Sample records for exchange variant gly796arg

  1. A novel erythroid anion exchange variant (Gly796Arg) of hereditary stomatocytosis associated with dyserythropoiesis (United States)

    Iolascon, Achille; De Falco, Luigia; Borgese, Franck; Esposito, Maria Rosaria; Avvisati, Rosa Anna; Izzo, Pietro; Piscopo, Carmelo; Guizouarn, Helene; Biondani, Andrea; Pantaleo, Antonella; De Franceschi, Lucia


    Background Stomatocytoses are a group of inherited autosomal dominant hemolytic anemias and include overhydrated hereditary stomatocytosis, dehydrated hereditary stomatocytosis, hereditary cryohydrocytosis and familial pseudohyperkalemia. Design and Methods We report a novel variant of hereditary stomatocytosis due to a de novo band 3 mutation (p. G796R-band3 CEINGE) associated with a dyserythropoietic phenotype. Band 3 genomic analysis, measurement at of hematologic parameters and red cell indices and morphological analysis of bone marrow were carried out. We then evaluated the red cell membrane permeability and ion transport systems by functional studies of the patient’s erythrocytes and Xenopus oocytes transfected with mutated band 3. We analyzed the red cell membrane tyrosine phosphorylation profile and the membrane association of the tyrosine kinases Syk and Lyn from the Src-family-kinase group, since the activity of the membrane cation transport pathways is related to cyclic phosphorylation-dephosphorylation events. Results The patient showed mild hemolytic anemia with circulating stomatocytes together with signs of dyserythropoiesis. Her red cells displayed increased Na+ content with decreased K+content and abnormal membrane cation transport activities. Functional characterization of band 3 CEINGE in Xenopus oocytes showed that the mutated band 3 is converted from being an anion exchanger (Cl−, HCO3−) to being a cation pathway for Na+ and K+. Increased tyrosine phosphorylation of some red cell membrane proteins was observed in diseased erythrocytes. Syk and Lyn membrane association was increased in the patient’s red cells compared to in normal controls, indicating perturbation of phospho-signaling pathways involved in cell volume regulation events. Conclusions Band 3 CEINGE alters function from that of anion exchange to cation transport, affects the membrane tyrosine phosphorylation profile, in particular of band 3 and stomatin, and its presence

  2. [Histone variants and histone exchange]. (United States)

    Wu, Nan; Gui, Jian-Fang


    Histones, as the basic components of nucleosome, are essential to chromatin structure and function. To adapt to various states of chromatin, corresponding histone variants are incorporated in nucleosome, and certain modifications also occur on the variants' tails. These variants change the conformation and stability of nucleosome to facilitate transcriptional activation or deactivation, DNA repairing, heterochromatin formation, and others. During histone exchange, chromatin remodeling complex facilitates histone variant deposition into nucleosome, and different variants have diverse deposition pathways. Recently, research on histone variants is not only a new hotspot in epigenetics, but also a new annotation of "histone code". In addition, histone exchange reveals new changing mechanism of DNA-histone interaction.

  3. An Assay for Measuring Histone Variant Exchange within Nucleosomes In Vitro. (United States)

    Laflamme, Liette; Guillemette, Benoit; Gaudreau, Luc


    The incorporation of histone variants into specific chromatin regions is a mechanism by which cells can regulate many important biological processes. One such example is H2A.Z, a highly conserved variant of H2A that is incorporated in genomic regulatory regions and contributes to control gene expression. H2A.Z variant exchange involves the removal of H2A-H2B dimers from a preassembled nucleosome and their replacement with H2A.Z-H2B dimers. A specific family of chromatin remodeling complexes, homologous to the yeast Swr1 complex, have been shown to be capable of this histone exchange activity both in vivo and in vitro. Here, we describe an assay to measure the histone H2A.Z exchange activity of recombinant human p400 on immobilized mononucleosomes in vitro. The assay can be adapted to other histone exchange complexes/catalytic subunits purified from any species.

  4. Two novel haemoglobin variants that affect haemoglobin A1c measurement by ion-exchange chromatography. (United States)

    Bots, Michael; Stroobants, An K; Delzenne, Barend; Soeters, Maarten R; de Vries, Johan E; Weykamp, Cas W; Norg, Roelf J C; Veldthuis, Martijn; Zwieten, Rob van


    Haemoglobin (Hb) variants are well-known factors interfering with accurate HbA1c testing. This report describes two novel Hb variants leading to inappropriate quantification of HbA1c by ion-exchange chromatography. Glycated forms of novel Hb variants were recognised in the blood of two patients with diabetes mellitus screened by HbA1c ion-exchange chromatography. Dedicated high-resolution cation-exchange chromatography and subsequent DNA sequencing revealed the exact nature of the variants. Other common techniques for quantifying HbA1c were applied on both samples and haematological parameters were determined to judge possible pathology associated with the novel Hb variants. A fraction of 15% of abnormal Hb was observed in a 37-year-old female. DNA sequencing revealed a heterozygous mutation in the α1-globin gene, resulting in a leucine-to-phenylalanine amino-acid substitution (HBA1: c.301C>T, p.Leu101Phe). We named this variant Hb Weesp. The other novel variant, Hb Haelen, presented as a 40% fraction in a 63-year-old male and resulted from a heterozygous amino acid substitution in the β-globin gene (HBB: c.335T>C, p.Val112Gly). The presence of both Hb variants resulted in aberrant separation of the Hb components, leading to an inadequate quantification of HbA1c. Close examination of HbA1c chromatograms revealed two novel, clinically silent Hb variants that interfere with HbA1c quantification. Healthcare providers need to be aware of the potential of such Hb variants when interpreting HbA1c results.

  5. Simulation model for overloaded monoclonal antibody variants separations in ion-exchange chromatography. (United States)

    Guélat, Bertrand; Ströhlein, Guido; Lattuada, Marco; Delegrange, Lydia; Valax, Pascal; Morbidelli, Massimo


    A model was developed for the design of a monoclonal antibody charge variants separation process based on ion-exchange chromatography. In order to account for a broad range of operating conditions in the simulations, an explicit pH and salt concentration dependence has been included in the Langmuir adsorption isotherm. The reliability of this model was tested using experimental chromatographic retention times as well as information about the structural characteristics of the different charge variants, e.g. C-terminal lysine groups and deamidated groups. Next, overloaded isocratic elutions at various pH and salt concentrations have been performed to determine the saturation capacity of the ion-exchanger. Furthermore, the column simulation model was applied for the prediction of monoclonal antibody variants separations with both pH and salt gradient elutions. A good prediction of the elution times and peak shapes was observed, even though none of the model parameters was adjusted to fit the experimental data. The trends in the separation performance obtained through the simulations were generally sufficient to identify the most promising operating conditions. The predictive column simulation model thus developed in this work, including a set of parameters determined through specific independent experiments, was experimentally validated and offers a useful basis for a rational optimization of monoclonal antibody variants separation processes on ion-exchange chromatography. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Electrostatic contributions to protein retention in ion-exchange chromatography. 1. Cytochrome C variants. (United States)

    Yao, Yan; Lenhoff, Abraham M


    Among the factors that modulate protein interactions, several protein structural properties, such as size, shape, and charge distribution, may play significant roles. In this work, we investigate the influence of protein structure on binding in ion-exchange chromatography, in which electrostatic interactions are dominant. Chromatographic experiments show separation of cytochrome c variants with a limited number of sequence differences to be feasible. To probe the molecular basis for this behavior, protein-adsorbent electrostatic interactions were modeled in the context of continuum electrostatics accounting for the full 3D protein structure. Protein retention was modeled by averaging over all protein-adsorbent configurations using the full accessible surface of the protein. The electrostatic interaction free energy distribution shows that configurations in which numerous positive protein charges are close to the cation exchanger functional groups produce the most favorable binding. The calculated binding equilibrium constant, found by averaging over the full 3D configurational space, captures the chromatographic differentiation of closely related cytochrome c variants. To obviate the need for full sampling of protein configurations, calculations of interaction free energies at short protein-adsorbent separation distances or of protein surface potentials were found to yield reasonable semiquantitative descriptions of the retention trends.

  7. Mechanistic modeling of ion-exchange process chromatography of charge variants of monoclonal antibody products. (United States)

    Kumar, Vijesh; Leweke, Samuel; von Lieres, Eric; Rathore, Anurag S


    Ion-exchange chromatography (IEX) is universally accepted as the optimal method for achieving process scale separation of charge variants of a monoclonal antibody (mAb) therapeutic. These variants are closely related to the product and a baseline separation is rarely achieved. The general practice is to fractionate the eluate from the IEX column, analyze the fractions and then pool the desired fractions to obtain the targeted composition of variants. This is, however, a very cumbersome and time consuming exercise. A mechanistic model that is capable of simulating the peak profile will be a much more elegant and effective way to make a decision on the pooling strategy. This paper proposes a mechanistic model, based on the general rate model, to predict elution peak profile for separation of the main product from its variants. The proposed approach uses inverse fit of process scale chromatogram for estimation of model parameters using the initial values that are obtained from theoretical correlations. The packed bed column has been modeled along with the chromatographic system consisting of the mixer, tubing and detectors as a series of dispersed plug flow and continuous stirred tank reactors. The model uses loading ranges starting at 25% to a maximum of 70% of the loading capacity and hence is applicable to process scale separations. Langmuir model has been extended to include the effects of salt concentration and temperature on the model parameters. The extended Langmuir model that has been proposed uses one less parameter than the SMA model and this results in a significant ease of estimating the model parameters from inverse fitting. The proposed model has been validated with experimental data and has been shown to successfully predict peak profile for a range of load capacities (15-28mg/mL), gradient lengths (10-30CV), bed heights (6-20cm), and for three different resins with good accuracy (as measured by estimation of residuals). The model has been also

  8. Protein adsorption on ion exchange resins and monoclonal antibody charge variant modulation. (United States)

    Guélat, Bertrand; Khalaf, Rushd; Lattuada, Marco; Costioli, Matteo; Morbidelli, Massimo


    A novel multicomponent adsorption equilibrium model for proteins on ion-exchange resins is developed on a statistical thermodynamic basis including surface coverage effects and protein-resin and protein-protein interactions. The resulting model exhibits a general competitive Langmuirian behavior and was applied to the study and optimization of the separation of monoclonal antibody charge variants on two strong cation exchangers. The model accounts explicitly for the effect of both pH and salt concentration, and its parameters can be determined in diluted conditions, that is, through physically sound assumptions, all model parameters can be obtained using solely experiments in diluted conditions, and be used to make predictions in overloaded conditions. The parameterization of the model and optimization of the separation is based on a two-step approach. First, gradient experiments in diluted conditions are undertaken in order to determine the model parameters. Based on these experiments and on information about the proteins of interest and the stationary phase used, all the model parameters can be estimated. Second, using the parameterized model, an initial Pareto optimization is undertaken where overloaded operating conditions are investigated. Experiments from this Pareto set are then used to refine the estimation of the model parameters. A second Pareto optimization can then be undertaken, this time with the refined parameters. This can be repeated until a satisfactory set of model parameters is found. This iterative approach is shown to be extremely efficient and to provide large amounts of knowledge based on only a few experiments. It is shown that due to the strong physical foundation of the model and the very low number of adjustable parameters, the number of iterations is expected to be at most two or three. Furthermore, the model based tool is improved as more experimental knowledge is provided, allowing for better estimations of the chromatographic

  9. lac repressor mutants with double or triple exchanges in the recognition helix bind specifically to lac operator variants with multiple exchanges. (United States)

    Sartorius, J; Lehming, N; Kisters, B; von Wilcken-Bergmann, B; Müller-Hill, B


    Several lac repressor mutants have been isolated which repress beta-galactosidase synthesis in Escherichia coli up to 200-fold. They do so by binding specifically to particular symmetrical lac Oc operator variants. The mutations in the lac repressor are localized in two separate parts of the recognition helix comprising (i) residues 1 and 2 which interact with base pairs 4 and 5 of lac operator and (ii) residue 6 which recognizes operator base pair 6. Mutations of residues 1 and 2 may be combined with a mutation of residue 6. The resulting mutant protein binds specifically to an operator variant with three symmetric exchanges in base pairs 4, 5 and 6. PMID:2663473

  10. Hydrogen Exchange Mass Spectrometry of Related Proteins with Divergent Sequences: A Comparative Study of HIV-1 Nef Allelic Variants (United States)

    Wales, Thomas E.; Poe, Jerrod A.; Emert-Sedlak, Lori; Morgan, Christopher R.; Smithgall, Thomas E.; Engen, John R.


    Hydrogen exchange mass spectrometry can be used to compare the conformation and dynamics of proteins that are similar in tertiary structure. If relative deuterium levels are measured, differences in sequence, deuterium forward- and back-exchange, peptide retention time, and protease digestion patterns all complicate the data analysis. We illustrate what can be learned from such data sets by analyzing five variants (Consensus G2E, SF2, NL4-3, ELI, and LTNP4) of the HIV-1 Nef protein, both alone and when bound to the human Hck SH3 domain. Regions with similar sequence could be compared between variants. Although much of the hydrogen exchange features were preserved across the five proteins, the kinetics of Nef binding to Hck SH3 were not the same. These observations may be related to biological function, particularly for ELI Nef where we also observed an impaired ability to downregulate CD4 surface presentation. The data illustrate some of the caveats that must be considered for comparison experiments and provide a framework for investigations of other protein relatives, families, and superfamilies with HX MS.

  11. Mechanistic Modeling Based PAT Implementation for Ion-Exchange Process Chromatography of Charge Variants of Monoclonal Antibody Products. (United States)

    Kumar, Vijesh; Rathore, Anurag S


    Process chromatography is typically used to remove product related impurities and variants that have very similar physicochemical properties to the product. Baseline separation may not be achieved in most cases due to high protein loading and thus, pooling of the elution peak can be challenging for maximizing yield and achieving consistency in product quality. Batch-to-batch variability in quality of the feed material also occurs in commercial manufacturing. Mechanistic modeling of process chromatography, though non-trivial, can be an enabler for implementation of Process Analytical Technology. This paper presents one such application involving prediction of the impact of variability in feed quality and in gradient shape on separation of charge variants by cation exchange process chromatography and thereby facilitating feed forward control. Five batches having different compositions of charge variants have been used to demonstrate the proposed pooling strategy based on simulated chromatograms and the outcome has been compared to offline pooling based on fractionation. For all the conditions examined and for the desired target of main product (67%), the proposed approach resulted in remarkable consistency in product quality (67 ± 2%) while delivering a yield of greater than 90%. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Identification of a rare variant haemoglobin (Hb Sinai-Baltimore) causing spuriously low haemoglobin A(1c) values on ion exchange chromatography. (United States)

    Smith, Geoff; Murray, Heather; Brennan, Stephen O


    Commonly used methods for assay of haemoglobin A(1c) (HbA(1c)) are susceptible to interference from the presence of haemoglobin variants. In many systems, the common variants can be identified but scientists and pathologists must remain vigilant for more subtle variants that may result in spuriously high or low HbA(1c) values. It is clearly important to recognize these events whether HbA(1c) is being used as a monitoring tool or, as is increasingly the case, for diagnostic purposes. We report a patient with a rare haemoglobin variant (Hb Sinai-Baltimore) that resulted in spuriously low values of HbA(1c) when assayed using ion exchange chromatography, and the steps taken to elucidate the nature of the variant.

  13. Chromatography of proteins on charge-variant ion exchangers and implications for optimizing protein uptake rates. (United States)

    Langford, John F; Xu, Xuankuo; Yao, Yan; Maloney, Sean F; Lenhoff, Abraham M


    Intraparticle transport of proteins usually represents the principal resistance controlling their uptake in preparative separations. In ion-exchange chromatography two limiting models are commonly used to describe such uptake: pore diffusion, in which only free protein in the pore lumen contributes to transport, and homogeneous diffusion, in which the transport flux is determined by the gradient in the total protein concentration, free or adsorbed. Several studies have noted a transition from pore to homogeneous diffusion with increasing ionic strength in some systems, and here we investigate the mechanistic basis for this transition. The studies were performed on a set of custom-synthesized methacrylate-based strong cation exchangers differing in ligand density into which uptake of two proteins was examined using confocal microscopy and frontal loading experiments. We find that the transition in uptake mechanism occurs in all cases studied, and generally coincides with an optimum in the dynamic binding capacity at moderately high flow rates. The transition appears to occur when protein-surface attraction is weakened sufficiently, and this is correlated with the isocratic retention factor k' for the system of interest: the transition occurs in the vicinity of k' approximately 3000. This result, which may indicate that adsorption is sufficiently weak to allow the protein to diffuse along or near the surface, provides a predictive basis for optimizing preparative separations using only isocratic retention data.

  14. Reorganization of Damaged Chromatin by the Exchange of Histone Variant H2A.Z-2

    Energy Technology Data Exchange (ETDEWEB)

    Nishibuchi, Ikuno [Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima (Japan); Department of Radiation Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Department of Radiation Oncology, Hiroshima Prefectural Hospital, Hiroshima (Japan); Suzuki, Hidekazu; Kinomura, Aiko; Sun, Jiying; Liu, Ning-Ang [Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima (Japan); Horikoshi, Yasunori [Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima (Japan); Research Center for Mathematics of Chromatin Live Dynamics, Hiroshima University, Hiroshima (Japan); Shima, Hiroki [Department of Biochemistry, Graduate School of Medical Sciences, Tohoku University, Sendai (Japan); Kusakabe, Masayuki; Harata, Masahiko [Laboratory of Molecular Biology, Graduate School of Agricultural Science, Tohoku University, Sendai (Japan); Fukagawa, Tatsuo [Department of Molecular Genetics, National Institute of Genetics and The Graduate University for Advanced Studies, Mishima (Japan); Ikura, Tsuyoshi [Laboratory of Chromatin Regulatory Network, Department of Mutagenesis, Radiation Biology Center, Kyoto University, Kyoto (Japan); Ishida, Takafumi [Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Nagata, Yasushi [Department of Radiation Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Tashiro, Satoshi, E-mail: [Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima (Japan); Research Center for Mathematics of Chromatin Live Dynamics, Hiroshima University, Hiroshima (Japan)


    Purpose: The reorganization of damaged chromatin plays an important role in the regulation of the DNA damage response. A recent study revealed the presence of 2 vertebrate H2A.Z isoforms, H2A.Z-1 and H2A.Z-2. However, the roles of the vertebrate H2A.Z isoforms are still unclear. Thus, in this study we examined the roles of the vertebrate H2A.Z isoforms in chromatin reorganization after the induction of DNA double-strand breaks (DSBs). Methods and Materials: To examine the dynamics of H2A.Z isoforms at damaged sites, we constructed GM0637 cells stably expressing each of the green fluorescent protein (GFP)-labeled H2A.Z isoforms, and performed fluorescence recovery after photobleaching (FRAP) analysis and inverted FRAP analysis in combination with microirradiation. Immunofluorescence staining using an anti-RAD51 antibody was performed to study the kinetics of RAD51 foci formation after 2-Gy irradiation of wild-type (WT), H2A.Z-1- and H2A.Z-2-deficient DT40 cells. Colony-forming assays were also performed to compare the survival rates of WT, H2A.Z-1-, and H2A.Z-2-deficient DT40 cells with control, and H2A.Z-1- and H2A.Z-2-depleted U2OS cells after irradiation. Results: FRAP analysis revealed that H2A.Z-2 was incorporated into damaged chromatin just after the induction of DSBs, whereas H2A.Z-1 remained essentially unchanged. Inverted FRAP analysis showed that H2A.Z-2 was released from damaged chromatin. These findings indicated that H2A.Z-2 was exchanged at DSB sites immediately after the induction of DSBs. RAD51 focus formation after ionizing irradiation was disturbed in H2A.Z-2-deficient DT40 cells but not in H2A.Z-1-deficient cells. The survival rate of H2A.Z-2-deficient cells after irradiation was lower than those of WT and H2A.Z-1- DT40 cells. Similar to DT40 cells, H2A.Z-2-depleted U2OS cells were also radiation-sensitive compared to control and H2A.Z-1-depleted cells. Conclusions: We found that vertebrate H2A.Z-2 is involved in the regulation of the DNA

  15. More than 150 novel variants of HLA class I genes detected in German Stem Cell Donor Registry and UCLA International Cell Exchange samples. (United States)

    Balz, V; Krause, S; Fischer, J; Enczmann, J


    High throughput analysis using amplicon-based next-generation sequencing (NGS) of HLA class I genes in samples of registered stem cell donors of the German Stem Cell Donor Registry Düsseldorf revealed 151 novel variants. In addition, four new variants were identified in well-defined samples obtained from the UCLA International Cell Exchange program. New alleles included 37 HLA-A, 57 HLA-B, and 61 HLA-C variant alleles. All variants were confirmed by NGS of HLA-A, HLA-B, and HLA-C genes including the respective 5' and 3' untranslated regions as well as Sanger sequence analysis. Mainly, the variants encompass single nucleotide changes in intronic as well as exonic parts of the genes. We identified intronic variations in 114 new alleles, nonsynonymous nucleotide changes in 25 alleles, synonymous nucleotide changes in nine alleles, and three hybrid alleles. Four alleles carry exonic deletions or insertions resulting in frameshift of peptide translation. Two novel alleles of HLA-C were shown to result in splicing defects of the transcript. Two alleles showed exonic as well as intronic changes. Thirty-four of the new alleles were found in multiple samples. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Investigating the Interaction between the Neonatal Fc Receptor and Monoclonal Antibody Variants by Hydrogen/Deuterium Exchange Mass Spectrometry

    DEFF Research Database (Denmark)

    Jensen, Pernille Foged; Larraillet, Vincent; Schlothauer, Tilman


    in understanding and modulating the IgG-FcRn interaction to optimize antibody pharmacokinetics and ultimately improve efficacy and safety. Here we studied the interaction between a full-length human IgG1 and human FcRn via hydrogen/deuterium exchange mass spectrometry and targeted electron transfer dissociation......-type glycosylated IgG. Our results provide new molecular insight into the IgG-FcRn interaction and illustrate the capability of hydrogen/deuterium exchange mass spectrometry to advance structural proteomics by providing detailed information on the conformation and dynamics of large protein complexes in solution....

  17. Beta-adducin and sodium-calcium exchanger 1 gene variants are associated with systemic lupus erythematosus and lupus nephritis. (United States)

    Ramirez, Giuseppe A; Lanzani, Chiara; Bozzolo, Enrica P; Zagato, Laura; Citterio, Lorena; Casamassima, Nunzia; Canti, Valentina; Sabbadini, Maria Grazia; Rovere-Querini, Patrizia; Manunta, Paolo; Manfredi, Angelo A


    Genetic research in systemic lupus erythematosus (SLE) is rapidly developing, and numerous sets of genes are being associated with specific clinical subphenotypes in the setting of SLE. On the other hand, basic science studies are revealing strong connections between salt-water balance and inflammation. The aim of this study was to evaluate whether variants of genes known to influence the individual susceptibility to hypertension also influence the renal function in a cohort of SLE patients with and without lupus nephritis (LN). This study is a case-control study with candidate gene approach. A total of 111 patients with SLE (50 with SLE without nephritis, 55 with LN and 6 with simple urinary sediment abnormalities) and 62 healthy controls (HC) were genotyped for NCX1 rs11893826 (NCX1a) and rs434082 (NCX1b) and ADD2 rs4984 SNPs. Patients with ADD2 CT genotype were protected from LN and skin involvement; ADD2 CC | NCX1a AA/AG genotypes were associated with the presence of anti-cardiolipin antibodies; NCX1a AA genotype was slightly more frequent in lupus patients than in HC and associated with relapse risk and higher creatinine in patients with LN. NCX1b GG patients with LN had increased chances to reach complete remission. NCX1b GG | NCX1a GG genotype is associated with joint involvement. ADD2 and NCX1 variants influence the risk and the clinical features of SLE and LN, highlighting their potential role in regulating systemic inflammation and/or the local response to immune-mediated injury.

