff that interact more closely with patients, indirectly enhance patient satisfaction. To the best of the authors' knowledge, no research has examined the relationship between

  11. Evaluation of insecticides in different dosages to control cicadas in parica plantations

    Directory of Open Access Journals (Sweden)

    Odineila Martins Monteiro

    2014-07-01

    Full Text Available This study aimed to determine the more efficient and economically viable dosage of chemical insecticide to control Quesada gigas (Hemiptera: Cicadidae nymphs in parica plantations. Three dosages of three products (carbofuran, imidacloprid and thiamethoxam were tested based on the maximum recommended dosage for the control of cicadas in coffee plants and applied in total area. The dosage of one kilogram of a commercial product based in thiamethoxam per hectare was more efficient economically and environmentally to control nymphs of Q. gigas in parica plantations.

  12. 42 CFR 413.102 - Compensation of owners.

    Science.gov (United States)

    2010-10-01

    ...) Definitions—(1) Compensation. Compensation means the total benefit received by the owner for the services he... 42 Public Health 2 2010-10-01 2010-10-01 false Compensation of owners. 413.102 Section 413.102... § 413.102 Compensation of owners. (a) Principle. A reasonable allowance of compensation for services of...

  13. Self Organization in Compensated Semiconductors

    Science.gov (United States)

    Berezin, Alexander A.

    2004-03-01

    In partially compensated semiconductor (PCS) Fermi level is pinned to donor sub-band. Due to positional randomness and almost isoenergetic hoppings, donor-spanned electronic subsystem in PCS forms fluid-like highly mobile collective state. This makes PCS playground for pattern formation, self-organization, complexity emergence, electronic neural networks, and perhaps even for origins of life, bioevolution and consciousness. Through effects of impact and/or Auger ionization of donor sites, whole PCS may collapse (spinodal decomposition) into microblocks potentially capable of replication and protobiological activity (DNA analogue). Electronic screening effects may act in RNA fashion by introducing additional length scale(s) to system. Spontaneous quantum computing on charged/neutral sites becomes potential generator of informationally loaded microstructures akin to "Carl Sagan Effect" (hidden messages in Pi in his "Contact") or informational self-organization of "Library of Babel" of J.L. Borges. Even general relativity effects at Planck scale (R.Penrose) may affect the dynamics through (e.g.) isotopic variations of atomic mass and local density (A.A.Berezin, 1992). Thus, PCS can serve as toy model (experimental and computational) at interface of physics and life sciences.

  14. Evidence of sex-bias in gene expression in the brain transcriptome of two populations of rainbow trout (Oncorhynchus mykiss) with divergent life histories.

    Science.gov (United States)

    Hale, Matthew C; McKinney, Garrett J; Thrower, Frank P; Nichols, Krista M

    2018-01-01

    Sex-bias in gene expression is a mechanism that can generate phenotypic variance between the sexes, however, relatively little is known about how patterns of sex-bias vary during development, and how variable sex-bias is between different populations. To that end, we measured sex-bias in gene expression in the brain transcriptome of rainbow trout (Oncorhynchus mykiss) during the first two years of development. Our sampling included from the fry stage through to when O. mykiss either migrate to the ocean or remain resident and undergo sexual maturation. Samples came from two F1 lines: One from migratory steelhead trout and one from resident rainbow trout. All samples were reared in a common garden environment and RNA sequencing (RNA-seq) was used to estimate patterns of gene expression. A total of 1,716 (4.6% of total) genes showed evidence of sex-bias in gene expression in at least one time point. The majority (96.7%) of sex-biased genes were differentially expressed during the second year of development, indicating that patterns of sex-bias in expression are tied to key developmental events, such as migration and sexual maturation. Mapping of differentially expressed genes to the O. mykiss genome revealed that the X chromosome is enriched for female upregulated genes, and this may indicate a lack of dosage compensation in rainbow trout. There were many more sex-biased genes in the migratory line than the resident line suggesting differences in patterns of gene expression in the brain between populations subjected to different forces of selection. Overall, our results suggest that there is considerable variation in the extent and identity of genes exhibiting sex-bias during the first two years of life. These differentially expressed genes may be connected to developmental differences between the sexes, and/or between adopting a resident or migratory life history.

  15. Low starting dosage of infliximab with possible escalating dosage in psoriatic arthritis gives the same treatment results as standard dosage of adalimumab or etanercept: results from the nationwide Icelandic ICEBIO registry

    Directory of Open Access Journals (Sweden)

    Gudbjornsson B

    2018-05-01

    Full Text Available Bjorn Gudbjornsson,1,2 Arni Jon Geirsson,3,4 Niels Steen Krogh5 1Centre for Rheumatology Research, University Hospital, Reykjavik, Iceland; 2Faculty of Medicine, University of Iceland, Reykjavik, Iceland; 3Department of Rheumatology, University Hospital, Reykjavik, Iceland; 4Laeknasetrid - Medical Clinic, University of Iceland, Reykjavik, Iceland; 5Zitelab Aps, Copenhagen, Denmark Objective: To explore differences in response to a low dosage regimen of infliximab with an escalating dosage in comparison to a standard dosage of etanercept and adalimumab in patients with psoriatic arthritis (PsA. Methods: Biologically naïve PsA patients who were beginning anti-TNF-α therapy were selected from the ICEBIO registry. Demographics and clinical differences were compared in four treatment groups: infliximab <4 mg/kg; infliximab >4 mg/kg; etanercept or adalimumab at baseline and on follow-up (6 and 12 months, last visit. The Kruskal–Wallis rank sum test was used for comparison of the groups and the Wilcoxon test to compare the two infliximab dosage regimens. Results: One hundred and eighty-five patients (61% female were identified; 84 patients received infliximab, 66 etanercept, and 35 adalimumab. A total of 19% of the patients treated with infliximab escalated their dosage ≥4 mg/kg. No significant differences were observed at baseline in respect to visual analog scale (VAS pain, VAS fatigue, Health Assessment Questionnaire, C-reactive protein (CRP, numbers of swollen or tender joints, or Disease Activity Score (DAS 28-CRP values. A similar treatment response was observed in all four treatment groups on follow-up. Conclusion: In respect to treatment effects, a low dosage of infliximab with possible escalating dosage is acceptable for the majority of PsA patients who are in need of biological treatment. Keywords: psoriatic arthritis, outcome, biological treatment, routine care, clinical nationwide registry

  16. Dosage of boron traces in graphite, uranium and beryllium oxide; Dosage de traces de bore dans le graphite, l'uranium et l'oxyde de beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Coursier, J [Ecole Nationale Superieure de Physique et Chimie Industrielles, 75 - Paris (France); Hure, J; Platzer, R [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1955-07-01

    The problem of the dosage of the boron in the materials serving to the construction of nuclear reactors arises of the following way: to determine to about 0,1 ppm close to the quantities of boron of the order of tenth ppm. We have chosen the colorimetric analysis with curcumin as method of dosage. To reach the indicated contents, it is necessary to do a previous separation of the boron and the materials of basis, either by extraction of tetraphenylarsonium fluoborate in the case of the boron dosage in uranium and the beryllium oxide, either by the use of a cations exchanger resin of in the case of graphite. (M.B.) [French] Le probleme du dosage du bore dans les materiaux servant a la construction de reacteurs nucleaires se pose de la facon suivante: determiner a environ 0,1 ppm pres des quantites de bore de l'ordre de quelques dixiemes de ppm. Nous avons choisit la colorimetrie a la curcumine comme methode de dosage. Pour atteindre les teneurs indiquees, il est necessaire d'effectuer une separation prealable du bore et des materiaux de base, soit par extraction du fluoborate de tetraphenylarsonium dans le cas du dosage de bore dans l'uranium et l'oxyde de beryllium, soit par l'utilisation d'une resine echangeuse de cations dans le cas du graphite. (M.B.)

  17. Biowaiver monographs for immediate release solid oral dosage forms: piroxicam.

    Science.gov (United States)

    Shohin, Igor E; Kulinich, Julia I; Ramenskaya, Galina V; Abrahamsson, Bertil; Kopp, Sabine; Langguth, Peter; Polli, James E; Shah, Vinod P; Groot, D W; Barends, Dirk M; Dressman, Jennifer B

    2014-02-01

    Literature and experimental data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing piroxicam in the free acid form are reviewed. Piroxicam solubility and permeability, its therapeutic use and therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA), and corresponding dissolution data are taken into consideration. The available data suggest that according to the current biopharmaceutics classification system (BCS) and all current guidances, piroxicam would be assigned to BCS Class II. The extent of piroxicam absorption seems not to depend on manufacturing conditions or excipients, so the risk of bioinequivalence in terms of area under the curve (AUC) is very low, but the rate of absorption (i.e., BE in terms of Cmax ) can be affected by the formulation. Current in vitro dissolution methods may not always reflect differences in terms of Cmax for BCS Class II weak acids; however, minor differences in absorption rate of piroxicam would not subject the patient to unacceptable risks: as piroxicam products may be taken before or after meals, the rate of absorption cannot be considered crucial to drug action. Therefore, a biowaiver for IR piroxicam solid oral dosage form is considered feasible, provided that (a) the test product contains only excipients, which are also present in IR solid oral drug products containing piroxicam, which have been approved in ICH or associated countries, for instance, those presented in Table 3 of this paper; (b) both the test and comparator drug products dissolve 85% in 30 min or less at pH 1.2, 4.5, and 6.8; and (c) the test product and comparator show dissolution profile similarity in pH 1.2, 4.5, and 6.8. When not all of these conditions can be fulfilled, BE of the products should be established in vivo. © 2013 Wiley Periodicals, Inc. and the

  18. Digitally compensated beam current transformer

    International Nuclear Information System (INIS)

    Kesselman, Martin

    2005-01-01

    The Spallation Neutron Source (SNS) is being built by a collaboration of six laboratories. Beam current monitors (BCMs) will be used to record the current of H-minus and H-plus beams ranging from 15 mA (tune-up in the Front End and Linac) to over 60A fully accumulated in the Ring and dumped to the load as a single pulse in the Ring to Beam Target (RTBT). The time structure of these beams ranges from 645 ns 'mini' bunches at the 1.05 MHz ring revolution rate, to an overall 1 ms long macro-pulse. The requirements for the BCMs will depend upon their location within the system. The need to measure individual mini-pulses, examine the characteristics of the chopper edge, as well as the longer average current pulse of the macropulse, or long duration pulses during Linac tuning place wide requirements upon the response of current transformers. To obtain the desired accuracy and resolution, current transformers must have <1 ns rise time and droops of 0.1%/ms. This places a significant design burden on the current transformer; such a design is almost impossible to achieve. Extremely large expensive cores are needed to meet the low droop, while leakage inductance increases with size, thereby reducing the achievable rise time. In this paper, I discuss a digital compensation approach [M. Kesselman, Spallation neutron source beam current monitor electronics, PAC2001 June 18-22, 2001, Chicago, IL.] that extends the lower cut-off frequency of the current transformer, optimized for high frequency response, so that it can be used in this application with improvements in droop of the order of 1000:1. Transformer saturation (current-time product) is a separate issue and the transformer must be designed to handle the current-time product of the signal to assure it does not saturate

  19. Towards Compensation Correctness in Interactive Systems

    Science.gov (United States)

    Vaz, Cátia; Ferreira, Carla

    One fundamental idea of service-oriented computing is that applications should be developed by composing already available services. Due to the long running nature of service interactions, a main challenge in service composition is ensuring correctness of failure recovery. In this paper, we use a process calculus suitable for modelling long running transactions with a recovery mechanism based on compensations. Within this setting, we discuss and formally state correctness criteria for compensable processes compositions, assuming that each process is correct with respect to failure recovery. Under our theory, we formally interpret self-healing compositions, that can detect and recover from failures, as correct compositions of compensable processes.

  20. Inductive voltage compensation in superconducting magnet systems

    International Nuclear Information System (INIS)

    Yeh, H.T.; Goddard, J.S.; Shen, S.S.

    1979-01-01

    This paper details several techniques of inductive voltage compensation developed for quench detection in superconducting magnet systems with multiple coils and power supplies, with particular application for the Large Coil Test Facility (LCTF). Sources of noise, their magnitudes, and the sensitivity required for normal zone detection to avoid damage to the magnets are discussed. Two passive compensation schemes (second difference and central difference) are introduced and illustrated by parameters of LCTF; these take advantage of coil symmetries and other system characteristics. An active compensation scheme based on current rate input fom pickup coils and utilizing theory on ac loss voltage for calibration was tested, and the experimental setup and test results are discussed

  1. Health Insurance Costs and Employee Compensation: Evidence from the National Compensation Survey.

    Science.gov (United States)

    Anand, Priyanka

    2017-12-01

    This paper examines the relationship between rising health insurance costs and employee compensation. I estimate the extent to which total compensation decreases with a rise in health insurance costs and decompose these changes in compensation into adjustments in wages, non-health fringe benefits, and employee contributions to health insurance premiums. I examine this relationship using the National Compensation Survey, a panel dataset on compensation and health insurance for a sample of establishments across the USA. I find that total hourly compensation reduces by $0.52 for each dollar increase in health insurance costs. This reduction in total compensation is primarily in the form of higher employee premium contributions, and there is no evidence of a change in wages and non-health fringe benefits. These findings show that workers are absorbing at least part of the increase in health insurance costs through lower compensation and highlight the importance of examining total compensation, and not just wages, when examining the relationship between health insurance costs and employee compensation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  2. Fumigant dosages below maximum label rate control some soilborne pathogens

    Directory of Open Access Journals (Sweden)

    Shachaf Triky-Dotan

    2016-08-01

    Full Text Available The activity of commercial soil fumigants on some key soilborne pathogens was assessed in sandy loam soil under controlled conditions. Seven soil fumigants that are registered in California or are being or have been considered for registration were used in this study: dimethyl disulfide (DMDS mixed with chloropicrin (Pic (79% DMDS and 21% Pic, Tri-Con (50% methyl bromide and 50% Pic, Midas Gold (33% methyl iodide [MI] and 67% Pic, Midas Bronze (50% MI and 50% Pic, Midas (MI, active ingredient [a.i.] 97.8%, Pic (a.i. 99% trichloronitromethane and Pic-Clor 60 (57% Pic and 37% 1,3-dichloropropene [1–3,D]. Dose-response models were calculated for pathogen mortality after 24 hours of exposure to fumigants. Overall, the tested fumigants achieved good efficacy with dosages below the maximum label rate against the tested pathogens. In this study, Pythium ultimum and citrus nematode were sensitive to all the fumigants and Verticillium dahliae was resistant. For most fumigants, California regulations restrict application rates to less than the maximum (federal label rate, meaning that it is possible that the fumigants may not control major plant pathogens. This research provides information on the effectiveness of these alternatives at these lower application rates. The results from this study will help growers optimize application rates for registered fumigants (such as Pic and 1,3-D and will help accelerate the adoption of new fumigants (such as DMDS if they are registered in California.

  3. Self-compacting concretes (SCC: comparison of methods of dosage

    Directory of Open Access Journals (Sweden)

    B. F. Tutikian

    Full Text Available The composition of a self-compacting concrete (SCC should be defined to fulfills a number of requirements, such as self-compactibility, strength and durability. This study aims to compare three methods of dosage for SCC with local materials, so as to determine which one is the most economical and rational, thus assisting the executor in making a decision and enabling economic and technical feasibility for its application. The methods used in the experimental program were: Nan Su et al., which was developed in 2001 [1]; Repette-Melo, which was proposed in 2005 [2]; and Tutikian & Dal Molin, which was developed in 2007 [3]. From the results obtained in the experimental program, it was observed that the method which presented the lowest cost and highest compressive strength at the ages of 7, 28 and 91 days was Tutikian & Dal Molin, while the one which reached the lowest chloride ion penetration, best compactness and highest elasticity modulus was Repette-Melo. In tests carried out in the fresh state, all tested methods yielded mixtures which comply with the self-compactibility levels required by ABNT NBR 15823:2010 [4].

  4. Dosage-dependent role of Rac1 in podocyte injury

    Science.gov (United States)

    Wan, Xiaoyang; Lee, Mi-Sun

    2016-01-01

    Activation of small GTPase Rac1 in podocytes is associated with rodent models of kidney injury and familial nephrotic syndrome. Induced Rac1 activation in podocytes in transgenic mice results in rapid transient proteinuria and foot process effacement, but not glomerular sclerosis. Thus it remains an open question whether abnormal activation of Rac1 in podocytes is sufficient to cause permanent podocyte damage. Using a number of transgenic zebrafish models, we showed that moderate elevation of Rac1 activity in podocytes did not impair the glomerular filtration barrier but aggravated metronidazole-induced podocyte injury, while inhibition of Rac1 activity ameliorated metronidazole-induced podocyte injury. Furthermore, a further increase in Rac1 activity in podocytes was sufficient to cause proteinuria and foot process effacement, which resulted in edema and lethality in juvenile zebrafish. We also found that activation of Rac1 in podocytes significantly downregulated the expression of nephrin and podocin, suggesting an adverse effect of Rac1 on slit diaphragm protein expression. Taken together, our data have demonstrated a causal link between excessive Rac1 activity and podocyte injury in a dosage-dependent manner, and transgenic zebrafish of variable Rac1 activities in podocytes may serve as useful animal models for the study of Rac1-related podocytopathy. PMID:26792065

  5. A step toward development of printable dosage forms for poorly soluble drugs

    DEFF Research Database (Denmark)

    Raijada, Dharaben Kaushikkumar; Genina, Natalja; Fors, Daniela

    2013-01-01

    The purpose of this study was to formulate printable dosage forms for a poorly soluble drug (piroxicam; PRX) and to gain understanding of critical parameters to be considered during development of such dosage forms. Liquid formulations of PRX were printed on edible paper using piezoelectric inkjet...

  6. 21 CFR 522.1662 - Oxytetracycline hydrochloride implantation or injectable dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride implantation or injectable dosage forms. 522.1662 Section 522.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1662 Oxytetracycline hydrochloride implantation or injectable...

  7. Estimated Effect of Epoetin Dosage on Survival among Elderly Hemodialysis Patients in the United States

    OpenAIRE

    Zhang, Yi; Thamer, Mae; Cotter, Dennis; Kaufman, James; Hernán, Miguel A.

    2009-01-01

    Background and objectives: The common finding that low achieved hemoglobin in observational studies and high target hemoglobin in randomized trials each were associated with increased mortality and high epoetin dosage has suggested the possibility that high epoetin dosage might explain the increased mortality risk.

  8. Mapping preclinical compensation in Parkinson's disease: an imaging genomics approach

    DEFF Research Database (Denmark)

    van Nuenen, Bart F L; van Eimeren, Thilo; van der Vegt, Joyce P M

    2009-01-01

    development of overt disease. In two separate experiments, Parkin mutation carriers displayed stronger activation of rostral supplementary motor area (SMA) and right dorsal premotor cortex (PMd) during a simple motor sequence task and anterior cingulate motor area and left rostral PMd during internal movement....... Extensions of this line of research involve fMRI paradigms probing nonmotor brain functions. Additionally, the same fMRI paradigms should be applied to nonmanifesting mutation carriers in genes linked to autosomal dominant PD. This will help to determine how "generically" the human brain compensates......Mutations in the Parkin (PARK2) and PINK1 gene (PARK 6) can cause recessively inherited Parkinson's disease (PD). The presence of a single Parkin or PINK1 mutation is associated with a dopaminergic nigrostriatal dysfunction and conveys an increased risk to develop PD throughout lifetime. Therefore...

  9. The risks and rewards of setting physician compensation internally.

    Science.gov (United States)

    Johnson, Jen

    2013-01-01

    To establish physician compensation internally, finance leaders should: Educate decision makers on basic regulatory guidance and valuation theory. Determine fair market value. Consider using a compensation calculator.

  10. Comprehensive Environmental Response, Compensation and Liability Act

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data represents geographic terms used within the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). CERCLA, commonly known as...

  11. Defense Contract Audit Agency Compensation Audits

    National Research Council Canada - National Science Library

    1999-01-01

    .... The Defense Contract Audit Agency (DCAA) assists the administrative contracting officer in accomplishing that responsibility by determining whether the contractor's compensation system is sound, reliable, consistently applied, and results...

  12. Mandatory Compensation to Commercial Agents upon Termination ...

    African Journals Online (AJOL)

    Kamil Abdu Oumer

    the compensation due to the agent upon the termination of the commercial .... Virginia School of Law Legal Studies Working Papers Series, Working Paper No. ..... grant up to a one year commission if they find the circumstances equitable.67 In.

  13. Shaft Seal Compensates for Cold Flow

    Science.gov (United States)

    Myers, W. N.; Hein, L. A.

    1985-01-01

    Seal components easy to install. Ring seal for rotating or reciprocating shafts spring-loaded to compensate for slow yielding (cold flow) of sealing material. New seal relatively easy to install because components preassembled, then installed in one piece.

  14. Integrated open source mine workers compensation system

    CSIR Research Space (South Africa)

    Coetzee, L

    2006-08-01

    Full Text Available This article describes the Mine Workers Compensation System developed by the CSIR and Molepe Consulting for the South African Department of Health. Mining activities increase the risk of certain occupational lung diseases. South African legislation...

  15. Convention on supplementary compensation for nuclear damage

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-07-22

    The document reproduces the text of the Convention on Supplementary Compensation for Nuclear Damage which was adopted on 12 September 1997 by a Diplomatic Conference held between 8-12 September 1997 in Vienna

  16. voltage compensation using artificial neural network

    African Journals Online (AJOL)

    Offor Theophilos

    Simulation results showed that DVR is effective in compensating for ... shutdown of heavy equipment, switching operations etc, ... station were carried out in MatLab 2013 application. ... semiconductor in a pulse width modulation (PWM).

  17. Convention on supplementary compensation for nuclear damage

    International Nuclear Information System (INIS)

    1998-01-01

    The document reproduces the text of the Convention on Supplementary Compensation for Nuclear Damage which was adopted on 12 September 1997 by a Diplomatic Conference held between 8-12 September 1997 in Vienna

  18. Increasing of AC compensation method accuracy

    International Nuclear Information System (INIS)

    Havlicek, V.; Pokorny, M.

    2003-01-01

    The original MMF compensation method allows the magnetic properties of single sheets and strips to be measured in the same way as the closed specimen properties. The accuracy of the method is limited due to the finite gain of the feedback loop fulfilling the condition of its stability. Digitalisation of the compensation loop appropriate processing of the error signal can rapidly improve the accuracy. The basic ideas of this new approach and the experimental results are described in this paper

  19. Increasing of AC compensation method accuracy

    Science.gov (United States)

    Havlíček, V.; Pokorný, M.

    2003-01-01

    The original MMF compensation method allows the magnetic properties of single sheets and strips to be measured in the same way as the closed specimen properties. The accuracy of the method is limited due to the finite gain of the feedback loop fulfilling the condition of its stability. Digitalisation of the compensation loop appropriate processing of the error signal can rapidly improve the accuracy. The basic ideas of this new approach and the experimental results are described in this paper.

  20. Radiotherapy dose compensation for lung patients

    International Nuclear Information System (INIS)

    Piyaratna, N.; Arnold, A.; Metcalfe, P.

    1999-01-01

    The purpose of the present paper is to provide a more homogeneous dose distribution in the target volume from compensated anterior and posterior fields while the healthy lung is spared by de-weighting the lateral fields. A compensation computation which used linear iterations to compute the most homogeneous dose distribution across the target volume was applied to produce optimum compensator designs. The equivalent tissue-air ratio (E-TAR) inhomogeneity correction was applied for the computations using a GE target series 11 planning computer. The compensators designed were tested for accuracy in a modified water/lung phantom using a scanning diode and an anthropomorphic phantom using thermoluminescent dosimeters. A comparison has been made between the compensated and uncompensated plans for the first nine patients who we have treated with this technique. The dose profiles produced by the computation agreed with the prediction of the computed isodose plans to within ± 2% at the target depth. The thermoluminescent dosimeter (TLD)-measured results in the anthropomorphic phantom agreed with the planning computer within ± 3%. A comparison of nine compensated plans of radiotherapy patients for large-volume targets in the lung region showed a maximum variation in the target to be 19% uncompensated versus 10% compensated. By providing compensated treatment fields from anterior and posterior treatment portals, a homogeneous dose that conforms well to the target volume is provided. As an added bonus, this enables the lateral lung fields to be significantly de-weighted and the healthy lung is spared considerable dose. Copyright (1999) Blackwell Science Pty Ltd

  1. Reversible thyristor converters of brushless synchronous compensators

    Directory of Open Access Journals (Sweden)

    А.М.Galynovskiy

    2013-12-01

    Full Text Available Behavior of models of three-phase-to-single-phase rotary reversible thyristor converters of brushless synchronous compensators in a circuit simulation system is analyzed. It is shown that combined control mode of opposite-connected thyristors may result in the exciter armature winding short circuits both at the thyristor feed-forward and lagging current delay angles. It must be taken into consideration when developing brushless compensator excitation systems.

  2. Executive Compensation and Principal-Agent Theory.

    OpenAIRE

    Garen, John E

    1994-01-01

    The empirical literature on executive compensation generally fails to specify a model of executive pay on which to base hypotheses regarding its determinants. In contrast, this paper analyzes a simple principal-agent model to determine how well it explains variations in CEO incentive pay and salaries. Many findings are consistent with the basic intuition of principle-agent models that compensation is structured to trade off incentives with insurance. However, statistical significance for some...

  3. Stock Option Compensation and Managerial Turnover

    OpenAIRE

    Raluca Georgiana NASTASESCU

    2009-01-01

    This study examines the association between managerial turnover and equity-based compensation. I investigate whether stock options act to bond executives to their firms and whether retention of managers is a motivation of companies in designing CEO incentive contracts. The results show that stock options do negatively influence the probability of a CEO leaving the company. The monetary cost of losing the value of equity-based compensation package keeps the manager with his company. I also fin...