  18. Investigating the Interaction between the Neonatal Fc Receptor and Monoclonal Antibody Variants by Hydrogen/Deuterium Exchange Mass Spectrometry* (United States)

    Jensen, Pernille Foged; Larraillet, Vincent; Schlothauer, Tilman; Kettenberger, Hubert; Hilger, Maximiliane; Rand, Kasper D.


    The recycling of immunoglobulins by the neonatal Fc receptor (FcRn) is of crucial importance in the maintenance of antibody levels in plasma and is responsible for the long half-lives of endogenous and recombinant monoclonal antibodies. From a therapeutic point of view there is great interest in understanding and modulating the IgG–FcRn interaction to optimize antibody pharmacokinetics and ultimately improve efficacy and safety. Here we studied the interaction between a full-length human IgG1 and human FcRn via hydrogen/deuterium exchange mass spectrometry and targeted electron transfer dissociation to map sites perturbed by binding on both partners of the IgG–FcRn complex. Several regions in the antibody Fc region and the FcRn were protected from exchange upon complex formation, in good agreement with previous crystallographic studies of FcRn in complex with the Fc fragment. Interestingly, we found that several regions in the IgG Fab region also showed reduced deuterium uptake. Our findings indicate the presence of hitherto unknown FcRn interaction sites in the Fab region or a possible conformational link between the IgG Fc and Fab regions upon FcRn binding. Further, we investigated the role of IgG glycosylation in the conformational response of the IgG–FcRn interaction. Removal of antibody glycans increased the flexibility of the FcRn binding site in the Fc region. Consequently, FcRn binding did not induce a similar conformational stabilization of deglycosylated IgG as observed for the wild-type glycosylated IgG. Our results provide new molecular insight into the IgG–FcRn interaction and illustrate the capability of hydrogen/deuterium exchange mass spectrometry to advance structural proteomics by providing detailed information on the conformation and dynamics of large protein complexes in solution. PMID:25378534

  19. Investigating the interaction between the neonatal Fc receptor and monoclonal antibody variants by hydrogen/deuterium exchange mass spectrometry. (United States)

    Jensen, Pernille Foged; Larraillet, Vincent; Schlothauer, Tilman; Kettenberger, Hubert; Hilger, Maximiliane; Rand, Kasper D


    The recycling of immunoglobulins by the neonatal Fc receptor (FcRn) is of crucial importance in the maintenance of antibody levels in plasma and is responsible for the long half-lives of endogenous and recombinant monoclonal antibodies. From a therapeutic point of view there is great interest in understanding and modulating the IgG-FcRn interaction to optimize antibody pharmacokinetics and ultimately improve efficacy and safety. Here we studied the interaction between a full-length human IgG(1) and human FcRn via hydrogen/deuterium exchange mass spectrometry and targeted electron transfer dissociation to map sites perturbed by binding on both partners of the IgG-FcRn complex. Several regions in the antibody Fc region and the FcRn were protected from exchange upon complex formation, in good agreement with previous crystallographic studies of FcRn in complex with the Fc fragment. Interestingly, we found that several regions in the IgG Fab region also showed reduced deuterium uptake. Our findings indicate the presence of hitherto unknown FcRn interaction sites in the Fab region or a possible conformational link between the IgG Fc and Fab regions upon FcRn binding. Further, we investigated the role of IgG glycosylation in the conformational response of the IgG-FcRn interaction. Removal of antibody glycans increased the flexibility of the FcRn binding site in the Fc region. Consequently, FcRn binding did not induce a similar conformational stabilization of deglycosylated IgG as observed for the wild-type glycosylated IgG. Our results provide new molecular insight into the IgG-FcRn interaction and illustrate the capability of hydrogen/deuterium exchange mass spectrometry to advance structural proteomics by providing detailed information on the conformation and dynamics of large protein complexes in solution. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Charge variants characterization of a monoclonal antibody by ion exchange chromatography coupled on-line to native mass spectrometry: Case study after a long-term storage at +5°C. (United States)

    Leblanc, Y; Ramon, C; Bihoreau, N; Chevreux, G


    Numerous putative post-translational modifications may induce variations of monoclonal antibodies charge distribution that can potentially affect their biological activity. The characterization and the monitoring of these charge variants are critical quality requirements to ensure stability and process consistency. Charge variants are usually characterized by preparative ion exchange chromatography, collection of fractions and subsequent reverse-phase liquid chromatography with mass spectrometry analysis. While this process can be automatized by on-line two-dimensional chromatography, it remains often complex and time consuming. For this reason, a straightforward on-line charge variant analysis method is highly desirable and analytical laboratories are actively pursuing efforts to overcome this challenge. In this study, a mixed mode ion exchange chromatographic method using volatile salts and coupled on-line to native mass spectrometry was developed in association with a middle-up approach for a detailed characterization of monoclonal antibodies charge variants. An aged monoclonal antibody, presenting a complex charge variant profile was successfully investigated by this methodology as a case study. Results demonstrate that deamidation of the heavy chain was the major degradation pathway after long-term storage at 5°C while oxidation was rather low. The method was also very useful to identify all the clipped forms of the antibody. Copyright © 2017 LFB Biotechnologies. Published by Elsevier B.V. All rights reserved.

  1. Validation of a pH gradient-based ion-exchange chromatography method for high-resolution monoclonal antibody charge variant separations. (United States)

    Rea, Jennifer C; Moreno, G Tony; Lou, Yun; Farnan, Dell


    Ion-exchange chromatography is widely used for profiling the charge heterogeneity of proteins, including monoclonal antibodies. Despite good resolving power and robustness, ionic strength-based ion-exchange separations are product-specific and time-consuming to develop. We have previously reported a novel pH-based separation of proteins by cation exchange chromatography that was multi-product, high-resolution, and robust against variations in sample matrix salt concentration and pH. In this study, a pH gradient-based separation method using cation exchange chromatography was evaluated in a mock validation. This method was shown to be robust for monoclonal antibodies and suitable for its intended purpose of charge heterogeneity analysis. Simple mixtures of defined buffer components were used to generate the pH gradients that separated closely related antibody species. Validation characteristics, such as precision and linearity, were evaluated. Robustness to changes in protein load, buffer pH and column oven temperature was demonstrated. The stability-indicating capability of this method was determined using thermally stressed antibody samples. In addition, intermediate precision was demonstrated using multiple instruments, multiple analysts, multiple column lots, and different column manufacturers. Finally, the precision for this method was compared to conventional ion-exchange chromatography and imaged capillary isoelectric focusing. These results demonstrate the superior precision and robustness of this multi-product method, which can be used for the high-throughput evaluation of in-process and final product samples. Copyright © 2010 Elsevier B.V. All rights reserved.

  2. Hydrogen-exchange stability analysis of Bergerac-Src homology 3 variants allows the characterization of a folding intermediate in equilibrium (United States)

    Viguera, Ana-Rosa; Serrano, Luis


    Amide hydrogen/deuterium exchange rates have been determined for two mutants of α-spectrin Src homology 3 domain (WT), containing an elongated stable (SHH) and unstable (SHA) distal loop. SHA, similarly to WT, follows a two-state transition, whereas SHH apparently folds via a three-state mechanism. Native-state amide hydrogen exchange is effective in ascribing energetic readjustments observed in kinetic experiments to species stabilized within the denatured base and distinguishing those from high-energy barrier crossings. Comparison of ΔGex and mex parameters for amide protons of these mutants demonstrates the existence of an intermediate and allows the identification of protons protected in this state. The consolidation of a form containing a prefolded long β-hairpin induces the switch to a three-state mechanism in an otherwise two-state folder. It can be inferred that the unbalanced high stability of individual elements of secondary structure in a polypeptide could ultimately complicate its folding mechanism. PMID:12719536

  3. Competing Noncovalent Host-guest Interactions and H/D Exchange: Reactions of Benzyloxycarbonyl-Proline Glycine Dipeptide Variants with ND3 (United States)

    Miladi, Mahsan; Olaitan, Abayomi D.; Zekavat, Behrooz; Solouki, Touradj


    A combination of density functional theory calculations, hydrogen/deuterium exchange (HDX) reactions, ion mobility-mass spectrometry, and isotope labeling tandem mass spectrometry was used to study gas-phase "host-guest" type interactions of a benzyloxycarbonyl (Z)-capped proline (P) glycine (G) model dipeptide (i.e., Z-PG) and its various structural analogues with ND3. It is shown that in a solvent-free environment, structural differences between protonated and alkali metal ion (Na+, K+, or Cs+)-complexed species of Z-PG affect ND3 adduct formation. Specifically, [Z-PG + H]+ and [Z-PG-OCH3 + H]+ formed gas-phase ND3 adducts ([Z-PG (or Z-PG-OCH3) + H + ND3]+) but no ND3 adducts were observed for [Z-PG + alkali metal]+ or [Z-PG + H - CO2]+. Experimentally measured and theoretically calculated collision cross sections (CCSs) of protonated and alkali metal ion-complexed Z-PG species showed similar trends that agreed with the observed structural differences from molecular modeling results. Moreover, results from theoretical ND3 affinity calculations were consistent with experimental HDX observations, indicating a more stable ND3 adduct for [Z-PG + H]+ compared to [Z-PG + alkali metal]+ species. Molecular modeling and experimental MS results for [Z-PG + H]+ and [Z-PG + alkali metal]+ suggest that optimized cation-π and hydrogen bonding interactions of carbonyl groups in final products are important for ND3 adduct formation.

  4. Barter exchanges

    DEFF Research Database (Denmark)

    Sudzina, Frantisek

    Although barter is often perceived as something that proceeded money, barter is still used. The focus of the paper is on barter exchanges. Barter exchanges are used both in developing countries as well as in developed countries (including the U.S.). They are used by both organizations...... and individuals. They usually allow to exchange good but some include also services. Some exchanges allow only for bi-directional barter, i.e. when only two parties are involved in the exchange. But probably most of the barter exchanges use barter money; this makes it easier to exchange goods and services...

  5. Histone variants in plant transcriptional regulation. (United States)

    Jiang, Danhua; Berger, Frédéric


    Chromatin based organization of eukaryotic genome plays a profound role in regulating gene transcription. Nucleosomes form the basic subunits of chromatin by packaging DNA with histone proteins, impeding the access of DNA to transcription factors and RNA polymerases. Exchange of histone variants in nucleosomes alters the properties of nucleosomes and thus modulates DNA exposure during transcriptional regulation. Growing evidence indicates the important function of histone variants in programming transcription during developmental transitions and stress response. Here we review how histone variants and their deposition machineries regulate the nucleosome stability and dynamics, and discuss the link between histone variants and transcriptional regulation in plants. This article is part of a Special Issue entitled: Plant Gene Regulatory Mechanisms and Networks, edited by Dr. Erich Grotewold and Dr. Nathan Springer. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Rare hemoglobin variants in Tunisian population. (United States)

    Zorai, A; Moumni, I; Mosbahi, I; Douzi, K; Chaouachi, D; Guemira, F; Abbes, S


    During the last 30 years, many studies concerning hemoglobinopathies were realized among Tunisians. More than twenty different thalassemic alleles were detected on the β-globin gene, and less are affecting the α-globin genes. Unusual hemoglobin (Hb) variants other than Hb S, Hb C, and Hb O-arab, which are the most frequent variants in Tunisia, were also detected. Eight Tunisian subjects were studied at phenotypic and molecular levels. Hematological indices and hemoglobin (Hb) pattern were performed by alkaline electrophoresis and isoelectric focusing (IEF),and the Hb fractions were quantitated by cation exchange HPLC. On genomic level, coding regions were amplified by polymerase chain reaction (PCR) followed by a sequencing of the purified PCR products using the dye terminator method. Seven uncommon Hb variants were detected and described for the first time among Tunisians. HbA2-Tunis [δ46(CD5), Gly → Glu, GGG → GAG] is the newly described δ-chain variant in our laboratory, and some other variants (Hb Constant Spring, G San Jose, and Hb J-Bangkok) are very uncommon in the Mediterranean region. We present here an updated review of the Hb variants detected among Tunisians. Twenty-one rare Hb variants were detected affecting the α1-, α2-, δ-, γ-, and β-globin genes, leading in some cases to a severe phenotype especially when the stability is completely altered. The ethnical history of Tunisia could explain this important variability of the observed rare Hb variants. © 2014 John Wiley & Sons Ltd.

  7. Counterflow Regolith Heat Exchanger (United States)

    Zubrin, Robert; Jonscher, Peter


    A problem exists in reducing the total heating power required to extract oxygen from lunar regolith. All such processes require heating a great deal of soil, and the heat energy is wasted if it cannot be recycled from processed material back into new material. The counterflow regolith heat exchanger (CoRHE) is a device that transfers heat from hot regolith to cold regolith. The CoRHE is essentially a tube-in-tube heat exchanger with internal and external augers attached to the inner rotating tube to move the regolith. Hot regolith in the outer tube is moved in one direction by a right-hand - ed auger, and the cool regolith in the inner tube is moved in the opposite direction by a left-handed auger attached to the inside of the rotating tube. In this counterflow arrangement, a large fraction of the heat from the expended regolith is transferred to the new regolith. The spent regolith leaves the heat exchanger close to the temperature of the cold new regolith, and the new regolith is pre-heated close to the initial temperature of the spent regolith. Using the CoRHE can reduce the heating requirement of a lunar ISRU system by 80%, reducing the total power consumption by a factor of two. The unique feature of this system is that it allows for counterflow heat exchange to occur between solids, instead of liquids or gases, as is commonly done. In addition, in variants of this concept, the hydrogen reduction can be made to occur within the counterflow heat exchanger itself, enabling a simplified lunar ISRU (in situ resource utilization) system with excellent energy economy and continuous nonbatch mode operation.

  8. Exchange Network (United States)

    The Environmental Information Exchange Network (EIEN) is an Internet-based system used by state, tribal and territorial partners to securely share environmental and health information with one another and EPA.

  9. Desmoplastic variant of ameloblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Jeong Ick; Kim, Dong Youn; Choi, Karp Shik [Dept. of Dental Radiology, College of Dentistry, Kyungpook National University, Daegu (Korea, Republic of)


    Desmoplastic variant of ameloblastoma is new and unusual variant of ameloblastoma with extensive stromal desmoplastic proliferation. The authors experienced a case of desmoplastic variant of amleloblastoma with moderate-defined radiolucency on the right maxillary anterior area in 62-year-old female. As a result of careful analysis of clinical, radiological examinations, we diagnosed it as desmoplastic variant of ameloblastoma. The following results were obtained; 1. Main clinical symptoms were nontender bony swelling with normal intact overlying mucosa on the right maxillary anterior area. 2. Radiographically, moderate-defined, multilocular radioluceney on the right maxillary anterior area were shown, and severe cortical bony thinning and expansion to labial and palatal sides were also observed. And this lesion was shown to be extended to the right nasal cavity. 3. Histopathologically, follicle-like epithelial islands with densely abundant collagenous stroma were morphologically compressed.

  10. Hydrogen exchange

    DEFF Research Database (Denmark)

    Jensen, Pernille Foged; Rand, Kasper Dyrberg


    Hydrogen exchange (HX) monitored by mass spectrometry (MS) is a powerful analytical method for investigation of protein conformation and dynamics. HX-MS monitors isotopic exchange of hydrogen in protein backbone amides and thus serves as a sensitive method for probing protein conformation...... and dynamics along the entire protein backbone. This chapter describes the exchange of backbone amide hydrogen which is highly quenchable as it is strongly dependent on the pH and temperature. The HX rates of backbone amide hydrogen are sensitive and very useful probes of protein conformation......, as they are distributed along the polypeptide backbone and form the fundamental hydrogen-bonding networks of basic secondary structure. The effect of pressure on HX in unstructured polypeptides (poly-dl-lysine and oxidatively unfolded ribonuclease A) and native folded proteins (lysozyme and ribonuclease A) was evaluated...


    Natural clinoptilolite from Castle Creek, Idaho, and its cation-exchanged variants (Na-Cpt, NaK-Cpt, K-Cpt, and Ca-Cpt) were studied by high-temperature calorimetry. The hydration enthalpy for all clinoptilolites is about -30 kJ/mol H2O (liquid water reference state) at 25 C. T...

  12. Exchange Options

    NARCIS (Netherlands)

    Jamshidian, F.


    The contract is described and market examples given. Essential theoretical developments are introduced and cited chronologically. The principles and techniques of hedging and unique pricing are illustrated for the two simplest nontrivial examples: the classical Black-Scholes/Merton/Margrabe exchange

  13. Hemoglobin Variants in Mice

    Energy Technology Data Exchange (ETDEWEB)

    Popp, Raymond A.


    Variability among mammalian hemoglobins was observed many years ago (35). The chemical basis for differences among hemoglobins from different species of mammals has been studied by several investigators (5, 11, 18, 48). As well as interspecies differences, hemoglobin variants are frequently found within a species of mammals (2, 3, 7, 16) The inheritance of these intraspecies variants can be studied, and pedigrees indicate that the type of hemoglobin synthesized in an individual is genetically controlled (20). Several of the variant human hemoglobins are f'unctionally deficient (7, 16). Such hemoglobin anomalies are of basic interest to man because of the vital role of hemoglobin for transporting oxygen to all tissues of the body.

  14. Ion exchange equilibrium constants

    CERN Document Server

    Marcus, Y


    Ion Exchange Equilibrium Constants focuses on the test-compilation of equilibrium constants for ion exchange reactions. The book first underscores the scope of the compilation, equilibrium constants, symbols used, and arrangement of the table. The manuscript then presents the table of equilibrium constants, including polystyrene sulfonate cation exchanger, polyacrylate cation exchanger, polymethacrylate cation exchanger, polysterene phosphate cation exchanger, and zirconium phosphate cation exchanger. The text highlights zirconium oxide anion exchanger, zeolite type 13Y cation exchanger, and

  15. Histone variants and lipid metabolism

    NARCIS (Netherlands)

    Borghesan, Michela; Mazzoccoli, Gianluigi; Sheedfar, Fareeba; Oben, Jude; Pazienza, Valerio; Vinciguerra, Manlio


    Within nucleosomes, canonical histones package the genome, but they can be opportunely replaced with histone variants. The incorporation of histone variants into the nucleosome is a chief cellular strategy to regulate transcription and cellular metabolism. In pathological terms, cellular steatosis

  16. VARIANT project - further progress (United States)

    Korepanov, V.; Negoda, O.; Alleyne, H.; Balikhin, M.; Fedorov, A.; Juchniewicz, J.; Klimov, S.; Krasnoselskikh, V.; Lefeuvre, F.; Lizunov, G.

    VARIANT is a joint international space experiment which will be performed onboard the Ukrainian remote sensing satellite SICH-1M, that will be launched in 2003 at the polar circular orbit with the altitude 670s30 km. The scientific payload includes three instruments for registration of space current density: split Langmuir probe, Rogovski coil and Faraday cup. The equipment also includes sensors for measurements of electric and magnetic fields in the frequency range from DC to 40 kHz. Main objectives of the VARIANT mission are as follows: u direct comparison of the spectral characteristics of the electric and magnetic fields with the characteristics of the field aligned currents in the polar regions; mapping of the field aligned current distribution; u comparative study of the field aligned current structures with the characteristics of the ionospheric convection observed by the system of radars SuperDARN; u comparative study of technological problems associated with different techniques of current density measurements; and the secondary objectives are: u active experiments with the onboard radar; registration of the signatures of the seismo-active and volcanic phenomena; investigation of the man-made impact upon the ionosphere (anthropogenichazards, pollution, etc). Recent space experiments tendency U smaller and cheaper U stimulated the new approach to the functions division between scientific instruments and DPU. The peculiarities of such approach and the practical example of onboard DPU for VARIANT experiment to be launched next year are reported. Flight model of the VARIANT instrument is already installed onboard the satellite and successfully tested. The methodological questions of the spatial current density direct measurement in space plasma are constantly studied and recent advances in this branch, as well as the experimental tests results are discussed. This work was partially supported by NSAU contract 1221 and INTAS grant 2000-465.

  17. Variants of glycoside hydrolases

    Energy Technology Data Exchange (ETDEWEB)

    Teter, Sarah; Ward, Connie; Cherry, Joel; Jones, Aubrey; Harris, Paul; Yi, Jung


    The present invention relates to variants of a parent glycoside hydrolase, comprising a substitution at one or more positions corresponding to positions 21, 94, 157, 205, 206, 247, 337, 350, 373, 383, 438, 455, 467, and 486 of amino acids 1 to 513 of SEQ ID NO: 2, and optionally further comprising a substitution at one or more positions corresponding to positions 8, 22, 41, 49, 57, 113, 193, 196, 226, 227, 246, 251, 255, 259, 301, 356, 371, 411, and 462 of amino acids 1 to 513 of SEQ ID NO: 2 a substitution at one or more positions corresponding to positions 8, 22, 41, 49, 57, 113, 193, 196, 226, 227, 246, 251, 255, 259, 301, 356, 371, 411, and 462 of amino acids 1 to 513 of SEQ ID NO: 2, wherein the variants have glycoside hydrolase activity. The present invention also relates to nucleotide sequences encoding the variant glycoside hydrolases and to nucleic acid constructs, vectors, and host cells comprising the nucleotide sequences.

  18. Segmented heat exchanger (United States)

    Baldwin, Darryl Dean; Willi, Martin Leo; Fiveland, Scott Byron; Timmons, Kristine Ann


    A segmented heat exchanger system for transferring heat energy from an exhaust fluid to a working fluid. The heat exchanger system may include a first heat exchanger for receiving incoming working fluid and the exhaust fluid. The working fluid and exhaust fluid may travel through at least a portion of the first heat exchanger in a parallel flow configuration. In addition, the heat exchanger system may include a second heat exchanger for receiving working fluid from the first heat exchanger and exhaust fluid from a third heat exchanger. The working fluid and exhaust fluid may travel through at least a portion of the second heat exchanger in a counter flow configuration. Furthermore, the heat exchanger system may include a third heat exchanger for receiving working fluid from the second heat exchanger and exhaust fluid from the first heat exchanger. The working fluid and exhaust fluid may travel through at least a portion of the third heat exchanger in a parallel flow configuration.