  4. Compensation for Combat Deaths: Policy Considerations

    Science.gov (United States)

    2012-01-01

    through the courts for deaths resulting from other parties’ negligence or criminal behavior; a key difference between the tort system and many other...funding facilities that function outside of the tort system— for example, workers’ compensation programs for workplace fatalities and the Victims...receive $100,000 if the 10-percent risk of a loss of $100,000 actually came to pass. Tort law generally uses an ex post approach to compensation and

  5. Reactive power compensation a practical guide

    CERN Document Server

    Hofmann, Wolfgang; Just, Wolfgang

    2012-01-01

    The comprehensive resource on reactive power compensation, presenting the design, application and operation of reactive power equipment and installations The area of reactive power compensation is gaining increasing importance worldwide. If suitably designed, it is capable of improving voltage quality significantly, meaning that losses in equipment and power systems are reduced, the permissible loading of equipment can be increased, and the over-all stability of system operation improved. Ultimately, energy use and CO2 emisson are reduced. This unique guide discusses the

  6. Environmental change, phenotypic plasticity, and genetic compensation.

    Science.gov (United States)

    Grether, Gregory F

    2005-10-01

    When a species encounters novel environmental conditions, some phenotypic characters may develop differently than in the ancestral environment. Most environmental perturbations of development are likely to reduce fitness, and thus selection would usually be expected to favor genetic changes that restore the ancestral phenotype. I propose the term "genetic compensation" to refer to this form of adaptive evolution. Genetic compensation is a subset of genetic accommodation and the reverse of genetic assimilation. When genetic compensation has occurred along a spatial environmental gradient, the mean trait values of populations in different environments may be more similar in the field than when representatives of the same populations are raised in a common environment (i.e., countergradient variation). If compensation is complete, genetic divergence between populations may be cryptic, that is, not detectable in the field. Here I apply the concept of genetic compensation to three examples involving carotenoid-based sexual coloration and then use these and other examples to discuss the concept in a broader context. I show that genetic compensation may lead to a cryptic form of reproductive isolation between populations evolving in different environments, may explain some puzzling cases in which heritable traits exposed to strong directional selection fail to show the expected evolutionary response, and may complicate efforts to monitor populations for signs of environmental deterioration.

  7. Intensity modulated radiotherapy (IMRT) with compensators

    International Nuclear Information System (INIS)

    Salz, H.; Wiezorek, T.; Scheithauer, M.; Kleen, W.; Schwedas, M.; Wendt, T.G.

    2002-01-01

    The irradiation with intensity-modulated fields is possible with static as well as dynamic methods. In our university hospital, the intensity-modulated radiotherapy (IMRT) with compensators was prepared and used for the first time for patient irradiation in July 2001. The compensators consist of a mixture of tin granulate and wax, which is filled in a milled negative mould. The treatment planning is performed with Helax-TMS (MDS Nordion). An additional software is used for editing the modulation matrix ('Modifix'). Before irradiation of the first patient, extensive measurements have been carried out in terms of quality assurance of treatment planning and production of compensators. The results of the verification measurements have shown that IMRT with compensators possesses high spatial and dosimetric exactness. The calculated dose distributions are applied correctly. The accuracy of the calculated monitor units is normally better than 3%; in small volumes, further dosimetric inaccuracies between calculated and measured dose distributions are mostly less than 3%. Therefore, the compensators contribute to the achievement of high-level IMRT even when apparatuses without MLC are used. This paper describes the use of the IMRT with compensators, presents the limits of this technology, and discusses the first practical experiences. (orig.) [de

  8. Increased Rrm2 gene dosage reduces fragile site breakage and prolongs survival of ATR mutant mice

    DEFF Research Database (Denmark)

    Lopez-Contreras, Andres J; Specks, Julia; Barlow, Jacqueline H

    2015-01-01

    In Saccharomyces cerevisiae, absence of the checkpoint kinase Mec1 (ATR) is viable upon mutations that increase the activity of the ribonucleotide reductase (RNR) complex. Whether this pathway is conserved in mammals remains unknown. Here we show that cells from mice carrying extra alleles of the...

  9. Klinefelter syndrome comorbidities linked to increased X chromosome gene dosage and altered protein interactome activity

    DEFF Research Database (Denmark)

    Belling, Kirstine González-Izarzugaza; Russo, Francesco; Jensen, Anders Boeck

    2017-01-01

    Klinefelter syndrome (KS) (47,XXY) is the most common male sex chromosome aneuploidy. Diagnosis and clinical supervision remain a challenge due to varying phenotypic presentation and insufficient characterization of the syndrome. Here we combine health data-driven epidemiology and molecular level...

  10. Preactivated thiolated nanoparticles: A novel mucoadhesive dosage form.

    Science.gov (United States)

    Menzel, Claudia; Bonengel, Sonja; Pereira de Sousa, Irene; Laffleur, Flavia; Prüfert, Felix; Bernkop-Schnürch, Andreas

    2016-01-30

    Within this study a novel form of mucoadhesive nanoparticles (NPs) exhibiting a prolonged residence time on mucosal tissues was developed. In order to achieve this goal a new thiomer was synthesized by the covalent attachment of the amino acid l-cysteine ethyl ester to poly(acrylic acid) (100 kDa). The free thiol groups were in the following preactivated with the aromatic thiol bearing ligand 2-mercaptonicotinic acid (2-MNA) and the amount of coupled l-cysteine ethyl ester as well as the amount of attached 2-MNA was determined. Based on this, preactivated thiomer NPs were prepared by ionic gelation with polyethylenimine (PEI). The resulting NPs were characterized regarding size and zeta potential. Furthermore their mucoadhesive properties were investigated via rheological measurements with porcine intestinal mucus and via determination of the particles' mucosal residence time. Results showed that 1666.74 μmol l-cysteine ethyl ester and 603.07 μmol 2-MNA could be attached per gram polymer. NPs were in a size range of 112.67-252.84 nm exhibiting a zeta potential of -29 mV. Thiolated NPs only led to a 2-fold increase in mucus viscosity whereas preactivated NPs showed a 6-fold higher mucus viscosity than unmodified NPs. The mucosal residence time of thiolated NPs was 1.6-fold prolonged and that of preactivated NPs even 4.4-fold higher compared to unmodified particles. Accordingly, preactivated thiolated NPs providing a prolonged residence time on mucosal membranes could be a promising dosage form for various applications. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Mathematical modeling of drug release from lipid dosage forms.

    Science.gov (United States)

    Siepmann, J; Siepmann, F

    2011-10-10

    Lipid dosage forms provide an interesting potential for controlled drug delivery. In contrast to frequently used poly(ester) based devices for parenteral administration, they do not lead to acidification upon degradation and potential drug inactivation, especially in the case of protein drugs and other acid-labile active agents. The aim of this article is to give an overview on the current state of the art of mathematical modeling of drug release from this type of advanced drug delivery systems. Empirical and semi-empirical models are described as well as mechanistic theories, considering diffusional mass transport, potentially limited drug solubility and the leaching of other, water-soluble excipients into the surrounding bulk fluid. Various practical examples are given, including lipid microparticles, beads and implants, which can successfully be used to control the release of an incorporated drug during periods ranging from a few hours up to several years. The great benefit of mechanistic mathematical theories is the possibility to quantitatively predict the effects of different formulation parameters and device dimensions on the resulting drug release kinetics. Thus, in silico simulations can significantly speed up product optimization. This is particularly useful if long release periods (e.g., several months) are targeted, since experimental trial-and-error studies are highly time-consuming in these cases. In the future it would be highly desirable to combine mechanistic theories with the quantitative description of the drug fate in vivo, ideally including the pharmacodynamic efficacy of the treatments. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Carboxymethyl starch mucoadhesive microspheres as gastroretentive dosage form.

    Science.gov (United States)

    Lemieux, Marc; Gosselin, Patrick; Mateescu, Mircea Alexandru

    2015-12-30

    Carboxymethyl starch microspheres (CMS-MS) were produced from carboxymethyl starch powder (CMS-P) with a degree of substitution (DS) from 0.1 to 1.5 in order to investigate the influence of DS on physicochemical, drug release and mucoadhesion properties as well as interactions with gastrointestinal tract (GIT) epithelial barrier models. Placebo and furosemide loaded CMS-MS were obtained by emulsion-crosslinking with sodium trimetaphosphate (STMP). DS had an impact on increasing equilibrium water uptake and modulating drug release properties of the CMS-MS according to the surrounding pH. The transepithelial electrical resistance (TEER) of NCI-N87 gastric cell monolayers was not influenced in presence of CMS-MS, whereas that of Caco-2 intestinal cell monolayers decreased with increasing DS but recovered initial values at about 15h post-treatment. CMS-MS with increasing DS also enhanced furosemide permeability across both NCI-N87 and Caco-2 monolayers at pH gradients from 3.0 to 7.4. Mucoadhesion of CMS-MS on gastric mucosa (acidic condition) increased with the DS up to 55% for a DS of 1.0 but decreased on neutral intestinal mucosa to less than 10% with DS of 0.1. The drug release, permeability enhancement and mucoadhesive properties of the CMS-MS suggest CMS-MS with DS between 0.6 and 1.0 as suitable excipient for gastroretentive oral delivery dosage forms. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Application of DBNPA dosage for biofouling control in spiral wound membrane systems

    KAUST Repository

    Siddiqui, Amber

    2017-05-30

    Biocides may be used to control biofouling in spiral-wound reverse osmosis (RO) and nanofiltration (NF) systems. The objective of this study was to investigate the effect of biocide 2,2-dibromo-3-ni-trilopropionamide (DBNPA) dosage on biofouling control. Preventive biofouling control was studied applying a continuous dosage of substrate (0.5 mg/L) and DBNPA (1 mg/L). Curative biofouling control was studied on pre-grown biofilms, once again applying a continuous dosage of substrate (0.5 mg acetate C/L) and DBNPA (1 and 20 mg/L). Biofouling studies were performed in membrane fouling simulators (MFSs) supplied with biodegradable substrate and DBNPA. The pressure drop was monitored in time and at the end of the study, the accumulated biomass in MFS was quantified by adenosine triphosphate (ATP) and total organic carbon (TOC) analysis. Continuous dosage of DBNPA (1 mg/L) prevented pressure drop increase and biofilm accumulation in the MFSs during a run time of 7 d, showing that biofouling can be managed by preventive DBNPA dosage. For biofouled systems, continuous dosage of DBNPA (1 and 20 mg/L) inactivated the accumulated biomass but did not restore the original pressure drop and did not remove the accumulated inactive cells and extracellular polymeric substances (EPS), indicating DBNPA dosage is not suitable for curative biofouling control.

  14. Synthetic dosage lethality in the human metabolic network is highly predictive of tumor growth and cancer patient survival.

    Science.gov (United States)

    Megchelenbrink, Wout; Katzir, Rotem; Lu, Xiaowen; Ruppin, Eytan; Notebaart, Richard A

    2015-09-29

    Synthetic dosage lethality (SDL) denotes a genetic interaction between two genes whereby the underexpression of gene A combined with the overexpression of gene B is lethal. SDLs offer a promising way to kill cancer cells by inhibiting the activity of SDL partners of activated oncogenes in tumors, which are often difficult to target directly. As experimental genome-wide SDL screens are still scarce, here we introduce a network-level computational modeling framework that quantitatively predicts human SDLs in metabolism. For each enzyme pair (A, B) we systematically knock out the flux through A combined with a stepwise flux increase through B and search for pairs that reduce cellular growth more than when either enzyme is perturbed individually. The predictive signal of the emerging network of 12,000 SDLs is demonstrated in five different ways. (i) It can be successfully used to predict gene essentiality in shRNA cancer cell line screens. Moving to clinical tumors, we show that (ii) SDLs are significantly underrepresented in tumors. Furthermore, breast cancer tumors with SDLs active (iii) have smaller sizes and (iv) result in increased patient survival, indicating that activation of SDLs increases cancer vulnerability. Finally, (v) patient survival improves when multiple SDLs are present, pointing to a cumulative effect. This study lays the basis for quantitative identification of cancer SDLs in a model-based mechanistic manner. The approach presented can be used to identify SDLs in species and cell types in which "omics" data necessary for data-driven identification are missing.

  15. Adaptive response to chronic mild ethanol stress involves ROS, sirtuins and changes in chromosome dosage in wine yeasts.

    Science.gov (United States)

    Adamczyk, Jagoda; Deregowska, Anna; Skoneczny, Marek; Skoneczna, Adrianna; Kwiatkowska, Aleksandra; Potocki, Leszek; Rawska, Ewa; Pabian, Sylwia; Kaplan, Jakub; Lewinska, Anna; Wnuk, Maciej

    2016-05-24

    Industrial yeast strains of economic importance used in winemaking and beer production are genomically diverse and subjected to harsh environmental conditions during fermentation. In the present study, we investigated wine yeast adaptation to chronic mild alcohol stress when cells were cultured for 100 generations in the presence of non-cytotoxic ethanol concentration. Ethanol-induced reactive oxygen species (ROS) and superoxide signals promoted growth rate during passages that was accompanied by increased expression of sirtuin proteins, Sir1, Sir2 and Sir3, and DNA-binding transcription regulator Rap1. Genome-wide array-CGH analysis revealed that yeast genome was shaped during passages. The gains of chromosomes I, III and VI and significant changes in the gene copy number in nine functional gene categories involved in metabolic processes and stress responses were observed. Ethanol-mediated gains of YRF1 and CUP1 genes were the most accented. Ethanol also induced nucleolus fragmentation that confirms that nucleolus is a stress sensor in yeasts. Taken together, we postulate that wine yeasts of different origin may adapt to mild alcohol stress by shifts in intracellular redox state promoting growth capacity, upregulation of key regulators of longevity, namely sirtuins and changes in the dosage of genes involved in the telomere maintenance and ion detoxification.

  16. Boxing and mixed martial arts: preliminary traumatic neuromechanical injury risk analyses from laboratory impact dosage data.

    Science.gov (United States)

    Bartsch, Adam J; Benzel, Edward C; Miele, Vincent J; Morr, Douglas R; Prakash, Vikas

    2012-05-01

    In spite of ample literature pointing to rotational and combined impact dosage being key contributors to head and neck injury, boxing and mixed martial arts (MMA) padding is still designed to primarily reduce cranium linear acceleration. The objects of this study were to quantify preliminary linear and rotational head impact dosage for selected boxing and MMA padding in response to hook punches; compute theoretical skull, brain, and neck injury risk metrics; and statistically compare the protective effect of various glove and head padding conditions. An instrumented Hybrid III 50th percentile anthropomorphic test device (ATD) was struck in 54 pendulum impacts replicating hook punches at low (27-29 J) and high (54-58 J) energy. Five padding combinations were examined: unpadded (control), MMA glove-unpadded head, boxing glove-unpadded head, unpadded pendulum-boxing headgear, and boxing glove-boxing headgear. A total of 17 injury risk parameters were measured or calculated. All padding conditions reduced linear impact dosage. Other parameters significantly decreased, significantly increased, or were unaffected depending on padding condition. Of real-world conditions (MMA glove-bare head, boxing glove-bare head, and boxing glove-headgear), the boxing glove-headgear condition showed the most meaningful reduction in most of the parameters. In equivalent impacts, the MMA glove-bare head condition induced higher rotational dosage than the boxing glove-bare head condition. Finite element analysis indicated a risk of brain strain injury in spite of significant reduction of linear impact dosage. In the replicated hook punch impacts, all padding conditions reduced linear but not rotational impact dosage. Head and neck dosage theoretically accumulates fastest in MMA and boxing bouts without use of protective headgear. The boxing glove-headgear condition provided the best overall reduction in impact dosage. More work is needed to develop improved protective padding to minimize

  17. 28 CFR 104.21 - Filing for compensation.

    Science.gov (United States)

    2010-07-01

    ... “Personal Injury Compensation Form” or a “Death Compensation Form.” A claim shall be deemed “filed” for... filing either a “Personal Injury Compensation Form” or a “Death Compensation Form,” the claim shall be..., when a Claims Evaluator determines that both the Eligibility Form and either a Personal Injury...

  18. 20 CFR 211.2 - Definition of compensation.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Definition of compensation. 211.2 Section 211.2 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT CREDITABLE RAILROAD COMPENSATION § 211.2 Definition of compensation. (a) The term compensation means any form...

  19. 50 CFR 296.4 - Claims eligible for compensation.

    Science.gov (United States)

    2010-10-01

    ... compensation. (a) Claimants. Damage or loss eligible for Fund compensation must be suffered by a commercial fisherman. (b) Damage or loss of fishing gear. Damage or loss is eligible for Fund compensation if it was... is not eligible for Fund compensation: (1) If the damage or loss was caused by the negligence or...

  20. 38 CFR 3.5 - Dependency and indemnity compensation.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Dependency and indemnity... ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation General § 3.5 Dependency and indemnity compensation. (a) Dependency and indemnity compensation. This term means a monthly payment made by...

  1. 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

  2. Pavor nocturnus: a complication of single daily tricyclic or neuroleptic dosage.

    Science.gov (United States)

    Flemenbaum, A

    1976-05-01

    The author tested the hypothesis that a single bedtime dosage schedule of tricyclic or neuroleptic medication produces increased frequency of night terrors by administering a questionnaire to 30 medical patients who were not receiving such medications and 100 psychiatric patients on either multiple- or single-dosage schedules. Psychiatric patients on multiple-dosage schedules reported no more frightening dreams than the medical patients, whereas almost three-fourths of those receiving single bedtime doses had frightening dreams, a significant difference from the medical sample. This preliminary report is presented to call attention to the possible undesirable effects of a single dose schedule.

  3. Temperature compensation and entrainment in circadian rhythms

    International Nuclear Information System (INIS)

    Bodenstein, C; Heiland, I; Schuster, S

    2012-01-01

    To anticipate daily variations in the environment and coordinate biological activities into a daily cycle many organisms possess a circadian clock. In the absence of external time cues the circadian rhythm persists with a period of approximately 24 h. The clock phase can be shifted by single pulses of light, darkness, chemicals, or temperature and this allows entrainment of the clock to exactly 24 h by cycles of these zeitgebers. On the other hand, the period of the circadian rhythm is kept relatively constant within a physiological range of constant temperatures, which means that the oscillator is temperature compensated. The mechanisms behind temperature compensation and temperature entrainment are not fully understood, neither biochemically nor mathematically. Here, we theoretically investigate the interplay of temperature compensation and entrainment in general oscillatory systems. We first give an analytical treatment for small temperature shifts and derive that every temperature-compensated oscillator is entrainable to external small-amplitude temperature cycles. Temperature compensation ensures that this entrainment region is always centered at the endogenous period regardless of possible seasonal temperature differences. Moreover, for small temperature cycles the entrainment region of the oscillator is potentially larger for rectangular pulses. For large temperature shifts we numerically analyze different circadian clock models proposed in the literature with respect to these properties. We observe that for such large temperature shifts sinusoidal or gradual temperature cycles allow a larger entrainment region than rectangular cycles. (paper)

  4. Engineering Compensations in Web Service Environment

    DEFF Research Database (Denmark)

    Schäfer, Micahel; Dolog, Peter; Nejdl, Wolfgang

    2007-01-01

    Business to business integration has recently been performed by employing Web service environments. Moreover, such environments are being provided by major players on the technology markets. Those environments are based on open specifications for transaction coordination. When a failure in such a......Business to business integration has recently been performed by employing Web service environments. Moreover, such environments are being provided by major players on the technology markets. Those environments are based on open specifications for transaction coordination. When a failure...... in such an environment occurs, a compensation can be initiated to recover from the failure. However, current environments have only limited capabilities for compensations, and are usually based on backward recovery. In this paper, we introduce an engineering approach and an environment to deal with advanced...... compensations based on forward recovery principles. We extend the existing Web service transaction coordination architecture and infrastructure in order to support flexible compensation operations. A contract-based approach is being used, which allows the specification of permitted compensations at runtime. We...

  5. Influence of dosage form on the intravitreal pharmacokinetics of diclofenac.

    Science.gov (United States)

    Durairaj, Chandrasekar; Kim, Stephen J; Edelhauser, Henry F; Shah, Jaymin C; Kompella, Uday B

    2009-10-01

    To prepare a suspension form of diclofenac and compare the influence of the injected form (suspension versus solution) on the intravitreal pharmacokinetics of diclofenac in Dutch belted pigmented rabbits. Diclofenac acid was prepared and characterized in a suspension formulation. Rabbit eyes were injected with either diclofenac sodium solution (0.3 mg) or diclofenac acid suspension (10 mg) prepared in 0.1 mL balanced salt solution. Rabbits were killed at regular time intervals, the eyes enucleated, and drug content quantified in the vitreous humor and retina-choroid tissue by high-performance liquid chromatography. Pharmacokinetic models were developed for both the dosage forms, and simulations were performed for different doses. Diclofenac acid with an approximate 5-mum particle size exhibited 3.5-fold lower solubility in vitreous humor, when compared with its sodium salt. The estimated settling velocity of the suspension in the vitreous humor was 3 cm/h. After diclofenac sodium salt solution injection, drug levels declined rapidly with no drug levels detectable after 24 hours in the vitreous humor and 4 hours in the RC. Throughout the assessed time course, drug levels were higher in the vitreous. However, sustained, high drug levels were observed in both the vitreous humor and the retina-choroid even on day 21 after diclofenac acid suspension injection, with retina-choroid drug levels being higher beginning at 0.25 hour. The elimination half-life of diclofenac suspension was 24 and 18 days in vitreous and retina-choroid, respectively, compared to 2.9 and 0.9 hours observed with diclofenac sodium. The pharmacokinetic models developed indicated a slow-release distribution or depot compartment for the diclofenac acid suspension in the posterior segment. Simulations indicated the inability of a 10-mg dose of diclofenac sodium solution to sustain drug levels in the vitreous beyond 11 days. By choosing a less soluble form of a drug such as diclofenac acid, vitreous

  6. Single-dose volume regulation algorithm for a gas-compensated intrathecal infusion pump.

    Science.gov (United States)

    Nam, Kyoung Won; Kim, Kwang Gi; Sung, Mun Hyun; Choi, Seong Wook; Kim, Dae Hyun; Jo, Yung Ho

    2011-01-01

    The internal pressures of medication reservoirs of gas-compensated intrathecal medication infusion pumps decrease when medication is discharged, and these discharge-induced pressure drops can decrease the volume of medication discharged. To prevent these reductions, the volumes discharged must be adjusted to maintain the required dosage levels. In this study, the authors developed an automatic control algorithm for an intrathecal infusion pump developed by the Korean National Cancer Center that regulates single-dose volumes. The proposed algorithm estimates the amount of medication remaining and adjusts control parameters automatically to maintain single-dose volumes at predetermined levels. Experimental results demonstrated that the proposed algorithm can regulate mean single-dose volumes with a variation of 98%. © 2010, Copyright the Authors. Artificial Organs © 2010, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  7. Dosage of the Abcg1-U2af1 region modifies locomotor and cognitive deficits observed in the Tc1 mouse model of Down syndrome.

    Directory of Open Access Journals (Sweden)

    Damien Marechal

    Full Text Available Down syndrome (DS results from one extra copy of human chromosome 21 and leads to several alterations including intellectual disabilities and locomotor defects. The transchromosomic Tc1 mouse model carrying an extra freely-segregating copy of human chromosome 21 was developed to better characterize the relation between genotype and phenotype in DS. The Tc1 mouse exhibits several locomotor and cognitive deficits related to DS. In this report we analyzed the contribution of the genetic dosage of 13 conserved mouse genes located between Abcg1 and U2af1, in the telomeric part of Hsa21. We used the Ms2Yah model carrying a deletion of the corresponding interval in the mouse genome to rescue gene dosage in the Tc1/Ms2Yah compound mice to determine how the different behavioral phenotypes are affected. We detected subtle changes with the Tc1/Ms2Yah mice performing better than the Tc1 individuals in the reversal paradigm of the Morris water maze. We also found that Tc1/Ms2Yah compound mutants performed better in the rotarod than the Tc1 mice. This data support the impact of genes from the Abcg1-U2af1 region as modifiers of Tc1-dependent memory and locomotor phenotypes. Our results emphasize the complex interactions between triplicated genes inducing DS features.

  8. Continuous intravenous infusion of ampicillin and gentamicin during parenteral nutrition to 36 newborn infants using a dosage schedule

    DEFF Research Database (Denmark)

    Colding, H; Møller, S; Andersen, G E

    1984-01-01

    Ampicillin and gentamicin were given continuously i.v. to 36 newborn infants using a dosage schedule and the results were compared with those obtained in an earlier study including 88 infants who received individually calculated dosages. With the dosage schedule the variation in the serum concent...

  9. Sources of compensation in hadronic calorimeters

    International Nuclear Information System (INIS)

    Goodman, M.S.; Gabriel, T.A.; Di Ciaccio, A.; Wilson, R.

    1988-12-01

    Monte Carlo simulations are presented using the CALOR code system to study the design of a large hybrid hadron calorimeter system employing a warm liquid active medium (tetramethylsilane, Si(CH 3 ) 4 ) and uranium plates in addition to a conventional Fe/plastic system. In the system described here, the uranium provides partial compensation by suppressing the electromagnetic cascade produced by incident electrons due to sampling inefficiencies. The results of the simulations also indicate that significant compensation is achieved (given small enough saturation) due to low energy recoil protons produced in collisions with low energy (1--20 MeV) cascade and fission neutrons in the active medium. Both compensation mechanisms are important to help balance the response of a calorimeter to incident electrons and hadrons, that is, to achieve a ratio of pulse heights (e/h ∼ 1) which will lead to the best energy resolution. 17 refs., 4 figs., 2 tabs

  10. Incomplete and imperfect information for sales compensation

    Directory of Open Access Journals (Sweden)

    Raluca Valeanu

    2010-12-01

    Full Text Available Sales force compensation represents the fix and / or variable payment by the company. To compensate agents based on the results, the company set a goal which is brought to their attention through the compensation plan. Applying the model of moral hazard, where the agent behavior cannot be verified, it cannot be specified in the contract what is the expected behavior of the agent. In order to make an offer to contract principal should know the effort that the agent will submit it to define the payment and the contract is determined optimally in trade between the two conflicting objectives of the two participants in the contract. Although agent behavior cannot be verified, the result of this behavior should be measurable at the end of the contract so that the employer may make the contract contingent on effort commission agent for sale of which is measured by the amount of earnings to the company.

  11. 'Compensation neurosis': a review of the literature.

    Science.gov (United States)

    Weighill, V E

    1983-01-01

    This review examines the literature on psychological reactions, often referred to as 'compensation neurosis', which occur after an accident and which are thought to be produced or maintained by a compensation claim. Theories and research are examined. The area is complicated and research so far is limited in scope and design. Few accident cases involve compensation claims and the incidence of psychological difficulties across the whole range of cases is unknown. Researchers have considered a number of background factors--severity of injury, pre-existing neurotic traits, social class, sex and age--but there has been little investigation of attitudinal, family, social and employment factors or of progress of the condition and follow-up after settlement. The review identifies a major research need for more adequate screening and sampling of cases and for more systematic investigation of personal and family factors.