  19. Identification of HPV variants. (United States)

    Cason, John; Bible, Jon; Mant, Christine


    The vast majority of anogenital carcinomas are caused by high-risk human papillomaviruses (HPVs), and among Western nations HPV-16 is usually the most predominant cancer-associated type. As a DNA virus, HPV type 16 has a relatively stable genome that is believed to have co-evolved with its host over the millennia. Nevertheless, among the "wild" populations of HPV-16 that are circulating, a large number of variants have been identified, and these may have considerably different pathogenic potentials. In this chapter, methods for screening and characterizing HPV-16 sequence variants are described. In particular, we describe methods for the identification of variation within the HPV-16 E5 open reading frame and for the detection of the nt 131 A-->G mutation of the E6 ORF, using restriction fragment length polymorphism assays. In addition, we describe approaches for DNA sequencing and analysis. Such methods are likely to be of particular interest to those involved in epidemiological investigations of virus transmission and pathogenicity studies.

  20. Variants of windmill nystagmus. (United States)

    Choi, Kwang-Dong; Shin, Hae Kyung; Kim, Ji-Soo; Kim, Sung-Hee; Choi, Jae-Hwan; Kim, Hyo-Jung; Zee, David S


    Windmill nystagmus is characterized by a clock-like rotation of the beating direction of a jerk nystagmus suggesting separate horizontal and vertical oscillators, usually 90° out of phase. We report oculographic characteristics in three patients with variants of windmill nystagmus in whom the common denominator was profound visual loss due to retinal diseases. Two patients showed a clock-like pattern, while in the third, the nystagmus was largely diagonal (in phase or 180° out of phase) but also periodically changed direction by 180°. We hypothesize that windmill nystagmus is a unique manifestation of "eye movements of the blind." It emerges when the central structures, including the cerebellum, that normally keep eye movements calibrated and gaze steady can no longer perform their task, because they are deprived of the retinal image motion that signals a need for adaptive recalibration.

  1. Totalization Data Exchange (TDEX) (United States)

    Social Security Administration — The Totalization Data Exchange (TDEX) process is an exchange between SSA and its foreign country partners to identify deaths of beneficiaries residing abroad. The...

  2. HGVS Recommendations for the Description of Sequence Variants: 2016 Update. (United States)

    den Dunnen, Johan T; Dalgleish, Raymond; Maglott, Donna R; Hart, Reece K; Greenblatt, Marc S; McGowan-Jordan, Jean; Roux, Anne-Francoise; Smith, Timothy; Antonarakis, Stylianos E; Taschner, Peter E M


    The consistent and unambiguous description of sequence variants is essential to report and exchange information on the analysis of a genome. In particular, DNA diagnostics critically depends on accurate and standardized description and sharing of the variants detected. The sequence variant nomenclature system proposed in 2000 by the Human Genome Variation Society has been widely adopted and has developed into an internationally accepted standard. The recommendations are currently commissioned through a Sequence Variant Description Working Group (SVD-WG) operating under the auspices of three international organizations: the Human Genome Variation Society (HGVS), the Human Variome Project (HVP), and the Human Genome Organization (HUGO). Requests for modifications and extensions go through the SVD-WG following a standard procedure including a community consultation step. Version numbers are assigned to the nomenclature system to allow users to specify the version used in their variant descriptions. Here, we present the current recommendations, HGVS version 15.11, and briefly summarize the changes that were made since the 2000 publication. Most focus has been on removing inconsistencies and tightening definitions allowing automatic data processing. An extensive version of the recommendations is available online, at © 2016 WILEY PERIODICALS, INC.

  3. dbVar structural variant cluster set for data analysis and variant comparison [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Lon Phan


    Full Text Available dbVar houses over 3 million submitted structural variants (SSV from 120 human studies including copy number variations (CNV, insertions, deletions, inversions, translocations, and complex chromosomal rearrangements. Users can submit multiple SSVs to dbVAR  that are presumably identical, but were ascertained by different platforms and samples,  to calculate whether the variant is rare or common in the population and allow for cross validation. However, because SSV genomic location reporting can vary – including fuzzy locations where the start and/or end points are not precisely known – analysis, comparison, annotation, and reporting of SSVs across studies can be difficult. This project was initiated by the Structural Variant Comparison Group for the purpose of generating a non-redundant set of genomic regions defined by counts of concordance for all human SSVs placed on RefSeq assembly GRCh38 (RefSeq accession GCF_000001405.26. We intend that the availability of these regions, called structural variant clusters (SVCs, will facilitate the analysis, annotation, and exchange of SV data and allow for simplified display in genomic sequence viewers for improved variant interpretation. Sets of SVCs were generated by variant type for each of the 120 studies as well as for a combined set across all studies. Starting from 3.64 million SSVs, 2.5 million and 3.4 million non-redundant SVCs with count >=1 were generated by variant type for each study and across all studies, respectively. In addition, we have developed utilities for annotating, searching, and filtering SVC data in GVF format for computing summary statistics, exporting data for genomic viewers, and annotating the SVC using external data sources.

  4. Variants of beta-glucosidase

    Energy Technology Data Exchange (ETDEWEB)

    Fidantsef, Ana; Lamsa, Michael; Gorre-Clancy, Brian


    The present invention relates to variants of a parent beta-glucosidase, comprising a substitution at one or more positions corresponding to positions 142, 183, 266, and 703 of amino acids 1 to 842 of SEQ ID NO: 2 or corresponding to positions 142, 183, 266, and 705 of amino acids 1 to 844 of SEQ ID NO: 70, wherein the variant has beta-glucosidase activity. The present invention also relates to nucleotide sequences encoding the variant beta-glucosidases and to nucleic acid constructs, vectors, and host cells comprising the nucleotide sequences.

  5. Variants of beta-glucosidases

    Energy Technology Data Exchange (ETDEWEB)

    Fidantsef, Ana; Lamsa, Michael; Gorre-Clancy, Brian


    The present invention relates to variants of a parent beta-glucosidase, comprising a substitution at one or more positions corresponding to positions 142, 183, 266, and 703 of amino acids 1 to 842 of SEQ ID NO: 2 or corresponding to positions 142, 183, 266, and 705 of amino acids 1 to 844 of SEQ ID NO: 70, wherein the variant has beta-glucosidase activity. The present invention also relates to nucleotide sequences encoding the variant beta-glucosidases and to nucleic acid constructs, vectors, and host cells comprising the nucleotide sequences.

  6. Variants of beta-glucosidase (United States)

    Fidantsef, Ana [Davis, CA; Lamsa, Michael [Davis, CA; Gorre-Clancy, Brian [Elk Grove, CA


    The present invention relates to variants of a parent beta-glucosidase, comprising a substitution at one or more positions corresponding to positions 142, 183, 266, and 703 of amino acids 1 to 842 of SEQ ID NO: 2 or corresponding to positions 142, 183, 266, and 705 of amino acids 1 to 844 of SEQ ID NO: 70, wherein the variant has beta-glucosidase activity. The present invention also relates to nucleotide sequences encoding the variant beta-glucosidases and to nucleic acid constructs, vectors, and host cells comprising the nucleotide sequences.

  7. Product Variant Master as a Means to Handle Variant Design

    DEFF Research Database (Denmark)

    Hildre, Hans Petter; Mortensen, Niels Henrik; Andreasen, Mogens Myrup


    be implemented in the CAD system I-DEAS. A precondition for high degree of computer support is identification of a product variant master from which new variants can be derived. This class platform defines how a product build up fit certain production methods and rules governing determination of modules......, assemblies, and parts. Implementation in an industrial company shows that considerable rationalisation effects can be achieved...

  8. Variant view: visualizing sequence variants in their gene context. (United States)

    Ferstay, Joel A; Nielsen, Cydney B; Munzner, Tamara


    Scientists use DNA sequence differences between an individual's genome and a standard reference genome to study the genetic basis of disease. Such differences are called sequence variants, and determining their impact in the cell is difficult because it requires reasoning about both the type and location of the variant across several levels of biological context. In this design study, we worked with four analysts to design a visualization tool supporting variant impact assessment for three different tasks. We contribute data and task abstractions for the problem of variant impact assessment, and the carefully justified design and implementation of the Variant View tool. Variant View features an information-dense visual encoding that provides maximal information at the overview level, in contrast to the extensive navigation required by currently-prevalent genome browsers. We provide initial evidence that the tool simplified and accelerated workflows for these three tasks through three case studies. Finally, we reflect on the lessons learned in creating and refining data and task abstractions that allow for concise overviews of sprawling information spaces that can reduce or remove the need for the memory-intensive use of navigation.

  9. Gene Variants Reduce Opioid Risks (United States)

    ... common variant (A). Text Description of Graphic Genetic Markers for Individualized Treatments Dr. Jamie Biswas, Chief of ... other health and disease indications—such as cancer, heart disease, and opportunistic infections.” The studies were supported by ...

  10. Charge variant analysis of proposed biosimilar to Trastuzumab. (United States)

    Dakshinamurthy, Pravinkumar; Mukunda, Pavithra; Prasad Kodaganti, Bhargav; Shenoy, Bharath Ravindra; Natarajan, Bairavabalakumar; Maliwalave, Amol; Halan, Vivek; Murugesan, Sathyabalan; Maity, Sunit


    Trastuzumab is a humanized monoclonal antibody (mAb) employed for the treatment of HER2 Positive Breast Cancer. A HER2 overexpressing tumor cell binds to Trastuzumab and attracts immune cells which lead to induction of Antibody Dependent Cellular Cytotoxicity (ADCC) by binding to Fc receptors (CD16a or FcγRIIIa) on an effector cell, such as natural killer (NK) cells. The most commonly expressed receptor on NK cell is CD16a which binds to the Fc portion of Trastuzumab. The ligand-independent HER2-HER3 dimerization is the most potent stimulator of downstream pathways for regulation of cell growth and survival. An attempt has been made in this study to understand the impact of charge heterogeneity on the binding kinetics and potency of the monoclonal antibody. Trastuzumab has a pI range of 8.7-8.9 and is composed of mixture of acidic and basic variants beside the main peak. Ion exchange chromatography was used to isolate the acidic, basic, and main peak fractions from in-house proposed biosimilar to Trastuzumab and their activities were compared to the Innovator Trastuzumab Herclon(®). Data from the mass analysis confirmed the potential modifications in both acidic and basic variant. Binding activity studies performed using Surface Plasmon Resonance (SPR) revealed that acidic variants had lesser binding to HER2 in comparison to the basic variants. Both acidic and basic variant showed no significant changes in their binding to soluble CD16a receptors. In vitro assay studies using a breast cancer cell line (BT-474) confirmed the binding potency of acidic variant to be lesser than basic variant, along with reduced anti-proliferative activity for the acidic variant of Trastuzumab. Overall, these data has provided meaningful insights to the impact of antibody charge variants on in vitro potency and CD16 binding affinity of trastuzumab. Copyright © 2016 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  11. VT Telephone Exchange Boundaries (United States)

    Vermont Center for Geographic Information — (Link to Metadata) The UtilityTelecom_EXCHANGE represents Vermont Telephone Exchange boundaries as defined by the VT Public Service Board. The original data was...

  12. Nominal and Real Exchange Rate Models in South Africa: How Robust Are They?


    Egert, Balazs


    This paper addresses difficulties in modelling exchange rates in South Africa. Real exchange rate models of earlier research seem to be sensitive to the sample period considered, alternative variable definition, data frequency and estimation methods. Alternative exchange rate models proposed in this paper including the stock-flow approach and variants of the monetary model are not fully robust to data frequency and alternative estimation periods, either. Nevertheless, adding openness to the s...

  13. Hemoglobin analyses in the Netherlands reveal more than 80 different variants including six novel ones

    NARCIS (Netherlands)

    van Zwieten, Rob; Veldthuis, Martijn; Delzenne, Barend; Berghuis, Jeffrey; Groen, Joke; Ait Ichou, Fatima; Clifford, Els; Harteveld, Cornelis L.; Stroobants, An K.


    Abstract More than 20 000 blood samples of individuals living in The Netherlands and suspected of hemolytic anemia or diabetes were analyzed by high resolution cation exchange high performance liquid chromatography (HPLC). Besides common disease-related hemoglobins (Hbs), rare variants were also

  14. Ideal Heat Exchange System (United States)

    Tsirlin, A. M.


    The requirements with which a heat exchange system should comply in order that at certain values of the total contact surface and heat load the entropy production in it should be minimal have been determined. It has been shown that this system can serve as a standard for real systems of irreversible heat exchange. We have found the conditions for physical realizability of a heat exchange system in which heat exchange occurs by a law linear with respect to the temperature difference between contacting flows. Analogous conditions are given without deriving for the case of heat exchange by the Fourier law.

  15. Resolution exchange simulation. (United States)

    Lyman, Edward; Ytreberg, F Marty; Zuckerman, Daniel M


    We extend replica-exchange simulation in two ways and apply our approaches to biomolecules. The first generalization permits exchange simulation between models of differing resolution--i.e., between detailed and coarse-grained models. Such "resolution exchange" can be applied to molecular systems or spin systems. The second extension is to "pseudoexchange" simulations, which require little CPU usage for most levels of the exchange ladder and also substantially reduce the need for overlap between levels. Pseudoexchanges can be used in either replica or resolution exchange simulations. We perform efficient, converged simulations of a 50-atom peptide to illustrate the new approaches.

  16. Data-variant kernel analysis

    CERN Document Server

    Motai, Yuichi


    Describes and discusses the variants of kernel analysis methods for data types that have been intensely studied in recent years This book covers kernel analysis topics ranging from the fundamental theory of kernel functions to its applications. The book surveys the current status, popular trends, and developments in kernel analysis studies. The author discusses multiple kernel learning algorithms and how to choose the appropriate kernels during the learning phase. Data-Variant Kernel Analysis is a new pattern analysis framework for different types of data configurations. The chapters include

  17. Certain variants of multipermutohedron ideals

    Indian Academy of Sciences (India)

    016-0313-4. Certain variants of multipermutohedron ideals. AJAY KUMAR1,2 and CHANCHAL KUMAR1,∗. 1Indian Institute of ... 2010 Mathematics Subject Classification. 05E40 .... eral questions and conjectures from [10] and [5]. In particular ...

  18. Adaptively Compressed Exchange Operator

    CERN Document Server

    Lin, Lin


    The Fock exchange operator plays a central role in modern quantum chemistry. The large computational cost associated with the Fock exchange operator hinders Hartree-Fock calculations and Kohn-Sham density functional theory calculations with hybrid exchange-correlation functionals, even for systems consisting of hundreds of atoms. We develop the adaptively compressed exchange operator (ACE) formulation, which greatly reduces the computational cost associated with the Fock exchange operator without loss of accuracy. The ACE formulation does not depend on the size of the band gap, and thus can be applied to insulating, semiconducting as well as metallic systems. In an iterative framework for solving Hartree-Fock-like systems, the ACE formulation only requires moderate modification of the code, and can be potentially beneficial for all electronic structure software packages involving exchange calculations. Numerical results indicate that the ACE formulation can become advantageous even for small systems with tens...

  19. Laser Processed Heat Exchangers (United States)

    Hansen, Scott


    The Laser Processed Heat Exchanger project will investigate the use of laser processed surfaces to reduce mass and volume in liquid/liquid heat exchangers as well as the replacement of the harmful and problematic coatings of the Condensing Heat Exchangers (CHX). For this project, two scale unit test articles will be designed, manufactured, and tested. These two units are a high efficiency liquid/liquid HX and a high reliability CHX.

  20. Microsoft Exchange 2013 cookbook

    CERN Document Server

    Van Horenbeeck, Michael


    This book is a practical, hands-on guide that provides the reader with a number of clear, step-by-step exercises.""Microsoft Exchange 2013 Cookbook"" is targeted at network administrators who deal with the Exchange server in their day-to-day jobs. It assumes you have some practical experience with previous versions of Exchange (although this is not a requirement), without being a subject matter expert.

  1. Microtube strip heat exchanger (United States)

    Doty, F. D.


    During the last quarter, Doty Scientific, Inc. (DSI) continued to make progress on the microtube strip (MTS) heat exchanger. The DSI completed a heat exchanger stress analysis of the ten-module heat exchanger bank; and performed a shell-side flow inhomogeneity analysis of the three-module heat exchanger bank. The company produced 50 tubestrips using an in-house CNC milling machine and began pressing them onto tube arrays. The DSI revised some of the tooling required to encapsulate a tube array and press tubestrips into the array to improve some of the prototype tooling.

  2. Swine Influenza/Variant Influenza Viruses (United States)

    ... Address What's this? Submit What's this? Submit Button Influenza Types Seasonal Avian Swine Variant Other Information on Swine Influenza/Variant Influenza Virus Language: English (US) Español Recommend ...

  3. Semantic prioritization of novel causative genomic variants


    Imane Boudellioua; Rozaimi B Mahamad Razali; Maxat Kulmanov; Yasmeen Hashish; Bajic, Vladimir B.; Eva Goncalves-Serra; Nadia Schoenmakers; Gkoutos, Georgios V.; Schofield, Paul N.; Robert Hoehndorf


    Discriminating the causative disease variant(s) for individuals with inherited or de novo mutations presents one of the main challenges faced by the clinical genetics community today. Computational approaches for variant prioritization include machine learning methods utilizing a large number of features, including molecular information, interaction networks, or phenotypes. Here, we demonstrate the PhenomeNET Variant Predictor (PVP) system that exploits semantic technologies and automated rea...

  4. DHAD variants and methods of screening

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, Kristen J.; Ye, Rick W.


    Methods of screening for dihydroxy-acid dehydratase (DHAD) variants that display increased DHAD activity are disclosed, along with DHAD variants identified by these methods. Such enzymes can result in increased production of compounds from DHAD requiring biosynthetic pathways. Also disclosed are isolated nucleic acids encoding the DHAD variants, recombinant host cells comprising the isolated nucleic acid molecules, and methods of producing butanol.

  5. Variant Humicola grisea CBH1.1

    Energy Technology Data Exchange (ETDEWEB)

    Goedegebuur, Frits; Gualfetti, Peter; Mitchinson, Colin; Larenas, Edmund


    Disclosed are variants of Humicola grisea CeI7A (CBH1.1), H. jecorina CBH1 variant or S. thermophilium CBH1, nucleic acids encoding the same and methods for producing the same. The variant cellulases have the amino acid sequence of a glycosyl hydrolase of family 7A wherein one or more amino acid residues are substituted.

  6. Clinical variants of Guillain-Barre syndrome: some aspects of differential diagnosis. (United States)

    Dididze, M N


    Acute Inflammatory Demyelinating Polyneuropathy--Guillain-Barre syndrome (GBS) affects spinal roots, peripheral and cranial nerves. Various clinical variants of GBS have been described. Isolated cranial nerve involvement without prominent signs of GBS is considered as rare variant of this disease. The aim of the study was to identify clinical characteristics of various forms of GBS particularly in rare variants of the disease. 57 patients with GBS were evaluated based on clinical and electrophysiological data. The following forms of GBS were revealed: 27 had acute inflammatory demyelinating polyradiculoneuropathy, 9--acute motor axonal neuropathy, 12--acute motor and sensory axonal neuropathy, 5--Fisher syndrome and 3--facial diplegia (rare clinical variant). 50 patients were graded 3 or more according to Hughes functional grading scale. Seasonal preponderance was found in spring (March-May) and autumn (September-November). 23 patients received IVIG and 34 were treated by plasma exchange within two weeks after onset. Follow up study revealed: 46 recovered satisfactory, 8 were persistently disabled, 3 died during admission to hospital. Guillain-Barre syndrome showed seasonal distribution and high frequency of axonal forms. Intravenous immunoglobulin therapy was more effective than plasma exchange. Poor outcomes were likely due to severe condition (required mechanical ventilation) and axonal forms. It is crucial to timely identify rare variants of GBS which recover with appropriate treatment.

  7. Soil exchange by means of hexagonal bung honeycombs. Selection of variants in close agreement with the development of te factory at MAN Muenchen-Allach; Bodenaustausch mithilfe von Sechseck-Spundelementen. Variantenwahl in enger Abstimmung mit der Werksentwicklung bei MAN Muenchen-Allach

    Energy Technology Data Exchange (ETDEWEB)

    Brunner, Michael; Dietl, Bernhard; Dietrich, Andreas; Royl, Martin; Wicke, Sabine; Ziebarth, Guenther; Zobel, Reinhard


    A nearly 20,000 cubic meters large, predominantly in the saturated ground zone located pollution of mineral oil had to be redeveloped in the course of measures of surface development at the location Munich-Allach of MAN Nutzfahrzeuge AG. In order to minimize conflicts with the comprehensively planned reorganization of the factory at the Osttor, Dachauer road, temporally, spatially and financially, a soil exchange by means of hexagonal bung honeycombs was planned, advertised and accomplished within a time period of six months. The redevelopment surface with an area of more than 5,000 square meters was released by the authorities of the state capital Munich for unrestricted use.

  8. Coronary artery anatomy and variants. (United States)

    Malagò, Roberto; Pezzato, Andrea; Barbiani, Camilla; Alfonsi, Ugolino; Nicolì, Lisa; Caliari, Giuliana; Pozzi Mucelli, Roberto


    Variants and congenital anomalies of the coronary arteries are usually asymptomatic, but may present with severe chest pain or cardiac arrest. The introduction of multidetector CT coronary angiography (MDCT-CA) allows the detection of significant coronary artery stenosis. Improved performance with isotropic spatial resolution and higher temporal resolution provides a valid alternative to conventional coronary angiography (CCA) in many patients. MDCT-CA is now considered the ideal tool for three-dimensional visualization of the complex and tortuous anatomy of the coronary arteries. With multiplanar and volume-rendered reconstructions, MDCT-CA may even outperform CCA in determining the relative position of vessels, thus providing a better view of the coronary vascular anatomy. The purpose of this review is to describe the normal anatomy of the coronary arteries and their main variants based on MDCT-CA with appropriate reconstructions.

  9. Coronary artery anatomy and variants

    Energy Technology Data Exchange (ETDEWEB)

    Malago, Roberto; Pezzato, Andrea; Barbiani, Camilla; Alfonsi, Ugolino; Nicoli, Lisa; Caliari, Giuliana; Pozzi Mucelli, Roberto [Policlinico G.B. Rossi, University of Verona, Department of Radiology, Verona (Italy)


    Variants and congenital anomalies of the coronary arteries are usually asymptomatic, but may present with severe chest pain or cardiac arrest. The introduction of multidetector CT coronary angiography (MDCT-CA) allows the detection of significant coronary artery stenosis. Improved performance with isotropic spatial resolution and higher temporal resolution provides a valid alternative to conventional coronary angiography (CCA) in many patients. MDCT-CA is now considered the ideal tool for three-dimensional visualization of the complex and tortuous anatomy of the coronary arteries. With multiplanar and volume-rendered reconstructions, MDCT-CA may even outperform CCA in determining the relative position of vessels, thus providing a better view of the coronary vascular anatomy. The purpose of this review is to describe the normal anatomy of the coronary arteries and their main variants based on MDCT-CA with appropriate reconstructions. (orig.)

  10. Clinicopathologic Variants of Mycosis Fungoides. (United States)

    Muñoz-González, H; Molina-Ruiz, A M; Requena, L


    Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma. The clinical course of the disease is typically characterized by progression from a nonspecific phase of erythematous macules to the appearance of plaques and ultimately, in some patients, tumors. However, numerous clinical and histopathologic variants of MF with specific therapeutic and prognostic implications have been described in recent decades. Clarification of the differential diagnosis can be frustrated by the wide range of clinical manifestations and histopathologic patterns of cutaneous infiltration, particularly in the early phases of the disease. In this paper, we review the main clinical, histopathologic, and immunohistochemical characteristics of the variants of MF described in the literature in order to facilitate early diagnosis of the disease. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. GRUNDTVIG in transnational exchange

    DEFF Research Database (Denmark)

    Grundtvig in transnational exchange is the report from the seminar in december 2015 in cooperation with University of Cape Town and University of Hamburg.......Grundtvig in transnational exchange is the report from the seminar in december 2015 in cooperation with University of Cape Town and University of Hamburg....