  12. Software compensation in Particle Flow reconstruction

    CERN Document Server

    Lan Tran, Huong; Sefkow, Felix; Green, Steven; Marshall, John; Thomson, Mark; Simon, Frank

    2017-01-01

    The Particle Flow approach to calorimetry requires highly granular calorimeters and sophisticated software algorithms in order to reconstruct and identify individual particles in complex event topologies. The high spatial granularity, together with analog energy information, can be further exploited in software compensation. In this approach, the local energy density is used to discriminate electromagnetic and purely hadronic sub-showers within hadron showers in the detector to improve the energy resolution for single particles by correcting for the intrinsic non-compensation of the calorimeter system. This improvement in the single particle energy resolution also results in a better overall jet energy resolution by improving the energy measurement of identified neutral hadrons and improvements in the pattern recognition stage by a more accurate matching of calorimeter energies to tracker measurements. This paper describes the software compensation technique and its implementation in Particle Flow reconstruct...

  13. Institutional directors and board compensation: Spanish evidence

    Directory of Open Access Journals (Sweden)

    Felix López-Iturriaga

    2015-07-01

    Full Text Available We address the influence of directors who represent institutional investors in three aspects of board compensation policies: level of compensation, composition, and performance sensitivity. We differentiate pressure-sensitive directors (i.e., with business links and pressure-resistant directors (i.e., without business links. Our results show that pressure-resistant directors decrease total board compensation and its fixed proportion, whereas they increase the variable proportion of total remuneration and the pay-for-performance sensitivity. By contrast, pressure-sensitive directors offer the opposite results. These findings are consistent with the view that institutional investors are not a homogeneous group and that pressure-resistant directors fulfill a more thorough monitoring role.

  14. Compensation: Will it provide a waste site?

    International Nuclear Information System (INIS)

    Pulsipher, A.G.

    1993-01-01

    Offering an attractive compensation package to persuade a community to voluntarily accept an otherwise undesirable facility may work in some cases, but it's not likely to work for high-level nuclear-waste disposal. The public perception of the risks involved and the public distrust of the institutions responsible for managing those risks are just too great. Much of the controversy stems from public perceptions that the site-selection process itself is unfair. Resentment builds when this occurs, and offers of compensation come to be labeled bribes or blood money. The driving force behind current nuclear-waste policy is intergenerational equity - the moral concept that the generation that produced the waste should dispose of it, permanently. Regardless of the moral appeal, doubts have been raised about the technical feasibility of this approach. Alternatives featuring intergenerational monetary compensation may better honor the commitment hor-ellipsis and reduce pressure to try to do what may be impossible

  15. Reexamining workers' compensation: a human rights perspective.

    Science.gov (United States)

    Boden, Leslie I

    2012-06-01

    Injured workers, particularly those with more severe injuries, have long experienced workers' compensation systems as stressful and demeaning, have found it difficult to obtain benefits, and, when able to obtain benefits, have found them inadequate. Moreover, the last two decades have seen a substantial erosion of the protections offered by workers' compensation. State after state has erected additional barriers to benefit receipt, making the workers' compensation experience even more difficult and degrading. These changes have been facilitated by a framing of the political debate focused on the free market paradigm, employer costs, and worker fraud and malingering. The articles in this special issue propose an alternate framework and analysis, a human rights approach, that values the dignity and economic security of injured workers and their families. Copyright © 2012 Wiley Periodicals, Inc.

  16. Determination of elements in citrus leaves; Dosage des elements dans les feuilles de citrus

    Energy Technology Data Exchange (ETDEWEB)

    Masozera, C.; Compernolle, G. van; Brandstetr, J.; Krivanek, M. [Centre nucléaire TRICO, Kinshasa (Congo, The Democratic Republic of the); Université Lovanium, Kinshasa (Congo, The Democratic Republic of the)

    1970-01-15

    facteurs, entre autres l'épuisement du sol ou l'application d'engrais dont la formule n’ est pas appropriée. L' appauvrissement chimique du sol est lié à deux causes: d' une part au phénomène de lessivage, d’entrainement de bases, d’autre part aux «exportations» d'éléments fertilisants sous forme de récoltes pendant des années sans contrepartie. Ces pertes sont particulièrement néfastes si la roche-mère ne contient pas suffisamment de réserves minérales susceptibles de les compenser par altération lente. Cet appauvrissement est mis en évidence par les analyses du sol et par les analyses foliaires. Les auteurs ont essayé de doser les éléments suivants: Mn, P, Cu, Cl, et K (ces derniers pour trois échantillons seulement) pour le Citrus. Après prélèvement ils ont traité les échantillons selon la méthode utilisée par Bransolten (Rapport de recherche TRICO n° 15/1968), séchage pendant au moins 12 h à 105°C et broyage des feuilles en poudre, puis ils ont procédé au dosage. Le dosage du Mn et du Cl est très facile, tout comme celui du Cu. Ce dernier est dosé par activation aux neutrons lents pour éviter la formation de Zn. Quant au phosphore, il a été dosé en mesurant le rayonnement ß émis par les radioéléments. Ici, des précautions particulières doivent être prises pour avoir la même couche pour les échantillons et les étalons vu que le rayonnement ß est absorbé par ces couches. Le K et le Na ont été dosés en utilisant les neutrons thermiques pour l'activation et un détecteur au Ge(Li) pour les mesures des spectres y. La grande résolution du détecteur a permis de doser ces deux éléments sans séparation. (author)

  17. 76 FR 81806 - Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution

    Science.gov (United States)

    2011-12-29

    .... FDA-2011-N-0003] Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution... solution of ivermectin. DATES: This rule is effective December 29, 2011. FOR FURTHER INFORMATION CONTACT... ANADA 200-318 for [[Page 81807

  18. Meta-analysis : High-dosage vitamin E supplementation may increase all-cause mortality

    NARCIS (Netherlands)

    Miller, ER; Pastor-Barriuso, R; Dalal, D; Riemersma, RA; Appel, LJ; Guallar, E

    2005-01-01

    Background: Experimental models and observational studies suggest that vitamin E supplementation may prevent cardiovascular disease and cancer. However, several trials of high-dosage vitamin E supplementation showed non-statistically significant increases in total mortality. Purpose: To perform a

  19. Low-dosage helical CT applications for chest medical checkup and lung cancer screening

    International Nuclear Information System (INIS)

    Wang Ping; Cui Fa; Liang Huanqing; Zheng Minfei

    2005-01-01

    Objective: A discussion on low-dosage helical CT applications on chest medical checkup and lung cancer screening. Methods: On the 100 chest medical check up with three different of protocols, including standard-dosage (the tube current was 230 mAs) were compared with low-dose (tube current was 50 mAs or 30 mAs). Results: Low-dosage helical CT scan provides excellent images. In 100 chest medical checkup, 39 nodules or masses were revealed, enlarged lymph node was noted in 1 case; emphysema or bullae was demonstrated in 3 segments; thickening of bronchial wall was shown in 2 cases; and localized pleural thickening was found in 1 case. Conclusion: In chest checkup or lung cancer screening low-dosage helical CT (tube current 30 mAs) will not only guarantee image quality but also reduce the radiation dose during the examination. (authors)

  20. Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Proguanil Hydrochloride.

    NARCIS (Netherlands)

    Plöger, Gerlinde F; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D I R K W; Langguth, Peter; Mehta, Mehul U; Parr, Alan; Polli, James E; Shah, Vinod P; Tajiri, Tomokazu; Dressman, Jennifer B

    2018-01-01

    Literature data relevant to the decision to waive in vivo bioequivalence testing for the approval of generic immediate release solid oral dosage forms of proguanil hydrochloride are reviewed. To clarify the Biopharmaceutics Classification System (BCS) classification, experimental solubility and

  1. Clinical criteria for medical staff exposure and reference dosage within the Galician health Service

    International Nuclear Information System (INIS)

    Garcia Comesana, J.

    2003-01-01

    The generalised use of ionising radiation tests is making these tests become the prime cause of exposure to artificial radiation, receiving one sixth of the dosage through background radiation. (Author)

  2. Weak hadronic currents in compensation theory

    International Nuclear Information System (INIS)

    Pappas, R.C.

    1975-01-01

    Working within the framework of a compensation theory of strong and weak interactions, it is shown that: (1) an axial vector baryon number current can be included in the weak current algebra if certain restrictions on the K-meson strong couplings are relaxed; (2) the theory does not permit the introduction of strange currents of the chiral form V + A; and (3) the assumption that the superweak currents of the theory cannot contain certain CP conserving terms can be justified on the basis of compensation requirements

  3. Skew quad compensation for SPEAR minibeta optics

    International Nuclear Information System (INIS)

    Wille, K.

    1984-06-01

    With the new minibeta insertion for SPEAR the betatron coupling and the perturbations of beam optics caused by the solenoid field of the MARK III detector can't be compensated by the simple coils used so far. Therefore another scheme with four skew quads arranged in two families has been chosen. Even though this scheme doesn't compensate the effect of the solenoid on the beam completely, the residual emittance coupling is much less than 1% which should be sufficient under all running conditions. The major advantage of this concept is its simplicity

  4. Convention on supplementary compensation for nuclear damage

    International Nuclear Information System (INIS)

    Chinese Nuclear Society, Beijing; U.S. Nuclear Energy Institute

    2000-01-01

    The Contracting parties recognize the importance of the measures provided in the Vienna Convention on Civil Liability for Nuclear Damage and the Paris Convention on Third party liability in the Field of Nuclear Energy as well as in national legislation on compensation for nuclear damage consistent with the principles of these conventions. The Contracting parties desire to establish a worldwide liability regime to supplement and enhance these measures with a view to increasing the amount of compensation for nuclear damage and encourage regional and global co-operation to promote a higher level of nuclear safety in accordance with the principle of international partnership and solidarity

  5. Static compensators (STATCOMs) in power systems

    CERN Document Server

    Shahnia, Farhad; Ghosh, Arindam

    2014-01-01

    A static compensator (STATCOM), also known as static synchronous compensator, is a member of the flexible alternating current transmission system (FACTS) devices. It is a power-electronics based regulating device which is composed of a voltage source converter (VSC) and is shunt-connected to alternating current electricity transmission and distribution networks. The voltage source is created from a DC capacitor and the STATCOM can exchange reactive power with the network. It can also supply some active power to the network, if a DC source of power is connected across the capacitor. A STATCOM

  6. Phase alteration compensation in reflection digital holography

    International Nuclear Information System (INIS)

    Rincon, O; Amezquita, R; Monroy, F

    2011-01-01

    The phase maps obtained from digital holographic microscopy techniques carry information about the axial lengths of the object under study. Additionally, these phase maps have information of tilt and curvatures with origin in the off-axis geometry and the magnification lenses system, respectively. Only a complete compensation of these extra phases allows a correct interpretation of the phase information. In this article a numerical strategy to compensate for these alterations is designed, using a phase mask located in different planes. This strategy is applied in the measurement of a phase steps plate using a digital holography setup.

  7. Security careers skills, compensation, and career paths

    CERN Document Server

    Walker, Stephen W

    2014-01-01

    The third edition of Security Careers is the authoritative reference for current job descriptions and pay practices of security, compliance, ethics, environmental, health and safety occupations. The job descriptions and compensation ranges in this report are drawn from research from the Foushée Group, which has been conducting this research since 1980. Security Careers includes more than 75 job descriptions for security-related positions, which range from the entry-level security guard to the top global corporate executive. It also provides four years of compensation trend data to give a th

  8. Kayenta advanced series compensation operational experience

    Energy Technology Data Exchange (ETDEWEB)

    1994-01-01

    The world's first three-phase, thyristor-controlled series compensation scheme with continuously variable impedance has been introduced into a transmission system. Energized and dedicated in September 1992, the installation was placed into commercial operation in January 1993 and has provided over one year of operating experience. This paper describes the 230 kV, 330 MVAr (60 Hz) advanced series compensation (ASC) project, located in north-eastern Arizona at Kayenta Substation on the 320 km Glen Canyon-Shiprock transmission line. The paper describes operating experiences, coordination with phase shifting transformer, phase shifter failure, platform power, system disturbances, and future plans.

  9. Radiation damage effects on calorimeter compensation

    International Nuclear Information System (INIS)

    Gabriel, T.A.; Handler, T.

    1990-01-01

    An important consideration in the design of a detector that is to be used at the Superconducting Super Collider (SSC) is the response of the calorimeter to electromagnetic and hadronic particles and the equality of those responses for different types of particles at equal incident energies, i.e. compensation. However, as the simulations that are reported show, the compensation characteristics of a calorimeter can be seriously compromised over a relatively short period of time due to the large radiation levels that are expected in the SSC environment. 6 refs., 3 figs

  10. Compensation systems for low temperature applications

    CERN Document Server

    Skoczen, Balzej T

    2004-01-01

    The book is dedicated to the behaviour of ductile materials at cryogenic temperatures, structural stability issues and reliability oriented parametric optimisation of compensation systems containing the corrugated bellows. The problems of local and global stability of systems containing bellows, coupling between the low-cycle fatigue and stability as well as evolution of plastic strain fields, micro-damage and strain induced phase transformation in the corrugated shells at cryogenic temperatures are presented. As a special feature reliability oriented optimum design of compensation systems under strength, stability, fatigue and geometrical constraints is discussed. The relevant applications in the particle accelerators and cryogenic transfer lines are shown.

  11. The marriage premium and compensating wage differentials.

    Science.gov (United States)

    Reed, W R; Harford, K

    1989-12-01

    This paper proposes and tests an alternative explanation of the marriage premium that relies upon differences in workers' tastes and compensating wage differentials. A key assumption is that marital status proxies for the consumption of family goods, such as children, and that these are costly. Workers whose greater demands for family goods are taste- generated and shown to choose jobs that offer greater wage, and less non-pecuniary compensation. This creates an observed wage premium that has nothing to do with differences in workers' productivities. Supporting empirical evidence for this hypothesis is presented, including a reevaluation of previous studies.

  12. Lossless Compression of Video using Motion Compensation

    DEFF Research Database (Denmark)

    Martins, Bo; Forchhammer, Søren

    1998-01-01

    We investigate lossless coding of video using predictive coding andmotion compensation. The methods incorporate state-of-the-art lossless techniques such ascontext based prediction and bias cancellation, Golomb coding, high resolution motion field estimation,3d-dimensional predictors, prediction...... using one or multiple previous images, predictor dependent error modelling, and selection of motion field by code length. For slow pan or slow zoom sequences, coding methods that use multiple previous images are up to 20% better than motion compensation using a single previous image and up to 40% better...

  13. Digital, electromagnetic rod position indicator with compensation

    International Nuclear Information System (INIS)

    Feilchenfeld, M.M.; Geis, C.G.

    1985-01-01

    A digital rod position indicator having discrete coils L 0 , L 1 , L 2 ..... spaced along the travel path of an elongate magnetically permeable member stores in digital form compensation signals for automatically adjusting the location relative to the coils at which a digital output signal representative of the position of the end of the elongate member transitions from one code to the next. The appropriate compensation signal is addressed using the digital output signal and a correction factor which takes into account the direction of movement including reversals. Reference is made to the positioning of the control rods in a pressurized water reactor. (author)

  14. Filament stretching rheometer: inertia compensation revisited

    DEFF Research Database (Denmark)

    Szabo, Peter; McKinley, Gareth H.

    2003-01-01

    The necessary inertia compensation used in the force balance for the filament stretching rheometer is derived for an arbitrary frame of reference. This enables the force balance to be used to extract correctly the extensional viscosity from measurements of the tensile force at either end of the e......The necessary inertia compensation used in the force balance for the filament stretching rheometer is derived for an arbitrary frame of reference. This enables the force balance to be used to extract correctly the extensional viscosity from measurements of the tensile force at either end...

  15. Administered activity of Tc-99m MDP for bone scintigraphy, standard or individual dosage?

    International Nuclear Information System (INIS)

    Vestergren, E.; Gretarsdottir, J.; Jacobsson, L.

    2002-01-01

    Background and Aim: Adult patients are generally, irrespective of size, given the same amount of activity for a certain type of nuclear medicine examination, a standard dosage. Identical image quality is essential when comparing different patient studies. The aim of this study is to evaluate different dosage methods for Tc-99m-MDP bone scintigraphy and to investigate whether individual dosage will decrease the variations in image quality between different patients. Material and Methods: 100 consecutive adult patients (aged between 40 and 89 years) undergoing whole body bone scintigraphy were studied. Eight patients were excluded from the study because of abnormal high uptake in the areas of interest. The patient weight and height were registered. The activity in the syringes was measured before and after the injection of about 600 MBq Tc-99m MDP. Scanning was performed, with a dual head gamma camera (Maxxus or Millennium VG, General Electric) equipped with a high-resolution collimator, at approximately 4 hours (mean 3.8 h) post-injection. Regions of interest (ROI) were drawn over the lumbar spine (posterior view), the right femur (anterior view) and also soft tissue background regions for each area. The total counts, maximum counts/pixel and number of pixels in the ROIs were registered. The maximum number of counts/pixel (background-subtracted), SPINEmax and FEMURmax were chosen as the image quality parameters. For each patient, SPINEmax and FEMURmax where recalculated to the number that would have been obtained with standard dosage (exactly 600 MBq), and dosage proportional to body weight, body surface area and body height. All values were corrected to a scanning time 3.8 h after injection. Results: Both with a standard activity dosage and a dosage proportional to body height, SPINEmax decreases with increasing body weight. Dosage proportional to body weight gives increasing values of SPINEmax with increasing body weight. Dosage proportional to body surface area

  16. Methotrexate Dosage Reduction Upon Adalimumab Initiation: Clinical and Ultrasonographic Outcomes from the Randomized Noninferiority MUSICA Trial.

    Science.gov (United States)

    Kaeley, Gurjit S; Evangelisto, Amy M; Nishio, Midori J; Goss, Sandra L; Liu, Shufang; Kalabic, Jasmina; Kupper, Hartmut

    2016-08-01

    To examine the clinical and ultrasonographic (US) outcomes of reducing methotrexate (MTX) dosage upon initiating adalimumab (ADA) in MTX-inadequate responders with moderately to severely active rheumatoid arthritis (RA). MUSICA (NCT01185288) was a double-blind, randomized, parallel-arm study of 309 patients with RA receiving MTX ≥ 15 mg/week for ≥ 12 weeks before screening. Patients were randomized to high dosage (20 mg/week) or low dosage (7.5 mg/week) MTX; all patients received 40 mg open-label ADA every other week for 24 weeks. The primary endpoint was Week 24 mean 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) to test for noninferiority of low-dosage MTX using a 15% margin. US images were scored using a 10-joint semiquantitative system incorporating OMERACT definitions for pathology, assessing synovial hypertrophy, vascularity, and bony erosions. Rapid improvement in clinical indices was observed in both groups after addition of ADA. The difference in mean DAS28-CRP (0.37, 95% CI 0.07-0.66) comparing low-dosage (4.12, 95% CI 3.88-4.34) versus high-dosage MTX (3.75, 95% CI 3.52-3.97) was statistically significant and non-inferiority was not met. Statistically significant differences were not detected for most clinical, functional, and US outcomes. Pharmacokinetic and safety profiles were similar. In MUSICA, Week 24 mean DAS28-CRP, the primary endpoint, did not meet non-inferiority for the low-dosage MTX group. Although the differences between the 2 MTX dosage groups were small, our study findings did not support routine MTX reduction in MTX inadequate responders initiating ADA.

  17. Miniaturized approach for excipient selection during the development of oral solid dosage form

    DEFF Research Database (Denmark)

    Raijada, Dharaben Kaushikkumar; Müllertz, Anette; Cornett, Claus

    2014-01-01

    The present study introduces a miniaturized high-throughput platform to understand the influence of excipients on the performance of oral solid dosage forms during early drug development. Wet massing of binary mixtures of the model drug (sodium naproxen) and representative excipients was followed...... for excipient selection and for early-stage performance testing of active pharmaceutical ingredient intended for oral solid dosage form. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:900-908, 2014....

  18. Efficiency of individual dosage of digoxin with calculated concentration

    Directory of Open Access Journals (Sweden)

    Zhao L

    2014-07-01

    digoxin and creatinine clearance, our results show that although there was a significant correlation between clearance of digoxin and creatinine clearance in the group overall, correlations were not evident within the different stages of renal function.Conclusion: The results of this study indicate that clearance of digoxin and the creatinine clearance rate cannot be explained by renal function alone and that the validity of the Konishi equation for individualizing the digoxin dosage in Chinese patients is limited, being applicable only in stage 3 renal disease. Further research in larger numbers of patients across all stages of renal function will be required in the future to verify the original Konishi model. Keywords: serum digoxin concentration, predicted concentration, renal insufficiency

  19. Measurement of the lowest dosage of phenobarbital that can produce drug discrimination in rats

    Science.gov (United States)

    Overton, Donald A.; Stanwood, Gregg D.; Patel, Bhavesh N.; Pragada, Sreenivasa R.; Gordon, M. Kathleen

    2009-01-01

    Rationale Accurate measurement of the threshold dosage of phenobarbital that can produce drug discrimination (DD) may improve our understanding of the mechanisms and properties of such discrimination. Objectives Compare three methods for determining the threshold dosage for phenobarbital (D) versus no drug (N) DD. Methods Rats learned a D versus N DD in 2-lever operant training chambers. A titration scheme was employed to increase or decrease dosage at the end of each 18-day block of sessions depending on whether the rat had achieved criterion accuracy during the sessions just completed. Three criterion rules were employed, all based on average percent drug lever responses during initial links of the last 6 D and 6 N sessions of a block. The criteria were: D%>66 and N%50 and N%33. Two squads of rats were trained, one immediately after the other. Results All rats discriminated drug versus no drug. In most rats, dosage decreased to low levels and then oscillated near the minimum level required to maintain criterion performance. The lowest discriminated dosage significantly differed under the three criterion rules. The squad that was trained 2nd may have benefited by partially duplicating the lever choices of the previous squad. Conclusions The lowest discriminated dosage is influenced by the criterion of discriminative control that is employed, and is higher than the absolute threshold at which discrimination entirely disappears. Threshold estimations closer to absolute threshold can be obtained when criteria are employed that are permissive, and that allow rats to maintain lever preferences. PMID:19082992

  20. X-linked gene transcription patterns in female and male in vivo, in vitro and cloned porcine individual blastocysts.

    Directory of Open Access Journals (Sweden)

    Chi-Hun Park

    Full Text Available To determine the presence of sexual dimorphic transcription and how in vitro culture environments influence X-linked gene transcription patterns in preimplantation embryos, we analyzed mRNA expression levels in in vivo-derived, in vitro-fertilized (IVF, and cloned porcine blastocysts. Our results clearly show that sex-biased expression occurred between female and male in vivo blastocysts in X-linked genes. The expression levels of XIST, G6PD, HPRT1, PGK1, and BEX1 were significantly higher in female than in male blastocysts, but ZXDA displayed higher levels in male than in female blastocysts. Although we found aberrant expression patterns for several genes in IVF and cloned blastocysts, similar sex-biased expression patterns (on average were observed between the sexes. The transcript levels of BEX1 and XIST were upregulated and PGK1 was downregulated in both IVF and cloned blastocysts compared with in vivo counterparts. Moreover, a remarkable degree of expression heterogeneity was observed among individual cloned embryos (the level of heterogeneity was similar in both sexes but only a small proportion of female IVF embryos exhibited variability, indicating that this phenomenon may be primarily caused by faulty reprogramming by the somatic cell nuclear transfer (SCNT process rather than in vitro conditions. Aberrant expression patterns in cloned embryos of both sexes were not ameliorated by treatment with Scriptaid as a potent HDACi, although the blastocyst rate increased remarkably after this treatment. Taken together, these results indicate that female and male porcine blastocysts produced in vivo and in vitro transcriptional sexual dimorphisms in the selected X-linked genes and compensation of X-linked gene dosage may not occur at the blastocyst stage. Moreover, altered X-linked gene expression frequently occurred in porcine IVF and cloned embryos, indicating that X-linked gene regulation is susceptible to in vitro culture and the SCNT process

  1. Transgenic mice with increased Cu/Zn-superoxide dismutase activity: animal model of dosage effects in Down syndrome

    International Nuclear Information System (INIS)

    Epstein, C.J.; Avraham, K.B.; Lovett, M.; Smith, S.; Elroy-Stein, O.; Rotman, G.; Bry, C.; Groner, Y.

    1987-01-01

    Down syndrome, the phenotypic expression of human trisomy 21, is presumed to result from a 1.5-fold increase in the expression of the genes on human chromosome 21. As an approach to the development of an animal model for Down syndrome, several strains of transgenic mice that carry the human Cu/Zn-superoxide dismutase gene have been prepared. The animals express the transgene in a manner similar to that of humans, with 0.9- and 0.7-kilobase transcripts in a 1:4 ratio, and synthesize the human enzyme in an active form capable of forming human-mouse enzyme heterodimers. Cu/Zn-superoxide dismutase activity is increased from 1.6- to 6.0-fold in the brains of four transgenic strains and to an equal or lesser extent in several other tissues. These animals provide a unique system for studying the consequences of increased dosage of the Cu/Zn-superoxide dismutase gene in Down syndrome and the role of this enzyme in a variety of other pathological processes

  2. Maintenance of Xist Imprinting Depends on Chromatin Condensation State and Rnf12 Dosage in Mice.

    Directory of Open Access Journals (Sweden)

    Atsushi Fukuda

    2016-10-01

    Full Text Available In female mammals, activation of Xist (X-inactive specific transcript is essential for establishment of X chromosome inactivation. During early embryonic development in mice, paternal Xist is preferentially expressed whereas maternal Xist (Xm-Xist is silenced. Unlike autosomal imprinted genes, Xist imprinting for Xm-Xist silencing was erased in cloned or parthenogenetic but not fertilized embryos. However, the molecular mechanism underlying the variable nature of Xm-Xist imprinting is poorly understood. Here, we revealed that Xm-Xist silencing depends on chromatin condensation states at the Xist/Tsix genomic region and on Rnf12 expression levels. In early preimplantation, chromatin decondensation via H3K9me3 loss and histone acetylation gain caused Xm-Xist derepression irrespective of embryo type. Although the presence of the paternal genome during pronuclear formation impeded Xm-Xist derepression, Xm-Xist was robustly derepressed when the maternal genome was decondensed before fertilization. Once Xm-Xist was derepressed by chromatin alterations, the derepression was stably maintained and rescued XmXpΔ lethality, indicating that loss of Xm-Xist imprinting was irreversible. In late preimplantation, Oct4 served as a chromatin opener to create transcriptional permissive states at Xm-Xist/Tsix genomic loci. In parthenogenetic embryos, Rnf12 overdose caused Xm-Xist derepression via Xm-Tsix repression; physiological Rnf12 levels were essential for Xm-Xist silencing maintenance in fertilized embryos. Thus, chromatin condensation and fine-tuning of Rnf12 dosage were crucial for Xist imprint maintenance by silencing Xm-Xist.