  12. Optimization of Heat Exchangers

    Energy Technology Data Exchange (ETDEWEB)

    Ivan Catton


    The objective of this research is to develop tools to design and optimize heat exchangers (HE) and compact heat exchangers (CHE) for intermediate loop heat transport systems found in the very high temperature reator (VHTR) and other Generation IV designs by addressing heat transfer surface augmentation and conjugate modeling. To optimize heat exchanger, a fast running model must be created that will allow for multiple designs to be compared quickly. To model a heat exchanger, volume averaging theory, VAT, is used. VAT allows for the conservation of mass, momentum and energy to be solved for point by point in a 3 dimensional computer model of a heat exchanger. The end product of this project is a computer code that can predict an optimal configuration for a heat exchanger given only a few constraints (input fluids, size, cost, etc.). As VAT computer code can be used to model characteristics )pumping power, temperatures, and cost) of heat exchangers more quickly than traditional CFD or experiment, optimization of every geometric parameter simultaneously can be made. Using design of experiment, DOE and genetric algorithms, GE, to optimize the results of the computer code will improve heat exchanger disign.

  13. Education and Industry Exchange (United States)

    Webb, Gerald A.


    Through an exchange plan a school representative worked at the personnel counter of a local company, and a supervisor from that company worked with counselors, faculty, administrators, and students from the local school. The exchange of ideas and insights were of benefit to the school and the company. (KP)

  14. Microcystic Variant of Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Anthony Kodzo-Grey Venyo


    Full Text Available Background. Microcystic variant of urothelial carcinoma is one of the new variants of urothelial carcinoma that was added to the WHO classification in 2004. Aims. To review the literature on microcystic variant of urothelial carcinoma. Methods. Various internet search engines were used to identify reported cases of the tumour. Results. Microscopic features of the tumour include: (i Conspicuous intracellular and intercellular lumina/microcysts encompassed by malignant urothelial or squamous cells. (ii The lumina are usually empty; may contain granular eosinophilic debris, mucin, or necrotic cells. (iii The cysts may be variable in size; round, or oval, up to 2 mm; lined by urothelium which are either flattened cells or low columnar cells however, they do not contain colonic epithelium or goblet cells; are infiltrative; invade the muscularis propria; mimic cystitis cystica and cystitis glandularis; occasionally exhibit neuroendocrine differentiation. (iv Elongated and irregular branching spaces are usually seen. About 17 cases of the tumour have been reported with only 2 patients who have survived. The tumour tends to be of high-grade and high-stage. There is no consensus opinion on the best option of treatment of the tumour. Conclusions. It would prove difficult at the moment to be dogmatic regarding its prognosis but it is a highly aggressive tumour. New cases of the tumour should be reported in order to document its biological behaviour.

  15. Heat exchanger design handbook

    CERN Document Server

    Thulukkanam, Kuppan


    Completely revised and updated to reflect current advances in heat exchanger technology, Heat Exchanger Design Handbook, Second Edition includes enhanced figures and thermal effectiveness charts, tables, new chapter, and additional topics--all while keeping the qualities that made the first edition a centerpiece of information for practicing engineers, research, engineers, academicians, designers, and manufacturers involved in heat exchange between two or more fluids.See What's New in the Second Edition: Updated information on pressure vessel codes, manufacturer's association standards A new c

  16. Anion exchange membrane (United States)

    Verkade, John G; Wadhwa, Kuldeep; Kong, Xueqian; Schmidt-Rohr, Klaus


    An anion exchange membrane and fuel cell incorporating the anion exchange membrane are detailed in which proazaphosphatrane and azaphosphatrane cations are covalently bonded to a sulfonated fluoropolymer support along with anionic counterions. A positive charge is dispersed in the aforementioned cations which are buried in the support to reduce the cation-anion interactions and increase the mobility of hydroxide ions, for example, across the membrane. The anion exchange membrane has the ability to operate at high temperatures and in highly alkaline environments with high conductivity and low resistance.

  17. Variant Interpretation: Functional Assays to the Rescue. (United States)

    Starita, Lea M; Ahituv, Nadav; Dunham, Maitreya J; Kitzman, Jacob O; Roth, Frederick P; Seelig, Georg; Shendure, Jay; Fowler, Douglas M


    Classical genetic approaches for interpreting variants, such as case-control or co-segregation studies, require finding many individuals with each variant. Because the overwhelming majority of variants are present in only a few living humans, this strategy has clear limits. Fully realizing the clinical potential of genetics requires that we accurately infer pathogenicity even for rare or private variation. Many computational approaches to predicting variant effects have been developed, but they can identify only a small fraction of pathogenic variants with the high confidence that is required in the clinic. Experimentally measuring a variant's functional consequences can provide clearer guidance, but individual assays performed only after the discovery of the variant are both time and resource intensive. Here, we discuss how multiplex assays of variant effect (MAVEs) can be used to measure the functional consequences of all possible variants in disease-relevant loci for a variety of molecular and cellular phenotypes. The resulting large-scale functional data can be combined with machine learning and clinical knowledge for the development of "lookup tables" of accurate pathogenicity predictions. A coordinated effort to produce, analyze, and disseminate large-scale functional data generated by multiplex assays could be essential to addressing the variant-interpretation crisis. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  18. Optimization of porous microchannel heat exchanger (United States)

    Kozhukhov, N. N.; Konovalov, D. A.


    The technical progress in information and communication sphere leads to a sharp increase in the use of radio electronic devices. Functioning of radio electronics is accompanied by release of thermal energy, which must be diverted from the heat-stressed element. Moreover, using of electronics at negative temperatures, on the contrary, requires supply of a certain amount of heat to start the system. There arises the task of creating a system that allows both to supply and to divert the necessary amount of thermal energy. The development of complex thermostabilization systems for radio electronic equipment is due to increasing the efficiency of each of its elements separately. For more efficient operation of a heat exchanger, which directly affects the temperature of the heat-stressed element, it is necessary to calculate the mode characteristics and to take into account the effect of its design parameters. The results of optimizing the microchannel heat exchanger are presented in the article. The target optimization functions are the mass, pressure drop and temperature. The parameters of optimization are the layout of porous fins, their geometric dimensions and coolant flow. For the given conditions, the optimum variant of porous microchannel heat exchanger is selected.

  19. Data Exchange Inventory System (DEXI) (United States)

    Social Security Administration — Enterprise tool used to identify data exchanges occurring between SSA and our trading partners. DEXI contains information on both incoming and outgoing exchanges and...

  20. Gardner's Minichess Variant is solved


    Mhalla, Mehdi; Prost, Frederic


    A 5x5 board is the smallest board on which one can set up all kind of chess pieces as a start position. We consider Gardner's minichess variant in which all pieces are set as in a standard chessboard (from Rook to King). This game has roughly 9x10^{18} legal positions and is comparable in this respect with checkers. We weakly solve this game, that is we prove its game-theoretic value and give a strategy to draw against best play for White and Black sides. Our approach requires surprisingly sm...

  1. Microplate Heat Exchanger Project (United States)

    National Aeronautics and Space Administration — We propose a microplate heat exchanger for cryogenic cooling systems used for continuous flow distributed cooling systems, large focal plane arrays, multiple cooling...

  2. Exchange Risk Management Policy

    CERN Document Server


    At the Finance Committee of March 2005, following a comment by the CERN Audit Committee, the Chairman invited the Management to prepare a document on exchange risk management policy. The Finance Committee is invited to take note of this document.

  3. HUD Exchange Grantee Database (United States)

    Department of Housing and Urban Development — The About Grantees section of the HUD Exchange brings up contact information, reports, award, jurisdiction, and location data for organizations that receive HUD...

  4. NASA Earth Exchange (NEX) (United States)

    National Aeronautics and Space Administration — The NASA Earth Exchange (NEX) represents a new platform for the Earth science community that provides a mechanism for scientific collaboration and knowledge sharing....

  5. Anion exchange polymer electrolytes (United States)

    Kim, Yu Seung; Kim, Dae Sik


    Anion exchange polymer electrolytes that include guanidinium functionalized polymers may be used as membranes and binders for electrocatalysts in preparation of anodes for electrochemical cells such as solid alkaline fuel cells.

  6. Cryptographic Combinatorial Securities Exchanges (United States)

    Thorpe, Christopher; Parkes, David C.

    We present a useful new mechanism that facilitates the atomic exchange of many large baskets of securities in a combinatorial exchange. Cryptography prevents information about the securities in the baskets from being exploited, enhancing trust. Our exchange offers institutions who wish to trade large positions a new alternative to existing methods of block trading: they can reduce transaction costs by taking advantage of other institutions’ available liquidity, while third party liquidity providers guarantee execution—preserving their desired portfolio composition at all times. In our exchange, institutions submit encrypted orders which are crossed, leaving a “remainder”. The exchange proves facts about the portfolio risk of this remainder to third party liquidity providers without revealing the securities in the remainder, the knowledge of which could also be exploited. The third parties learn either (depending on the setting) the portfolio risk parameters of the remainder itself, or how their own portfolio risk would change if they were to incorporate the remainder into a portfolio they submit. In one setting, these third parties submit bids on the commission, and the winner supplies necessary liquidity for the entire exchange to clear. This guaranteed clearing, coupled with external price discovery from the primary markets for the securities, sidesteps difficult combinatorial optimization problems. This latter method of proving how taking on the remainder would change risk parameters of one’s own portfolio, without revealing the remainder’s contents or its own risk parameters, is a useful protocol of independent interest.

  7. Histone variants: emerging players in cancer biology (United States)

    Vardabasso, Chiara; Hasson, Dan; Ratnakumar, Kajan; Chung, Chi-Yeh; Duarte, Luis F.


    Histone variants are key players in shaping chromatin structure, and, thus, in regulating fundamental cellular processes such as chromosome segregation and gene expression. Emerging evidence points towards a role for histone variants in contributing to tumor progression, and, recently, the first cancer-associated mutation in a histone variant-encoding gene was reported. In addition, genetic alterations of the histone chaperones that specifically regulate chromatin incorporation of histone variants are rapidly being uncovered in numerous cancers. Collectively, these findings implicate histone variants as potential drivers of cancer initiation and/or progression, and, therefore, targeting histone deposition or the chromatin remodeling machinery may be of therapeutic value. Here, we review the mammalian histone variants of the H2A and H3 families in their respective cellular functions, and their involvement in tumor biology. PMID:23652611

  8. Nested Variant of Urothelial Carcinoma (United States)

    Venyo, Anthony Kodzo-Grey


    Background. Nested variant of urothelial carcinoma was added to the WHO's classification in 2004. Aims. To review the literature on nested variant of urothelial carcinoma. Results. About 200 cases of the tumour have been reported so far and it has the ensuing morphological features: large numbers of small confluent irregular nests of bland-appearing, closely packed, haphazardly arranged, and poorly defined urothelial cells infiltrating the lamina propria and the muscularis propria. The tumour has a bland histomorphologic appearance, has an aggressive biological behaviour, and has at times been misdiagnosed as a benign lesion which had led to a significant delay in the establishment of the correct diagnosis and contributing to the advanced stage of the disease. Immunohistochemically, the tumour shares some characteristic features with high-risk conventional urothelial carcinomas such as high proliferation index and loss of p27 expression. However, p53, bcl-2, or EGF-r immunoreactivity is not frequently seen. The tumour must be differentiated from a number of proliferative lesions of the urothelium. Conclusions. Correct and early diagnosis of this tumour is essential to provide early curative treatment to avoid diagnosis at an advanced stage. A multicentre trial is required to identify treatment options that would improve the outcome of this tumour. PMID:24587796

  9. Hemoglobin analyses in the Netherlands reveal more than 80 different variants including six novel ones. (United States)

    van Zwieten, Rob; Veldthuis, Martijn; Delzenne, Barend; Berghuis, Jeffrey; Groen, Joke; Ait Ichou, Fatima; Clifford, Els; Harteveld, Cornelis L; Stroobants, An K


    More than 20,000 blood samples of individuals living in The Netherlands and suspected of hemolytic anemia or diabetes were analyzed by high resolution cation exchange high performance liquid chromatography (HPLC). Besides common disease-related hemoglobins (Hbs), rare variants were also detected. The variant Hbs were retrospectively analyzed by capillary zone electrophoresis (CZE) and by isoelectric focusing (IEF). For unambiguous identification, the globin genes were sequenced. Most of the 80 Hb variants detected by initial screening on HPLC were also separated by capillary electrophoresis (CE), but a few variants were only detectable with one of these methods. Some variants were unstable, had thalassemic properties or increased oxygen affinity, and some interfered with Hb A2 measurement, detection of sickle cell Hb or Hb A1c quantification. Two of the six novel variants, Hb Enschede (HBA2: c.308G  > A, p.Ser103Asn) and Hb Weesp (HBA1: c.301C > T, p.Leu101Phe), had no clinical consequences. In contrast, two others appeared clinically significant: Hb Ede (HBB: c.53A > T, p.Lys18Met) caused thalassemia and Hb Waterland (HBB: c.428C > T, pAla143Val) was related to mild polycytemia. Hb A2-Venlo (HBD: c.193G > A, p.Gly65Ser) and Hb A2-Rotterdam (HBD: c.38A > C, p.Asn13Thr) interfered with Hb A2 quantification. This survey shows that HPLC analysis followed by globin gene sequencing of rare variants is an effective method to reveal Hb variants.

  10. A review of variant hemoglobins interfering with hemoglobin A1c measurement. (United States)

    Little, Randie R; Roberts, William L


    Hemoglobin A1c (HbA1c) is used routinely to monitor long-term glycemic control in people with diabetes mellitus, as HbA1c is related directly to risks for diabetic complications. The accuracy of HbA1c methods can be affected adversely by the presence of hemoglobin (Hb) variants or elevated levels of fetal hemoglobin (HbF). The effect of each variant or elevated HbF must be examined with each specific method. The most common Hb variants worldwide are HbS, HbE, HbC, and HbD. All of these Hb variants have single amino acid substitutions in the Hb beta chain. HbF is the major hemoglobin during intrauterine life; by the end of the first year, HbF falls to values close to adult levels of approximately 1%. However, elevated HbF levels can occur in certain pathologic conditions or with hereditary persistence of fetal hemoglobin. In a series of publications over the past several years, the effects of these four most common Hb variants and elevated HbF have been described. There are clinically significant interferences with some methods for each of these variants. A summary is given showing which methods are affected by the presence of the heterozygous variants S, E, C, and D and elevated HbF. Methods are divided by type (immunoassay, ion-exchange high-performance liquid chromatography, boronate affinity, other) with an indication of whether the result is artificially increased or decreased by the presence of a Hb variant. Laboratorians should be aware of the limitations of their method with respect to these interferences. 2009 Diabetes Technology Society.

  11. Reliably Detecting Clinically Important Variants Requires Both Combined Variant Calls and Optimized Filtering Strategies.

    Directory of Open Access Journals (Sweden)

    Matthew A Field

    Full Text Available A diversity of tools is available for identification of variants from genome sequence data. Given the current complexity of incorporating external software into a genome analysis infrastructure, a tendency exists to rely on the results from a single tool alone. The quality of the output variant calls is highly variable however, depending on factors such as sequence library quality as well as the choice of short-read aligner, variant caller, and variant caller filtering strategy. Here we present a two-part study first using the high quality 'genome in a bottle' reference set to demonstrate the significant impact the choice of aligner, variant caller, and variant caller filtering strategy has on overall variant call quality and further how certain variant callers outperform others with increased sample contamination, an important consideration when analyzing sequenced cancer samples. This analysis confirms previous work showing that combining variant calls of multiple tools results in the best quality resultant variant set, for either specificity or sensitivity, depending on whether the intersection or union, of all variant calls is used respectively. Second, we analyze a melanoma cell line derived from a control lymphocyte sample to determine whether software choices affect the detection of clinically important melanoma risk-factor variants finding that only one of the three such variants is unanimously detected under all conditions. Finally, we describe a cogent strategy for implementing a clinical variant detection pipeline; a strategy that requires careful software selection, variant caller filtering optimizing, and combined variant calls in order to effectively minimize false negative variants. While implementing such features represents an increase in complexity and computation the results offer indisputable improvements in data quality.

  12. Exchanging Description Logic Knowledge Bases

    NARCIS (Netherlands)

    Arenas, M.; Botoeva, E.; Calvanese, D.; Ryzhikov, V.; Sherkhonov, E.


    In this paper, we study the problem of exchanging knowledge between a source and a target knowledge base (KB), connected through mappings. Differently from the traditional database exchange setting, which considers only the exchange of data, we are interested in exchanging implicit knowledge. As

  13. Mitochondrial DNA variants in obesity.

    Directory of Open Access Journals (Sweden)

    Nadja Knoll

    Full Text Available Heritability estimates for body mass index (BMI variation are high. For mothers and their offspring higher BMI correlations have been described than for fathers. Variation(s in the exclusively maternally inherited mitochondrial DNA (mtDNA might contribute to this parental effect. Thirty-two to 40 mtDNA single nucleotide polymorphisms (SNPs were available from genome-wide association study SNP arrays (Affymetrix 6.0. For discovery, we analyzed association in a case-control (CC sample of 1,158 extremely obese children and adolescents and 435 lean adult controls. For independent confirmation, 7,014 population-based adults were analyzed as CC sample of n = 1,697 obese cases (BMI ≥ 30 kg/m2 and n = 2,373 normal weight and lean controls (BMI<25 kg/m2. SNPs were analyzed as single SNPs and haplogroups determined by HaploGrep. Fisher's two-sided exact test was used for association testing. Moreover, the D-loop was re-sequenced (Sanger in 192 extremely obese children and adolescents and 192 lean adult controls. Association testing of detected variants was performed using Fisher's two-sided exact test. For discovery, nominal association with obesity was found for the frequent allele G of m.8994G/A (rs28358887, p = 0.002 located in ATP6. Haplogroup W was nominally overrepresented in the controls (p = 0.039. These findings could not be confirmed independently. For two of the 252 identified D-loop variants nominal association was detected (m.16292C/T, p = 0.007, m.16189T/C, p = 0.048. Only eight controls carried the m.16292T allele, five of whom belonged to haplogroup W that was initially enriched among these controls. m.16189T/C might create an uninterrupted poly-C tract located near a regulatory element involved in replication of mtDNA. Though follow-up of some D-loop variants still is conceivable, our hypothesis of a contribution of variation in the exclusively maternally inherited mtDNA to the observed larger correlations for BMI between mothers and

  14. Resistance of Abaca Somaclonal Variant Against Fusarium

    Directory of Open Access Journals (Sweden)



    Full Text Available The objectives of this study were (i to evaluate responses against F. oxysporum f.sp. cubense (Foc infection of abaca variants regenerated using four different methods, (ii to determine initial root length and plant height effects on survival of inoculated abaca variants, and (iii to identify Foc resistance abaca variants. In the previous experiment, four abaca variant lines were regenerated from (i embryogenic calli (TC line, (ii ethyl methyl sulphonate (EMS treated embryogenic calli (EMS line, (iii EMS treated embryogenic calli, followed by in vitro selection on Foc culture filtrate (EMS+CF line, and (iv EMS treated embryogenic calli, followed by in vitro selection on fusaric acid (EMS+FA line. All abaca variants were grown in a glasshouse and inoculated with Banyuwangi isolate of Foc (Foc Bw. Initial root length (RL and plant height (PH of the abaca variants were recorded before inoculation, while scores of plant damage (SPD, and their survival were recorded at 60 days after inoculation (DAI. The results showed that the initial RL and PH did not affect survival of the tested abaca variants. Regardless of their initial RL and PH, susceptible abaca variants died before 60 DAI while resistance ones still survived. Abaca variants regenerated from single clump of embryogenic callus showed an array of responses against Foc Bw infection, indicating the existence of a mix cells population. The Foc Bw resistance abaca variants were successfully identified from four tested abaca variant lines, although with different frequencies. However, more Foc Bw resistance abaca plants were identified from EMS+CF line than the others. Using the developed procedures, 8 resistance abaca plants were identified from abaca cv. Tangongon and 12 from abaca cv. Sangihe-1.

  15. Detection of variants in SLC6A8 and functional analysis of unclassified missense variants

    NARCIS (Netherlands)

    Betsalel, Ofir T; Pop, Ana; Rosenberg, Efraim H; Fernandez-Ojeda, Matilde; Jakobs, Cornelis; Salomons, Gajja S; Koning, Klaziena

    Creatine transporter deficiency is an X-linked disorder caused by mutations in the SLC6A8 gene. Currently, 38 pathogenic, including 15 missense variants, are reported. In this study, we report 33 novel, including 6 missense variants. To classify all known missense variants, we transfected creatine

  16. Detection of variants in SLC6A8 and functional analysis of unclassified missense variants

    NARCIS (Netherlands)

    Betsalel, O.T.; Pop, A.; Rosenberg, E.H.; Fernandez-Ojeda, M.; Jakobs, C.; Salomons, G.S.; Brouwer, A.P. de; Wevers, R.A.; Yntema, H.G.


    Creatine transporter deficiency is an X-linked disorder caused by mutations in the SLC6A8 gene. Currently, 38 pathogenic, including 15 missense variants, are reported. In this study, we report 33 novel, including 6 missense variants. To classify all known missense variants, we transfected creatine

  17. Microgravity condensing heat exchanger (United States)

    Thomas, Christopher M. (Inventor); Ma, Yonghui (Inventor); North, Andrew (Inventor); Weislogel, Mark M. (Inventor)


    A heat exchanger having a plurality of heat exchanging aluminum fins with hydrophilic condensing surfaces which are stacked and clamped between two cold plates. The cold plates are aligned radially along a plane extending through the axis of a cylindrical duct and hold the stacked and clamped portions of the heat exchanging fins along the axis of the cylindrical duct. The fins extend outwardly from the clamped portions along approximately radial planes. The spacing between fins is symmetric about the cold plates, and are somewhat more closely spaced as the angle they make with the cold plates approaches Passageways extend through the fins between vertex spaces which provide capillary storage and communicate with passageways formed in the stacked and clamped portions of the fins, which communicate with water drains connected to a pump externally to the duct. Water with no entrained air is drawn from the capillary spaces.

  18. Ion exchange phenomena

    Energy Technology Data Exchange (ETDEWEB)

    Bourg, I.C.; Sposito, G.


    Ion exchange phenomena involve the population of readily exchangeable ions, the subset of adsorbed solutes that balance the intrinsic surface charge and can be readily replaced by major background electrolyte ions (Sposito, 2008). These phenomena have occupied a central place in soil chemistry research since Way (1850) first showed that potassium uptake by soils resulted in the release of an equal quantity of moles of charge of calcium and magnesium. Ion exchange phenomena are now routinely modeled in studies of soil formation (White et al., 2005), soil reclamation (Kopittke et al., 2006), soil fertilitization (Agbenin and Yakubu, 2006), colloidal dispersion/flocculation (Charlet and Tournassat, 2005), the mechanics of argillaceous media (Gajo and Loret, 2007), aquitard pore water chemistry (Tournassat et al., 2008), and groundwater (Timms and Hendry, 2007; McNab et al., 2009) and contaminant hydrology (Chatterjee et al., 2008; van Oploo et al., 2008; Serrano et al., 2009).