  3. Performance of Nile tilapia juvenile fed diet containing different dosages ofrecombinant common carpgrowth hormone

    Directory of Open Access Journals (Sweden)

    Dian Hardiantho

    2013-11-01

    Full Text Available The studywas conductedtodetermine thedose of recombinant common carp growth hormone (rCcGH supplemented in the commercial diet that generates the best performanceonbodyweight, biomass, andfeed conversion rate of juvenile tilapia.The dose of rCcGH administered was10, 20, and30mg/kg of commercial feed, andnorGH supplementation as control. Eachtreatment was designed in triplicates. Juveniles at average bodylengthof about2cm(average body weight of 0.7 g were reared in a density of25fish/m2, for three weeks in hapa net at a size of 2×2×1 m3. Fish were fed diet containing rCcGH twicea week with an interval ofthreedays. The juvenile were fed with the rCcGH supplemented diet three times daily at satiation. The results showedthat average body weight andbiomass of fish treated by rCcGH with the doses of 20 and 30 mg/kg feed was higher (p<0.05 than that of 10 mg/kg and control. In addition, feed conversionrate of 20 and 30 mg/kg feed treatments was lower (p<0.05 than that of 10 mg/kg and control. RT-PCR analysisshowedthat expression level of IGF-1 gene in juvenile liver was increased in parallel with the increasing of rCcGH dosages supplemented in diet.This suggestedthatIGF-1 plays an important rolein the induction ofgrowth,andfeed conversionefficiencyof tilapiafed diet containing rCcGH. The bestperformance of juvenile can be obtainedby feeding with diet containingrCcGH20‒30mg/kgof feed. Keywords: rCcGH, IGF-I, recombinant growthhormone,performance, Nile tilapia.

  4. Adaptive friction compensation: a globally stable approach

    NARCIS (Netherlands)

    Verbert, K.A.; Tóth, R.; Babuska, R.

    2016-01-01

    In this paper, an adaptive friction compensation scheme is proposed. The friction force is computed as a timevarying friction coefficient multiplied by the sign of the velocity and an on-line update law is designed to estimate this coefficient based on the actual position and velocity errors.

  5. 33 CFR 136.235 - Compensation allowable.

    Science.gov (United States)

    2010-07-01

    ... allowable. The amount of compensation allowable is limited to the actual net reduction or loss of earnings or profits suffered. Calculations for net reductions or losses must clearly reflect adjustments for... available; (d) Any saved overhead or normal expenses not incurred as a result of the incident; and (e) State...

  6. On the compensation effect in heterogeneous catalysis

    DEFF Research Database (Denmark)

    Pedersen, Thomas Bligaard; Honkala, Johanna Karoliina; Logadottir, Ashildur

    2003-01-01

    For a class of heterogeneously catalyzed reactions, we explain the compensation effect in terms of a switching of kinetic regimes leading to a concomitant change in the apparent activation energy and in the prefactor for the overall rate of the reaction. We first use the ammonia synthesis...

  7. Annual compensation for pipelines in Alberta

    International Nuclear Information System (INIS)

    2008-11-01

    The Surface Rights Board (SRB) in Alberta held a hearing in November 2007 to address three issues involving a pipeline for Enbridge Pipelines (Athabasca) Inc. as well as several land owner issues in Townships 66-68 and Ranges 17-19, all west of the 4th Meridian. The issues the SRB examined were the appropriate amount (i.e. magnitude) of compensation payable under right of entry orders under consideration; the appropriate structure of the compensation award; and to whom the compensation was payable. This document presented a review by the Farmer's Advocate Office (FAO) of the published decision of the SRB. The verbatim decision and rationale used by the SRB to award annual compensation for loss and/or ongoing nuisance and inconvenience was presented. The document could be useful to landowners as they determine their negotiation strategy when faced with considering future pipeline access agreements. The document included a discussion of the context for the decision and a case review. Specific topics that were covered included the rationale for the decision; long term effects of pipeline arguments and SRB commentary; the award and determination; and what still needs to be done. It was concluded that the SRB requires evidence in order to answer several questions regarding the magnitude of any losses, and to what degree, if any, had the nuisance, inconvenience, and loss of rights already been anticipated and factored into the operator's final offer

  8. 7 CFR 1280.208 - Compensation.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Compensation. 1280.208 Section 1280.208 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... INFORMATION ORDER Lamb Promotion, Research, and Information Order Lamb Promotion, Research, and Information...

  9. Evaluation of the implementation of Employees Compensation ...

    African Journals Online (AJOL)

    Since the passage into law of the Employees Compensation Act in 2011, countless cases of workplace accidents have occurred in Nigeria. Yet there seems to be no succour for the Nigerian worker as many state governments have either refused to register with or do not have the will power to implement the legislation in ...

  10. Employing Conjoint Analysis in Making Compensation Decisions.

    Science.gov (United States)

    Kienast, Philip; And Others

    1983-01-01

    Describes a method employing conjoint analysis that generates utility/cost ratios for various elements of the compensation package. Its superiority to simple preference surveys is examined. Results of a study of the use of this method in fringe benefit planning in a large financial institution are reported. (Author/JAC)

  11. Executive Compensation and the Cost of Debt

    NARCIS (Netherlands)

    Kabir, Mohammed Rezaul; Li, Hao; Veld-Merkoulova, Yulia V.

    2010-01-01

    We examine how executive compensation affects the cost of debt financing. Analyzing CEO pay data from the UK, we find that debt-like and equity-like pay components have opposite effects on the cost of debt. An increase in defined benefit pensions is associated with lower bond yield spread, while an

  12. ARCC Teacher Compensation Initiative: Literature Review

    Science.gov (United States)

    Appalachia Regional Comprehensive Center, 2014

    2014-01-01

    In February 2014, the Tennessee State Board of Education (SBE) requested that the Appalachia Regional Comprehensive Center (ARCC) provide assistance to the SBE's Basic Education Program (BEP) Review Committee. The SBE requested additional information on the use and effectiveness of market-based teacher compensation and market-based incentives by…

  13. Open Business Models: New Compensation Mechanisms for ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Open Business Models: New Compensation Mechanisms for Creativity and Inclusion ... This research aims to explore important new business models in the networked society ... Linking research to urban planning at the ICLEI World Congress 2018 ... In partnership with UNESCO's Organization for Women in Science for the ...

  14. Inertia compensated force and pressure sensors

    Energy Technology Data Exchange (ETDEWEB)

    Bill, B.; Engeler, P.; Gossweiler, C. [Kistler Instrumente AG, Winterthur (Switzerland)

    2001-07-01

    Any moving structure is affected by inertial effects. In case of force and pressure sensors, inertial effects cause measurement errors. The paper deals with novel signal conditioning methods and mechanical design features to minimize inertial effects. A novel solution for passive compensation of pressure sensors is presented. (orig.)

  15. Compensation of coupling in the SSC complex

    International Nuclear Information System (INIS)

    Pilat, F.; Bourianoff, G.

    1991-10-01

    This paper will describe a study of the coupling effects and their compensation by means of local depending techniques for some of the accelerators in the SSC Complex. Results concerning corrections and decoupling for the Low Energy and Medium Energy Boosters will be compared to results obtained for the Collider Ring. Some preliminary experimental data about measurement of coupling quantities will also be presented

  16. 44 CFR 295.21 - Allowable compensation.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Allowable compensation. 295.21 Section 295.21 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT... no-cost crisis counseling services available in the community. FEMA will not reimburse for treatment...

  17. Executive Compensation and the Cost of Debt

    NARCIS (Netherlands)

    Kabir, Rezaul; Liu, Hao; Veld-Merkoulova, Yulia V.

    2013-01-01

    This study examines how different components of executive compensation affect the cost of debt. We find that debt-like and equity-like pay components have differing effects: an increase in defined benefit pensions is associated with lower bond yield spread, while higher share holdings lead to higher

  18. The Compensation Act 2006 and School Trips

    Science.gov (United States)

    Hunter-Jones, John

    2006-01-01

    The Compensation Act 2006 received its Royal Assent on 25 July 2006. The Act allows the courts to have regard to the social utility of "desirable activities", including school trips, in considering negligence claims. The article reviews the law of negligence as it affects teachers of the very young and considers the possible impact of…

  19. 22 CFR 96.34 - Compensation.

    Science.gov (United States)

    2010-04-01

    ... actually rendered, taking into account the country in which the adoption services are provided and norms... norms are known to the accrediting entity; the location, number, and qualifications of staff; workload requirements; budget; and size of the agency or person. (e) Any other compensation paid to the agency's or...

  20. Flywheels Would Compensate for Rotor Imbalance

    Science.gov (United States)

    Hrastar, J. A. S.

    1982-01-01

    Spinning flywheels within rotor can null imbalance forces in rotor. Flywheels axes are perpendicular to each other and to rotor axis. Feedback signals from accelerometers or strain gages in platform control flywheel speeds and rotation directions. Concept should be useful for compensating rotating bodies on Earth. For example, may be applied to large industrial centrifuge, particularly if balance changes during operation.

  1. Paraxial charge compensator for electron cryomicroscopy

    International Nuclear Information System (INIS)

    Berriman, John A.; Rosenthal, Peter B.

    2012-01-01

    We describe a multi-hole condenser aperture for the production of several electron beams in the transmission electron microscope (TEM) making it possible to simultaneously image and irradiate spatially separated regions of a specimen. When the specimen is a thin film of vitreous ice suspended over a holey carbon film, simultaneous irradiation of the adjacent carbon support with the off-axis beam compensates for some of the effects of charging in the image formed by a beam irradiating only the ice. Because the intervening region is not irradiated, charge-neutralization of frozen-hydrated specimens can occur by a through-space mechanism such as the emission of secondary electrons from a grounded carbon support film. We use paraxial charge compensation (PCC) to control the amount of charge build-up on the specimen and observe the effects of charge on images. The multi-hole aperture thus provides a tool for investigating the mechanism of charging and charge mitigation during the imaging of radiation sensitive biological specimens by cryomicroscopy. -- Highlights: ► A multi-hole condenser aperture produces multiple (paraxial) beams in TEM. ► Paraxial charge compensation is used to study electron-optical effects of charging. ► Emission of secondary electrons controls charging by a through space mechanism. ► Paraxial beams compensate for charging effects in frozen-hydrated specimens.

  2. Feedback loop compensates for rectifier nonlinearity

    Science.gov (United States)

    1966-01-01

    Signal processing circuit with two negative feedback loops rectifies two sinusoidal signals which are 180 degrees out of phase and produces a single full-wave rectified output signal. Each feedback loop incorporates a feedback rectifier to compensate for the nonlinearity of the circuit.

  3. Compensation Services Advisor | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Job Summary The Compensation Services Advisor is accountable for the effective ... Coordinates the annual Performance Review and Assessment System ... by IDRC and the broader financial and social implications of working in Canada. ... in areas such as mortgages, credit and so on to individuals not accustomed to ...

  4. Wavefront compensation applied to AVLIS laser systems

    International Nuclear Information System (INIS)

    Gonsiorowski, T.; Wirth, A.

    1995-01-01

    The efficiency of an AVLIS system depends upon the power density and uniformity of the laser system. Because of wavefront aberrations the realized beam quality is not ideal. Wavefront compensation provides a means to improve beam quality and system efficiency. (author)

  5. Software compensation in particle flow reconstruction

    Energy Technology Data Exchange (ETDEWEB)

    Tran, Huong Lan; Krueger, Katja; Sefkow, Felix [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Green, Steven; Marshall, John; Thomson, Mark [Cavendish Laboratory, Cambridge (United Kingdom); Simon, Frank [Max-Planck-Institut fuer Physik, Muenchen (Germany)

    2017-10-15

    The particle flow approach to calorimetry benefits from highly granular calorimeters and sophisticated software algorithms in order to reconstruct and identify individual particles in complex event topologies. The high spatial granularity, together with analogue energy information, can be further exploited in software compensation. In this approach, the local energy density is used to discriminate electromagnetic and purely hadronic sub-showers within hadron showers in the detector to improve the energy resolution for single particles by correcting for the intrinsic non-compensation of the calorimeter system. This improvement in the single particle energy resolution also results in a better overall jet energy resolution by improving the energy measurement of identified neutral hadrons and improvements in the pattern recognition stage by a more accurate matching of calorimeter energies to tracker measurements. This paper describes the software compensation technique and its implementation in particle flow reconstruction with the Pandora Particle Flow Algorithm (PandoraPFA). The impact of software compensation on the choice of optimal transverse granularity for the analogue hadronic calorimeter option of the International Large Detector (ILD) concept is also discussed.

  6. Software compensation in particle flow reconstruction

    Energy Technology Data Exchange (ETDEWEB)

    Tran, Huong Lan; Krueger, Katja; Sefkow, Felix [Deutsches Elektronen-Synchrotron DESY, Hamburg (Germany); Green, Steven; Marshall, John; Thomson, Mark [Cavendish Laboratory, Cambridge (United Kingdom); Simon, Frank [Max-Planck-Institut fuer Physik, Muenchen (Germany)

    2017-10-15

    The particle flow approach to calorimetry benefits from highly granular calorimeters and sophisticated software algorithms in order to reconstruct and identify individual particles in complex event topologies. The high spatial granularity, together with analogue energy information, can be further exploited in software compensation. In this approach, the local energy density is used to discriminate electromagnetic and purely hadronic sub-showers within hadron showers in the detector to improve the energy resolution for single particles by correcting for the intrinsic non-compensation of the calorimeter system. This improvement in the single particle energy resolution also results in a better overall jet energy resolution by improving the energy measurement of identified neutral hadrons and improvements in the pattern recognition stage by a more accurate matching of calorimeter energies to tracker measurements. This paper describes the software compensation technique and its implementation in particle flow reconstruction with the Pandora Particle Flow Algorithm (PandoraPFA). The impact of software compensation on the choice of optimal transverse granularity for the analogue hadronic calorimeter option of the International Large Detector (ILD) concept is also discussed. (orig.)

  7. Software compensation in particle flow reconstruction

    International Nuclear Information System (INIS)

    Tran, Huong Lan; Krueger, Katja; Sefkow, Felix; Green, Steven; Marshall, John; Thomson, Mark; Simon, Frank

    2017-10-01

    The particle flow approach to calorimetry benefits from highly granular calorimeters and sophisticated software algorithms in order to reconstruct and identify individual particles in complex event topologies. The high spatial granularity, together with analogue energy information, can be further exploited in software compensation. In this approach, the local energy density is used to discriminate electromagnetic and purely hadronic sub-showers within hadron showers in the detector to improve the energy resolution for single particles by correcting for the intrinsic non-compensation of the calorimeter system. This improvement in the single particle energy resolution also results in a better overall jet energy resolution by improving the energy measurement of identified neutral hadrons and improvements in the pattern recognition stage by a more accurate matching of calorimeter energies to tracker measurements. This paper describes the software compensation technique and its implementation in particle flow reconstruction with the Pandora Particle Flow Algorithm (PandoraPFA). The impact of software compensation on the choice of optimal transverse granularity for the analogue hadronic calorimeter option of the International Large Detector (ILD) concept is also discussed.

  8. 31 CFR 28.515 - Compensation.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Compensation. 28.515 Section 28.515 Money and Finance: Treasury Office of the Secretary of the Treasury NONDISCRIMINATION ON THE BASIS OF... a rate less than that paid to employees of the opposite sex for equal work on jobs the performance...

  9. Wire compensation: Performance, SPS MDs, pulsed system

    CERN Document Server

    Dorda, U

    2008-01-01

    A wire compensation (BBLR) scheme has been proposed in order to improve the long range beam-beam performance of the nominal LHC and its phase 1 and phase 2 upgrades[1]. In this paper we present experimental experience of the CERN SPS wires (BBLR) and report on progress with the RF BBLR.

  10. Compensation techniques for operational amplifier bias current

    International Nuclear Information System (INIS)

    Silva, M.S.

    1981-01-01

    Two techniques are proposed for the compensation of the input current on operational amplifiers that can be used on inverting and non-inverting configurations. A qualitative analysis of temperature drift problems is made, and as a practical application, the construction of a voltage follower for high impedance measurements is presented. (Author) [pt

  11. Paraxial charge compensator for electron cryomicroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Berriman, John A. [Division of Physical Biochemistry, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA (United Kingdom); Rosenthal, Peter B., E-mail: peter.rosenthal@nimr.mrc.ac.uk [Division of Physical Biochemistry, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA (United Kingdom)

    2012-05-15

    We describe a multi-hole condenser aperture for the production of several electron beams in the transmission electron microscope (TEM) making it possible to simultaneously image and irradiate spatially separated regions of a specimen. When the specimen is a thin film of vitreous ice suspended over a holey carbon film, simultaneous irradiation of the adjacent carbon support with the off-axis beam compensates for some of the effects of charging in the image formed by a beam irradiating only the ice. Because the intervening region is not irradiated, charge-neutralization of frozen-hydrated specimens can occur by a through-space mechanism such as the emission of secondary electrons from a grounded carbon support film. We use paraxial charge compensation (PCC) to control the amount of charge build-up on the specimen and observe the effects of charge on images. The multi-hole aperture thus provides a tool for investigating the mechanism of charging and charge mitigation during the imaging of radiation sensitive biological specimens by cryomicroscopy. -- Highlights: Black-Right-Pointing-Pointer A multi-hole condenser aperture produces multiple (paraxial) beams in TEM. Black-Right-Pointing-Pointer Paraxial charge compensation is used to study electron-optical effects of charging. Black-Right-Pointing-Pointer Emission of secondary electrons controls charging by a through space mechanism. Black-Right-Pointing-Pointer Paraxial beams compensate for charging effects in frozen-hydrated specimens.

  12. 7 CFR 301.74-5 - Compensation.

    Science.gov (United States)

    2010-01-01

    ... exclusively at farmers markets or similar outlets that require orchard owners to sell only fruit that they... of commercial stone fruit orchards. Owners of commercial stone fruit orchards are eligible to receive... marketers. Orchard owners eligible for compensation under this paragraph who market all fruit they produce...

  13. Women's Experience in the Workers' Compensation System.

    Science.gov (United States)

    Guthrie, Robert; Jansz, Janis

    2006-09-01

    Gender differences is a question of major importance within workers' compensation given the increased role of women in the workforce over the past several decades. This article reviews literature relating to women's experiences following work injury. An Australian study is used as background to exploring the broad issue of the question of gender equity in workers' compensation. In doing so it takes account of historical, legal and medical issues. Women's experience in the workers' compensation system is different to that of men due to a range of factors. It is heavily influenced by the industrial environment in which they work. Women are paid less than men in many instances and work in gender-segregated circumstances, which often reduces their industrial bargaining power. Women also suffer different forms of injury and disease to men because of the different nature of their work. The Australian experience suggests that as a consequence of the combination of lesser industrial bargaining power, lower wages and differing forms of injury and disease women often receive less than men in compensation payments, struggle to obtain equity in the dispute resolution process and experience greater difficulties in returning to work following injury or disease.

  14. 1979-1980 Administrative Compensation Survey.

    Science.gov (United States)

    Bryan, James; And Others

    Results of the 1979-80 Administrative Compensation Survey Report conducted by the College and University Personnel Association are presented. The survey is based on 1,383 responses and covers 77 positions. Salary data are indicated for the median and interquartile range for each position. Data are provided by type of institution, by size of…

  15. 1981-1982 Administrative Compensation Survey.

    Science.gov (United States)

    Miller, Jan P.; And Others

    Results of the College and University Personnel Association's 1981-1982 Administrative Compensation Survey, which provides data on 94 positions, is presented. Questionnaires were sent to 2,770 higher education institutions, and 1,391 usable responses were obtained. Salary data indicate the median and the interquartile range for each position and…

  16. Administrative Compensation Survey, 1983-84.

    Science.gov (United States)

    Benedict, Forest C.; And Others

    Results of the College and University Personnel Association's 1983-1984 Administrative Compensation Survey, which provides data on 99 positions, is presented. Questionnaires were sent to 2,856 higher education institutions, and 1,515 usable responses were obtained. Salary data indicate the median and the interquartile range for each position and…

  17. 77 FR 5381 - Plum Pox Compensation

    Science.gov (United States)

    2012-02-03

    ... orchards, including direct marketers, and fruit tree nurseries. Compensation payments are provided to... stone fruit growers and direct marketers and in fruit tree nurseries, along with the effects of... economic losses experienced by grove owners, direct marketers, and nursery owners who are subject to an EAN...

  18. Attitudes toward the dubious compensation claim.

    Science.gov (United States)

    LEGGO, C

    1951-07-01

    Laws providing for compensation of workmen for occupational injury are a powerful socio-economic force. In settlement of compensation claims the goal, difficult to achieve, is fairness to employee, employer and insurance carrier. Often, medical, legal, economic and social considerations conflict with one another. A "fact" in one field may not be considered so in another. Since medical data and testimony often guide the ultimate decision of a compensation claim, the physician's attitude is a large factor not only immediately and directly in determination of the case at hand but, perhaps more important, in the ultimate direction of the socio-economic forces which spring from the sum of all such determinations. To perpetuate the good in workmen's compensation laws, the next generation of physicians-and of lawyers and business administrators as well, for they, too, are involved-ought to have basic training in the social sciences in order that they may have a broad rather than a segmental view of the problems with which they deal.

  19. Hybrid VAR compensator with improved efficiency

    Directory of Open Access Journals (Sweden)

    V. V. Burlaka

    2015-03-01

    Full Text Available In modern electrical networks thyristor-switched capacitors (TSC are most used devices for VAR compensation. These devices don’t contain rotating parts and mechanical contacts, provide a stepwise control of reactive power and no generation of harmonics to the network. However, with the help of TSC it’s not possible to ensure smooth control of reactive power and capacitor banks (CB are exposed to the negative impact of higher harmonic components of the network voltage. Hybrid VAR compensator don’t have such drawbacks. It consists of active filter (AF and capacitor bank with discrete regulation. The main drawback of such systems is the necessity of accessing all six terminals of CB, while most of them are manufactured with three terminals, internally delta-connected. In the article, the topology and control system of hybrid VAR compensator free from beforementioned drawback, is proposed. The control system provides operating modes of overcompensation or undercompensation reactive power. VAR distribution regulator performs redistribution of reactive power between active filter and capacitor banks with the condition to minimize active filter’s power. Scheme of the hybrid VAR compensator, which includes a three-phase three-terminal delta-connected capacitor banks, is shown. Proposed approach allows to provide smooth control of reactive power, isolate the capacitor bank from harmonic currents and use a more effective low-voltage power components

  20. A Study on the Effectiveness of the Manufacture of Compensator and Setup Position for Total Body Irradiation Using Computed Tomography-simulator's Images

    International Nuclear Information System (INIS)

    Lee, Woo Suk; Kim, Dae Sup; Park, Seong Ho; Yun, In Ha; Back, Geum Mun; Kim, Jeong Man

    2005-01-01

    We should use a computed tomography-simulator for the body measure and compensator manufacture process was practiced with TBI's positioning in process and to estimate the availability. Patient took position that lied down. and got picture through computed tomography-simulator. This picture transmitted to Somavision and measured about body measure point on the picture. Measurement was done with skin, and used the image to use measure the image about lungs. We decided thickness of compensator through value that was measured by the image. Also, We decided and confirmed position of compensator through image. Finally, We measured dosage with TLD in the treatment department. About thickness at body measure point. we could find difference of 1-2 cm relationship general measure and image measure. General measure and image measure of body length was seen difference of 3-4 cm. Also, we could paint first drawing of compensator through the image. The value of dose measurement used TLD on head, neck, axilla, chest(lungs inclusion), knee region were measured by 92-98% and abdomen, pelvis, inquinal region, feet region were measured by 102-109%. It was useful for TBI's positioning to use an image of computed tomography-simulator in the process. There was not that is difference of body thickness measure point, but measure about length was achieved definitely. Like this, manufacture of various compensator that consider body density if use image is available. Positioning of compensator could be done exactly, and produce easily without shape of compensator is courted Positioning in the treatment department could shortened overall 15 minute time. and reduce compensator manufacture time about 15 minutes.

  1. Nature of gene action for fruit quality characters of tomato (Solanum ...

    African Journals Online (AJOL)

    Prof. P. Hazra

    2013-05-15

    May 15, 2013 ... additive x additive type non-allelic interaction with negative sign for the characters, which will hinder ..... artificial gene dosage series in tomato to study the mechanisms by ... physical properties affected by food processing.

  2. Modifier Genes for Mouse Phosphatidylinositol Transfer Protein alpha (vibrator) That Bypass Juvenile Lethality

    NARCIS (Netherlands)

    Concepcion, Dorothy; Johannes, Frank; Lo, Yuan Hung; Yao, Jay; Fong, Jerry; Hamilton, Bruce A.

    Phosphatidylinositol transfer proteins (PITPs) mediate lipid signaling and membrane trafficking in eukaryotic cells. Loss-of-function mutations of the gene encoding PITP alpha in mice result in a range of dosage-sensitive phenotypes, including neurological dysfunction, neurodegeneration, and

  3. Exploring the importance of different items as reasons for leaving emergency medical services between fully compensated, partially compensated, and non-compensated/volunteer samples.

    Science.gov (United States)

    Blau, Gary; Chapman, Susan; Gibson, Gregory; Bentley, Melissa A

    2011-01-01

    The purpose of our study was to investigate the importance of different items as reasons for leaving the Emergency Medical Service (EMS) profession. An exit survey was returned by three distinct EMS samples: 127 full compensated, 45 partially compensated and 72 non-compensated/volunteer respondents, who rated the importance of 17 different items for affecting their decision to leave EMS. Unfortunately, there were a high percentage of "not applicable" responses for 10 items. We focused on those seven items that had a majority of useable responses across the three samples. Results showed that the desire for better pay and benefits was a more important reason for leaving EMS for the partially compensated versus fully compensated respondents. Perceived lack of advancement opportunity was a more important reason for leaving for the partially compensated and volunteer groups versus the fully compensated group. Study limitations are discussed and suggestions for future research offered.

  4. 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 ...