  19. Using LSI and its variants in Text Classification (United States)

    Batra, Shalini; Bawa, Seema

    Latent Semantic Indexing (LSI), a well known technique in Information Retrieval has been partially successful in text retrieval and no major breakthrough has been achieved in text classification as yet. A significant step forward in this regard was made by Hofmann[3], who presented the probabilistic LSI (PLSI) model, as an alternative to LSI. If we wish to consider exchangeable representations for documents and words, PLSI is not successful which further led to the Latent Dirichlet Allocation (LDA) model [4]. A new local Latent Semantic Indexing method has been proposed by some authors called "Local Relevancy Ladder-Weighted LSI" (LRLW-LSI) to improve text classification [5]. In this paper we study LSI and its variants in detail , analyze the role played by them in text classification and conclude with future directions in this area.

  20. Heat exchanger panel (United States)

    Warburton, Robert E. (Inventor); Cuva, William J. (Inventor)


    The present invention relates to a heat exchanger panel which has broad utility in high temperature environments. The heat exchanger panel has a first panel, a second panel, and at least one fluid containment device positioned intermediate the first and second panels. At least one of the first panel and the second panel have at least one feature on an interior surface to accommodate the at least one fluid containment device. In a preferred embodiment, each of the first and second panels is formed from a high conductivity, high temperature composite material. Also, in a preferred embodiment, the first and second panels are joined together by one or more composite fasteners.

  1. Microscale Regenerative Heat Exchanger (United States)

    Moran, Matthew E.; Stelter, Stephan; Stelter, Manfred


    The device described herein is designed primarily for use as a regenerative heat exchanger in a miniature Stirling engine or Stirling-cycle heat pump. A regenerative heat exchanger (sometimes called, simply, a "regenerator" in the Stirling-engine art) is basically a thermal capacitor: Its role in the Stirling cycle is to alternately accept heat from, then deliver heat to, an oscillating flow of a working fluid between compression and expansion volumes, without introducing an excessive pressure drop. These volumes are at different temperatures, and conduction of heat between these volumes is undesirable because it reduces the energy-conversion efficiency of the Stirling cycle.

  2. Semantic prioritization of novel causative genomic variants

    KAUST Repository

    Boudellioua, Imene


    Discriminating the causative disease variant(s) for individuals with inherited or de novo mutations presents one of the main challenges faced by the clinical genetics community today. Computational approaches for variant prioritization include machine learning methods utilizing a large number of features, including molecular information, interaction networks, or phenotypes. Here, we demonstrate the PhenomeNET Variant Predictor (PVP) system that exploits semantic technologies and automated reasoning over genotype-phenotype relations to filter and prioritize variants in whole exome and whole genome sequencing datasets. We demonstrate the performance of PVP in identifying causative variants on a large number of synthetic whole exome and whole genome sequences, covering a wide range of diseases and syndromes. In a retrospective study, we further illustrate the application of PVP for the interpretation of whole exome sequencing data in patients suffering from congenital hypothyroidism. We find that PVP accurately identifies causative variants in whole exome and whole genome sequencing datasets and provides a powerful resource for the discovery of causal variants.

  3. Cryptanalysis of SIMON Variants with Connections

    DEFF Research Database (Denmark)

    Alizadeh, Javad; Alkhzaimi, Hoda A.; Aref, Mohammad Reza


    attacks extend to all variants of SIMON covering more rounds compared to any known results using linear cryptanalysis. We present a key recovery attack against SIMON128/256 which covers 35 out of 72 rounds with data complexity 2123. We have implemented our attacks for small scale variants of SIMON and our...

  4. Beta-glucosidase I variants with improved properties (United States)

    Bott, Richard R.; Kaper, Thijs; Kelemen, Bradley; Goedegebuur, Frits; Hommes, Ronaldus Wilhelmus; Kralj, Slavko; Kruithof, Paulien; Nikolaev, Igor; Van Der Kley, Wilhelmus Antonious Hendricus; Van Lieshout, Johannes Franciscus Thomas; Van Stigt Thans, Sander


    The present disclosure is generally directed to enzymes and in particular beta-glucosidase variants. Also described are nucleic acids encoding beta-glucosidase variants, compositions comprising beta-glucosidase variants, methods of using beta-glucosidase variants, and methods of identifying additional useful beta-glucosidase variants.

  5. 76 FR 48769 - Metadata Standards To Support Nationwide Electronic Health Information Exchange (United States)


    ... implemented, the research indicated that privacy metadata related to the underlying contents (i.e., what kind..., ``some kind of extensible markup language (an XML variant, for example) capable of exchanging data from... Names and Codes (LOINC) codes be used to provide additional granularity. Sensitivity: HL7 vocabulary for...

  6. Local binary patterns new variants and applications

    CERN Document Server

    Jain, Lakhmi; Nanni, Loris; Lumini, Alessandra


    This book introduces Local Binary Patterns (LBP), arguably one of the most powerful texture descriptors, and LBP variants. This volume provides the latest reviews of the literature and a presentation of some of the best LBP variants by researchers at the forefront of textual analysis research and research on LBP descriptors and variants. The value of LBP variants is illustrated with reported experiments using many databases representing a diversity of computer vision applications in medicine, biometrics, and other areas. There is also a chapter that provides an excellent theoretical foundation for texture analysis and LBP in particular. A special section focuses on LBP and LBP variants in the area of face recognition, including thermal face recognition. This book will be of value to anyone already in the field as well as to those interested in learning more about this powerful family of texture descriptors.

  7. Cellular defects caused by hypomorphic variants of the Bloom syndrome helicase gene BLM. (United States)

    Shastri, Vivek M; Schmidt, Kristina H


    Bloom syndrome is an autosomal recessive disorder characterized by extraordinary cancer incidence early in life and an average life expectancy of ~27 years. Premature stop codons in BLM, which encodes a DNA helicase that functions in DNA double-strand-break repair, make up the vast majority of Bloom syndrome mutations, with only 13 single amino acid changes identified in the syndrome. Sequencing projects have identified nearly one hundred single nucleotide variants in BLM that cause amino acid changes of uncertain significance. Here, in addition to identifying five BLM variants incapable of complementing certain defects of Bloom syndrome cells, making them candidates for new Bloom syndrome causing mutations, we characterize a new class of BLM variants that cause some, but not all, cellular defects of Bloom syndrome. We find elevated sister-chromatid exchanges, a delayed DNA damage response and inefficient DNA repair. Conversely, hydroxyurea sensitivity and quadriradial chromosome accumulation, both characteristic of Bloom syndrome cells, are absent. These intermediate variants affect sites in BLM that function in ATP hydrolysis and in contacting double-stranded DNA. Allele frequency and cellular defects suggest candidates for new Bloom syndrome causing mutations, and intermediate BLM variants that are hypomorphic which, instead of causing Bloom syndrome, may increase a person's risk for cancer or possibly other Bloom-syndrome-associated disorders, such as type-2 diabetes.

  8. Nature's Heat Exchangers. (United States)

    Barnes, George


    Discusses the heat-transfer systems of different animals. Systems include heat conduction into the ground, heat transferred by convection, heat exchange in lizards, fish and polar animals, the carotid rete system, electromagnetic radiation from animals and people, and plant and animal fiber optics. (MDH)

  9. Basic Exchange Rate Theories

    NARCIS (Netherlands)

    J.G.M. van Marrewijk (Charles)


    textabstractThis four-chapter overview of basic exchange rate theories discusses (i) the elasticity and absorption approach, (ii) the (long-run) implications of the monetary approach, (iii) the short-run effects of monetary and fiscal policy under various economic conditions, and (iv) the transition

  10. Technology Performance Exchange

    Energy Technology Data Exchange (ETDEWEB)


    To address the need for accessible, high-quality data, the Department of Energy has developed the Technology Performance Exchange (TPEx). TPEx enables technology suppliers, third-party testing laboratories, and other entities to share product performance data. These data are automatically transformed into a format that technology evaluators can easily use in their energy modeling assessments to inform procurement decisions.

  11. Telephone Exchange Maintenance

    CERN Document Server


    Urgent maintenance work on CERN telephone exchanges will be performed on 24 March from 6 a.m. to 8 a.m. Telephone services may be disrupted or even interrupted during this time. For more details, please contact us by email at

  12. Baltic Exchange toodi Tallinna

    Index Scriptorium Estoniae


    Viimane osa merekonteineritesse kokkupakitud Londoni laevandus- ja merebörsi Baltic Exchange'i endise peakorteri detailidest jõudis 2007. a. juunis Tallinna. Hoone detailid ostnud ärimehed Heiti Hääl ja Eerik-Niiles Kross plaanivad leida hoonele koha Tallinna kesklinnas. E.-N. Krossi kommentaar

  13. Heat exchanger. Varmeveksler

    Energy Technology Data Exchange (ETDEWEB)

    Rosman, I.E.; Wagner, W.R.


    The invention concerns a manifold for a plate-type heat exchanger, and includes a side channel connected the inlet of the manifold. The plates can be designed as an integral assembly together with the integrated side- and external end-manifolds as well. 16 drawings.

  14. Chemical exchange program analysis.

    Energy Technology Data Exchange (ETDEWEB)

    Waffelaert, Pascale


    As part of its EMS, Sandia performs an annual environmental aspects/impacts analysis. The purpose of this analysis is to identify the environmental aspects associated with Sandia's activities, products, and services and the potential environmental impacts associated with those aspects. Division and environmental programs established objectives and targets based on the environmental aspects associated with their operations. In 2007 the most significant aspect identified was Hazardous Materials (Use and Storage). The objective for Hazardous Materials (Use and Storage) was to improve chemical handling, storage, and on-site movement of hazardous materials. One of the targets supporting this objective was to develop an effective chemical exchange program, making a business case for it in FY07, and fully implementing a comprehensive chemical exchange program in FY08. A Chemical Exchange Program (CEP) team was formed to implement this target. The team consists of representatives from the Chemical Information System (CIS), Pollution Prevention (P2), the HWMF, Procurement and the Environmental Management System (EMS). The CEP Team performed benchmarking and conducted a life-cycle analysis of the current management of chemicals at SNL/NM and compared it to Chemical Exchange alternatives. Those alternatives are as follows: (1) Revive the 'Virtual' Chemical Exchange Program; (2) Re-implement a 'Physical' Chemical Exchange Program using a Chemical Information System; and (3) Transition to a Chemical Management Services System. The analysis and benchmarking study shows that the present management of chemicals at SNL/NM is significantly disjointed and a life-cycle or 'Cradle-to-Grave' approach to chemical management is needed. This approach must consider the purchasing and maintenance costs as well as the cost of ultimate disposal of the chemicals and materials. A chemical exchange is needed as a mechanism to re-apply chemicals on site. This

  15. Somatic cancer variant curation and harmonization through consensus minimum variant level data

    Directory of Open Access Journals (Sweden)

    Deborah I. Ritter


    Full Text Available Abstract Background To truly achieve personalized medicine in oncology, it is critical to catalog and curate cancer sequence variants for their clinical relevance. The Somatic Working Group (WG of the Clinical Genome Resource (ClinGen, in cooperation with ClinVar and multiple cancer variant curation stakeholders, has developed a consensus set of minimal variant level data (MVLD. MVLD is a framework of standardized data elements to curate cancer variants for clinical utility. With implementation of MVLD standards, and in a working partnership with ClinVar, we aim to streamline the somatic variant curation efforts in the community and reduce redundancy and time burden for the interpretation of cancer variants in clinical practice. Methods We developed MVLD through a consensus approach by i reviewing clinical actionability interpretations from institutions participating in the WG, ii conducting extensive literature search of clinical somatic interpretation schemas, and iii survey of cancer variant web portals. A forthcoming guideline on cancer variant interpretation, from the Association of Molecular Pathology (AMP, can be incorporated into MVLD. Results Along with harmonizing standardized terminology for allele interpretive and descriptive fields that are collected by many databases, the MVLD includes unique fields for cancer variants such as Biomarker Class, Therapeutic Context and Effect. In addition, MVLD includes recommendations for controlled semantics and ontologies. The Somatic WG is collaborating with ClinVar to evaluate MVLD use for somatic variant submissions. ClinVar is an open and centralized repository where sequencing laboratories can report summary-level variant data with clinical significance, and ClinVar accepts cancer variant data. Conclusions We expect the use of the MVLD to streamline clinical interpretation of cancer variants, enhance interoperability among multiple redundant curation efforts, and increase submission of

  16. Analytical applications of ion exchangers

    CERN Document Server

    Inczédy, J


    Analytical Applications of Ion Exchangers presents the laboratory use of ion-exchange resins. This book discusses the development in the analytical application of ion exchangers. Organized into 10 chapters, this book begins with an overview of the history and significance of ion exchangers for technical purposes. This text then describes the properties of ion exchangers, which are large molecular water-insoluble polyelectrolytes having a cross-linked structure that contains ionic groups. Other chapters consider the theories concerning the operation of ion-exchange resins and investigate th

  17. Variability extraction and modeling for product variants. (United States)

    Linsbauer, Lukas; Lopez-Herrejon, Roberto Erick; Egyed, Alexander


    Fast-changing hardware and software technologies in addition to larger and more specialized customer bases demand software tailored to meet very diverse requirements. Software development approaches that aim at capturing this diversity on a single consolidated platform often require large upfront investments, e.g., time or budget. Alternatively, companies resort to developing one variant of a software product at a time by reusing as much as possible from already-existing product variants. However, identifying and extracting the parts to reuse is an error-prone and inefficient task compounded by the typically large number of product variants. Hence, more disciplined and systematic approaches are needed to cope with the complexity of developing and maintaining sets of product variants. Such approaches require detailed information about the product variants, the features they provide and their relations. In this paper, we present an approach to extract such variability information from product variants. It identifies traces from features and feature interactions to their implementation artifacts, and computes their dependencies. This work can be useful in many scenarios ranging from ad hoc development approaches such as clone-and-own to systematic reuse approaches such as software product lines. We applied our variability extraction approach to six case studies and provide a detailed evaluation. The results show that the extracted variability information is consistent with the variability in our six case study systems given by their variability models and available product variants.

  18. Ultrasonographic imaging of papillary thyroid carcinoma variants

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Jung Hee [Dept. of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)


    Ultrasonography (US) is routinely used to evaluate thyroid nodules. The US features of papillary thyroid carcinoma (PTC), the most common thyroid malignancy, include hypoechogenicity, spiculated/microlobulated margins, microcalcifications, and a nonparallel orientation. However, many PTC variants have been identified, some of which differ from the classic type of PTC in terms of biological behavior and clinical outcomes. This review describes the US features and clinical implications of the variants of PTC. With the introduction of active surveillance replacing immediate biopsy or surgical treatment of indolent, small PTCs, an understanding of the US characteristics of PTC variants will facilitate the individualized management of patients with PTC.

  19. Provably-Secure Authenticated Group Diffie-Hellman KeyExchange

    Energy Technology Data Exchange (ETDEWEB)

    Bresson, Emmanuel; Chevassut, Olivier; Pointcheval, David


    Authenticated key exchange protocols allow two participantsA and B, communicating over a public network and each holding anauthentication means, to exchange a shared secret value. Methods designedto deal with this cryptographic problem ensure A (resp. B) that no otherparticipants aside from B (resp. A) can learn any information about theagreed value, and often also ensure A and B that their respective partnerhas actually computed this value. A natural extension to thiscryptographic method is to consider a pool of participants exchanging ashared secret value and to provide a formal treatment for it. Startingfrom the famous 2-party Diffie-Hellman (DH) key exchange protocol, andfrom its authenticated variants, security experts have extended it to themulti-party setting for over a decade and completed a formal analysis inthe framework of modern cryptography in the past few years. The presentpaper synthesizes this body of work on the provably-secure authenticatedgroup DH key exchange.

  20. Data Exchange Inventory (DEXI) System (United States)

    Social Security Administration — DEXI is an intranet application used by SSA users to track all incoming and outgoing data exchanges between SSA and our data exchange partners. Information such as...

  1. Dynamical Clustering of Exchange Rates


    Fenn, Daniel J.; Porter, Mason A.; Mucha, Peter J; Mark McDonald; Stacy Williams; Johnson, Neil F.; Jones, Nick S


    We use techniques from network science to study correlations in the foreign exchange (FX) market over the period 1991--2008. We consider an FX market network in which each node represents an exchange rate and each weighted edge represents a time-dependent correlation between the rates. To provide insights into the clustering of the exchange rate time series, we investigate dynamic communities in the network. We show that there is a relationship between an exchange rate's functional role withi...

  2. Serial tempering without exchange. (United States)

    Nymeyer, Hugh


    Serial tempering is a computational method that turns the temperature T (or more generally any independent λ parameter) into a dynamical variable. It is shown that, under conditions for which this variable is fast, serial tempering is equivalent to the umbrella sampling method with a single effective potential. This equivalence is demonstrated using both a small one-dimensional system and a small solvated peptide. The suggestion is then made to replace the serial tempering protocol with the equivalent umbrella sampling calculation. This approach, serial tempering without exchange (STeWiE), has the same performance as serial tempering in the limit that exchanges are frequent, is simpler to implement, and has fewer adjustable parameters than conventional serial tempering. The equivalence of serial tempering and STeWiE also provides a convenient route for estimating and optimizing the performance of serial tempering simulations and other generalized-ensemble methods.

  3. Lipid exchange by ultracentrifugation

    DEFF Research Database (Denmark)

    Drachmann, Nikolaj Düring; Olesen, Claus


    Lipids play an important role in maintaining P-type ATPase structure and function, and often they are crucial for ATPase activity. When the P-type ATPases are in the membrane, they are surrounded by a mix of different lipids species with varying aliphatic chain lengths and saturation......, and the complex interplay between the lipids and the P-type ATPases are still not well understood. We here describe a robust method to exchange the majority of the lipids surrounding the ATPase after solubilisation and/or purification with a target lipid of interest. The method is based on an ultracentrifugation...... step, where the protein sample is spun through a dense buffer containing large excess of the target lipid, which results in an approximately 80-85 % lipid exchange. The method is a very gently technique that maintains protein folding during the process, hence allowing further characterization...

  4. Exchange rate rebounds after foreign exchange market interventions (United States)

    Hoshikawa, Takeshi


    This study examined the rebounds in the exchange rate after foreign exchange intervention. When intervention is strongly effective, the exchange rate rebounds at next day. The effect of intervention is reduced slightly by the rebound after the intervention. The exchange rate might have been 67.12-77.47 yen to a US dollar without yen-selling/dollar-purchasing intervention of 74,691,100 million yen implemented by the Japanese government since 1991, in comparison to the actual exchange rate was 103.19 yen to the US dollar at the end of March 2014.

  5. O3 and NOx Exchange

    NARCIS (Netherlands)

    Loubet, B.; Castell, J.F.; Laville, P.; Personne, E.; Tuzet, A.; Ammann, C.; Emberson, L.; Ganzeveld, L.; Kowalski, A.S.; Merbold, L.; Stella, P.; Tuovinen, J.P.


    This discussion was based on the background document “Review on modelling atmosphere-biosphere exchange of Ozone and Nitrogen oxides”, which reviews the processes contributing to biosphere-atmosphere exchange of O3 and NOx, including stomatal and non-stomatal exchange of O3 and NO, NO2.

  6. The stability of exchange networks

    NARCIS (Netherlands)

    Doğan, G.; Assen, M. van; Rijt, A. van de; Buskens, V.W.


    Economic and sociological exchange theories predict divisions of exchange benefits given an assumed fixed network of exchange relations. Since network structure has been found to have a large impact on actors’ payoffs, actors have strong incentives for network change.Weanswer the question what

  7. Integrated foreign exchange risk management

    DEFF Research Database (Denmark)

    Aabo, Tom; Høg, Esben; Kuhn, Jochen


    Empirical research has focused on export as a proxy for exchange rate exposure and the use of foreign exchange derivatives as an instrument to deal with this exposure. This empirical study applies an integrated foreign exchange risk management approach with a particular focus on the role of impor...

  8. Integrated Foreign Exchange Risk Management

    DEFF Research Database (Denmark)

    Aabo, Tom; Høg, Esben; Kuhn, Jochen

    Empirical research has focused on export as a proxy for the exchange rate exposure and the use of foreign exchange derivatives as the instrument to deal with this exposure. This empirical study applies an integrated foreign exchange risk management approach with a particular focus on the role...

  9. Scraped surface heat exchangers. (United States)

    Rao, Chetan S; Hartel, Richard W


    Scraped surface heat exchangers (SSHEs) are commonly used in the food, chemical, and pharmaceutical industries for heat transfer, crystallization, and other continuous processes. They are ideally suited for products that are viscous, sticky, that contain particulate matter, or that need some degree of crystallization. Since these characteristics describe a vast majority of processed foods, SSHEs are especially suited for pumpable food products. During operation, the product is brought in contact with a heat transfer surface that is rapidly and continuously scraped, thereby exposing the surface to the passage of untreated product. In addition to maintaining high and uniform heat exchange, the scraper blades also provide simultaneous mixing and agitation. Heat exchange for sticky and viscous foods such as heavy salad dressings, margarine, chocolate, peanut butter, fondant, ice cream, and shortenings is possible only by using SSHEs. High heat transfer coefficients are achieved because the boundary layer is continuously replaced by fresh material. Moreover, the product is in contact with the heating surface for only a few seconds and high temperature gradients can be used without the danger of causing undesirable reactions. SSHEs are versatile in the use of heat transfer medium and the various unit operations that can be carried out simultaneously. This article critically reviews the current understanding of the operations and applications of SSHEs.

  10. Timing Foreign Exchange Markets

    Directory of Open Access Journals (Sweden)

    Samuel W. Malone


    Full Text Available To improve short-horizon exchange rate forecasts, we employ foreign exchange market risk factors as fundamentals, and Bayesian treed Gaussian process (BTGP models to handle non-linear, time-varying relationships between these fundamentals and exchange rates. Forecasts from the BTGP model conditional on the carry and dollar factors dominate random walk forecasts on accuracy and economic criteria in the Meese-Rogoff setting. Superior market timing ability for large moves, more than directional accuracy, drives the BTGP’s success. We explain how, through a model averaging Monte Carlo scheme, the BTGP is able to simultaneously exploit smoothness and rough breaks in between-variable dynamics. Either feature in isolation is unable to consistently outperform benchmarks throughout the full span of time in our forecasting exercises. Trading strategies based on ex ante BTGP forecasts deliver the highest out-of-sample risk-adjusted returns for the median currency, as well as for both predictable, traded risk factors.