  5. Determination of the mechanical properties of solid and cellular polymeric dosage forms by diametral compression.

    Science.gov (United States)

    Blaesi, Aron H; Saka, Nannaji

    2016-07-25

    At present, the immediate-release solid dosage forms, such as the oral tablets and capsules, are granular solids. They release drug rapidly and have adequate mechanical properties, but their manufacture is fraught with difficulties inherent in processing particulate matter. Such difficulties, however, could be overcome by liquid-based processing. Therefore, we have recently introduced polymeric cellular (i.e., highly porous) dosage forms prepared from a melt process. Experiments have shown that upon immersion in a dissolution medium, the cellular dosage forms with polyethylene glycol (PEG) as excipient and with predominantly open-cell topology disintegrate by exfoliation, thus enabling rapid drug release. If the volume fraction of voids of the open-cell structures is too large, however, their mechanical strength is adversely affected. At present, the common method for determining the tensile strength of brittle, solid dosage forms (such as select granular forms) is the diametral compression test. In this study, the theory of diametral compression is first refined to demonstrate that the relevant mechanical properties of ductile and cellular solids (i.e., the elastic modulus and the yield strength) can also be extracted from this test. Diametral compression experiments are then conducted on PEG-based solid and cellular dosage forms. It is found that the elastic modulus and yield strength of the open-cell structures are about an order of magnitude smaller than those of the non-porous solids, but still are substantially greater than the stiffness and strength requirements for handling the dosage forms manually. This work thus demonstrates that melt-processed polymeric cellular dosage forms that release drug rapidly can be designed and manufactured to have adequate mechanical properties. Copyright © 2016. Published by Elsevier B.V.

  6. Semi-solid dosage form of clonazepam for rapid oral mucosal absorption.

    Science.gov (United States)

    Sakata, Osamu; Machida, Yoshiharu; Onishi, Hiraku

    2011-07-01

    In order to obtain an alternative to the intravenous (i.v.) dosage form of clonazepam (CZ), an oral droplet formulation of CZ was developed previously; however, the droplet was physically unstable. Therefore, in the present study, it was attempted to develop an easily-handled dosage form, which was more physically stable and allowed rapid drug absorption from oral mucosa. A semi-solid dosage form, composed of polyethylene glycol 1500 (PEG), CZ, and oleic acid (OA) at 37/1/2 (w/w) and named PEG/CZ/OA, and a semi-solid dosage form containing PEG and CZ at 39/1 (w/w), called PEG/CZ, were prepared. Their physical stability in air at room temperature and oral mucosal absorption in rats were investigated. The semi-solid dosage forms were much more stable physically than the droplet, that is, no recrystallization of CZ was observed for at least 8 days. The effective concentration for humans and rats (20 ng/mL or more) was achieved within 30 min after buccal administration for both PEG/CZ/OA and PEG/CZ. The plasma concentration increased gradually and less varied at each time point for PEG/CZ/OA. PEG/CZ/OA was found to show more rapid and higher absorption of CZ in buccal administration than in sublingual administration. Buccal administration with the semi-solid dosage PEG/CZ with or without OA was suggested to be a possibly useful novel dosage form as an alternative to i.v. injection.

  7. Intrathecal baclofen in multiple sclerosis and spinal cord injury: complications and long-term dosage evolution.

    Science.gov (United States)

    Draulans, Nathalie; Vermeersch, Kristof; Degraeuwe, Bart; Meurrens, Tom; Peers, Koen; Nuttin, Bart; Kiekens, Carlotte

    2013-12-01

    To investigate the long-term dosage evolution and complication rate of intrathecal baclofen use in multiple sclerosis and spinal cord injury patients, based on a large population with a long follow-up. Retrospective data analysis. Academic hospital. Patients with multiple sclerosis (n = 81) or spinal cord injury (n = 49) having an intrathecal baclofen pump implanted at the University Hospitals Leuven between 1988 and 2009. Medical records review of included patients in August 2010. Complications linked to intrathecal baclofen therapy. Daily baclofen dosage after 3 and 6 months, and yearly thereafter. Data on dosage evolution were analysed using a mixed-effect linear model. In 130 patients with a mean follow-up of 63 months, comprising 797 pump years, 104 complications were recorded. This corresponds to a complication rate of 0.011 per month, equally divided among both groups. Seventy-eight of these complications were catheter related. The mean dosage of baclofen stabilizes two years after implantation at 323 µg/day in the multiple sclerosis population. In spinal cord injury patients the daily dose only stabilizes after five years at a significantly higher dosage (504 µg/day). No significant increase in dosage is seen in the long term. In multiple sclerosis and spinal cord injury patients, intrathecal baclofen therapy has a complication rate of 1% per month. Complications are mainly due to catheter-related problems (74%). The intrathecal baclofen dosage stabilizes in the long term, indicating that long-term tolerance, defined as progressive diminution of the susceptibility to the effects of a drug, is not present.

  8. Deformation compensation in dynamic tomography; Compensation de deformations en tomographie dynamique

    Energy Technology Data Exchange (ETDEWEB)

    Desbat, L. [Universite Joseph Fourier, UMR CNRS 5525, 38 - Grenoble (France); Roux, S. [Universite Joseph Fourier, TIMC-IMAG, In3S, Faculte de Medecine, 38 - Grenoble (France)]|[CEA Grenoble, Lab. d' Electronique et de Technologie de l' Informatique (LETI), 38 (France); Grangeat, P. [CEA Grenoble, Lab. d' Electronique et de Technologie de l' Informatique (LETI), 38 (France)

    2005-07-01

    This work is a contribution to the compensation of motion in tomography. New classes of deformation are proposed, that compensates analytically by an algorithm of a F.B.P. type reconstruction. This work makes a generalisation of the known results for affine deformations, in parallel geometry and fan-beam, to deformation classes of infinite dimension able to include strong non linearities. (N.C.)

  9. Re-Planning for Compensator-Based IMRT with Original Compensators

    International Nuclear Information System (INIS)

    Zhang, Geoffrey; Feygelman, Vladimir; Stevens, Craig; Li Weiqi; Leuthold, Susan; Springett, Gregory; Hoffe, Sarah

    2011-01-01

    Compared with multileaf collimator (MLC)-based intensity-modulated radiotherapy (IMRT) for moving targets, compensator-based IMRT has advantages such as shorter beam-on time, fewer monitor units with potentially decreased secondary carcinogenesis risk, better optimization-to-deliverable dose conversion, and often better dose conformity. Some of the disadvantages include additional time for the compensators to be built and delivered, as well as extra cost. Patients undergoing treatment of abdominal cancers often experience weight loss. It would be necessary to account for this change in weight with a new plan and a second set of compensators. However, this would result in treatment delays and added costs. We have developed a method to re-plan the patient using the same set of compensators. Because the weight changes seen with the treatment of abdominal cancers are usually relatively small, a new 4D computed tomography (CT) acquired in the treatment position with markers on the original isocenter tattoos can be registered to the original planning scan. The contours of target volumes from the original scans are copied to the new scan after fusion. The original compensator set can be used together with a few field-in-field (FiF) beams defined by the MLC (or beams with cerrobend blocks for accelerators not equipped with a MLC). The weights of the beams with compensators are reduced so that the FiF or blocked beams can be optimized to mirror the original plan and dose distribution. Seven abdominal cancer cases are presented using this technique. The new plan on the new planning CT images usually has the same dosimetric quality as the original. The target coverage and dose uniformity are improved compared with the plan without FiF/block modification. Techniques combining additional FiF or blocked beams with the original compensators optimize the treatment plans when patients lose weight and save time and cost compared with generating plans with a new set of compensators.

  10. Global patterns and trends in human-wildlife conflict compensation.

    Science.gov (United States)

    Ravenelle, Jeremy; Nyhus, Philip J

    2017-12-01

    Human-wildlife conflict is a major conservation challenge, and compensation for wildlife damage is a widely used economic tool to mitigate this conflict. The effectiveness of this management tool is widely debated. The relative importance of factors associated with compensation success is unclear, and little is known about global geographic or taxonomic differences in the application of compensation programs. We reviewed research on wildlife-damage compensation to determine geographic and taxonomic gaps, analyze patterns of positive and negative comments related to compensation, and assess the relative magnitude of global compensation payments. We analyzed 288 publications referencing wildlife compensation and identified 138 unique compensation programs. These publications reported US$222 million (adjusted for inflation) spent on compensation in 50 countries since 1980. Europeans published the most articles, and compensation funding was highest in Europe, where depredation by wolves and bears was the most frequently compensated damage. Authors of the publications we reviewed made twice as many negative comments as positive comments about compensation. Three-quarters of the negative comments related to program administration. Conversely, three-quarters of the positive comments related to program outcomes. The 3 most common suggestions to improve compensation programs included requiring claimants to employ damage-prevention practices, such as improving livestock husbandry or fencing of crops to receive compensation (n = 25, 15%); modifying ex post compensation schemes to some form of outcome-based performance payment (n = 21, 12%); and altering programs to make compensation payments more quickly (n = 14, 8%). We suggest that further understanding of the strengths and weaknesses of compensation as a conflict-mitigation tool will require more systematic evaluation of the factors driving these opinions and that differentiating process and outcomes and understanding

  11. The Nature of Whiplash in a Compensable Environment: Injury, Disability, Rehabilitation, and Compensation Systems.

    Science.gov (United States)

    Connelly, Luke B

    2017-07-01

    Synopsis Whiplash is a compensable injury in many jurisdictions, but there is considerable heterogeneity in the compensation arrangements that apply across jurisdictions, even within some countries. These compensation schemes have, however, been subject to a common set of interrelated concerns, chiefly concerning the incentives, behaviors, and outcomes that may arise when financial compensation for injuries is available to injured parties. This article provides a nontechnical overview of some of those concerns through the lens of economics: principally, insurance economics and health economics, including related subsets such as information economics and agency theory, as well as economics and the law. It notes that because it is generally infeasible to randomize the treatment (ie, compensation) via trials, analyses of observational data are necessary to discover more about the relationship between compensation and health outcomes. This poses the analytical challenge of discovering causal connections between phenomena from nonrandomized data sets. The present article calls for further research that would enable convincing causal interpretations of such relationships via the careful analysis of rich observational data sets using modern econometric methods. J Orthop Sports Phys Ther 2017;47(7):503-508. Epub 16 Jun 2017. doi:10.2519/jospt.2017.7533.

  12. US-LHC IR magnet error analysis and compensation

    International Nuclear Information System (INIS)

    Wei, J.; Ptitsin, V.; Pilat, F.; Tepikian, S.; Gelfand, N.; Wan, W.; Holt, J.

    1998-01-01

    This paper studies the impact of the insertion-region (IR) magnet field errors on LHC collision performance. Compensation schemes including magnet orientation optimization, body-end compensation, tuning shims, and local nonlinear correction are shown to be highly effective

  13. MTB-USDH Compensation Tracking System (MTB-CTS)

    Data.gov (United States)

    US Agency for International Development — MTB-USDH Compensation Tracking System: is the USDH Compensation Tracking System (MTB-CTS) to assist managers in monitoring their payroll costs for U.S. direct hires....

  14. The relationship between South African CEO compensation and ...

    African Journals Online (AJOL)

    1A study of corporate financial performance and CEO compensation by Firth, Lohne,. Ropstad .... requires both a qualitative and quantitative analysis. REMCOs, in ...... 'Executive compensation as an agency problem', Journal of. Economic ...

  15. A time averaged background compensator for Geiger-Mueller counters

    International Nuclear Information System (INIS)

    Bhattacharya, R.C.; Ghosh, P.K.

    1983-01-01

    The GM tube compensator described stores background counts to cancel an equal number of pulses from the measuring channel providing time averaged compensation. The method suits portable instruments. (orig.)

  16. Hyperintense acute reperfusion marker is associated with higher contrast agent dosage in acute ischaemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Ostwaldt, Ann-Christin; Schaefer, Tabea; Villringer, Kersten; Fiebach, Jochen B. [Charite Universitaetsmedizin Berlin, Academic Neuroradiology, Center for Stroke Research Berlin (CSB), Berlin (Germany); Rozanski, Michal; Ebinger, Martin [Charite Universitaetsmedizin Berlin, Academic Neuroradiology, Center for Stroke Research Berlin (CSB), Berlin (Germany); Charite Universitaetsmedizin, Department of Neurology, Berlin (Germany); Jungehuelsing, Gerhard J. [Stiftung des Buergerlichen Rechts, Juedisches Krankenhaus Berlin, Berlin (Germany)

    2015-11-15

    The hyperintense acute reperfusion marker (HARM) on fluid-attenuated inversion recovery (FLAIR) images is associated with blood-brain barrier (BBB) permeability changes. The aim of this study was to examine the influence of contrast agent dosage on HARM incidence in acute ischaemic stroke patients. We prospectively included 529 acute ischaemic stroke patients (204 females, median age 71 years). Patients underwent a first stroke-MRI within 24 hours from symptom onset and had a follow-up on day 2. The contrast agent Gadobutrol was administered to the patients for perfusion imaging or MR angiography. The total dosage was calculated as ml/kg body weight and ranged between 0.04 and 0.31 mmol/kg on the first examination. The incidence of HARM was evaluated on day 2 FLAIR images. HARM was detected in 97 patients (18.3 %). HARM incidence increased significantly with increasing dosages of Gadobutrol. Also, HARM positive patients were significantly older. HARM was not an independent predictor of worse clinical outcome, and we did not find an association with increase risk of haemorrhagic transformation. A higher dosage of Gadobutrol in acute stroke patients on initial MRI is associated with increased HARM incidence on follow-up. MRI studies on BBB should therefore standardize contrast agent dosages. (orig.)

  17. Dependence of surface smoothing, sputtering and etching phenomena on cluster ion dosage

    CERN Document Server

    Song, J H; Choi, W K

    2002-01-01

    The dependence of surface smoothing and sputtering phenomena of Si (1 0 0) solid surfaces irradiated by CO sub 2 cluster ions on cluster-ion dosage was investigated using an atomic force microscope. The flux and total ion dosage of impinging cluster ions at the acceleration voltage of 50 kV were fixed at 10 sup 9 ions/cm sup 2 s and were scanned from 5x10 sup 1 sup 0 to 5x10 sup 1 sup 3 ions/cm sup 2 , respectively. The density of hillocks induced by cluster ion impact was gradually increased with the dosage up to 5x10 sup 1 sup 1 ions/cm sup 2 , which caused that the irradiated surface became rough from 0.4 to 1.24 nm in root-mean-square roughness (sigma sub r sub m sub s). At the boundary of the ion dosage of 10 sup 1 sup 2 ions/cm sup 2 , the density of the induced hillocks was decreased and sigma sub r sub m sub s was about 1.21 nm, not being deteriorated further. At the dosage of 5x10 sup 1 sup 3 ions/cm sup 2 , the induced hillocks completely disappeared and the surface became very flat as much as sigma...

  18. Adrenal Insufficiency under Standard Dosage of Glucocorticoid Replacement after Unilateral Adrenalectomy for Cushing’s Syndrome

    Directory of Open Access Journals (Sweden)

    Kentaro Fujii

    2016-01-01

    Full Text Available Glucocorticoid replacement is needed for patients after adrenal surgery for Cushing’s syndrome; however, the adequate dosage is not easily determined. The patient was a 62-year-old woman who has had hypertension for 5 years and presented with heart failure due to hypertrophic cardiomyopathy. She consulted with us because of general fatigue, facial edema, and muscle weakness and was diagnosed with Cushing’s syndrome. A laparoscopic left adrenalectomy was performed, standard dosage of postoperative replacement was administered, and she was discharged with 30 mg/day of hydrocortisone (cortisol. However, she suffered from loss of appetite and was transferred to an emergency unit with the symptoms of adrenal insufficiency on postoperative day 15. After initial hydrocortisone replacement with 200 mg/day, the dosage was gradually decreased during hospitalization; however, reduction of hydrocortisone dosage lower than 60 mg/day was difficult because of nausea and fatigue. Her circadian cortisol profile after hydrocortisone administration showed delayed and lowered peaks, which suggested that hydrocortisone absorption in the intestine was impaired. Therefore, complicated heart failure may have led to the adrenal insufficiency in the patient. In such cases, we should consider postoperative administration of more than the standard dosage of hydrocortisone to avoid adrenal insufficiency after surgery for Cushing’s syndrome.

  19. Dosage-dependent non-linear effect of L-dopa on human motor cortex plasticity.

    Science.gov (United States)

    Monte-Silva, Katia; Liebetanz, David; Grundey, Jessica; Paulus, Walter; Nitsche, Michael A

    2010-09-15

    The neuromodulator dopamine affects learning and memory formation and their likely physiological correlates, long-term depression and potentiation, in animals and humans. It is known from animal experiments that dopamine exerts a dosage-dependent, inverted U-shaped effect on these functions. However, this has not been explored in humans so far. In order to reveal a non-linear dose-dependent effect of dopamine on cortical plasticity in humans, we explored the impact of 25, 100 and 200 mg of L-dopa on transcranial direct current (tDCS)-induced plasticity in twelve healthy human subjects. The primary motor cortex served as a model system, and plasticity was monitored by motor evoked potential amplitudes elicited by transcranial magnetic stimulation. As compared to placebo medication, low and high dosages of L-dopa abolished facilitatory as well as inhibitory plasticity, whereas the medium dosage prolonged inhibitory plasticity, and turned facilitatory plasticity into inhibition. Thus the results show clear non-linear, dosage-dependent effects of dopamine on both facilitatory and inhibitory plasticity, and support the assumption of the importance of a specific dosage of dopamine optimally suited to improve plasticity. This might be important for the therapeutic application of dopaminergic agents, especially for rehabilitative purposes, and explain some opposing results in former studies.

  20. Effects of pharmaceutical processing on pepsin activity during the formulation of solid dosage forms.

    Science.gov (United States)

    Kristó, Katalin; Pintye-Hódi, Klára

    2013-02-01

    The main aim of this study was to investigate the effects of pharmaceutical technological methods on pepsin activity during the formulation of solid dosage forms. The circumstances of direct compression and wet granulation were modeled. During direct compression, the heat and the compression force must be taken into consideration. The effects of these parameters were investigated in three materials (pure pepsin, and 1:1 (w/w) pepsin-tartaric acid and 1:1 (w/w) pepsin-citric acid powder mixtures). It was concluded that direct compression is appropriate for the formulation of solid dosage forms containing pepsin through application without acids or with acids at low compression force. The effects of wet granulation were investigated with a factorial design for the same three materials. The factors were time, temperature and moisture content. There was no significant effect of the factors when acids were not applied. Temperature was a significant factor when acids were applied. The negative effect was significantly higher for citric acid than for tartaric acid. It was found that wet granulation can be utilized for the processing of pepsin into solid dosage forms under well-controlled circumstances. The application of citric acid is not recommended during the formulation of solid dosage forms through wet granulation. A mathematically based optimization may be necessary for preformulation studies of the preparation of dosage forms containing sensitive enzymes.

  1. Sales compensation governance: the last frontier of corporate reform.

    Science.gov (United States)

    Gundy, Peter R; Gaeta, Elizabeth C

    2004-01-01

    The area of sales compensation has remained relatively untouched by recent pressures for compensation reform. This article highlights some of the ways that sales organizations stumble in managing their compensation programs, and why it takes more than a simple tactical fix to address these problems effectively. The authors describe a more structured governance framework that not only identifies and resolves key sales compensation issues, but ultimately safeguards the effectiveness and financial integrity of the sales organization itself.

  2. Zero energy buildings and mismatch compensation factors

    DEFF Research Database (Denmark)

    Lund, Henrik; Marszal, Anna Joanna; Heiselberg, Per

    2011-01-01

    This paper takes an overall energy system approach to analysing the mismatch problem of zero energy and zero emission buildings (ZEBs). The mismatch arises from hourly differences in energy production and consumption at the building level and results in the need for exchange of electricity via...... the public grid even though the building has an annual net-exchange of zero. This paper argues that, when looked upon from the viewpoint of the overall electricity supply system, a mismatch can be both negative and positive. Moreover, there are often both an element of levelling out mismatches between...... of the energy production unit. Based on historical data for the electricity supply area in western Denmark, this paper makes a first attempt to quantify mismatch compensation factors. The results indicate that such compensation factors are a little below one for buildings with photovoltaics (PV) and a little...

  3. Adaptive Engine Torque Compensation with Driveline Model

    Directory of Open Access Journals (Sweden)

    Park Jinrak

    2018-01-01

    Full Text Available Engine net torque is the total torque generated by the engine side, and includes the fuel combustion torque, the friction torque, and additionally the starter motor torque in case of hybrid vehicles. The engine net torque is utilized to control powertrain items such as the engine itself, the transmission clutch, also the engine clutch, and it must be accurate for the precise powertrain control. However, this net torque can vary with the engine operating conditions like the engine wear, the changes of the atmospheric pressure and the friction torque. Thus, this paper proposes the adaptive engine net torque compensator using driveline model which can cope with the net torque change according to engine operating conditions. The adaptive compensator was applied on the parallel hybrid vehicle and investigated via MATLAB Simcape Driveline simulation.

  4. Chromaticity compensation scheme for the Main Injector

    International Nuclear Information System (INIS)

    Bogacz, S.A.

    1993-05-01

    The current Main Injector lattice is studied in the context of full chromaticity compensation in the presence of the eddy current, saturation and the end-pack sextupole fields generated by the dipole magnets. Two families of correcting sextupole magnets are placed to compensate these fields and to adjust the chromaticity (in both planes) to some desired value. Variation of the dipole induced sextupole fields with the B-field (changing along a ramp) are modeled according to recent experimental measurements of the Main Injector dipole magnet Analysis of the required sextupole strengths is carried out along two realistic momentum ramps. The results of our calculation give quantitative insight into the requisite performance of the sextupole magnets

  5. Percentage compensation arrangements: suspect, but not illegal.

    Science.gov (United States)

    Fedor, F P

    2001-01-01

    Percentage compensation arrangements, in which a service is outsourced to a contractor that is paid in accordance with the level of its performance, are widely used in many business sectors. The HHS Office of Inspector General (OIG) has shown concern that these arrangements in the healthcare industry may offer incentives for the performance of unnecessary services or cause false claims to be made to Federal healthcare programs in violation of the antikickback statute and the False Claims Act. Percentage compensation arrangements can work and need not run afoul of the law as long as the healthcare organization carefully oversees the arrangement and sets specific safeguards in place. These safeguards include screening contractors, carefully evaluating their compliance programs, and obligating them contractually to perform within the limits of the law.

  6. Compensating for telecommunication delays during robotic telerehabilitation.

    Science.gov (United States)

    Consoni, Leonardo J; Siqueira, Adriano A G; Krebs, Hermano I

    2017-07-01

    Rehabilitation robotic systems may afford better care and telerehabilitation may extend the use and benefits of robotic therapy to the home. Data transmissions over distance are bound by intrinsic communication delays which can be significant enough to deem the activity unfeasible. Here we describe an approach that combines unilateral robotic telerehabilitation and serious games. This approach has a modular and distributed design that permits different types of robots to interact without substantial code changes. We demonstrate the approach through an online multiplayer game. Two users can remotely interact with each other with no force exchanges, while a smoothing and prediction algorithm compensates motions for the delay in the Internet connection. We demonstrate that this approach can successfully compensate for data transmission delays, even when testing between the United States and Brazil. This paper presents the initial experimental results, which highlight the performance degradation with increasing delays as well as improvements provided by the proposed algorithm, and discusses planned future developments.

  7. Phase Noise Compensation for OFDM Systems

    Science.gov (United States)

    Leshem, Amir; Yemini, Michal

    2017-11-01

    We describe a low complexity method for time domain compensation of phase noise in OFDM systems. We extend existing methods in several respects. First we suggest using the Karhunen-Lo\\'{e}ve representation of the phase noise process to estimate the phase noise. We then derive an improved datadirected choice of basis elements for LS phase noise estimation and present its total least square counterpart problem. The proposed method helps overcome one of the major weaknesses of OFDM systems. We also generalize the time domain phase noise compensation to the multiuser MIMO context. Finally we present simulation results using both simulated and measured phased noise. We quantify the tracking performance in the presence of residual carrier offset.

  8. Motion compensation via redundant-wavelet multihypothesis.

    Science.gov (United States)

    Fowler, James E; Cui, Suxia; Wang, Yonghui

    2006-10-01

    Multihypothesis motion compensation has been widely used in video coding with previous attention focused on techniques employing predictions that are diverse spatially or temporally. In this paper, the multihypothesis concept is extended into the transform domain by using a redundant wavelet transform to produce multiple predictions that are diverse in transform phase. The corresponding multiple-phase inverse transform implicitly combines the phase-diverse predictions into a single spatial-domain prediction for motion compensation. The performance advantage of this redundant-wavelet-multihypothesis approach is investigated analytically, invoking the fact that the multiple-phase inverse involves a projection that significantly reduces the power of a dense-motion residual modeled as additive noise. The analysis shows that redundant-wavelet multihypothesis is capable of up to a 7-dB reduction in prediction-residual variance over an equivalent single-phase, single-hypothesis approach. Experimental results substantiate the performance advantage for a block-based implementation.

  9. CGI delay compensation. [Computer Generated Image

    Science.gov (United States)

    Mcfarland, R. E.

    1986-01-01

    Computer-generated graphics in real-time helicopter simulation produces objectionable scene-presentation time delays. In the flight simulation laboratory at Ames Research Center, it has been determined that these delays have an adverse influence on pilot performance during agressive tasks such as nap of the earth (NOE) maneuvers. Using contemporary equipment, computer generated image (CGI) time delays are an unavoidable consequence of the operations required for scene generation. However, providing that magnitude distortions at higher frequencies are tolerable, delay compensation is possible over a restricted frequency range. This range, assumed to have an upper limit of perhaps 10 or 15 rad/sec, conforms approximately to the bandwidth associated with helicopter handling qualities research. A compensation algorithm is introduced here and evaluated in terms of tradeoffs in frequency responses. The algorithm has a discrete basis and accommodates both a large, constant transport delay interval and a periodic delay interval, as associated with asynchronous operations.

  10. Design of a dynamic compensated temperature sensor

    International Nuclear Information System (INIS)

    Yan, Wu; Katz, E.M.; Kerlin, T.W.

    1991-01-01

    One important function of a temperature sensor in a nuclear power plant is to track changing process temperatures, but the sensor output lags the changing temperature. This lag may have a large influence when the sensor is used in control or safety systems. Therefore, it is advantageous to develop methods that increase the sensor response speed. The goal of this project is to develop a fast-responding temperature sensor, the dynamic compensated temperature sensor (DCTS), based on signal dynamic compensation technology. To verify the theoretical basis of the DCTS and incorporate the DCTS into a real temperature measurement process, several experiments have been performed. The DCTS is a simple approach that can decrease the temperature sensor's response time, and it can provide faster temperature signals to the nuclear power plant safety system

  11. Dosage-sensitive function of retinoblastoma related and convergent epigenetic control are required during the Arabidopsis life cycle.

    Directory of Open Access Journals (Sweden)

    Amal J Johnston

    2010-06-01

    Full Text Available The plant life cycle alternates between two distinct multi-cellular generations, the reduced gametophytes and the dominant sporophyte. Little is known about how generation-specific cell fate, differentiation, and development are controlled by the core regulators of the cell cycle. In Arabidopsis, RETINOBLASTOMA RELATED (RBR, an evolutionarily ancient cell cycle regulator, controls cell proliferation, differentiation, and regulation of a subset of Polycomb Repressive Complex 2 (PRC2 genes and METHYLTRANSFERASE 1 (MET1 in the male and female gametophytes, as well as cell fate establishment in the male gametophyte. Here we demonstrate that RBR is also essential for cell fate determination in the female gametophyte, as revealed by loss of cell-specific marker expression in all the gametophytic cells that lack RBR. Maintenance of genome integrity also requires RBR, because diploid plants heterozygous for rbr (rbr/RBR produce an abnormal portion of triploid offspring, likely due to gametic genome duplication. While the sporophyte of the diploid mutant plants phenocopied wild type due to the haplosufficiency of RBR, genetic analysis of tetraploid plants triplex for rbr (rbr/rbr/rbr/RBR revealed that RBR has a dosage-dependent pleiotropic effect on sporophytic development, trichome differentiation, and regulation of PRC2 subunit genes CURLY LEAF (CLF and VERNALIZATION 2 (VRN2, and MET1 in leaves. There were, however, no obvious cell cycle and cell proliferation defects in these plant tissues, suggesting that a single functional RBR copy in tetraploids is capable of maintaining normal cell division but is not sufficient for distinct differentiation and developmental processes. Conversely, in leaves of mutants in sporophytic PRC2 subunits, trichome differentiation was also affected and expression of RBR and MET1 was reduced, providing evidence for a RBR-PRC2-MET1 regulatory feedback loop involved in sporophyte development. Together, dosage-sensitive RBR

  12. Dosage of fission products in irradiated fuel treatment effluents (radio-chemical method); Dosage des produits de fission dans les effluents du traitement des combustibles irradies (methode radiochimique)

    Energy Technology Data Exchange (ETDEWEB)

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

    1966-07-01

    The dosage methods presented here are applicable to relatively long-lived fission products present in the effluents resulting from irradiated fuel treatment processes (Sr - Cs - Ce - Zr - Nb - Ru - I). The methods are based on the same principle: - addition of a carrying-over agent - chemical separation over several purification stages, - determination of the chemical yield by calorimetry - counting of an aliquot liquid portion. (author) [French] Les methodes de dosage presentees concernent les produits de fission a vie relativement longue presents dans les effluents de traitement des combustibles irradies (Sr - Cs - Ce - Zr - Nb - Ru - I). Elles sont toutes basees sur le meme principe: - addition d'entraineur, - separation chimique en plusieurs stades de purification, - determination du rendement chimique par calorimetrie, - comptage d'une aliquote liquide. (auteur)

  13. Dosage of cesium 137 in radioactive wastes by the application of sodium tetraphenylborate; Dosage du cesium 137 dans les effluents radioactifs par le tetraphenylborate de sodium

    Energy Technology Data Exchange (ETDEWEB)

    Testemale, G; Girault, J [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

    1967-07-01

    A simple technique of the dosage of {sup 137}Cs has been developed. The technique consists in the formation of cesium tetraphenyl borate, followed by a double extraction with isoamyl acetate, and washing of the organic phase. The counting of known parts of the cesium solution assaying of its purity by {gamma} spectrometry enable the determination of the {sup 137}Cs. The yield is about 98 per cent. (authors) [French] Une technique simple du dosage du {sup 137}Cs a ete mise au point. Elle consiste en une double extraction du tetraphenylborate de cesium forme par l'acetate d'isoamyle suivie d'un lavage de la phase organique. Des comptages sur des parties aliquotes de la solution de cesium et un controle de purete par spectrometrie {gamma} permettent la determination de cet element. Rendement: environ 98 pour cent. (auteurs)

  14. Glass scintillator pair for compensation neutron logging

    International Nuclear Information System (INIS)

    Ji Changsong; Li Xuezhi; Yiu Guangduo

    1985-01-01

    Glass scintillator pair types ST 1604 and ST 1605 for compensation of neutron logging is developed. The neutron sensitive material used is multistick lithium glass scintillators 3 and 4 mm in diameter respectively. Thermoneutron detection efficiencies are 50-60% and 100% respectively. The detection efficiency for 60 Co γ ray is lower than 0.3%. The type ST 1604 and ST 1605 may also be used as high sensitive neutron detectors in an intensive γ ray field

  15. Compensation for gravitational sag of bent mirror

    Energy Technology Data Exchange (ETDEWEB)

    Mao, Chengwen; Jiang, Hui; He, Yan; Liang, Dongxu; Lan, Xuying; Yan, Shuai [Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, CAS, Shanghai 201800 (China); Shu, De-ming [Advanced Photon Source, Argonne National Laboratory, Argonne, IL 60439 (United States); Li, Aiguo, E-mail: aiguo.li@sinap.ac.cn [Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, CAS, Shanghai 201800 (China)

    2017-05-01

    The gravitational sag of aspheric bent mirrors with face-up or face-down geometry produces a nonnegligible optical error. As an effective compensation, width optimization is used to match the combined effects of the gravitational and bending moments. This method is described by analytical expressions and two calculation algorithms. The results of theoretical simulations and finite element analysis have proved that this method can reduce the slope error resulting from gravitational sag to the level of nano radians.

  16. Compensation for gravitational sag of bent mirror

    International Nuclear Information System (INIS)

    Mao, Chengwen; Jiang, Hui; He, Yan; Liang, Dongxu; Lan, Xuying; Yan, Shuai; Shu, De-ming; Li, Aiguo

    2017-01-01

    The gravitational sag of aspheric bent mirrors with face-up or face-down geometry produces a nonnegligible optical error. As an effective compensation, width optimization is used to match the combined effects of the gravitational and bending moments. This method is described by analytical expressions and two calculation algorithms. The results of theoretical simulations and finite element analysis have proved that this method can reduce the slope error resulting from gravitational sag to the level of nano radians.

  17. Review of beamloading and compensation in synchrotrons

    International Nuclear Information System (INIS)

    Koscielniak, S.

    2001-10-01

    This paper discusses the theory and state-of-the-art applications of beam loading and compensation in synchrotrons. In particular it discusses the developments in the introduction of Magnetic Alloy (e.g. Finemet) cores and adoption of low Q cavities; e plus-e minus factories with very large current (e.g. KEKB, PEP II) and developments at p,p factories (e.g. LHC) and simulation codes

  18. Lithium compensation of GaAs

    International Nuclear Information System (INIS)

    Alexiev, D.; Tavendale, A.J.

    1988-08-01

    Defects generated following Li diffusion into GaAs were studied by optical deep level transient spectroscopy (ODLTS) and deep level transient spectroscopy (DLTS). In an exploratory series of experiments, the effect of Li diffusion on existing trap spectra, defect generation and as a means for the compensation of GaAs was studied. The variables included diffusion temperature, initial trap spectra of GaAs and annealing periods. Detailed measurements of trap energies were made

  19. 45 CFR 302.65 - Withholding of unemployment compensation.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 2 2010-10-01 2010-10-01 false Withholding of unemployment compensation. 302.65... HUMAN SERVICES STATE PLAN REQUIREMENTS § 302.65 Withholding of unemployment compensation. The State plan... State agency charged with the administration of the State unemployment compensation laws in accordance...

  20. An EMTDC Model of a Three Level four MVAR Compensator

    DEFF Research Database (Denmark)

    Rasmussen, Tonny Wederberg

    1997-01-01

    The paper discusses the dynamic characteristics of a three level ±4mvar solid state var compensator which is built and will be used for dynamic reactive power compensation in a wind farm. An investigation has been carried out of the influence of the compensator reactor, the DC intermediate voltage...

  1. 26 CFR 31.3231(e)-1 - Compensation.

    Science.gov (United States)

    2010-04-01

    .... (a) Definition—(1) The term compensation has the same meaning as the term wages in section 3121(a... regarding the inclusion of fringe benefits in compensation, see § 31.3121(a)-1T. (6) Split-dollar life... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Compensation. 31.3231(e)-1 Section 31.3231(e)-1...

  2. 20 CFR 701.401 - Coverage under state compensation programs.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Coverage under state compensation programs...; DEFINITIONS AND USE OF TERMS Coverage Under State Compensation Programs § 701.401 Coverage under state compensation programs. (a) Exclusions from the definition of “employee” under § 701.301(a)(12), and the...

  3. 12 CFR 918.2 - Annual directors' compensation policy.

    Science.gov (United States)

    2010-01-01

    ... § 918.3. At a minimum, such policy shall address the activities or functions for which attendance is... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Annual directors' compensation policy. 918.2... HOME LOAN BANKS BANK DIRECTOR COMPENSATION AND EXPENSES § 918.2 Annual directors' compensation policy...

  4. 29 CFR 505.3 - Prevailing minimum compensation.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Prevailing minimum compensation. 505.3 Section 505.3 Labor... HUMANITIES § 505.3 Prevailing minimum compensation. (a)(1) In the absence of an alternative determination...)(2) of this section, the prevailing minimum compensation required to be paid under the Act to the...

  5. 14 CFR 250.8 - Denied boarding compensation.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Denied boarding compensation. 250.8 Section... PROCEEDINGS) ECONOMIC REGULATIONS OVERSALES § 250.8 Denied boarding compensation. (a) Every carrier shall tender to a passenger eligible for denied boarding compensation, on the day and place the denied boarding...

  6. 39 CFR 3.2 - Compensation of Board.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Compensation of Board. 3.2 Section 3.2 Postal Service UNITED STATES POSTAL SERVICE THE BOARD OF GOVERNORS OF THE U.S. POSTAL SERVICE BOARD OF GOVERNORS (ARTICLE III) § 3.2 Compensation of Board. Section 202(a)(1) of title 39 provides for the compensation of...

  7. Assessment of Wetland Valuation Processes for Compensation in ...

    African Journals Online (AJOL)

    The issue of compensation has been debated in various fora; however compensation on wetland resources has not been given the primary place. Wetland valuation like any other type of valuation requires going through stages, which may be more complex than real estate valuation for compensation. This study therefore ...

  8. Critical Issues in Assessing Teacher Compensation. Backgrounder. No. 2638

    Science.gov (United States)

    Richwine, Jason; Biggs, Andrew G.

    2012-01-01

    A November 2011 Heritage Foundation report--"Assessing the Compensation of Public-School Teachers"--presented data on teacher salaries and benefits in order to inform debates about teacher compensation reform. The report concluded that public-school teacher compensation is far ahead of what comparable private-sector workers enjoy, and that…

  9. 31 CFR 30.0 - Executive compensation and corporate governance.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Executive compensation and corporate governance. 30.0 Section 30.0 Money and Finance: Treasury Office of the Secretary of the Treasury TARP STANDARDS FOR COMPENSATION AND CORPORATE GOVERNANCE § 30.0 Executive compensation and corporate governance...

  10. 20 CFR 10.15 - May compensation rights be waived?

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false May compensation rights be waived? 10.15 Section 10.15 Employees' Benefits OFFICE OF WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR FEDERAL... AMENDED General Provisions Rights and Penalties § 10.15 May compensation rights be waived? No employer or...

  11. 28 CFR 301.301 - Compensable and noncompensable injuries.

    Science.gov (United States)

    2010-07-01

    ... only those injuries suffered during the performance of an inmate's regular work assignment. However... institution, when such work has been approved by staff, may also be compensable. (c) Compensation is not paid... in any activity not related to the actual performance of the work assignment are not compensable, and...

  12. 34 CFR 75.519 - Dual compensation of staff.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Dual compensation of staff. 75.519 Section 75.519... by a Grantee? Project Staff § 75.519 Dual compensation of staff. A grantee may not use its grantee to pay a project staff member for time or work for which that staff member is compensated from some other...

  13. 10 CFR 39.53 - Energy compensation source.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Energy compensation source. 39.53 Section 39.53 Energy NUCLEAR REGULATORY COMMISSION LICENSES AND RADIATION SAFETY REQUIREMENTS FOR WELL LOGGING Equipment § 39.53 Energy compensation source. The licensee may use an energy compensation source (ECS) which is...

  14. Adaptive pseudolinear compensators of dynamic characteristics of automatic control systems

    Science.gov (United States)

    Skorospeshkin, M. V.; Sukhodoev, M. S.; Timoshenko, E. A.; Lenskiy, F. V.

    2016-04-01

    Adaptive pseudolinear gain and phase compensators of dynamic characteristics of automatic control systems are suggested. The automatic control system performance with adaptive compensators has been explored. The efficiency of pseudolinear adaptive compensators in the automatic control systems with time-varying parameters has been demonstrated.

  15. 38 CFR 3.658 - Offsets; dependency and indemnity compensation.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Offsets; dependency and... AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation Adjustments and Resumptions § 3.658 Offsets; dependency and indemnity compensation. (a) When an award of dependency and...

  16. 38 CFR 3.461 - Dependency and indemnity compensation.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Dependency and indemnity... ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation Apportionments § 3.461 Dependency...'s award of dependency and indemnity compensation will be apportioned where there is a child or...

  17. 38 CFR 3.702 - Dependency and indemnity compensation.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Dependency and indemnity... ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation Concurrent Benefits and Elections § 3.702 Dependency and indemnity compensation. (a) Right to elect. A person who is eligible for death...

  18. Installation of the sag compensator for HANARO

    International Nuclear Information System (INIS)

    Kim, Hyungkyoo; Jung, Hoansung; Lim, Incheol; Ahn, Gukhoon

    2008-01-01

    Electric power is essential for all industrial plants and also for nuclear facilities. HANARO is a research reactor which produces a 30 MW thermal power. HANARO is designed to be tripped automatically when interruptions or some extent of sags occur. HANARO has the reactor regulation system(RRS) and reactor protection system(RPS). HANARO is designed so as to be tripped automatically by insertion of control absorber rods(CAR) and shut-off rods(SOR). When voltage sag or momentary interruption occurs, the reactor has an unwanted trip by insertion of CARs and SORs even though the process systems are still in operation. HANARO was experienced in a nuisance trip as often as the unexpected voltage sag and/or momentary interruption occurs. We installed the voltage sag compensator on the power supply for CARs and SORs so as to prevent an unwanted trip. We undertook voltage sag assessment of the AC coil contactor which is a component of the power supply unit for the SORs. The compensation time is determined to be less than 1 sec in consideration of the reactor safety. This paper is concerned with the impact of the momentary interruption on the reactor and the effect of the voltage sag compensator. (author)

  19. Doppler Shift Compensation Schemes in VANETs

    Directory of Open Access Journals (Sweden)

    F. Nyongesa

    2015-01-01

    Full Text Available Over the last decade vehicle-to-vehicle (V2V communication has received a lot of attention as it is a crucial issue in intravehicle communication as well as in Intelligent Transportation System (ITS. In ITS the focus is placed on integration of communication between mobile and fixed infrastructure to execute road safety as well as nonsafety information dissemination. The safety application such as emergence alerts lays emphasis on low-latency packet delivery rate (PDR, whereas multimedia and infotainment call for high data rates at low bit error rate (BER. The nonsafety information includes multimedia streaming for traffic information and infotainment applications such as playing audio content, utilizing navigation for driving, and accessing Internet. A lot of vehicular ad hoc network (VANET research has focused on specific areas including channel multiplexing, antenna diversity, and Doppler shift compensation schemes in an attempt to optimize BER performance. Despite this effort few surveys have been conducted to highlight the state-of-the-art collection on Doppler shift compensation schemes. Driven by this cause we survey some of the recent research activities in Doppler shift compensation schemes and highlight challenges and solutions as a stock-taking exercise. Moreover, we present open issues to be further investigated in order to address the challenges of Doppler shift in VANETs.

  20. Optical compensation device for chest film radiography

    Science.gov (United States)

    Gould, Robert G.; Hasegawa, Bruce H.; DeForest, Sherman E.; Schmidt, Gregory W.; Hier, Richard G.

    1990-07-01

    Although chest radiography is the most commonly performed radiographic examination and one of the most valuable and cost-effective studies in medicine it suffers from relatively high error rates in both missing pathology and false positive interpretations. Detectability of lung nodules and other structures in underpenetrated regions of the chest film can be improved by both exposure and optical compensation but current compensation systems require major capital cost or a significant change in normal clinical practice. A new optical compensation system called the " Intelligent X-Ray Illuminator" (IXI) automatically and virtually instantaneously generates a patient-specific optical unsharp mask that is projected directly on a radiograph. When a radiograph is placed on the IXI which looks much like a conventional viewbox it acquires a low-resolution electronic image of this film from which the film transmission is derived. The transmission information is inverted and blurred in an image processor to form an unsharp mask which is fed into a spatial light modulator (SLM) placed between a light source and the radiograph. The SLM tailors the viewbox luminance by decreasing illumination to underexposed (i. e. transmissive) areas of the radiograph presenting the observer with an optically unsharp-masked image. The IXI uses the original radiograph and will allow it to be viewed on demand with conventional (uniform illumination. Potentially the IXI could introduce the known beneficial aspects of optical unsharp masking into radiology at low capital

  1. Installation of the sag compensator for HANARO

    International Nuclear Information System (INIS)

    Kim, H. K.; Jung, H. S.; Ahn, G. H.; Lim, I. C.

    2008-01-01

    Electric power is essential for all industrial plants and also for nuclear facilities. HANARO is a research reactor which produces a 30MW thermal power. HANARO is designed to be tripped automatically when interruptions or some extents of sags occur. HANARO has the reactor regulation system (RRS) and reactor protection system (RPS). HANARO is designed so as to tripped automatically by insertion of control absorber rods (CAR) and shut-off rods (SOR). When voltage or momentary interruption occurs, the reactor has an unwanted trip by insertion of CARs and SORs even though the process systems are still in operation. HANARO was experienced in a nuisance trip as often as the unexpected voltage sag and/or momentary interruption occurs. We installed the voltage sag compensator on the power supply for CARs and SORs so as to prevent an unwanted trip. We undertook voltage sag assessment of the AC coil contactor which is a component of the power supply unit for the SORs. The compensation time is determined to be less than 1 sec in consideration of the reactor safety. This paper is concerned with the impact of the momentary interruption on the reactor and the effect of the voltage sag compensator

  2. Installation of the sag compensator for HANARO

    International Nuclear Information System (INIS)

    Kim, Hyung Kyoo; Jung, Hoan Sung; Lim, In Cheol; Ahn, Guk Hoon

    2008-01-01

    Electric power is essential for all industrial plants and also for nuclear facilities. HANARO is a research reactor which produces a 30MW thermal power. HANARO is designed to be tripped automatically when interruptions or some extent of sags occur. HANARO has the reactor regulation system(RRs) and reactor protection system(RPS). HANARO is designed so as to be tripped automatically by insertion of control absorber rods(CAR) and shut off rods(SOR). When voltage sag or momentary interruption occurs, the reactor has an unwanted trip by insertion of CARs and SORs even though the process systems are still in operation. HANARO was experienced in a nuisance trip as often as the unexpected voltage sag and/or momentary interruption occurs. We installed the voltage sag compensator voltage sag assessment of the AC coil contactor which is a component of the power supply unit for the SORs. The compensation time is determined to be less than 1 sec in consideration of the reactor safety. This paper is concerned with the impact of the momentary interruption on the reactor and the effect of the voltage sag compensator

  3. Direct Lorentz force compensation flowmeter for electrolytes

    Energy Technology Data Exchange (ETDEWEB)

    Vasilyan, S., E-mail: suren.vasilyan@tu-ilmenau.de; Froehlich, Th. [Institute of Process Measurement and Sensor Technology, Ilmenau University of Technology, 98684 Ilmenau (Germany)

    2014-12-01

    A simplified method of contactless Lorentz force (LF) measurements for flow meters on electrolytes is described and realized. Modification and comparative representation are discussed against recently well-developed methods. Based on the catapult effect, that current carrying conductor experiences a repulsive force in a magnetic field, we demonstrate force measurement method of LF velocimetry applications by commonly known “electromagnetic force” compensation principle. Measurement approach through zero point stability is considered to minimize mechanical influences and avoid gravimetric uncertainties. Here, the current carrying wires are static fixed in the vicinity of magnet system at zero point stable position, while occurring deflection of magnets by electrolyte flow is compensated by external applied current within wires. Measurements performed by developed servo-system which drives control loop by means of optical position sensor for simplified (i) single wire and (ii) coil-like extended compensation schemes. Guided by experiments on electrolyte flow, we demonstrate the applicability of adopted principle for conductivities ranging from 2 to 20 S/m. Further improvements are discussed in agreement with the parameters of demonstration setup, straightforward theory, and experimental results. We argue that this method is potentially suitable for: (a) applications with higher conductivity like molten metal (order of 10{sup 6 }S/m) assuming spatial configuration of setup and (b) for lower range of conductivity (below 1 S/m) while this is strongly subject to stiffness of system and noise mainly mechanical and thermal radiations.

  4. Influence of prenatal EGCG treatment and Dyrk1a dosage reduction on craniofacial features associated with Down syndrome.

    Science.gov (United States)

    McElyea, Samantha D; Starbuck, John M; Tumbleson-Brink, Danika M; Harrington, Emily; Blazek, Joshua D; Ghoneima, Ahmed; Kula, Katherine; Roper, Randall J

    2016-11-15

    Trisomy 21 (Ts21) affects craniofacial precursors in individuals with Down syndrome (DS). The resultant craniofacial features in all individuals with Ts21 may significantly affect breathing, eating and speaking. Using mouse models of DS, we have traced the origin of DS-associated craniofacial abnormalities to deficiencies in neural crest cell (NCC) craniofacial precursors early in development. Hypothetically, three copies of Dyrk1a (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A), a trisomic gene found in most humans with DS and mouse models of DS, may significantly affect craniofacial structure. We hypothesized that we could improve DS-related craniofacial abnormalities in mouse models using a Dyrk1a inhibitor or by normalizing Dyrk1a gene dosage. In vitro and in vivo treatment with Epigallocatechin-3-gallate (EGCG), a Dyrk1a inhibitor, modulated trisomic NCC deficiencies at embryonic time points. Furthermore, prenatal EGCG treatment normalized some craniofacial phenotypes, including cranial vault in adult Ts65Dn mice. Normalization of Dyrk1a copy number in an otherwise trisomic Ts65Dn mice normalized many dimensions of the cranial vault, but did not correct all craniofacial anatomy. These data underscore the complexity of the gene–phenotype relationship in trisomy and suggest that changes in Dyrk1a expression play an important role in morphogenesis and growth of the cranial vault. These results suggest that a temporally specific prenatal therapy may be an effective way to ameliorate some craniofacial anatomical changes associated with DS.

  5. Asbestos-related occupational cancers compensated under the Industrial Accident Compensation Insurance in Korea.

    Science.gov (United States)

    Ahn, Yeon-Soon; Kang, Seong-Kyu

    2009-04-01

    Compensation for asbestos-related cancers occurring in occupationally-exposed workers is a global issue; this is also an issue in Korea. To provide basic information regarding compensation for workers exposed to asbestos, 60 cases of asbestos-related occupational lung cancer and mesothelioma that were compensated during 15 yr; from 1993 (the year the first case was compensated) to 2007 by the Korea Labor Welfare Corporation (KLWC) are described. The characteristics of the cases were analyzed using the KLWC electronic data and the epidemiologic investigation data conducted by the Occupational Safety and Health Research Institute (OSHRI) of the Korea Occupational Safety and Health Agency (KOSHA). The KLWC approved compensation for 41 cases of lung cancer and 19 cases of mesothelioma. Males accounted for 91.7% (55 cases) of the approved cases. The most common age group was 50-59 yr (45.0%). The mean duration of asbestos exposure for lung cancer and mesothelioma cases was 19.2 and 16.0 yr, respectively. The mean latency period for lung cancer and mesothelioma cases was 22.1 and 22.6 yr, respectively. The major industries associated with mesothelioma cases were shipbuilding and maintenance (4 cases) and manufacture of asbestos textiles (3 cases). The major industries associated with lung cancer cases were shipbuilding and maintenance (7 cases), construction (6 cases), and manufacture of basic metals (4 cases). The statistics pertaining to asbestos-related occupational cancers in Korea differ from other developed countries in that more cases of mesothelioma were compensated than lung cancer cases. Also, the mean latency period for disease onset was shorter than reported by existing epidemiologic studies; this discrepancy may be related to the short history of occupational asbestos use in Korea. Considering the current Korean use of asbestos, the number of compensated cases in Korea is expected to increase in the future but not as much as developed countries.

  6. Effect of Calcium Ions on the Disintegration of Enteric-Coated Solid Dosage Forms.

    Science.gov (United States)

    Al-Gousous, Jozef; Langguth, Peter

    2016-02-01

    To investigate the effect of calcium ions on the disintegration of enteric-coated dosage forms, disintegration testing was performed on enteric-coated aspirin tablets in the presence and absence of calcium in the test media. The results show that the presence of calcium ions retards the disintegration of enteric-coated dosage forms. This finding, which has not been reported in scientific literature, sheds light on the importance of conducting well-designed detailed investigations into the potential of calcium from dietary sources, calcium supplements, antacids, and/or phosphate binders affecting the absorption of drugs formulated into enteric-coated dosage forms. Moreover, it shows the necessity to investigate the potential of the occurrence of additional nutrient-excipient interactions. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  7. Histomorphological study of submandibulary glands of rats submitted to low dosage of X-radiation

    International Nuclear Information System (INIS)

    Navarro, Claudia Maria; Onofre, Mirian Aparecida; Chan, Carolina; Cordeiro, Rita de Cassis Loiola; Raveli, Dirceu Barnabe

    1996-01-01

    The minimal dosage of X-ray that is likely to induce cellular alterations is unknown and there are just a few reports with low dosage in odontologic literature. The authors developed a histomorphological analysis of the submandibulary glands of rat that received low dosage of X radiation. The body of the animals was covered with a lead lamin leaving the cervical area uncovered. The submandibular glands were exposed to 1,80 Gy of X-radiation in a single dose. After 24, 48, 72 hours, 7, 14 and 21 days the glands were excised, fixed and prepared for analysis in light microscopy. Mild degenerative changes and nuclear pleomorfism, mainly on the first three experimental periods were observed. (author)

  8. Optimal Antibiotic Dosage for Chronic Kidney Disease Patient: A Pharmacological Manual for Oral Clinicians.

    Science.gov (United States)

    Chidambaram, Ramasamy

    2015-01-01

    Chronic kidney disease, (CKD) a gradual and inevitable deterioration in renal function, is the disease with the most associations in dentistry. Dosage adjustment is one amongst the vital elements to be familiar with during their oral care. CKD patients take extended duration to filter out medications, therefore dosage must always be tailored under the supervision of nephrologist. The relished benefits from antibiotic could transform as anti-microbial resistance on their abuse and nephrotoxic when contraindicated drugs are encouraged. New patented drug belonging to oxazoliodine group has driven the researchers to handle the emerging AMR. The present communication discusses the pharmacological factors influencing in prescribing the antibiotics for CKD patient from the dentist's point of view. The formulas destined for calculating the optimal dosage of antibiotics have been documented to aid oral physicians.