  11. Paste heat exchange

    Energy Technology Data Exchange (ETDEWEB)


    The subject of coal paste heat exchangers is discussed in this letter report from Gelsenberg A.G. to I.G. Farbenindustrie A.G. Gelsenberg had given little consideration to the heating of coal paste by means of regeneration (heat exchange) because of the lack of experience in paste regeneration with bituminous coal, especially at 700 atmospheres. At the I.G. Farben plant at Poelitz, paste regeneration was carried out so that low concentration coal paste was heated in the regenerator together with the process gas, and the remaining coal was fed into the cold pass of the preheater in a thicker paste. Later tests proved this process viable. Gelsenberg heated normal coal paste and the gas in heat exchangers with the goal of relieving the preheater. Good results were achieved without change in design. The coal paste was heated with process gas in the regenerator at up to 315 degrees with constant pressure difference, so that after three months no decrease in K-values and no deposition or thickening was observed. Through the omission of paste gas, the pressure difference of the system became more constant and did not rise above the former level. The temperature also was more controllable, the chamber smoother running. Principal thermal data are given in a table. 1 table, 1 graph.

  12. The exchangeability of shape

    Directory of Open Access Journals (Sweden)

    Kaba Dramane


    Full Text Available Abstract Background Landmark based geometric morphometrics (GM allows the quantitative comparison of organismal shapes. When applied to systematics, it is able to score shape changes which often are undetectable by traditional morphological studies and even by classical morphometric approaches. It has thus become a fast and low cost candidate to identify cryptic species. Due to inherent mathematical properties, shape variables derived from one set of coordinates cannot be compared with shape variables derived from another set. Raw coordinates which produce these shape variables could be used for data exchange, however they contain measurement error. The latter may represent a significant obstacle when the objective is to distinguish very similar species. Results We show here that a single user derived dataset produces much less classification error than a multiple one. The question then becomes how to circumvent the lack of exchangeability of shape variables while preserving a single user dataset. A solution to this question could lead to the creation of a relatively fast and inexpensive systematic tool adapted for the recognition of cryptic species. Conclusions To preserve both exchangeability of shape and a single user derived dataset, our suggestion is to create a free access bank of reference images from which one can produce raw coordinates and use them for comparison with external specimens. Thus, we propose an alternative geometric descriptive system that separates 2-D data gathering and analyzes.

  13. Hemilaryngeal Microsomia: An Anatomic Variant. (United States)

    Urban, Matthew J; Mattioni, Jillian; Jaworek, Aaron; Potigailo, Valeria; Sataloff, Robert T


    This study aims to describe a congenital laryngeal structural variant, hemilaryngeal microsomia (HLM), and to correlate identification on physical examination with computerized tomography scan (CT) and laryngoscopy findings. The study was conducted at a tertiary care center. Six patients presenting with hoarseness were admitted to a tertiary care otolaryngology office. These patients had asymmetrical thyroid cartilage prominence on palpation during physical examination. A diagnosis of HLM was made. All patients underwent laryngostroboscopy and CT scan. Four control patients with normal thyroid cartilage anatomy on physical examination, CT, and stroboscopy results were included for comparison. Disparities in thyroid cartilage angles correlated with documented physical examination findings for six out of six HLM patients. On CT scan, the average difference in left and right thyroid laminar angles was 30.2° ± 18.3° in HLM patients vs 4.00° ± 1.63° in control patients (P = 0.023). Strobosocopic findings also correlated with HLM. The arytenoid cartilage was anteriorly or medially displaced on the microsomic side in all six HLM patients. Three patients had anterior placement of the vocal process resulting in shortening of the vocal fold on the microsomic side of the larynx. HLM is a congenital structural anomaly of the larynx that may be palpated on physical examination. HLM found on physical examination can be correlated with asymmetries found on CT scan and endoscopy. There is no evidence that the structural features of HLM were causally related to voice symptoms, but the findings on HLM may lead to misdiagnosis. A larger study is indicated to confirm laryngeal structural differences between patients with HLM on physical examination and the general population. Whether or not HLM affects clinical or surgical outcomes remains to be studied. Copyright © 2017. Published by Elsevier Inc.

  14. Variant (Swine Origin) Influenza Viruses in Humans (United States)

    ... at Commercial Swine Farms Fair Organizers & Exhibitors In Humans Key Facts about Human Infections with Variant Viruses Interim Guidance for Clinicians on Human Infections Background, Risk Assessment & Reporting Reported Infections with ...

  15. Splicing variants of porcine synphilin-1

    DEFF Research Database (Denmark)

    Larsen, Knud Erik; Madsen, Lone Bruhn; Farajzadeh, Leila


    %) and to mouse (84%) synphilin-1. Three shorter transcript variants of the synphilin-1 gene were identified, all lacking one or more exons. SNCAIP transcripts were detected in most examined organs and tissues and the highest expression was found in brain tissues and lung. Conserved splicing variants and a novel......RNA was investigated by RNAseq. The presented work reports the molecular cloning and characterization of the porcine (Sus scrofa) synphilin-1 cDNA (SNCAIP) and three splice variants hereof. The porcine SNCAIP cDNA codes for a protein (synphilin-1) of 919 amino acids which shows a high similarity to human (90...... splice form of synhilin-1 were found in this study. All synphilin-1 isoforms encoded by the identified transcript variants lack functional domains important for protein degradation....

  16. Improving bioinformatic pipelines for exome variant calling


    Ji, Hanlee P.


    Exome sequencing analysis is a cost-effective approach for identifying variants in coding regions. However, recognizing the relevant single nucleotide variants, small insertions and deletions remains a challenge for many researchers and diagnostic laboratories typically do not have access to the bioinformatic analysis pipelines necessary for clinical application. The Atlas2 suite, recently released by Baylor Genome Center, is designed to be widely accessible, runs on desktop computers but is ...

  17. Demography and the age of rare variants. (United States)

    Mathieson, Iain; McVean, Gil


    Large whole-genome sequencing projects have provided access to much rare variation in human populations, which is highly informative about population structure and recent demography. Here, we show how the age of rare variants can be estimated from patterns of haplotype sharing and how these ages can be related to historical relationships between populations. We investigate the distribution of the age of variants occurring exactly twice (ƒ(2) variants) in a worldwide sample sequenced by the 1000 Genomes Project, revealing enormous variation across populations. The median age of haplotypes carrying ƒ(2) variants is 50 to 160 generations across populations within Europe or Asia, and 170 to 320 generations within Africa. Haplotypes shared between continents are much older with median ages for haplotypes shared between Europe and Asia ranging from 320 to 670 generations. The distribution of the ages of ƒ(2) haplotypes is informative about their demography, revealing recent bottlenecks, ancient splits, and more modern connections between populations. We see the effect of selection in the observation that functional variants are significantly younger than nonfunctional variants of the same frequency. This approach is relatively insensitive to mutation rate and complements other nonparametric methods for demographic inference.

  18. Hemoglobin Variant Profiles among Brazilian Quilombola Communities. (United States)

    Santiago, Rayra P; Oliveira, Rodrigo M; Soares, Leonardo F; Figueiredo, Camylla V B; Silva, Denise Oliveira; Hurtado-Guerrero, Ana F; Fiuza, Luciana M; Guarda, Caroline C; Adorno, Elisângela V; Barbosa, Cynara G; Gonçalves, Marilda S


    Brazilian Quilombolas are communities composed of African-derived populations that have their territories guaranteed by the Brazilian Constitution. The present study investigated the hemoglobin (Hb) variants among these population groups. This study was conducted in a total of 2843 individuals of Brazilian Quilombola communities of the Bahia, Pará, and Piauí states. All the participants had their Hb profiles evaluated. The Hb S (HBB: c.20A>T) variant was described in all the studied localities. However, the individuals in Bahia State had the highest frequency of the Hb C (HBB: c.19G>A) variant; individuals from Piauí State had a higher frequency of the Hb D-Punjab (HBB: c.364G>C) variant compared to the other states, and individuals from Pará State only carried the Hb S variant. The present study revealed a specific distribution of Hb variants that could represent different waves of African influence in these Brazilian populations.

  19. Detection of variants in SLC6A8 and functional analysis of unclassified missense variants. (United States)

    Betsalel, Ofir T; Pop, Ana; Rosenberg, Efraim H; Fernandez-Ojeda, Matilde; Jakobs, Cornelis; Salomons, Gajja S


    Creatine transporter deficiency is an X-linked disorder caused by mutations in the SLC6A8 gene. Currently, 38 pathogenic, including 15 missense variants, are reported. In this study, we report 33 novel, including 6 missense variants. To classify all known missense variants, we transfected creatine deficient fibroblasts with the SLC6A8 ORF containing one of the unique variants and tested their ability to restore creatine uptake. This resulted in the definitive classification of 2 non-disease associated and 19 pathogenic variants of which 3 have residual activity. Furthermore, we report the development and validation of a novel DHPLC method for the detection of heterozygous SLC6A8 variants. The method was validated by analysis of DNAs that in total contained 67 unique variants of which 66 could be detected. Therefore, this rapid screening method may prove valuable for the analysis of large cohorts of females with mild intellectual disability of unknown etiology, since in this group heterozygous SLC6A8 mutations may be detected. DHPLC proved also to be important for the detection of somatic mosaicism in mothers of patients who have a pathogenic mutation in SLC6A8. All variants reported in the present and previous studies are included in the Leiden Open Source Variant Database (LOVD) of SLC6A8 ( Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Procedure to reduce sulphite in wine with anion-exchange resin

    Directory of Open Access Journals (Sweden)

    Miroslav Horák


    Full Text Available The aim of this experiment was to eliminate SO2 ions present in wine using the anion-exchanger resins. To compare the effectiveness, 2 following strongly basic anion-exchange resin were used. When activated, the sodium bicarbonate solution (activation solution I is used to prevent parallel reduction of sulphites, tartates and malates, so the anion-exchange resins were activated in two-step activation. In the second step, it was immersed into a mixture of malic acid and tartaric acid (1:1. After the application of anex into wine, the content of total SO2 was reduced to 97–201 mg.L−1 (depending on the amount of anex added into the wine sample. According to our expectations, the variants with anion-exchange resin activated only with bicarbonate solution, the tartrates and malates were significantly reduced. If the anion-exchange resin was activated with a two-steps activation, the tartaric acid and malic acid were reduced in the range of ± 0.13 g.L−1. This phenomenon was strongly reflected at the anion-exchanger Aqua Osmotic 02. The changes in antioxidant content were not affected by the type of anion-exchange resin, the method of activation, or an amount of used anion-exchanger. The color parameters of wine, expressed by the L * a * b *, were not significantly affected by the effects of anion-exchange resin use.

  1. Capillary ion-exchange chromatography with nanogram sensitivity for the analysis of monoclonal antibodies. (United States)

    Rea, Jennifer C; Freistadt, Benny S; McDonald, Daniel; Farnan, Dell; Wang, Yajun Jennifer


    Ion-exchange chromatography (IEC) is widely used for profiling the charge heterogeneity of proteins, including monoclonal antibodies (mAbs). Despite good resolving power and robustness, ionic strength-based ion-exchange separations are generally product specific and can be time consuming to develop. In addition, conventional analytical scale ion-exchange separations require tens of micrograms of mAbs for each injection, amounts that are often unavailable in sample-limited applications. We report the development of a capillary IEC (c-IEC) methodology for the analysis of nanogram amounts of mAb charge variants. Several key modifications were made to a commercially available liquid chromatography system to perform c-IEC for charge variant analysis of mAbs with nanogram sensitivity. We demonstrate the method for multiple monoclonal antibodies, including antibody fragments, on different columns from different manufacturers. Relative standard deviations of <10% were achieved for relative peak areas of main peak, acidic and basic regions, which are common regions of interest for quantifying monoclonal antibody charge variants using IEC. The results herein demonstrate the excellent sensitivity of this c-IEC characterization method, which can be used for analyzing charge variants in sample-limited applications, such as early-stage candidate screening and in vivo studies. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. The Dynamics of Multilateral Exchange (United States)

    Hausken, Kjell; Moxnes, John F.

    The article formulates a dynamic mathematical model where arbitrarily many players produce, consume, exchange, loan, and deposit arbitrarily many goods over time to maximize utility. Consuming goods constitutes a benefit, and producing, exporting, and loaning away goods constitute a cost. Utilities are benefits minus costs, which depend on the exchange ratios and bargaining functions. Three-way exchange occurs when one player acquires, through exchange, one good from another player with the sole purpose of using this good to exchange against the desired good from a third player. Such a triple handshake is not merely a set of double handshakes since the player assigns no interest to the first good in his benefit function. Cognitive and organization costs increase dramatically for higher order exchanges. An exchange theory accounting for media of exchange follows from simple generalization of two-way exchange. The examples of r-way exchange are the triangle trade between Africa, the USA, and England in the 17th and 18th centuries, the hypothetical hypercycle involving RNAs as players and enzymes as goods, and reaction-diffusion processes. The emergence of exchange, and the role of trading agents are discussed. We simulate an example where two-way exchange gives zero production and zero utility, while three-way exchange causes considerable production and positive utility. Maximum utility for each player is reached when exchanges of the same order as the number of players in society are allowed. The article merges micro theory and macro theory within the social, natural, and physical sciences.

  3. [Frequency of chromosome variants in human populations]. (United States)

    Kuleshov, N P; Kulieva, L M


    Chromosome variants were analyzed in the course of the population chromosome investigation of 6000 newborns and clinical cytogenetic studies of 403 married couples with recurrent spontaneous abortions, stillbirths or offsprings having congenital malformations or Down's syndrome. The following variants were determined: 1) Igh+, 9gh+, 16gh+ - the enlargement of the secondary constrictions of the size, more than 1/4 of the long arm of the chromosome; 2) Dp+ or Gp+ - the enlargement of the short arms of acrocentrics, their size being more than the short arm of the chromosome 18; 3) Ds+ or Gs - large satellites of the acrocentrics which are equal or more than the thickness of the chromatids of the long arms; 4) Es+ - satellites on the short arms of the chromosomes 17 or 18; 5) Dss of Gss - double satellites; 6) Yq+ - the enlargement of the long arm of Y chromosome, the size of which being more than G chromosome; 7) Yq- - deletion of the long arm of Y chromosome, the size of the long arm being less than chromosomes 21--22. The total frequency of variants in newborns was 12.8/1000 births. The incidence of different types of variants per 1000 births was as follows: Igh+ - 0.33; 9gh+ - 0.17; 16gh+ - 0.50; Ds+ - 2.33; Dp+ - 1.50; Dp- - 0.17; Gs+ - 0.83; Gp+ - 2.17; Yq+ - 6.91/1000 males; Yg- - 0.99/1000 males; double variants - 0.33; other variants - 0.33. 4.0% of married couples with recurrent spontaneous abortions had major chromosome aberrations, 14.6% - extreme variants of chromosomes. Among 113 couples with the history of congenital malformations in their offsprings major chromosome abnormalities were found in 4.4%, chromosome variants - 13.3%. The frequency of chromosome variants among 139 patients with Down's syndrome was 7.2%. In one case Robertsonian translocation t(DqGa) was determined. The most frequent types of variant chromosomes were Ds+, Dp+, Es+, Yq+.

  4. Beta-glucosidase variants and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Wogulis, Mark; Harris, Paul; Osborn, David


    The present invention relates to beta-glucosidase variants, e.g. beta-glucosidase variants of a parent Family GH3A beta-glucosidase from Aspergillus fumigatus. The present invention also relates to polynucleotides encoding the beta-glucosidase variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the beta-glucosidase variants.

  5. Cryogenic regenerative heat exchangers

    CERN Document Server

    Ackermann, Robert A


    An in-depth survey of regenerative heat exchangers, this book chronicles the development and recent commercialization of regenerative devices for cryogenic applications. Chapters cover historical background, concepts, practical applications, design data, and numerical solutions, providing the latest information for engineers to develop advanced cryogenic machines. The discussions include insights into the operation of a regenerator; descriptions of the cyclic and fluid temperature distributions in a regenerator; data for various matrix geometries and materials, including coarse and fine bronze, stainless steel-woven wire mesh screens, and lead spheres; and unique operating features of cryocoolers that produce deviations from ideal regenerator theory.

  6. Molecular digital pathology: progress and potential of exchanging molecular data. (United States)

    Roy, Somak; Pfeifer, John D; LaFramboise, William A; Pantanowitz, Liron


    Many of the demands to perform next generation sequencing (NGS) in the clinical laboratory can be resolved using the principles of telepathology. Molecular telepathology can allow facilities to outsource all or a portion of their NGS operation such as cloud computing, bioinformatics pipelines, variant data management, and knowledge curation. Clinical pathology laboratories can electronically share diverse types of molecular data with reference laboratories, technology service providers, and/or regulatory agencies. Exchange of electronic molecular data allows laboratories to perform validation of rare diseases using foreign data, check the accuracy of their test results against benchmarks, and leverage in silico proficiency testing. This review covers the emerging subject of molecular telepathology, describes clinical use cases for the appropriate exchange of molecular data, and highlights key issues such as data integrity, interoperable formats for massive genomic datasets, security, malpractice and emerging regulations involved with this novel practice.

  7. Registered report: androgen receptor splice variants determine taxane sensitivity in prostate cancer

    Directory of Open Access Journals (Sweden)

    Xiaochuan Shan


    Full Text Available The Prostate Cancer Foundation-Movember Foundation Reproducibility Initiative seeks to address growing concerns about reproducibility in scientific research by conducting replications of recent papers in the field of prostate cancer. This Registered Report describes the proposed replication plan of key experiments from “Androgen Receptor Splice Variants Determine Taxane Sensitivity in Prostate Cancer” by Thadani-Mulero and colleagues (2014 published in Cancer Research in 2014. The experiment that will be replicated is reported in Fig. 6A. Thadani-Mulero and colleagues generated xenografts from two prostate cancer cell lines; LuCaP 86.2, which expresses predominantly the ARv567 splice variant of the androgen receptor (AR, and LuCaP 23.1, which expresses the full length AR as well as the ARv7 variant. Treatment of the tumors with the taxane docetaxel showed that the drug inhibited tumor growth of the LuCaP 86.2 cells but not of the LuCaP 23.1 cells, indicating that expression of splice variants of the AR can affect sensitivity to docetaxel. The Prostate Cancer Foundation-Movember Foundation Reproducibility Initiative is a collaboration between the Prostate Cancer Foundation, the Movember Foundation and Science Exchange, and the results of the replications will be published by PeerJ.

  8. Target-specific variants of Flp recombinase mediate genome engineering reactions in mammalian cells. (United States)

    Shah, Riddhi; Li, Feng; Voziyanova, Eugenia; Voziyanov, Yuri


    Genome engineering relies on DNA-modifying enzymes that are able to locate a DNA sequence of interest and initiate a desired genome rearrangement. Currently, the field predominantly utilizes site-specific DNA nucleases that depend on the host DNA repair machinery to complete a genome modification task. We show here that genome engineering approaches that employ target-specific variants of the self-sufficient, versatile site-specific DNA recombinase Flp can be developed into promising alternatives. We demonstrate that the Flp variant evolved to recombine an FRT-like sequence, FL-IL10A, which is located upstream of the human interleukin-10 gene, and can target this sequence in the model setting of Chinese hamster ovary and human embryonic kidney 293 cells. This target-specific Flp variant is able to perform the integration reaction and, when paired with another recombinase, the dual recombinase-mediated cassette exchange reaction. The efficiency of the integration reaction in human cells can be enhanced by 'humanizing' the Flp variant gene and by adding the nuclear localization sequence to the recombinase. © 2015 FEBS.

  9. Registered report: androgen receptor splice variants determine taxane sensitivity in prostate cancer. (United States)

    Shan, Xiaochuan; Danet-Desnoyers, Gwenn; Fung, Juan José; Kosaka, Alan H; Tan, Fraser; Perfito, Nicole; Lomax, Joelle; Iorns, Elizabeth


    The Prostate Cancer Foundation-Movember Foundation Reproducibility Initiative seeks to address growing concerns about reproducibility in scientific research by conducting replications of recent papers in the field of prostate cancer. This Registered Report describes the proposed replication plan of key experiments from "Androgen Receptor Splice Variants Determine Taxane Sensitivity in Prostate Cancer" by Thadani-Mulero and colleagues (2014) published in Cancer Research in 2014. The experiment that will be replicated is reported in Fig. 6A. Thadani-Mulero and colleagues generated xenografts from two prostate cancer cell lines; LuCaP 86.2, which expresses predominantly the ARv567 splice variant of the androgen receptor (AR), and LuCaP 23.1, which expresses the full length AR as well as the ARv7 variant. Treatment of the tumors with the taxane docetaxel showed that the drug inhibited tumor growth of the LuCaP 86.2 cells but not of the LuCaP 23.1 cells, indicating that expression of splice variants of the AR can affect sensitivity to docetaxel. The Prostate Cancer Foundation-Movember Foundation Reproducibility Initiative is a collaboration between the Prostate Cancer Foundation, the Movember Foundation and Science Exchange, and the results of the replications will be published by PeerJ.

  10. Variants of sequence family B Thermococcus kodakaraensis DNA polymerase with increased mismatch extension selectivity.

    Directory of Open Access Journals (Sweden)

    Claudia Huber

    Full Text Available Fidelity and selectivity of DNA polymerases are critical determinants for the biology of life, as well as important tools for biotechnological applications. DNA polymerases catalyze the formation of DNA strands by adding deoxynucleotides to a primer, which is complementarily bound to a template. To ensure the integrity of the genome, DNA polymerases select the correct nucleotide and further extend the nascent DNA strand. Thus, DNA polymerase fidelity is pivotal for ensuring that cells can replicate their genome with minimal error. DNA polymerases are, however, further optimized for more specific biotechnological or diagnostic applications. Here we report on the semi-rational design of mutant libraries derived by saturation mutagenesis at single sites of a 3'-5'-exonuclease deficient variant of Thermococcus kodakaraensis DNA polymerase (KOD pol and the discovery for variants with enhanced mismatch extension selectivity by screening. Sites of potential interest for saturation mutagenesis were selected by their proximity to primer or template strands. The resulting libraries were screened via quantitative real-time PCR. We identified three variants with single amino acid exchanges-R501C, R606Q, and R606W-which exhibited increased mismatch extension selectivity. These variants were further characterized towards their potential in mismatch discrimination. Additionally, the identified enzymes were also able to differentiate between cytosine and 5-methylcytosine. Our results demonstrate the potential in characterizing and developing DNA polymerases for specific PCR based applications in DNA biotechnology and diagnostics.

  11. Frequency of thermostability variants: estimation of total rare variant frequency in human populations

    Energy Technology Data Exchange (ETDEWEB)

    Mohrenweiser, H.W.; Neel, J.V.


    Eight erythrocyte enzymes were examine for thermostability in an unselected sample of 100 newborn infants. Three thermolabile variants, one each of lactate dehydrogenase, glucosephosphate isomerase, and glucose-6-phosphate dehydrogenase, were identified, none of which was detectable as a variant by standard electrophoretic techniques. All were inherited. This frequency of 3.8 heritable thermostability variants per 1000 determinations is to be compared with a frequency of electrophoretically detectable variants of 1.1 per 1000 determinations, a frequency of 2.4 enzyme-deficiency variants per 1000 determinations, and a frequency of individuals with rare enzyme deficiency or electrophoretic or thermostability (or both) variants at these loci is 8.4 per 1000 determinations. A similar distribution and frequency is seen when the comparison is limited to the seven loci studied by all techniques. it is clear that not all of the electrophoretic and thermostability variants present in the population are detected by the techniques used in this study. Accordingly, it is estimated that the true frequency of carriers of a rare variant for each of these enzyme-coding loci averages greater than 10/1000. Some implications of these frequencies for human disease are discussed.

  12. Word Variant Identification in Old French

    Directory of Open Access Journals (Sweden)

    Peter Willett


    Full Text Available Increasing numbers of historical texts are available in machine-readable form, which retain the original spelling, which can be very different from the modern-day equivalents due to the natural evolution of a language, and because the concept of standardisation in spelling is comparatively modern. Among medieval vernacular writers, the same word could be spelled in different ways and the same author (or scribe might even use several alternative spellings in the same passage. Thus, we do not know,a priori, how many variant forms of a particular word there are in such texts, let alone what these variants might be. Searching on the modern equivalent, or even the commonest historical variant, of a particular word may thus fail to retrieve an appreciable number of occurrences unless the searcher already has an extensive knowledge of the language of the documents. Moreover, even specialist scholars may be unaware of some idiosyncratic variants. Here, we consider the use of computer methods to retrieve variant historical spellings.

  13. Developing bulk exchange spring magnets

    Energy Technology Data Exchange (ETDEWEB)

    Mccall, Scott K.; Kuntz, Joshua D.


    A method of making a bulk exchange spring magnet by providing a magnetically soft material, providing a hard magnetic material, and producing a composite of said magnetically soft material and said hard magnetic material to make the bulk exchange spring magnet. The step of producing a composite of magnetically soft material and hard magnetic material is accomplished by electrophoretic deposition of the magnetically soft material and the hard magnetic material to make the bulk exchange spring magnet.

  14. Characteristics of model heat exchanger (United States)

    Kolínský, Jan


    The aim of this paper is thermal analysis of model water to water heat exchanger at different mass flow rates. Experimental study deals with determination of total heat transfer - power of the heat exchanger. Furthermore the paper deals with analysis of heat exchanger charakcteristic using a definition of thermal efficiency. It is demonstrated that it is advisable to monitor the dependence of thermal efficiency and flow ratio.

  15. Hemoglobin Variants: Biochemical Properties and Clinical Correlates (United States)

    Thom, Christopher S.; Dickson, Claire F.; Gell, David A.; Weiss, Mitchell J.


    Diseases affecting hemoglobin synthesis and function are extremely common worldwide. More than 1000 naturally occurring human hemoglobin variants with single amino acid substitutions throughout the molecule have been discovered, mainly through their clinical and/or laboratory manifestations. These variants alter hemoglobin structure and biochemical properties with physiological effects ranging from insignificant to severe. Studies of these mutations in patients and in the laboratory have produced a wealth of information on hemoglobin biochemistry and biology with significant implications for hematology practice. More generally, landmark studies of hemoglobin performed over the past 60 years have established important paradigms for the disciplines of structural biology, genetics, biochemistry, and medicine. Here we review the major classes of hemoglobin variants, emphasizing general concepts and illustrative examples. PMID:23388674

  16. Genetics in psychiatry: common variant association studies

    Directory of Open Access Journals (Sweden)

    Buxbaum Joseph D


    Full Text Available Abstract Many psychiatric conditions and traits are associated with significant heritability. Genetic risk for psychiatric conditions encompass rare variants, identified due to major effect, as well as common variants, the latter analyzed by association analyses. We review guidelines for common variant association analyses, undertaking after assessing evidence of heritability. We highlight the importance of: suitably large sample sizes; an experimental design that controls for ancestry; careful data cleaning; correction for multiple testing; small P values for positive findings; assessment of effect size for positive findings; and, inclusion of an independent replication sample. We also note the importance of a critical discussion of any prior findings, biological follow-up where possible, and a means of accessing the raw data.

  17. Warty Carcinoma Penis: An Uncommon Variant. (United States)

    Thapa, Sushma; Ghosh, Arnab; Shrestha, Santosh; Ghartimagar, Dilasma; Narasimhan, Raghavan; Talwar, O P


    Penile carcinoma frequency varies widely in different parts of the world and comprises 1-10% of all the malignancies in males. Majority of the cases of penile carcinoma are squamous cell carcinoma of penis comprising 60% to 70% of all cases. Warty carcinoma of penis is an unusual neoplasm and a variant of penile squamous cell carcinoma comprising 5%-10% of all the variants. The other histological variants include basaloid, verrucous, papillary, sarcomatous, mixed, and adenosquamous carcinoma. The various histological entities with an exophytic papillary lesions including warty carcinoma are together referred to as the "verruciform" group of neoplasms. The warty carcinoma has to be differentiated from these lesions and is typically distinguished by histological features of hyperkeratosis, arborescent papillomatosis, acanthosis, and prominent koilocytosis with nuclear pleomorphism. We present a case of 65-year-old male with growth measuring 6 × 4 cm in the penis who underwent total penectomy and was diagnosed as warty carcinoma penis.

  18. Variants of Monteggia Type Injury: Case Reports

    Directory of Open Access Journals (Sweden)

    Kamudin NAF


    Full Text Available Background: Monteggia fracture-dislocation is rare in children. Various reports attest to its rarity, while recording the many variant of this injury. It is, therefore, easy to miss the diagnosis in the absence of proper clinical examination and radiographs. Case Report : This report highlights two rare variants of Monteggia fracture-dislocation seen in children. The first case was a 12-year old girl alleged to have fallen from a 15-feet tall tree and sustaining a combined type III Monteggia injury with ipsilateral Type II Salter-Harris injury of distal end radius with a metaphyseal fracture of the distal third of the ulna. The second case was a 13-year old who had sustained a closed fracture of atypical Type I Monteggia hybrid lesion, in a road traffic accident. Conclusion: This report highlights the rare variants of Monteggia fracture dislocation which could have been missed without proper clinical examinations and radiographs.

  19. Development of industrial variant specification systems

    DEFF Research Database (Denmark)

    Hansen, Benjamin Loer

    With globalisation and increased competition industrial companies must be prepared to satisfy individual customer needs and still stay competitive with regards to lead times, quality, and prices. These factors require companies to be better prepared to handle specification activities during order...... and the challenge of understanding the variant specification tasks and the connections between variant specification, product development, sales, manufacturing, and information technology. The present thesis seeks to meet this challenge with a procedure, concepts and tools. This is done through an extensive answer...... acquisition and order fulfilment, i.e. the creation of drawings, bill-of-materials, routings, product descriptions, quote letters etc. The present thesis is rooted in the assumption that variant specification systems supporting the cross-functional processes of order acquisition and order fulfilment must...

  20. A case of reninoma with variant angina

    Directory of Open Access Journals (Sweden)

    Hyung Ah Jo


    Full Text Available Reninoma is a tumor of the renal juxtaglomerular cell apparatus that causes hypertension and hypokalemia because of hypersecretion of renin. We present a case of a 29-year-old female patient with reninoma and concomitant variant angina. The patient had uncontrolled hypertension and elevated plasma renin activity and aldosterone levels. Imaging studies revealed a mass in the left kidney, which was further confirmed as a renin-producing lesion via selective venous catheterization. During the evaluation, the patient had acute-onset chest pain that was diagnosed as variant angina after a provocation test. After partial nephrectomy, the plasma renin activity and plasma aldosterone levels decreased and blood pressure normalized. We report a case of reninoma with variant angina.

  1. What Drives Stock Exchange Integration?

    National Research Council Canada - National Science Library

    Ekaterina Dorodnykh


    .... After a broad discussion of the existent literature, the investigation combines a large number of potentially relevant determinants for the explanation of whether stock exchanges are participating...

  2. Mastering Microsoft Exchange Server 2013

    CERN Document Server

    Elfassy, David


    The bestselling guide to Exchange Server, fully updated for the newest version Microsoft Exchange Server 2013 is touted as a solution for lowering the total cost of ownership, whether deployed on-premises or in the cloud. Like the earlier editions, this comprehensive guide covers every aspect of installing, configuring, and managing this multifaceted collaboration system. It offers Windows systems administrators and consultants a complete tutorial and reference, ideal for anyone installing Exchange Server for the first time or those migrating from an earlier Exchange Server version.Microsoft

  3. Hybrid Heat Exchangers (United States)

    Tu, Jianping Gene; Shih, Wei


    A hybrid light-weight heat exchanger concept has been developed that uses high-conductivity carbon-carbon (C-C) composites as the heat-transfer fins and uses conventional high-temperature metals, such as Inconel, nickel, and titanium as the parting sheets to meet leakage and structural requirements. In order to maximize thermal conductivity, the majority of carbon fiber is aligned in the fin direction resulting in 300 W/m.K or higher conductivity in the fin directions. As a result of this fiber orientation, the coefficient of thermal expansion (CTE) of the C-C composite in both non-fiber directions matches well with the CTE of various high-temperature metal alloys. This allows the joining of fins and parting sheets by using high-temperature braze alloys.

  4. The Radioecology Exchange

    Energy Technology Data Exchange (ETDEWEB)

    Barnett, Catherine L.; Beresford, Nicholas A.; Patel, Sabera; Wells, Claire; Howard, Brenda J. [NERC Centre for Ecology and Hydrology, CEH Lancaster, Lancaster Environment Centre, Library Av., Bailrigg, Lancaster, LA1 4AP (United Kingdom); Mora, Juan Carlos; Real, Almudena [Centro de Investigaciones Energeticas, Medioambientales y Tecnologicas (CIEMAT), Avenida complutense 22, Madrid, 28040 (Spain); Beaugelin-Seiller, Karine; Gilbin, Rodolphe; Hinton, Thomas [IRSN-Institut de Radioprotection et de Surete Nucleaire, 31, Avenue de la Division Leclerc, 92260 Fontenay-Aux-Roses (France); Vesterbacka, Pia; Muikku, Maarit; Outola, Iisa [Radiation and Nuclear Safety Authority, P.O. Box 14, FI-00881 Helsinki (Finland); Skuterud, Lavrans; AlbumYtre-Eide, Martin [Norwegian Radiation Protection Authority, Grini Naeringspark 13, Oesteraas, 1332 (Norway); Bradshaw, Clare; Stark, Karolina; Jaeschke, Ben [Stockholms Universitet, Universitetsvaegen 10, Stockholm, 10691 (Sweden); Oughton, Deborah; Skipperud, Lindis [NMBU Norwegian University of Life Science P.O. Box 5003N-1432 Aas, Oslo (Norway); Vandenhove, Hildegarde; Vanhoudt, Nathalie [SCK.CEN, Studiecentrum voor Kernenergie/Centre d' Etude de l' Energie Nucleaire, Avenue Herrmann-Debroux 40, BE-1160 Brussels (Belgium); Willrodt, Christine; Steiner, Martin [Bundesamt fuer Strahlenschutz, Willy-Brandt-Strasse 5, 38226 Salzgitter (Germany)


    The Radioecology Exchange ( was created in 2011 under the EU FP7 STAR (Strategy for Allied Radioecology) network of excellence. The project aims to integrate the research efforts on radioecology of nine European organisations into a sustainable network. The web site (together with associated Twitter feeds and Facebook page) currently provides the gateway to project outputs and other on-line radiation protection and radioecological resources. In 2013, the EU FP7 COMET (Coordination and implementation of a pan-European instrument for radioecology) project commenced; it aims to strengthen research on the impact of radiation on man and the environment. COMET includes the STAR partners with the addition of one Japanese and two Ukrainian research institutes. As STAR and COMET interact closely together and with the European Radioecology Alliance (, the Radioecology Exchange will be modified to become an international 'hub' for information related to radioecology. Project specific information will be hosted on separate web sites and This paper will present an overview of the resources hosted on the Radioecology Exchange inviting other scientists to contribute. Highlighted aspects of the site include: Social media (News blog, Twitter, Facebook) - Items announcing project outputs, training courses, jobs, studentships etc. Virtual laboratory - Information which encourages integration through joint research and integrated use of data and sample materials. These pages will focus on three categories: (1) Methodological: descriptions and video clips of commonly used analytical methods and protocols and the procedures used in STAR and COMET; (2) Informative: databases made available by STAR/COMET partners together with details of sample archives held. Fact-sheets on radio-ecologically important radionuclides and 'topical descriptions' which show absorbed

  5. Variant profiling of evolving prokaryotic populations

    Directory of Open Access Journals (Sweden)

    Markus Zojer


    Full Text Available Genomic heterogeneity of bacterial species is observed and studied in experimental evolution experiments and clinical diagnostics, and occurs as micro-diversity of natural habitats. The challenge for genome research is to accurately capture this heterogeneity with the currently used short sequencing reads. Recent advances in NGS technologies improved the speed and coverage and thus allowed for deep sequencing of bacterial populations. This facilitates the quantitative assessment of genomic heterogeneity, including low frequency alleles or haplotypes. However, false positive variant predictions due to sequencing errors and mapping artifacts of short reads need to be prevented. We therefore created VarCap, a workflow for the reliable prediction of different types of variants even at low frequencies. In order to predict SNPs, InDels and structural variations, we evaluated the sensitivity and accuracy of different software tools using synthetic read data. The results suggested that the best sensitivity could be reached by a union of different tools, however at the price of increased false positives. We identified possible reasons for false predictions and used this knowledge to improve the accuracy by post-filtering the predicted variants according to properties such as frequency, coverage, genomic environment/localization and co-localization with other variants. We observed that best precision was achieved by using an intersection of at least two tools per variant. This resulted in the reliable prediction of variants above a minimum relative abundance of 2%. VarCap is designed for being routinely used within experimental evolution experiments or for clinical diagnostics. The detected variants are reported as frequencies within a VCF file and as a graphical overview of the distribution of the different variant/allele/haplotype frequencies. The source code of VarCap is available at In order to provide this workflow to

  6. Variantes estruturalistas no ensino de Lacan


    Riaviz, Eduardo


    Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Comunicação e Expressão. Programa de Pós-Graduação em Literatura A presente tese estuda as variantes estruturalistas no ensino de Lacan. Para introduzir estas variantes, parte dos antecedentes desse ensino, i.e., dos textos de Lacan que ainda não são lacanianos. Mostra, nestes antecedentes, uma intuição estruturalista em Lacan, um estruturalismo em estado prático. Será justamente este proto-estruturalismo a permitir que L...

  7. 78 FR 69910 - Joint Industry Plan; BATS Exchange, Inc., BATS-Y Exchange, Inc., BOX Options Exchange LLC, C2... (United States)


    ... COMMISSION Joint Industry Plan; BATS Exchange, Inc., BATS-Y Exchange, Inc., BOX Options Exchange LLC, C2... LLC, NYSE Arca, Inc. and Topaz Exchange, LLC; Notice of Filing of Proposed National Market System Plan... and Exchange Commission (``Commission'') the proposed National Market System (``NMS'') Plan Governing...

  8. Liquid/liquid heat exchanger (United States)

    Miller, C. G.


    Conceptual design for heat exchanger, utilizing two immiscible liquids with dissimilar specific gravities in direct contact, is more efficient mechanism of heat transfer than conventional heat exchangers with walls or membranes. Concept could be adapted for collection of heat from solar or geothermal sources.

  9. Educators Exchange: A Program Evaluation. (United States)

    Armstrong, William B.

    The Educators Exchange Program (EEP) was established under a training and educational exchange agreement reached by California's San Diego Community College District (SDCCD) and the republic of Mexico. In the program, the District provided a 4-week technological training program to faculty at Centros de Capacitacion Tecnologica Industrial…

  10. Risk Balance in Exchange Protocols

    NARCIS (Netherlands)

    M.T. Dashti (Mohammad); Y. Wang (Yanjing); I. Cervesato


    htmlabstractWe study the behaviour of rational agents in exchange protocols which rely on trustees. We allow malicious parties to compromise the trustee by paying a cost and, thereby, present a game analysis that advocates exchange protocols which induce balanced risks on the participants. We also

  11. Professional Exchange: Mapping the Future. (United States)

    Dingman, Robert L.


    New associate editor of Professional Exchange section of "Journal of Mental Health Counseling" discusses importance of section. Lists potential topics suggested in 1989, then adds several other topics to the list. Concludes with guidelines for submission to Professional Exchange section. (NB)

  12. Numerical Simulation of Different Models of Heat Pipe Heat Exchanger Using AcuSolve

    Directory of Open Access Journals (Sweden)

    Zainal Nurul Amira


    Full Text Available In this paper, a numerical simulation of heat pipe heat exchanger (HPHE is computed by using CFD solver program i.e. AcuSolve. Two idealized model of HPHE are created with different variant of entry’s dimension set to be case 1 and case 2. The geometry of HPHE is designed in SolidWorks and imported to AcuSolve to simulate the fluid flow numerically. The design of HPHE is the key to provide a heat exchanger system to work proficient as expected. Finally, the result is used to optimize and improving heat recovery systems of the increasing demand for energy efficiency in industry.

  13. Heat exchanger leakage problem location

    Directory of Open Access Journals (Sweden)

    Jícha Miroslav


    Full Text Available Recent compact heat exchangers are very often assembled from numerous parts joined together to separate heat transfer fluids and to form the required heat exchanger arrangement. Therefore, the leak tightness is very important property of the compact heat exchangers. Although, the compact heat exchangers have been produced for many years, there are still technological problems associated with manufacturing of the ideal connection between the individual parts, mainly encountered with special purpose heat exchangers, e.g. gas turbine recuperators. This paper describes a procedure used to identify the leakage location inside the prime surface gas turbine recuperator. For this purpose, an analytical model of the leaky gas turbine recuperator was created to assess its performance. The results obtained are compared with the experimental data which were acquired during the recuperator thermal performance analysis. The differences between these two data sets are used to indicate possible leakage areas.

  14. Transendothelial lipoprotein exchange and microalbuminuria

    DEFF Research Database (Denmark)

    Jensen, Jan Skov; Feldt-Rasmussen, Bo; Jensen, Kurt Svarre


    OBJECTIVE: Microalbuminuria associates with increased risk of atherosclerosis in individuals without diabetes. We hypothesized that transendothelial lipoprotein exchange is elevated among such individuals, possibly explaining increased intimal lipoprotein accumulation and thus atherosclerosis....... METHODS: Using an in vivo isotope technique, transendothelial exchange of low density lipoprotein (LDL) was measured in 77 non-diabetic individuals. Autologous 131-iodinated LDL was reinjected intravenously, and the 1-h fractional escape rate was calculated as index of transendothelial exchange. RESULTS......: There was no difference in transendothelial LDL exchange between subjects with microalbuminuria versus normoalbuminuria (mean (95% confidence interval) 3.8%/h (3.3-4.3%/h) versus 4.2%/h (3.7-4.7%/h); P=0.33). In contrast, there was a positive correlation between transendothelial LDL exchange and (logarithmically...

  15. Next Generation Microchannel Heat Exchangers

    CERN Document Server

    Ohadi, Michael; Dessiatoun, Serguei; Cetegen, Edvin


    In Next Generation Microchannel Heat Exchangers, the authors’ focus on the new generation highly efficient heat exchangers and presentation of novel data and technical expertise not available in the open literature.  Next generation micro channels offer record high heat transfer coefficients with pressure drops much less than conventional micro channel heat exchangers. These inherent features promise fast penetration into many mew markets, including high heat flux cooling of electronics, waste heat recovery and energy efficiency enhancement applications, alternative energy systems, as well as applications in mass exchangers and chemical reactor systems. The combination of up to the minute research findings and technical know-how make this book very timely as the search for high performance heat and mass exchangers that can cut costs in materials consumption intensifies.

  16. High Temperature Heat Exchanger Project

    Energy Technology Data Exchange (ETDEWEB)

    Anthony E. Hechanova, Ph.D.


    The UNLV Research Foundation assembled a research consortium for high temperature heat exchanger design and materials compatibility and performance comprised of university and private industry partners under the auspices of the US DOE-NE Nuclear Hydrogen Initiative in October 2003. The objectives of the consortium were to conduct investigations of candidate materials for high temperature heat exchanger componets in hydrogen production processes and design and perform prototypical testing of heat exchangers. The initial research of the consortium focused on the intermediate heat exchanger (located between the nuclear reactor and hydrogen production plan) and the components for the hydrogen iodine decomposition process and sulfuric acid decomposition process. These heat exchanger components were deemed the most challenging from a materials performance and compatibility perspective

  17. Mining business process variants: Challenges, scenarios, algorithms

    NARCIS (Netherlands)

    Li, C.; Reichert, M.U.; Wombacher, Andreas

    During the last years a new generation of process-aware information systems has emerged, which enables process model configurations at buildtime as well as process instance changes during runtime. Respective model adaptations result in a large number of model variants that are derived from the same

  18. Probabilistic Transcriptome Assembly and Variant Graph Genotyping

    DEFF Research Database (Denmark)

    Sibbesen, Jonas Andreas

    that this approach outperforms existing state-of-the-art methods measured using sensitivity and precision on both simulated and real data. The second is a novel probabilistic method that uses exact alignment of k-mers to a set of variants graphs to provide unbiased estimates of genotypes in a population...

  19. HLogo: a parallel Haskell variant of Netlogo

    NARCIS (Netherlands)

    N. Bezirgiannis (Nikolaos); Prasetya, I.S.W.B.; Sakellariou, I.


    textabstractAgent-based Modeling (ABM) has become quite popular to the simulation community for its usability and wide area of applicability. However, speed is not usually a trait that ABM tools are characterized of attaining. This paper presents HLogo, a parallel variant of the NetLogo ABM

  20. XVCL: XML-based Variant Configuration Language

    DEFF Research Database (Denmark)

    Jarzabek, Stan; Basset, Paul; Zhang, Hongyu


    XVCL (XML-based Variant Configuration Language) is a meta-programming technique and tool that provides effective reuse mechanisms. XVCL is an open source software developed at the National University of Singapore. Being a modern and versatile version of Bassett's frames, a technology that has...

  1. Variants of the left aortic arch branches

    African Journals Online (AJOL)

    ORIGINAL ARTICLE. Variants of the left aortic arch branches. N Z Makhanya. MB ChB. R T Mamogale. MB 0113. N Khan. FCRaD (0). Department of Diagnostic Radiology. Medical University of Southern Africa. Abstract. The normal aorta has three branches from its arch, but variations in this pattern are not uncommon. Our.

  2. New genetic variants associated with prostate cancer (United States)

    Researchers have newly identified 23 common genetic variants -- one-letter changes in DNA known as single-nucleotide polymorphisms or SNPs -- that are associated with risk of prostate cancer. These results come from an analysis of more than 10 million SNP

  3. Psychiatric misdiagnoses in Dandy-Walker variant. (United States)

    Blaettner, C; Pfaffenberger, N M; Cartes-Zumelzu, F; Hofer, A


    Cases of intellectual impairment and aberrant behavior in patients with cerebellar diseases have been described since the early nineteenth century. Here, we report on a patient suffering from Dandy-Walker variant who presented with symptoms of obsessive compulsive disorder and delusional disorder. The current findings emphasize the potential relevance of focal cerebellar lesions as organic correlates of these disorders.

  4. Developing consistent pronunciation models for phonemic variants

    CSIR Research Space (South Africa)

    Davel, M


    Full Text Available from a lexicon containing variants. In this paper we (the authors) address both these issues by creating ‘pseudo-phonemes’ associated with sets of ‘generation restriction rules’ to model those pronunciations that are consistently realised as two or more...