  9. In situ experimental study for the optimization of chlorine dosage in seawater cooling systems

    Energy Technology Data Exchange (ETDEWEB)

    Nebot, E.; Casanueva, T.; Fernandez-Baston, M.M.; Sales, D. [Department of Chemical Engineering, Food Technology and Environmental Technologies, University of Cadiz (Spain); Casanueva, J.F. [Department of Thermal Engines, University of Cadiz (Spain)

    2006-11-15

    The paper details an in situ study for the evaluation of the evolution of fouling heat transfer resistance and to optimize the antifouling chlorine dosage at a 550MW power station. A portable pilot plant has been designed to simulate the steam surface condenser and used as an accurate fouling monitor that takes the seawater from the same intake point as the power station. This study includes fouling extraction and its characterization for different dosage patterns. The residual chlorine concentration at the cooling-water discharge from the power station is 0.2mg/l and has been considered appropriate for the prevention of the formation of fouling, because with this concentration approximately 90% reduction in the amount of fouling is obtained. Residual chlorine dosages lower than 0.2ppm could be effective in controlling fouling development if mechanical techniques of fouling control are also available. (author)

  10. On the exfoliating polymeric cellular dosage forms for immediate drug release.

    Science.gov (United States)

    Blaesi, Aron H; Saka, Nannaji

    2016-06-01

    The most prevalent pharmaceutical dosage forms at present-the oral immediate-release tablets and capsules-are granular solids. Though effective in releasing drug rapidly, development and manufacture of such dosage forms are fraught with difficulties inherent to particulate processing. Predictable dosage form manufacture could be achieved by liquid-based processing, but cast solid dosage forms are not suitable for immediate drug release due to their resistance to fluid percolation. To overcome this limitation, we have recently introduced cellular dosage forms that can be readily prepared from polymeric melts. It has been shown that open-cell structures comprising polyethylene glycol 8000 (PEG 8k) excipient and a drug exfoliate upon immersion in a dissolution medium. The drug is then released rapidly due to the large specific surface area of the exfoliations. In this work, we vary the molecular weight of the PEG excipient and investigate its effect on the drug release kinetics of structures with predominantly open-cell topology. We demonstrate that the exfoliation rate decreases substantially if the excipient molecular weight is increased from 12 to 100kg/mol, which causes the drug dissolution time to increase by more than a factor of ten. A model is then developed to elucidate the exfoliation behavior of cellular structures. Diverse transport processes are considered: percolation due to capillarity, diffusion of dissolution medium through the cell walls, and viscous flow of the saturated excipient. It is found that the lower exfoliation rate and the longer dissolution time of the dosage forms with higher excipient molecular weight are primarily due to the greater viscosity of the cell walls after fluid penetration. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. The effect of decreasing computed tomography dosage on radiostereometric analysis (RSA) accuracy at the glenohumeral joint.

    Science.gov (United States)

    Fox, Anne-Marie V; Kedgley, Angela E; Lalone, Emily A; Johnson, James A; Athwal, George S; Jenkyn, Thomas R

    2011-11-10

    Standard, beaded radiostereometric analysis (RSA) and markerless RSA often use computed tomography (CT) scans to create three-dimensional (3D) bone models. However, ethical concerns exist due to risks associated with CT radiation exposure. Therefore, the aim of this study was to investigate the effect of decreasing CT dosage on RSA accuracy. Four cadaveric shoulder specimens were scanned using a normal-dose CT protocol and two low-dose protocols, where the dosage was decreased by 89% and 98%. 3D computer models of the humerus and scapula were created using each CT protocol. Bi-planar fluoroscopy was used to image five different static glenohumeral positions and two dynamic glenohumeral movements, of which a total of five static and four dynamic poses were selected for analysis. For standard RSA, negligible differences were found in bead (0.21±0.31mm) and bony landmark (2.31±1.90mm) locations when the CT dosage was decreased by 98% (p-values>0.167). For markerless RSA kinematic results, excellent agreement was found between the normal-dose and lowest-dose protocol, with all Spearman rank correlation coefficients greater than 0.95. Average root mean squared errors of 1.04±0.68mm and 2.42±0.81° were also found at this reduced dosage for static positions. In summary, CT dosage can be markedly reduced when performing shoulder RSA to minimize the risks of radiation exposure. Standard RSA accuracy was negligibly affected by the 98% CT dose reduction and for markerless RSA, the benefits of decreasing CT dosage to the subject outweigh the introduced errors. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Study of thick, nuclear-compensated silicon detectors; Etude des detecteurs epais au silicium compense nucleairement

    Energy Technology Data Exchange (ETDEWEB)

    Le Coroller, Y. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1964-09-01

    A study is made here, from the point of view of the realization and the performance, of thick nuclear-compensated silicon detectors. After recalling the need for compensation and reviewing the existing methods, the author describes in detail the controlled realization of thick detectors by nuclear compensation from the theoretical and experimental points of view. The practical precautions which should be observed are given: control of the homogeneity of the starting material, control of the evolution of the compensation, elimination of parasitic processes. The performances of the detectors obtained are then studied: electrical characteristics (current, life-time) on the one hand, detection and spectrometry of penetrating radiations on the other hand. The results show, that the compensated diodes having an effective thickness of two millimeters operate satisfactorily as detectors for applied voltages of about 500 volts. The resolutions observed are then about 2 per cent for mono-energetic electrons and about 4 per cent for the gamma; they can be improved by the use of a pre-amplifier of very low background noise. (author) [French] Les detecteurs epais au silicium compense nucleairement sont etudies ici du double point de vue realisation et performances. Apres un rappel sur la necessite de la compensation et les procedes existants, la realisation controlee des detecteurs epais par compensation nucleaire est decrite en detail sous l'aspect theorique et l'aspect experimental. On met en evidence les precautions a prendre dans la pratique: controle de l'homogeneite du materiau de base, controle de l'evolution de la compensation, elimination des processus parasites. On etudie ensuite les performances de detecteurs obtenus : caracteristiques electriques (courant, duree de vie) d'une part, d'autre part detection et spectrometrie des rayonnements penetrants. Les resultats montrent que les diodes compensees ayant une epaisseur utile de deux

  13. Study of thick, nuclear-compensated silicon detectors; Etude des detecteurs epais au silicium compense nucleairement

    Energy Technology Data Exchange (ETDEWEB)

    Le Coroller, Y [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1964-09-01

    A study is made here, from the point of view of the realization and the performance, of thick nuclear-compensated silicon detectors. After recalling the need for compensation and reviewing the existing methods, the author describes in detail the controlled realization of thick detectors by nuclear compensation from the theoretical and experimental points of view. The practical precautions which should be observed are given: control of the homogeneity of the starting material, control of the evolution of the compensation, elimination of parasitic processes. The performances of the detectors obtained are then studied: electrical characteristics (current, life-time) on the one hand, detection and spectrometry of penetrating radiations on the other hand. The results show, that the compensated diodes having an effective thickness of two millimeters operate satisfactorily as detectors for applied voltages of about 500 volts. The resolutions observed are then about 2 per cent for mono-energetic electrons and about 4 per cent for the gamma; they can be improved by the use of a pre-amplifier of very low background noise. (author) [French] Les detecteurs epais au silicium compense nucleairement sont etudies ici du double point de vue realisation et performances. Apres un rappel sur la necessite de la compensation et les procedes existants, la realisation controlee des detecteurs epais par compensation nucleaire est decrite en detail sous l'aspect theorique et l'aspect experimental. On met en evidence les precautions a prendre dans la pratique: controle de l'homogeneite du materiau de base, controle de l'evolution de la compensation, elimination des processus parasites. On etudie ensuite les performances de detecteurs obtenus : caracteristiques electriques (courant, duree de vie) d'une part, d'autre part detection et spectrometrie des rayonnements penetrants. Les resultats montrent que les diodes compensees ayant une epaisseur utile de deux millimetres fonctionnent

  14. Short-time, high-dosage penicillin infusion therapy of syphilis

    DEFF Research Database (Denmark)

    Lomholt, Hans; Poulsen, Asmus; Brandrup, Flemming

    2003-01-01

    The optimal dosage and duration of penicillin treatment for the various stages of syphilis are not known. We present data on 20 patients with syphilis (primary, secondary or latent) treated with high-dose, short-time penicillin infusion therapy. Patients were given 10 MIU of penicillin G intraven......The optimal dosage and duration of penicillin treatment for the various stages of syphilis are not known. We present data on 20 patients with syphilis (primary, secondary or latent) treated with high-dose, short-time penicillin infusion therapy. Patients were given 10 MIU of penicillin G...

  15. Derivative spectrophotometric method for simultaneous determination of clindamycin phosphate and tretinoin in pharmaceutical dosage forms.

    Science.gov (United States)

    Barazandeh Tehrani, Maliheh; Namadchian, Melika; Fadaye Vatan, Sedigheh; Souri, Effat

    2013-04-10

    A derivative spectrophotometric method was proposed for the simultaneous determination of clindamycin and tretinoin in pharmaceutical dosage forms. The measurement was achieved using the first and second derivative signals of clindamycin at (1D) 251 nm and (2D) 239 nm and tretinoin at (1D) 364 nm and (2D) 387 nm.The proposed method showed excellent linearity at both first and second derivative order in the range of 60-1200 and 1.25-25 μg/ml for clindamycin phosphate and tretinoin respectively. The within-day and between-day precision and accuracy was in acceptable range (CVpharmaceutical dosage form.

  16. Compensating for the harms of family violence: statutory barriers in Australian victims of crime compensation schemes.

    Science.gov (United States)

    Forster, Christine

    2014-09-01

    This article considers the compensative capacity of the victims of crime statutory schemes that are present in all eight Australian jurisdictions for primary victims of family violence. It argues that the recommendations of the Final Report on Family Violence conducted jointly by the Australian Law Reform Commission and the New South Wales Law Reform Commission in 2010, although a positive step, are insufficient to facilitate meaningful compensation to victims of family violence. In addition to the primary limitations identified by the Commissions--a requirement to report the crime to the police within a reasonable time and a requirement for multiple acts of violence to be reduced to a single act if they are related--there are other statutory barriers that disproportionately disadvantage victims of family violence. These include time limitation provisions, a requirement to report the crime to police, the restriction of compensation to prescribed categories of loss which exclude many of the social, vocational, emotional and psychological harms suffered by victims of family violence, and significant cut-backs on the non-economic component of the schemes. This article further argues that the statutory barriers cumulatively contribute to the perception of a crime as an isolated event perpetrated by a deviant individual. The article recommends that specific provisions for family violence victims should be introduced into all schemes including three categories of compensation not tied to criminal offences but rather the different forms of family violence, with a generous compensation range, and no requirement for proof of injury.

  17. Executive compensation and firm performance: Evidence from Indian firms

    Directory of Open Access Journals (Sweden)

    Mehul Raithatha

    2016-09-01

    Full Text Available The study examines the relationship between executive compensation and firm performance among Indian firms. The evidence suggests that firm performance measured by accounting, as well as market-based measures, significantly affects executive compensation. We also test for the presence of persistence in executive compensation by employing the system-generalised methods of moments (GMM estimator. We find significant persistence in executive compensation among the sample firms. Further, we report the absence of pay–performance relationship among the smaller sample firms and business group affiliated firms. Thus, our findings cast doubts over the performance-based executive compensation practices of Indian business group affiliated firms.

  18. Gene Duplicability of Core Genes Is Highly Consistent across All Angiosperms[OPEN

    Science.gov (United States)

    Li, Zhen; Van de Peer, Yves; De Smet, Riet

    2016-01-01

    Gene duplication is an important mechanism for adding to genomic novelty. Hence, which genes undergo duplication and are preserved following duplication is an important question. It has been observed that gene duplicability, or the ability of genes to be retained following duplication, is a nonrandom process, with certain genes being more amenable to survive duplication events than others. Primarily, gene essentiality and the type of duplication (small-scale versus large-scale) have been shown in different species to influence the (long-term) survival of novel genes. However, an overarching view of “gene duplicability” is lacking, mainly due to the fact that previous studies usually focused on individual species and did not account for the influence of genomic context and the time of duplication. Here, we present a large-scale study in which we investigated duplicate retention for 9178 gene families shared between 37 flowering plant species, referred to as angiosperm core gene families. For most gene families, we observe a strikingly consistent pattern of gene duplicability across species, with gene families being either primarily single-copy or multicopy in all species. An intermediate class contains gene families that are often retained in duplicate for periods extending to tens of millions of years after whole-genome duplication, but ultimately appear to be largely restored to singleton status, suggesting that these genes may be dosage balance sensitive. The distinction between single-copy and multicopy gene families is reflected in their functional annotation, with single-copy genes being mainly involved in the maintenance of genome stability and organelle function and multicopy genes in signaling, transport, and metabolism. The intermediate class was overrepresented in regulatory genes, further suggesting that these represent putative dosage-balance-sensitive genes. PMID:26744215

  19. Gene Duplicability of Core Genes Is Highly Consistent across All Angiosperms.

    Science.gov (United States)

    Li, Zhen; Defoort, Jonas; Tasdighian, Setareh; Maere, Steven; Van de Peer, Yves; De Smet, Riet

    2016-02-01

    Gene duplication is an important mechanism for adding to genomic novelty. Hence, which genes undergo duplication and are preserved following duplication is an important question. It has been observed that gene duplicability, or the ability of genes to be retained following duplication, is a nonrandom process, with certain genes being more amenable to survive duplication events than others. Primarily, gene essentiality and the type of duplication (small-scale versus large-scale) have been shown in different species to influence the (long-term) survival of novel genes. However, an overarching view of "gene duplicability" is lacking, mainly due to the fact that previous studies usually focused on individual species and did not account for the influence of genomic context and the time of duplication. Here, we present a large-scale study in which we investigated duplicate retention for 9178 gene families shared between 37 flowering plant species, referred to as angiosperm core gene families. For most gene families, we observe a strikingly consistent pattern of gene duplicability across species, with gene families being either primarily single-copy or multicopy in all species. An intermediate class contains gene families that are often retained in duplicate for periods extending to tens of millions of years after whole-genome duplication, but ultimately appear to be largely restored to singleton status, suggesting that these genes may be dosage balance sensitive. The distinction between single-copy and multicopy gene families is reflected in their functional annotation, with single-copy genes being mainly involved in the maintenance of genome stability and organelle function and multicopy genes in signaling, transport, and metabolism. The intermediate class was overrepresented in regulatory genes, further suggesting that these represent putative dosage-balance-sensitive genes. © 2016 American Society of Plant Biologists. All rights reserved.

  20. Compensation for oil pollution damage caused by oil spills from ships and the International Oil Pollution Compensation Fund

    International Nuclear Information System (INIS)

    Jacobsson, M.

    1994-01-01

    Liability and compensation for pollution damage caused by oil spills from laden tankers is governed by two international conventions: the 1969 Civil Liability Convention and the 1971 Fund Convention. The Civil Liability Convention established a system of strict liability for tanker owners and introduced compulsory liability insurance. The Fund Convention created a system of supplementary compensation administered by an intergovernmental organization, the International Oil Pollution Compensation Fund (IOPC Fund), which at present has 56 member states (August 1993). The IOPC Fund pays compensation to victims of oil pollution in member states when the compensation from the ship owner and his insurer is insufficient. (author)

  1. Illumination compensation in ground based hyperspectral imaging

    Science.gov (United States)

    Wendel, Alexander; Underwood, James

    2017-07-01

    Hyperspectral imaging has emerged as an important tool for analysing vegetation data in agricultural applications. Recently, low altitude and ground based hyperspectral imaging solutions have come to the fore, providing very high resolution data for mapping and studying large areas of crops in detail. However, these platforms introduce a unique set of challenges that need to be overcome to ensure consistent, accurate and timely acquisition of data. One particular problem is dealing with changes in environmental illumination while operating with natural light under cloud cover, which can have considerable effects on spectral shape. In the past this has been commonly achieved by imaging known reference targets at the time of data acquisition, direct measurement of irradiance, or atmospheric modelling. While capturing a reference panel continuously or very frequently allows accurate compensation for illumination changes, this is often not practical with ground based platforms, and impossible in aerial applications. This paper examines the use of an autonomous unmanned ground vehicle (UGV) to gather high resolution hyperspectral imaging data of crops under natural illumination. A process of illumination compensation is performed to extract the inherent reflectance properties of the crops, despite variable illumination. This work adapts a previously developed subspace model approach to reflectance and illumination recovery. Though tested on a ground vehicle in this paper, it is applicable to low altitude unmanned aerial hyperspectral imagery also. The method uses occasional observations of reference panel training data from within the same or other datasets, which enables a practical field protocol that minimises in-field manual labour. This paper tests the new approach, comparing it against traditional methods. Several illumination compensation protocols for high volume ground based data collection are presented based on the results. The findings in this paper are

  2. Disclosed Values of Option-Based Compensation

    DEFF Research Database (Denmark)

    Bechmann, Ken L.; Hjortshøj, Toke Lilhauge

    New accounting standards require firms to expense the costs of option-based compensation (OBC), but the associated valuations offer many challenges for firms. Earlier research has documented that firms in the U.S. generally underreport the values of OBC by manipulating the inputs used for valuation......-Scholes parameters in their valuations. Furthermore, firms determine the expected time to maturity in a way that is generally consistent with the guidelines provided by the new accounting standards. The findings differ from those of the U.S., but is consistent with the more limited use of OBC and the lower level...

  3. No-fault compensation and performance review.

    Science.gov (United States)

    Knight, B

    1993-01-01

    Two major issues in relation to medical malpractice are discussed. The first is "no-fault compensation", an alternative to the present tort system long established in most countries, including Singapore, where negligence must be proved before a claim can succeed. The second is "performance review", a new concept for monitoring and correcting under-performing medical practitioners against whom a complaint has been laid. Both these issues are currently under active discussion and are arousing political notice and professional controversy. Though the article describes the British situation, there is much of contemporary relevance for Singapore, which has such a similar system of medical practice.

  4. Hybrid compensation arrangement in dispersed generation systems

    DEFF Research Database (Denmark)

    Chen, Zhe; Blaabjerg, Frede; Pedersen, John Kim

    2005-01-01

    This paper presents a hybrid compensation system consisting of an active filter and distributed passive filters. In the system, each individual passive filter is connected to a distortion source and designed to eliminate main harmonics and supply reactive power for the distortion source, while...... filter system consisting of distributed passive filters and an active filter....... the active filter is responsible for the correction of the system unbalance and the cancellation of the remaining harmonics. The paper also analyzes the effects of the circuit configuration on the system impedance characteristics and consequently the effectiveness of the filter system. Simulation studies...

  5. DC-Compensated Current Transformer †

    Science.gov (United States)

    Ripka, Pavel; Draxler, Karel; Styblíková, Renata

    2016-01-01

    Instrument current transformers (CTs) measure AC currents. The DC component in the measured current can saturate the transformer and cause gross error. We use fluxgate detection and digital feedback compensation of the DC flux to suppress the overall error to 0.15%. This concept can be used not only for high-end CTs with a nanocrystalline core, but it also works for low-cost CTs with FeSi cores. The method described here allows simultaneous measurements of the DC current component. PMID:26805830

  6. Material Considerations for Fused-Filament Fabrication of Solid Dosage Forms

    Directory of Open Access Journals (Sweden)

    Evert Fuenmayor

    2018-04-01

    Full Text Available Material choice is a fundamental consideration when it comes to designing a solid dosage form. The matrix material will ultimately determine the rate of drug release since the physical properties (solubility, viscosity, and more of the material control both fluid ingress and disintegration of the dosage form. The bulk properties (powder flow, concentration, and more of the material should also be considered since these properties will influence the ability of the material to be successfully manufactured. Furthermore, there is a limited number of approved materials for the production of solid dosage forms. The present study details the complications that can arise when adopting pharmaceutical grade polymers for fused-filament fabrication in the production of oral tablets. The paper also presents ways to overcome each issue. Fused-filament fabrication is a hot-melt extrusion-based 3D printing process. The paper describes the problems encountered in fused-filament fabrication with Kollidon® VA64, which is a material that has previously been utilized in direct compression and hot-melt extrusion processes. Formulation and melt-blending strategies were employed to increase the printability of the material. The paper defines for the first time the essential parameter profile required for successful 3D printing and lists several pre-screening tools that should be employed to guide future material formulation for the fused-filament fabrication of solid dosage forms.

  7. 75 FR 26647 - Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution

    Science.gov (United States)

    2010-05-12

    .... FDA-2010-N-0002] Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution... are treated with a topical solution of ivermectin. DATES: This rule is effective May 12, 2010. FOR... ANADA 200-340 for PRIVERMECTIN (ivermectin), a topical solution used on cattle to control infestations...

  8. The effect of different dosages of caffeine on endurance performance time

    NARCIS (Netherlands)

    Pasman, W.J.; Baak, M.A. van; Jeukendrup, A.E.; Haan, A. de

    1995-01-01

    The effect of different dosages of caffeine (0 - 5 - 9 - 13 mg · kg body weight-1) on endurance performance was examined. Nine well-trained cyclists participated in this study (VO2max 65.1 + 2.6 ml · kg-1 · min-1). Caffeine capsules were administered in random order and double-blind. One hour after

  9. Biowaiver monograph for immediate-release solid oral dosage forms: bisoprolol fumarate.

    Science.gov (United States)

    Charoo, Naseem A; Shamsher, Areeg A A; Lian, Lai Y; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James; Shah, Vinod P; Dressman, Jennifer

    2014-02-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release (IR) solid oral dosage forms containing bisoprolol as the sole active pharmaceutical ingredient (API) are reviewed. Bisoprolol is classified as a Class I API according to the current Biopharmaceutics Classification System (BCS). In addition to the BCS class, its therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions, and reported BE/bioavailability problems are taken into consideration. Qualitative compositions of IR tablet dosage forms of bisoprolol with a marketing authorization (MA) in ICH (International Conference on Harmonisation) countries are tabulated. It was inferred that these tablets had been demonstrated to be bioequivalent to the innovator product. No reports of failure to meet BE standards have been made in the open literature. On the basis of all these pieces of evidence, a biowaiver can currently be recommended for bisoprolol fumarate IR dosage forms if (1) the test product contains only excipients that are well known, and used in normal amounts, for example, those tabulated for products with MA in ICH countries and (2) both the test and comparator dosage form are very rapidly dissolving, or, rapidly dissolving with similarity of the dissolution profiles demonstrated at pH 1.2, 4.5, and 6.8. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  10. 76 FR 22610 - Implantation or Injectable Dosage Form New Animal Drugs; Enrofloxacin

    Science.gov (United States)

    2011-04-22

    .... FDA-2011-N-0003] Implantation or Injectable Dosage Form New Animal Drugs; Enrofloxacin AGENCY: Food... the indications for use of enrofloxacin solution in cattle, as a single injection, for the treatment... supplement to NADA 141-068 for BAYTRIL 100 (enrofloxacin), an injectable solution. The supplemental NADA...

  11. 78 FR 30197 - Oral Dosage Form New Animal Drugs; Clindamycin; Enrofloxacin

    Science.gov (United States)

    2013-05-22

    ...-0002] Oral Dosage Form New Animal Drugs; Clindamycin; Enrofloxacin AGENCY: Food and Drug Administration...- Tallaght, Dublin Oral Drops. 940. 24, Ireland. 200-551........ Putney, Inc., 400 Enrofloxacin Original....812 Enrofloxacin. (a) Specifications. Each tablet contains 22.7, 68.0, or 136.0 milligrams (mg) of...

  12. Application of DBNPA dosage for biofouling control in spiral wound membrane systems

    KAUST Repository

    Siddiqui, Amber; Pinel, I.; Prest, E.I.; Bucs, Szilard; van Loosdrecht, M.C.M.; Kruithof, J.C.; Vrouwenvelder, Johannes S.

    2017-01-01

    in MFS was quantified by adenosine triphosphate (ATP) and total organic carbon (TOC) analysis. Continuous dosage of DBNPA (1 mg/L) prevented pressure drop increase and biofilm accumulation in the MFSs during a run time of 7 d, showing that biofouling can

  13. Use of fluorescence spectroscopy to control ozone dosage in recirculating aquaculture systems

    DEFF Research Database (Denmark)

    Spiliotopoulou, Aikaterini; Martin, Richard; Pedersen, Lars-Flemming

    2017-01-01

    , in order to optimise ozonation treatment. Water samples from six different Danish facilities (two rearing units from a commercial trout RAS, a commercial eel RAS, a pilot RAS and two marine water aquariums) were treated with different O3 dosages (1.0–20.0 mg/L ozone) in bench-scale experiments, following...

  14. Rheology as a tool for evaluation of melt processability of innovative dosage forms

    DEFF Research Database (Denmark)

    Aho, Johanna Maaria; Boetker, Johan P; Baldursdottir, Stefania

    2015-01-01

    ) printing, will have an increasingly important role when designing products for flexible dosing, since dosage forms based on compacting of a given powder mixture do not enable manufacturing of optimal pharmaceutical products for personalized treatments. The melt processability of polymers and API...

  15. Absorption of macronutrients by cassava in different harvest dates and dosages of nitrogen

    Directory of Open Access Journals (Sweden)

    Nádia Souza dos Santos

    Full Text Available A field experiment was carried out in 2010-2011 crop years in the experimental area of the Centro de Ciências Agrárias of the Universidade Federal de Roraima, in Boa Vista, Roraima, Brazil. This study aimed to evaluate the effect of nitrogen availability on the concentrations of N, P, K, Ca, Mg and S in cassava, cultivar Aciolina, in different harvest times. A randomized block design was used in split-plot, with four replications. Dosages of N in cover were applied randomly on the plots (0, 30, 60, 150 and 330 kg ha-1, and in the subplot the harvest dates 120, 150, 180, 210, 240, 270 and 300 days after emergence (DAE. The vegetal material was collected, ground and then underwent an analysis for determination of nutrients concentrations in the leaves (N, P, K, Ca Mg and S. The harvest dates and dosages of N affect the nutrient concentrations in the cassava leaves, cv. Aciolina. The macronutrients dosage in the leaves, 120 DAE, is a good indicator of the nutritional status of the cassava plant. The dosage of 150 kg ha-1 of N raises the tubers roots per plant. The sequence of the macronutrients concentration in the leaves of the cassava, cv. Aciolina is N>Ca>K>Mg>P>S.

  16. Study of hydrogels based on polyacrilamide as new controlled release dosage forms produced by frontal polymerization

    OpenAIRE

    Sechi, Rossana; Gavini, Elisabetta; Mariani, Alberto; Bidali, Simone; Bonferoni, Maria Cristina; Sanna, Vanna Annunziata; Rassu, Giovanna; Pirisino, Gerolamo Antonio; Giunchedi, Paolo

    2006-01-01

    The work purpose was the evaluation of the potential application of the Frontal Polymerization (FP) technique as a new method for the preparation of controlled release dosage forms based on polyacrilamide, in which the drug loading and the polymer preparation occur at the same time.

  17. 76 FR 3488 - Implantation or Injectable Dosage Form New Animal Drugs; Oxytetracycline and Flunixin

    Science.gov (United States)

    2011-01-20

    .... FDA-2010-N-0002] Implantation or Injectable Dosage Form New Animal Drugs; Oxytetracycline and Flunixin... combination drug injectable solution containing oxytetracycline and flunixin meglumine in cattle. [[Page 3489... veterinary prescription use of HEXASOL (oxytetracycline and flunixin meglumine) Injection for the treatment...

  18. Accelerated in-vitro release testing methods for extended-release parenteral dosage forms.

    Science.gov (United States)

    Shen, Jie; Burgess, Diane J

    2012-07-01

    This review highlights current methods and strategies for accelerated in-vitro drug release testing of extended-release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in-situ depot-forming systems and implants. Extended-release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, 'real-time' in-vitro release tests for these dosage forms are often run over a long time period. Accelerated in-vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in-vitro release methods using United States Pharmacopeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended-release parenteral dosage forms, along with the accelerated in-vitro release testing methods currently employed are discussed. Accelerated in-vitro release testing methods with good discriminatory ability are critical for quality control of extended-release parenteral products. Methods that can be used in the development of in-vitro-in-vivo correlation (IVIVC) are desirable; however, for complex parenteral products this may not always be achievable. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

  19. Accelerated in vitro release testing methods for extended release parenteral dosage forms

    Science.gov (United States)

    Shen, Jie; Burgess, Diane J.

    2012-01-01

    Objectives This review highlights current methods and strategies for accelerated in vitro drug release testing of extended release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in situ depot-forming systems, and implants. Key findings Extended release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, “real-time” in vitro release tests for these dosage forms are often run over a long time period. Accelerated in vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in vitro release methods using United States Pharmacopoeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended release parenteral dosage forms, along with the accelerated in vitro release testing methods currently employed are discussed. Conclusions Accelerated in vitro release testing methods with good discriminatory ability are critical for quality control of extended release parenteral products. Methods that can be used in the development of in vitro-in vivo correlation (IVIVC) are desirable, however for complex parenteral products this may not always be achievable. PMID:22686344

  20. 3D printing of high drug loaded dosage forms using thermoplastic polyurethanes.

    Science.gov (United States)

    Verstraete, G; Samaro, A; Grymonpré, W; Vanhoorne, V; Van Snick, B; Boone, M N; Hellemans, T; Van Hoorebeke, L; Remon, J P; Vervaet, C

    2018-01-30

    It was the aim of this study to develop high drug loaded (>30%, w/w), thermoplastic polyurethane (TPU)-based dosage forms via fused deposition modelling (FDM). Model drugs with different particle size and aqueous solubility were pre-processed in combination with diverse TPU grades via hot melt extrusion (HME) into filaments with a diameter of 1.75 ± 0.05 mm. Subsequently, TPU-based filaments which featured acceptable quality attributes (i.e. consistent filament diameter, smooth surface morphology and good mechanical properties) were printed into tablets. The sustained release potential of the 3D printed dosage forms was tested in vitro. Moreover, the impact of printing parameters on the in vitro drug release was investigated. TPU-based filaments could be loaded with 60% (w/w) fine drug powder without observing severe shark skinning or inconsistent filament diameter. During 3D printing experiments, HME filaments based on hard TPU grades were successfully converted into personalized dosage forms containing a high concentration of crystalline drug (up to 60%, w/w). In vitro release kinetics were mainly affected by the matrix composition and tablet infill degree. Therefore, this study clearly demonstrated that TPU-based FDM feedstock material offers a lot of formulation freedom for the development of personalized dosage forms. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Improved sentinel node visualization in breast cancer by optimizing the colloid particle concentration and tracer dosage

    NARCIS (Netherlands)

    Valdés Olmos, R. A.; Tanis, P. J.; Hoefnagel, C. A.; Nieweg, O. E.; Muller, S. H.; Rutgers, E. J.; Kooi, M. L.; Kroon, B. B.

    2001-01-01

    Faint lymph uptake may hamper sentinel node (SN) identification by scintigraphy and subsequent gamma probe localization. The aim of the present study was to evaluate an adjustment in the colloid particle concentration and tracer dosage to optimize mammary lymphoscintigraphy. Scintigraphy was

  2. Minimum effective dosages of anti-TNF in rheumatoid arthritis: a cross-sectional study.

    Science.gov (United States)

    de la Torre, Inmaculada; Valor, Lara; Nieto, Juan Carlos; Montoro, María; Carreño, Luis

    2014-01-01

    To evaluate the modified dosages of anti-TNF in controlling disease activity in rheumatoid arthritis (RA) measured by DAS28-ESR. Cross-sectional study: RA patients treated with etanercept (ETN), adalimumab (ADA) or infliximab (IFX), at standard or modified doses. dosage, concomitant disease modifying drugs (DMARDs), DAS28-ESR. 195 RA patients included (79% women, mean age 58.1 years): ETN=81, ADA=56, IFX=58. Mean disease duration and time to first biological treatment was higher in IFX group (P=.01). Patients distribution by dosage: standard: ETN (72.8%), ADA (69.6%), IFX (27.6%); escalated: IFX (69%), ADA (5.4%), ETN (0%); reduced: ETN (27.1%), ADA (25%), IFX (3.4%). Concomitant DMARDs use was lower in ETN (58.2%) than ADA (66.07%) and IFX (79.31%). Higher proportion of responders (DAS28 ≤3.2) in ADA (65.3%) and ETN (61.7%) than IFX (48.3%). RA clinical control can be preserved with modified anti-TNF dosages. Controlled prospective studies should be performed to define when therapy can be tailored and for which patients. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  3. 75 FR 21162 - Certain Other Dosage Form New Animal Drugs; Detomidine

    Science.gov (United States)

    2010-04-23

    .... FDA-2010-N-0002] Certain Other Dosage Form New Animal Drugs; Detomidine AGENCY: Food and Drug... NADA provides for veterinary prescription use of detomidine hydrochloride oromucosal gel for sedation... prescription use of DORMOSEDAN GEL (detomidine hydrochloride) for sedation and restraint of horses. The...

  4. 76 FR 16533 - Certain Other Dosage Form New Animal Drugs; Detomidine; Correction

    Science.gov (United States)

    2011-03-24

    .... FDA-2010-N-0002] Certain Other Dosage Form New Animal Drugs; Detomidine; Correction AGENCY: Food and... paragraph describing limitations to the approved conditions of use for detomidine hydrochloride oromucosal... conditions of use for detomidine hydrochloride oromucosal gel in horses. This correction is being made to...

  5. LABORATORY PROTECTION RATE OF TORN BEDNETS TREATED WITH THREE DOSAGES OF PYRETHROIDE AGAINST ANOPHELES CULICIFACIES

    Directory of Open Access Journals (Sweden)

    G. Babaee

    2007-05-01

    Full Text Available Evaluated under laboratory condition. The objective of the present study was to observe the effect of impregnated torn bednets on the number of bites by An. culicifacies A glass made tunnel test was designed to The effect of torn bednets treated with three dosages of cyfluthrin 5% EW, were induce hungry female mosquitoes to pass through holes cut in the pyrethroid treated nets. A guinea pig used as bait to attract mosquitoes through circular holes in the netting. With untreated netting, 72-87% of laboratory-reared females passed through the holes overnight, 64-92% blood-fed successfully and 0.3/9-4/3% died. When the netting was treated with cyfluthrin at doses of 25, 50 and 100 mg a.i./m2, the entry Index (the proportions that passed through the holes overnight were 43.37%, 42.82% and 24.72%; mortality rates were 66.31%, 81.45% and 95.99%; and the feeding rate were 45%, 27% and 3%. In conclusion it should be stressed that efficacy of pyrethroid impregnated bednets using “Tunnel Tests” showing acceptable protection rate both in lower and higher dosages as well as cause dead in the blood-fed mosquitoes. In addition, the higher dosages of these three dosages pyrethroid provided good levels of protection against An. culicifacies.

  6. Plasma concentrations of caspofungin at two different dosage regimens in a patient with hepatic dysfunction

    NARCIS (Netherlands)

    van der Elst, K.C.; Bruggemann, R.J.M.; Rodgers, M.G.; Alffenaar, J.W.C.

    2012-01-01

    The currently recommended dosage regimen of caspofungin (50 mg/day) was developed for patients with invasive candidiasis. With invasive aspergillosis, successful outcomes occur in less than half the patients. We evaluate the pharmacokinetics in a patient with elevated liver enzyme levels after liver

  7. Plasma concentrations of caspofungin at two different dosage regimens in a patient with hepatic dysfunction

    NARCIS (Netherlands)

    van der Elst, K. C. M.; Bruggemann, R. J. M.; Rodgers, M. G. G.; Alffenaar, J. W. C.

    The currently recommended dosage regimen of caspofungin (50 mg/day) was developed for patients with invasive candidiasis. With invasive aspergillosis, successful outcomes occur in less than half the patients. We evaluate the pharmacokinetics in a patient with elevated liver enzyme levels after liver

  8. 75 FR 20268 - Implantation or Injectable Dosage Form New Animal Drugs; Change of Sponsor; Propofol

    Science.gov (United States)

    2010-04-19

    ... 21 CFR Part 522 Animal drugs. Therefore, under the Federal Food, Drug, and Cosmetic Act and under... use in dogs and cats--(1) Amount. The drug is administered by intravenous injection as follows: (i) Dogs. For induction of general anesthesia without the use of preanesthetics the dosage is 5.5 to 7.0 mg...

  9. Unilateral brief-pulse electroconvulsive therapy and cognition: effects of electrode placement, stimulus dosage and time.

    Science.gov (United States)

    Semkovska, Maria; Keane, Deborah; Babalola, Oyemi; McLoughlin, Declan M

    2011-06-01

    To clarify advantages of unilateral electrode placement as an optimisation technique for electroconvulsive therapy (ECT) for depression, aims were to meta-analyse unilateral ECT effects on cognitive performance relative to: (1) bitemporal electrode placement, (2) electrical dosage, and (3) time interval between final treatment and cognitive reassessment. Relevant electronic databases were systematically searched through May 2009, using the terms: "electroconvulsive therapy" and ["cogniti∗", "neuropsycholog∗", "memory", "attention", "executive", "spatial", or "intellectual"]. Inclusion criteria were: independent study of depressed patients receiving unilateral or bitemporal brief-pulse ECT; within-subjects design; use of objective cognitive assessments; available mean electrical dosage for unilateral samples. Standardized pre-post ECT weighted effect sizes were computed and pooled within 16 cognitive domains by a mixed-effects model. Thirty-nine studies (1415 patients) were meta-analysed. Up to three days after final treatment, unilateral ECT was associated with significantly smaller decreases in global cognition, delayed verbal memory retrieval, and autobiographical memory, compared to bitemporal ECT. Significant publication bias was found for autobiographical memory, favouring reporting of larger percentage loss. Higher unilateral ECT electrical dosage predicted larger decreases in verbal learning, delayed verbal memory retrieval, visual recognition, and semantic memory retrieval. When retested more than three days after completing ECT, no significant differences remained between the two electrode placements; for unilateral ECT, electrical dosage no longer predicted cognitive performance whereas increasing interval between final treatment and retesting predicted growing improvement in some variables. This interval is a more useful long-term predictor of cognitive function than electrode placement or electrical dosage following unilateral ECT. Copyright © 2010

  10. Study on image quality and dosage comparison of F/S system and DR system

    International Nuclear Information System (INIS)

    Kim, Sun Chil; Jung, Jae Eun

    2003-01-01

    Currently, many hospital are hastening to introduce digital radiography systems. This is a direct result of the intentions to improve medical services and to digitalized radiology information systems, and is also leading to the improvement of medical imaging technology. Throughout F/S system's long history, many people have researched the image quality and dosage concerning these systems, and as a result, huge improvements in the dosage of patients were possible. Similarly, I believe that DR systems need the same kind of effort. Of course, decreases in dosage that ignore image quality are unthinkable. The results of experiments conducted by five hospitals during a period of 3 months brought to us the conclusions listed below. Based on the comparison and analysis of the exposure control of F/S systems and DR systems, DR systems generally showed higher exposure control for parts of the phantom that became thicker, and the exposure control improved rapidly as the thickness increased. DR systems still proved to be somewhat deficient in resolution measurements compared to existing F/S systems. The image processing part of DR systems contributed much to these result. Under conditions used clinically, the dosage measurements of DR systems were generally higher regardless of region. According to the evaluation of image quality, DR systems showed a higher degree of satisfaction as the thickness of the region became thinner. As mentioned above and based on the mutual relationship experiments between the dosage and image quality of F/S systems and DR systems, research to increase the satisfaction of DR systems must be considered

  11. Unilateral brief-pulse electroconvulsive therapy and cognition: Effects of electrode placement, stimulus dosage and time.

    LENUS (Irish Health Repository)

    Semkovska, Maria

    2010-11-23

    To clarify advantages of unilateral electrode placement as an optimisation technique for electroconvulsive therapy (ECT) for depression, aims were to meta-analyse unilateral ECT effects on cognitive performance relative to: (1) bitemporal electrode placement, (2) electrical dosage, and (3) time interval between final treatment and cognitive reassessment. Relevant electronic databases were systematically searched through May 2009, using the terms: "electroconvulsive therapy" and ["cogniti∗", "neuropsycholog∗", "memory", "attention", "executive", "spatial", or "intellectual"]. Inclusion criteria were: independent study of depressed patients receiving unilateral or bitemporal brief-pulse ECT; within-subjects design; use of objective cognitive assessments; available mean electrical dosage for unilateral samples. Standardized pre-post ECT weighted effect sizes were computed and pooled within 16 cognitive domains by a mixed-effects model. Thirty-nine studies (1415 patients) were meta-analysed. Up to three days after final treatment, unilateral ECT was associated with significantly smaller decreases in global cognition, delayed verbal memory retrieval, and autobiographical memory, compared to bitemporal ECT. Significant publication bias was found for autobiographical memory, favouring reporting of larger percentage loss. Higher unilateral ECT electrical dosage predicted larger decreases in verbal learning, delayed verbal memory retrieval, visual recognition, and semantic memory retrieval. When retested more than three days after completing ECT, no significant differences remained between the two electrode placements; for unilateral ECT, electrical dosage no longer predicted cognitive performance whereas increasing interval between final treatment and retesting predicted growing improvement in some variables. This interval is a more useful long-term predictor of cognitive function than electrode placement or electrical dosage following unilateral ECT.

  12. Predictors of Energy Compensation during Exercise Interventions: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Marie-Ève Riou

    2015-05-01

    Full Text Available Weight loss from exercise-induced energy deficits is usually less than expected. The objective of this systematic review was to investigate predictors of energy compensation, which is defined as body energy changes (fat mass and fat-free mass over the total amount of exercise energy expenditure. A search was conducted in multiple databases without date limits. Of 4745 studies found, 61 were included in this systematic review with a total of 928 subjects. The overall mean energy compensation was 18% ± 93%. The analyses indicated that 48% of the variance of energy compensation is explained by the interaction between initial fat mass, age and duration of exercise interventions. Sex, frequency, intensity and dose of exercise energy expenditure were not significant predictors of energy compensation. The fitted model suggested that for a shorter study duration, lower energy compensation was observed in younger individuals with higher initial fat mass (FM. In contrast, higher energy compensation was noted for younger individuals with lower initial FM. From 25 weeks onward, energy compensation was no longer different for these predictors. For studies of longer duration (about 80 weeks, the energy compensation approached 84%. Lower energy compensation occurs with short-term exercise, and a much higher level of energy compensation accompanies long-term exercise interventions.

  13. Report of the working group for nuclear damage compensation system

    International Nuclear Information System (INIS)

    1989-01-01

    The Working Group for Nuclear Damage Compensation System was established within the Atomic Energy Commision of Japan on August 2, 1988. The Group has held five meetings to make a study on the revision of the reserve for nuclear damage compensation. The nuclear damage compensation system in Japan has been established under the Law Concerning Compensation for Nuclear Damages and the Law Concerning Contract for Compensation for Nuclear Damages. The former law requires the nuclear power plant operators to set up a reserve for damage compensation to ensure positive and quick payment of compensation in the event of an accident. The reserve is currently rely on liability insurance and a government compensation contract. The Working Group has concluded that the total reserve should be increased from the current yen10 bill. to yen30 bill. The amount of the reserve specified in the enforcement law for the Law Concerning Compensation for Nuclear Damages should also be increased accordingly. The Law Concerning compensation for Nuclear damage will also be applied to damage which occurs overseas as a result of an accident in Japan. (N.K.)

  14. Do compensation processes impair mental health? A meta-analysis.

    Science.gov (United States)

    Elbers, Nieke A; Hulst, Liesbeth; Cuijpers, Pim; Akkermans, Arno J; Bruinvels, David J

    2013-05-01

    Victims who are involved in a compensation processes generally have more health complaints compared to victims who are not involved in a compensation process. Previous research regarding the effect of compensation processes has concentrated on the effect on physical health. This meta-analysis focuses on the effect of compensation processes on mental health. Prospective cohort studies addressing compensation and mental health after traffic accidents, occupational accidents or medical errors were identified using PubMed, EMBASE, PsycInfo, CINAHL, and the Cochrane Library. Relevant studies published between January 1966 and 10 June 2011 were selected for inclusion. Ten studies were included. The first finding was that the compensation group already had higher mental health complaints at baseline compared to the non-compensation group (standardised mean difference (SMD)=-0.38; 95% confidence interval (CI) -0.66 to -0.10; p=.01). The second finding was that mental health between baseline and post measurement improved less in the compensation group compared to the non-compensation group (SMD=-0.35; 95% CI -0.70 to -0.01; p=.05). However, the quality of evidence was limited, mainly because of low quality study design and heterogeneity. Being involved in a compensation process is associated with higher mental health complaints but three-quarters of the difference appeared to be already present at baseline. The findings of this study should be interpreted with caution because of the limited quality of evidence. The difference at baseline may be explained by a selection bias or more anger and blame about the accident in the compensation group. The difference between baseline and follow-up may be explained by secondary gain and secondary victimisation. Future research should involve assessment of exposure to compensation processes, should analyse and correct for baseline differences, and could examine the effect of time, compensation scheme design, and claim settlement on

  15. Fixman compensating potential for general branched molecules

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Abhinandan, E-mail: Abhi.Jain@jpl.nasa.gov [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Pasadena, California 91109 (United States); Kandel, Saugat; Wagner, Jeffrey; Larsen, Adrien; Vaidehi, Nagarajan, E-mail: nvaidehi@coh.org [Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, California 91010 (United States)

    2013-12-28

    The technique of constraining high frequency modes of molecular motion is an effective way to increase simulation time scale and improve conformational sampling in molecular dynamics simulations. However, it has been shown that constraints on higher frequency modes such as bond lengths and bond angles stiffen the molecular model, thereby introducing systematic biases in the statistical behavior of the simulations. Fixman proposed a compensating potential to remove such biases in the thermodynamic and kinetic properties calculated from dynamics simulations. Previous implementations of the Fixman potential have been limited to only short serial chain systems. In this paper, we present a spatial operator algebra based algorithm to calculate the Fixman potential and its gradient within constrained dynamics simulations for branched topology molecules of any size. Our numerical studies on molecules of increasing complexity validate our algorithm by demonstrating recovery of the dihedral angle probability distribution function for systems that range in complexity from serial chains to protein molecules. We observe that the Fixman compensating potential recovers the free energy surface of a serial chain polymer, thus annulling the biases caused by constraining the bond lengths and bond angles. The inclusion of Fixman potential entails only a modest increase in the computational cost in these simulations. We believe that this work represents the first instance where the Fixman potential has been used for general branched systems, and establishes the viability for its use in constrained dynamics simulations of proteins and other macromolecules.

  16. Instability of compensated beam-beam collisions

    International Nuclear Information System (INIS)

    Rosenzweig, J.B.; Autin, B.; Chen, Pisin.

    1989-01-01

    The beam-beam disruption phenomena in linear colliders are increasingly seen as a source of serious problems for these machines. A plasma compensation scheme, in which the motion of the plasma electrons in the presence of the colliding beams provides neutralizing charge and current densities, has been proposed and studied. But natural alternative to this scheme is to consider the overlapping of nearly identical high energy e + and e/sup /minus// bunches, and the collision of two such pairs - in other words, collision of two opposing relativistic positronium plasmas. It should be noticed that while the luminosity for all collisions is increased by a factor of four in this scheme, the event rate for e + e/sup /minus// collisions is only increased by a factor of two. The other factor of two corresponds to the addition of e + e + and e/sup /minus//e/sup /minus// collisions to the interaction point. This beam compensation scheme, which has been examined through computer simulation by Balakin and Solyak in the Soviet Union, promises full neutralization of beam charges and currents. These numerical investigations have shown that plasma instabilities exist in this nominally neutral system. Although the implementation of this idea seems technically daunting, the potential benefits (beamstrahlung and disruption suppression, relaxation of final focus system constraints) are such that we should consider the physics of these collisions further. In the remainder of this paper, we theoretically analyze the issues of stability and bunch parameter tolerances in this scheme. 11 refs

  17. Background compensation methodologies for contamination monitoring systems

    International Nuclear Information System (INIS)

    Raman, Anand; Chaudhury, Probal; Pradeepkumar, K.S.

    2014-01-01

    Radiation surveillance program in the various nuclear facilities incorporate contamination monitoring as an important component. Contamination monitoring programs constitute monitoring for alpha and beta contamination of the physical entities associated with the working personnel that include his hands, feet, clothing, shoes as well as the general surface areas in the working environment like floors. All these measurements are fraught with the contribution of the ambient gamma background radiation fields. These inhibit a proper and precise estimation of the contamination concentration being monitored. This paper investigates the efficacy of two methodologies that have been incorporated in two of the contamination monitoring systems developed in the Division. In the first system discussed, a high degree of gamma compensation has been achieved for an uniform exposure of the order of 50 nSv/hr to 100 mSv/hr. In the second system discussed, the degree of gamma compensation achieved is equal to those dictated by the statistical nature of the uncertainties associated with the subtraction of background from the source data. These two methods can be very effectively employed depending on the application requirement. A minimum detection level equivalent to 0.37 Bq/cdm 2 has been achieved in both these cases

  18. 76 FR 6009 - Shareholder Approval of Executive Compensation and Golden Parachute Compensation

    Science.gov (United States)

    2011-02-02

    .... Consideration of Impact on the Economy, Burden on Competition, and Promotion of Efficiency, Competition, and... Act are available on our Web site at http://www.sec.gov/comments/df-title-ix/executive-compensation...\\ See, e.g., letters from International Corporate Governance Network (``ICGN'') and Teachers Insurance...

  19. Glycine receptor mutants of the mouse: what are possible routes of inhibitory compensation?

    Directory of Open Access Journals (Sweden)

    Natascha eSchaefer

    2012-10-01

    Full Text Available Defects in glycinergic inhibition result in a complex neuromotor disorder in humans known as hyperekplexia (OMIM 149400 with similar phenotypes in rodents characterized by an exaggerated startle reflex and hypertonia. Analogous to genetic defects in humans, single point mutations, microdeletions, or insertions in the Glra1 gene but also in the Glrb gene underlie the pathology in mice. The mutations either localized in the α (spasmodic, oscillator, cincinnati, Nmf11 or the β (spastic subunit of the GlyR are much less tolerated in mice than in humans, leaving the question for the existence of different regulatory elements of the pathomechanisms in humans and rodents. In addition to the spontaneous mutations, new insights into understanding of the regulatory pathways in hyperekplexia or glycine encephalopathy arose from the constantly increasing number of knock-out as well as knock-in mutants of GlyRs. Over the last five years, various efforts using in vivo whole cell recordings provided a detailed analysis of the kinetic parameters underlying glycinergic dysfunction. Presynaptic compensation as well as postsynaptic compensatory mechanisms in these mice by other GlyR subunits or GABAA receptors, and the role of extra-synaptic GlyRs is still a matter of debate. A recent study on the mouse mutant oscillator, displayed a novel aspect for compensation of functionality by complementation of receptor domains that fold independently. This review focuses on defects in glycinergic neurotransmission in mice discussed with the background of human hyperekplexia en route to strategies of compensation.

  20. Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial.

    Science.gov (United States)

    Kosaka, H; Okamoto, Y; Munesue, T; Yamasue, H; Inohara, K; Fujioka, T; Anme, T; Orisaka, M; Ishitobi, M; Jung, M; Fujisawa, T X; Tanaka, S; Arai, S; Asano, M; Saito, D N; Sadato, N; Tomoda, A; Omori, M; Sato, M; Okazawa, H; Higashida, H; Wada, Y

    2016-08-23

    Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD); however, factors influencing its efficacy are still unclear. We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy. This trial consisted of double-blind (12 weeks), open-label (12 weeks) and follow-up phases (8 weeks). To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase. Next, we measured single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR). In the intention-to-treat population, no outcomes were improved after oxytocin administration. However, in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group. Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants. We found that >21 IU per day oxytocin was more effective than ⩽21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment. No severe adverse events occurred. These results suggest that efficacy of long-term oxytocin administration in young men with high-functioning ASD depends on the oxytocin dosage and genetic background of the oxytocin receptor, which contributes to the effectiveness of oxytocin treatment of ASD.