  5. Mining Process Model Variants: Challenges, Techniques, Examples

    NARCIS (Netherlands)

    Li, C.


    During the last years a new generation of process-aware information systems has emerged, which enables process model configurations at buildtime as well as process instance changes during runtime. Respective model adaptations result in large collections of process model variants that are derived

  6. Cellobiohydrolase I gene and improved variants (United States)

    Adney, William S [Golden, CO; Decker, Stephen R [Berthoud, CO; Mc Carter, Suzanne [San Carlos, CA; Baker, John O [Golden, CO; Nieves, Raphael [Lakewood, CO; Himmel, Michael E [Littleton, CO; Vinzant, Todd B [Golden, CO


    The disclosure provides a method for preparing an active exoglucanase in a heterologous host of eukaryotic origin. The method includes mutagenesis to reduce glycosylation of the exoglucanase when expressed in a heterologous host. It is further disclosed a method to produce variant cellobiohydrolase that is stable at high temperature through mutagenesis.

  7. Report of a rare anatomic variant

    DEFF Research Database (Denmark)

    De Brucker, Y; Ilsen, B; Muylaert, C


    We report the CT findings in a case of partial anomalous pulmonary venous return (PAPVR) from the left upper lobe in an adult. PAPVR is an anatomic variant in which one to three pulmonary veins drain into the right atrium or its tributaries, rather than into the left atrium. This results in a lef...

  8. PIN1 gene variants in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Siedlecki Janusz


    Full Text Available Abstract Background Peptidyl-prolyl isomerase, NIMA-interacting 1 (PIN1 plays a significant role in the brain and is implicated in numerous cellular processes related to Alzheimer's disease (AD and other neurodegenerative conditions. There are confounding results concerning PIN1 activity in AD brains. Also PIN1 genetic variation was inconsistently associated with AD risk. Methods We performed analysis of coding and promoter regions of PIN1 in early- and late-onset AD and frontotemporal dementia (FTD patients in comparison with healthy controls. Results Analysis of eighteen PIN1 common polymorphisms and their haplotypes in EOAD, LOAD and FTD individuals in comparison with the control group did not reveal their contribution to disease risk. In six unrelated familial AD patients four novel PIN1 sequence variants were detected. c.58+64C>T substitution that was identified in three patients, was located in an alternative exon. In silico analysis suggested that this variant highly increases a potential affinity for a splicing factor and introduces two intronic splicing enhancers. In the peripheral leukocytes of one living patient carrying the variant, a 2.82 fold decrease in PIN1 expression was observed. Conclusion Our data does not support the role of PIN1 common polymorphisms as AD risk factor. However, we suggest that the identified rare sequence variants could be directly connected with AD pathology, influencing PIN1 splicing and/or expression.

  9. Fault-Tolerant Heat Exchanger (United States)

    Izenson, Michael G.; Crowley, Christopher J.


    A compact, lightweight heat exchanger has been designed to be fault-tolerant in the sense that a single-point leak would not cause mixing of heat-transfer fluids. This particular heat exchanger is intended to be part of the temperature-regulation system for habitable modules of the International Space Station and to function with water and ammonia as the heat-transfer fluids. The basic fault-tolerant design is adaptable to other heat-transfer fluids and heat exchangers for applications in which mixing of heat-transfer fluids would pose toxic, explosive, or other hazards: Examples could include fuel/air heat exchangers for thermal management on aircraft, process heat exchangers in the cryogenic industry, and heat exchangers used in chemical processing. The reason this heat exchanger can tolerate a single-point leak is that the heat-transfer fluids are everywhere separated by a vented volume and at least two seals. The combination of fault tolerance, compactness, and light weight is implemented in a unique heat-exchanger core configuration: Each fluid passage is entirely surrounded by a vented region bridged by solid structures through which heat is conducted between the fluids. Precise, proprietary fabrication techniques make it possible to manufacture the vented regions and heat-conducting structures with very small dimensions to obtain a very large coefficient of heat transfer between the two fluids. A large heat-transfer coefficient favors compact design by making it possible to use a relatively small core for a given heat-transfer rate. Calculations and experiments have shown that in most respects, the fault-tolerant heat exchanger can be expected to equal or exceed the performance of the non-fault-tolerant heat exchanger that it is intended to supplant (see table). The only significant disadvantages are a slight weight penalty and a small decrease in the mass-specific heat transfer.

  10. Electrically switched ion exchange

    Energy Technology Data Exchange (ETDEWEB)

    Lilga, M.A. [Pacific Northwest National Lab., Richland, WA (United States); Schwartz, D.T.; Genders, D.


    A variety of waste types containing radioactive {sup 137}Cs are found throughout the DOE complex. These waste types include water in reactor cooling basins, radioactive high-level waste (HLW) in underground storage tanks, and groundwater. Safety and regulatory requirements and economics require the removal of radiocesium before these wastes can be permanently disposed of. Electrically Switched Ion Exchange (ESIX) is an approach for radioactive cesium separation that combines IX and electrochemistry to provide a selective, reversible, and economic separation method that also produces little or no secondary waste. In the ESIX process, an electroactive IX film is deposited electrochemically onto a high-surface area electrode, and ion uptake and elution are controlled directly by modulating the potential of the film. For cesium, the electroactive films under investigation are ferrocyanides, which are well known to have high selectivities for cesium in concentrated sodium solutions. When a cathode potential is applied to the film, Fe{sup +3} is reduced to the Fe{sup +2} state, and a cation must be intercalated into the film to maintain charge neutrality (i.e., Cs{sup +} is loaded). Conversely, if an anodic potential is applied, a cation must be released from the film (i.e., Cs{sup +} is unloaded). Therefore, to load the film with cesium, the film is simply reduced; to unload cesium, the film is oxidized.


    Directory of Open Access Journals (Sweden)

    Olga V. Olshevska


    Full Text Available Creating a computer program to calculate microchannel air condensers to reduce design time and carrying out variant calculations. Software packages for thermophysical properties of the working substance and the coolant, the correlation equation for calculating heat transfer, aerodynamics and hydrodynamics, the thermodynamic equations for the irreversible losses and their minimization in the heat exchanger were used in the process of creating. Borland Delphi 7 is used for creating software package.

  12. Custom, contract, and kidney exchange. (United States)

    Healy, Kieran; Krawiec, Kimberly D


    In this Essay, we examine a case in which the organizational and logistical demands of a novel form of organ exchange (the nonsimultaneous, extended, altruistic donor (NEAD) chain) do not map cleanly onto standard cultural schemas for either market or gift exchange, resulting in sociological ambiguity and legal uncertainty. In some ways, a NEAD chain resembles a form of generalized exchange, an ancient and widespread instance of the norm of reciprocity that can be thought of simply as the obligation to “pay it forward” rather than the obligation to reciprocate directly with the original giver. At the same time, a NEAD chain resembles a string of promises and commitments to deliver something in exchange for some valuable consideration--that is, a series of contracts. Neither of these salient "social imaginaries" of exchange--gift giving or formal contract--perfectly meets the practical demands of the NEAD system. As a result, neither contract nor generalized exchange drives the practice of NEAD chains. Rather, the majority of actual exchanges still resemble a simpler form of exchange: direct, simultaneous exchange between parties with no time delay or opportunity to back out. If NEAD chains are to reach their full promise for large-scale, nonsimultaneous organ transfer, legal uncertainties and sociological ambiguities must be finessed, both in the practices of the coordinating agencies and in the minds of NEAD-chain participants. This might happen either through the further elaboration of gift-like language and practices, or through a creative use of the cultural form and motivational vocabulary, but not necessarily the legal and institutional machinery, of contract.

  13. Rare variant density across the genome and across populations


    Raska Paola; Zhu Xiaofeng


    Abstract Next-generation sequencing allows for a new focus on rare variant density for conducting analyses of association to disease and for narrowing down the genomic regions that show evidence of functionality. In this study we use the 1000 Genomes Project pilot data as distributed by Genetic Analysis Workshop 17 to compare rare variant densities across seven populations. We made the comparisons using regressions of rare variants on total variant counts per gene for each population and Taji...

  14. Probing the Conformational and Functional Consequences of Disulfide Bond Engineering in Growth Hormone by Hydrogen-Deuterium Exchange Mass Spectrometry Coupled to Electron Transfer Dissociation

    DEFF Research Database (Denmark)

    Seger, Signe T; Breinholt, Jens; Faber, Johan H


    Human growth hormone (hGH), and its receptor interaction, is essential for cell growth. To stabilize a flexible loop between helices 3 and 4, while retaining affinity for the hGH receptor, we have engineered a new hGH variant (Q84C/Y143C). Here, we employ hydrogen-deuterium exchange mass...... spectrometry (HDX-MS) to map the impact of the new disulfide bond on the conformational dynamics of this new hGH variant. Compared to wild type hGH, the variant exhibits reduced loop dynamics, indicating a stabilizing effect of the introduced disulfide bond. Furthermore, the disulfide bond exhibits longer...



    Podobeková, Veronika; Peráčková, Jana


    The article discusses utilization of heat from waste water in sewage. During the year, temperature of water in sewage ranges between 10 °C and 20 °C and the heat from sewage could be used for heating, cooling and hot water preparation in building. The heat is extracted through a transfer surface area of the heat exchanger into the heat pump, which is able to utilize the low–potential energy. Different design and types of the heat exchangers in sewage are dealt with: heat exchangers embedded i...

  16. Relational and XML Data Exchange

    CERN Document Server

    Arenas, Marcelo


    Data exchange is the problem of finding an instance of a target schema, given an instance of a source schema and a specification of the relationship between the source and the target. Such a target instance should correctly represent information from the source instance under the constraints imposed by the target schema, and it should allow one to evaluate queries on the target instance in a way that is semantically consistent with the source data. Data exchange is an old problem that re-emerged as an active research topic recently, due to the increased need for exchange of data in various for

  17. Heat exchanger using graphite foam (United States)

    Campagna, Michael Joseph; Callas, James John


    A heat exchanger is disclosed. The heat exchanger may have an inlet configured to receive a first fluid and an outlet configured to discharge the first fluid. The heat exchanger may further have at least one passageway configured to conduct the first fluid from the inlet to the outlet. The at least one passageway may be composed of a graphite foam and a layer of graphite material on the exterior of the graphite foam. The layer of graphite material may form at least a partial barrier between the first fluid and a second fluid external to the at least one passageway.

  18. Prevalence of hemoglobin variants in a diabetic population at high risk of hemoglobinopathies and optimization of HbA1c monitoring by incorporating HPLC in the laboratory workup. (United States)

    Bouzid, Kahena; Ahmed, Habib B; Kalai, Eya; Blibeche, Salma; Couque, Nathalie; Khiari, Karima; Bahlous, Afef; Abdelmoula, Jaouida


    In Tunisia, diabetes mellitus and hemoglobinopathies are major public health problems. Glycated hemoglobin (HbA1c) is recommended for long-term monitoring of diabetes mellitus, but the presence of hemoglobin variants may interfere with HbA1c measurement. The aim was to determine the prevalence of hemoglobin variants in Tunisian diabetics and optimize the monitoring of diabetics using HbA1c. The study enrolled 9,792 Tunisian diabetic patients. HbA1c was measured by cation-exchange high-pressure liquid chromatography (HPLC). All the chromatograms were analyzed for the presence of Hb variants. We identified 228 cases (2.33%) of Hb variants with D-10 HPLC (Bio-Rad): 191 with HbA/S trait, 27 with HbA/C trait, and 10 hemoglobin variants with the mention 'Variant-Window' on the chromatograms and subsequently identified as HbA/S on Variant I HPLC (Bio-Rad). Thus, the prevalence of HbS was 2.05%. We did not find any homozygous variant. All HbA1c results were reported to the treating physician. To evaluate glycated hemoglobin in populations with a high prevalence of hemoglobinopathies, we should use the HPLC method, which is easy, economical, and reliable. Based on an algorithm, hemoglobin variants visualized on HPLC should be reported to the physician to improve the management of patients.

  19. Dietary intake, FTO genetic variants and adiposity

    DEFF Research Database (Denmark)

    Qi, Qibin; Downer, Mary K; Oskari Kilpeläinen, Tuomas


    between the FTO rs9939609 variant (or a proxy) and total energy and macronutrient intake; and 2) the interaction between the FTO variant and dietary intake, and the effect on BMI. We found that the BMI-increasing allele (minor allele) of the FTO variant was associated with increased total energy intake...

  20. Processing of No-Release Variants in Connected Speech (United States)

    LoCasto, Paul C.; Connine, Cynthia M.


    The cross modal repetition priming paradigm was used to investigate how potential lexically ambiguous no-release variants are processed. In particular we focus on segmental regularities that affect the variant's frequency of occurrence (voicing of the critical segment) and phonological context in which the variant occurs (status of the following…

  1. The power of multiplexed functional analysis of genetic variants. (United States)

    Gasperini, Molly; Starita, Lea; Shendure, Jay


    New technologies have recently enabled saturation mutagenesis and functional analysis of nearly all possible variants of regulatory elements or proteins of interest in single experiments. Here we discuss the past, present, and future of such multiplexed (functional) assays for variant effects (MAVEs). MAVEs provide detailed insight into sequence-function relationships, and they may prove critical for the prospective clinical interpretation of genetic variants.

  2. GAVIN : Gene-Aware Variant INterpretation for medical sequencing

    NARCIS (Netherlands)

    van der Velde, K Joeri; de Boer, Eddy N; van Diemen, Cleo C; Sikkema-Raddatz, Birgit; Abbott, Kristin M; Knopperts, Alain; Franke, Lude; Sijmons, Rolf H; de Koning, Tom J; Wijmenga, Cisca; Sinke, Richard J; Swertz, Morris A


    We present Gene-Aware Variant INterpretation (GAVIN), a new method that accurately classifies variants for clinical diagnostic purposes. Classifications are based on gene-specific calibrations of allele frequencies from the ExAC database, likely variant impact using SnpEff, and estimated

  3. Variant of Rett syndrome and CDKL5 gene

    DEFF Research Database (Denmark)

    Pini, Giorgio; Bigoni, Stefania; Engerström, Ingegerd Witt


    UNLABELLED: Rett syndrome (RTT) is a severe neurodevelopmental disorder affecting almost exclusively females. The Hanefeld variant, or early-onset seizure variant, has been associated with mutations in CDKL5 gene. AIMS: In recent years more than 60 patients with mutations in the CDKL5 gene have...... the general Rett population, suggesting a specific behavioral and cardiorespiratory phenotype of the RTT the Hanefeld variant....

  4. Citrate-stabilized gold nanoparticles hinder fibrillogenesis of a pathological variant of β2-microglobulin. (United States)

    Cantarutti, Cristina; Raimondi, Sara; Brancolini, Giorgia; Corazza, Alessandra; Giorgetti, Sofia; Ballico, Maurizio; Zanini, Stefano; Palmisano, Giovanni; Bertoncin, Paolo; Marchese, Loredana; Patrizia Mangione, P; Bellotti, Vittorio; Corni, Stefano; Fogolari, Federico; Esposito, Gennaro


    Nanoparticles have repeatedly been shown to enhance fibril formation when assayed with amyloidogenic proteins. Recently, however, evidence casting some doubt about the generality of this conclusion started to emerge. Therefore, to investigate further the influence of nanoparticles on the fibrillation process, we used a naturally occurring variant of the paradigmatic amyloidogenic protein β2-microglobulin (β2m), namely D76N β2m where asparagine replaces aspartate at position 76. This variant is responsible for aggressive systemic amyloidosis. After characterizing the interaction of the variant with citrate-stabilized gold nanoparticles (Cit-AuNPs) by NMR and modeling, we analyzed the fibril formation by three different methods: thioflavin T fluorescence, native agarose gel electrophoresis and transmission electron microscopy. The NMR evidence indicated a fast-exchange interaction involving preferentially specific regions of the protein that proved, by subsequent modeling, to be consistent with a dimeric adduct interacting with Cit-AuNPs. The fibril detection assays showed that AuNPs are able to hamper D76N β2m fibrillogenesis through an effective interaction that competes with protofibril formation or recruitment. These findings open promising perspectives for the optimization of the nanoparticle surface to design tunable interactions with proteins.

  5. Spectrum of hemoglobin variants in the population of northern region of West Bengal: An ethnogenetic proposition

    Directory of Open Access Journals (Sweden)

    Bidyut Krishna Goswami


    Full Text Available Context: The birth of transfusion-dependent states of hemoglobinopathies including thalassemias is preventable by population screening and genetic counseling. Magnitude is not addressed in the Northern Region of West Bengal where many ethnic variants inhabit. Aims and Objectives: The aim of the following study is to find out the burden of different entities of hemoglobinopathies, their correlation with ethnicity and the "at risk" groups. Subjects and Methods: A descriptive study was conducted from the Hematology Unit of North Bengal Medical College over 1 year on the subjects underwent screening for hemoglobinopathies for detection of abnormal hemoglobin (Hb variants by "cation-exchange high-performance liquid chromatography" principle along with other relevant tests. Statistical Analysis: Data was analyzed by frequency distribution and Chi-square test assuming P value as 95% of the level of significance using the SPSS version 16 (SPSS Inc., Chicago, Illinois, U.S.A. Result: Abnormal Hb variant was 47.5% among 1872. Hb E trait (34.4% was most common followed by Hb E disease (25.3% and others. Hb E disorders (92.7% were observed mostly among Rajbangsi population while E-β-thalassemias (40% in the Muslims and a heterogeneous pattern noted among tribal and mongoloid. Conclusion: Hb E hemoglobinopathies was high among Rajbangsi and Muslims with identification of some other hemoglobinopathies involving tribal and mongoloid.

  6. Spectrum of Hemoglobin Variants in the Population of Northern Region of West Bengal: An Ethnogenetic Proposition (United States)

    Goswami, Bidyut Krishna; Pramanik, Raghunath; Chakrabarty, Sudipta; Pal, Partha Pratim; Banerjee, Sarama; Bandyopadhyay, Arghya


    Context: The birth of transfusion-dependent states of hemoglobinopathies including thalassemias is preventable by population screening and genetic counseling. Magnitude is not addressed in the Northern Region of West Bengal where many ethnic variants inhabit. Aims and Objectives: The aim of the following study is to find out the burden of different entities of hemoglobinopathies, their correlation with ethnicity and the “at risk” groups. Subjects and Methods: A descriptive study was conducted from the Hematology Unit of North Bengal Medical College over 1 year on the subjects underwent screening for hemoglobinopathies for detection of abnormal hemoglobin (Hb) variants by “cation-exchange high-performance liquid chromatography” principle along with other relevant tests. Statistical Analysis: Data was analyzed by frequency distribution and Chi-square test assuming P value as 95% of the level of significance using the SPSS version 16 (SPSS Inc., Chicago, Illinois, U.S.A). Result: Abnormal Hb variant was 47.5% among 1872. Hb E trait (34.4%) was most common followed by Hb E disease (25.3%) and others. Hb E disorders (92.7%) were observed mostly among Rajbangsi population while E-β-thalassemias (40%) in the Muslims and a heterogeneous pattern noted among tribal and mongoloid. Conclusion: Hb E hemoglobinopathies was high among Rajbangsi and Muslims with identification of some other hemoglobinopathies involving tribal and mongoloid. PMID:25374858

  7. Pu Anion Exchange Process Intensification

    Energy Technology Data Exchange (ETDEWEB)

    Taylor-Pashow, K. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)


    This project seeks to improve the efficiency of the plutonium anion-exchange process for purifying Pu through the development of alternate ion-exchange media. The objective of the project in FY15 was to develop and test a porous foam monolith material that could serve as a replacement for the current anion-exchange resin, Reillex® HPQ, used at the Savannah River Site (SRS) for purifying Pu. The new material provides advantages in efficiency over the current resin by the elimination of diffusive mass transport through large granular resin beads. By replacing the large resin beads with a porous foam there is much more efficient contact between the Pu solution and the anion-exchange sites present on the material. Several samples of a polystyrene based foam grafted with poly(4-vinylpyridine) were prepared and the Pu sorption was tested in batch contact tests.

  8. Liquid droplet heat exchanger studies (United States)

    Bruckner, A. P.; Hedges, D. E.; Yungster, S.


    Recent analytical and experimental investigations of the liquid droplet heat exchanger (LDHX) concept for space power applications are described. The performance of the LDHX is compared to that of a conventional heat exchanger for heat rejection applications in a Brayton cycle, using the mass-specific heat exchanger effectiveness as a figure of merit. It is shown that the LDHX has an order of magnitude advantage over the conventional heat exchanger. Furthermore, significant improvement in cycle efficiency and power to mass ratio is possible. Two-phase flow experiments in a laboratory scale LDHX, using air and water as the two media, show very good agreement with the quasi-one-dimensional model used in the parametric studies.

  9. Estimating Foreign Exchange Reserve Adequacy

    Directory of Open Access Journals (Sweden)

    Abdul Hakim


    Full Text Available Accumulating foreign exchange reserves, despite their cost and their impacts on other macroeconomics variables, provides some benefits. This paper models such foreign exchange reserves. To measure the adequacy of foreign exchange reserves for import, it uses total reserves-to-import ratio (TRM. The chosen independent variables are gross domestic product growth, exchange rates, opportunity cost, and a dummy variable separating the pre and post 1997 Asian financial crisis. To estimate the risky TRM value, this paper uses conditional Value-at-Risk (VaR, with the help of Glosten-Jagannathan-Runkle (GJR model to estimate the conditional volatility. The results suggest that all independent variables significantly influence TRM. They also suggest that the short and long run volatilities are evident, with the additional evidence of asymmetric effects of negative and positive past shocks. The VaR, which are calculated assuming both normal and t distributions, provide similar results, namely violations in 2005 and 2008.

  10. VLER Health Exchange by Area (United States)

    Department of Veterans Affairs — “Connect Your Docs” through the Virtual Lifetime Electronic Record (VLER) Health Exchange program. This program gives VA and community health care providers secure...

  11. Counterflow Regolith Heat Exchanger Project (United States)

    National Aeronautics and Space Administration — The counterflow regolith heat exchanger (CoRHE) is a device that transfers heat from hot regolith to cold regolith. The CoRHE is essentially a tube-in-tube heat...

  12. MIPEP recessive variants cause a syndrome of left ventricular non-compaction, hypotonia, and infantile death. (United States)

    Eldomery, Mohammad K; Akdemir, Zeynep C; Vögtle, F-Nora; Charng, Wu-Lin; Mulica, Patrycja; Rosenfeld, Jill A; Gambin, Tomasz; Gu, Shen; Burrage, Lindsay C; Al Shamsi, Aisha; Penney, Samantha; Jhangiani, Shalini N; Zimmerman, Holly H; Muzny, Donna M; Wang, Xia; Tang, Jia; Medikonda, Ravi; Ramachandran, Prasanna V; Wong, Lee-Jun; Boerwinkle, Eric; Gibbs, Richard A; Eng, Christine M; Lalani, Seema R; Hertecant, Jozef; Rodenburg, Richard J; Abdul-Rahman, Omar A; Yang, Yaping; Xia, Fan; Wang, Meng C; Lupski, James R; Meisinger, Chris; Sutton, V Reid


    Mitochondrial presequence proteases perform fundamental functions as they process about 70 % of all mitochondrial preproteins that are encoded in the nucleus and imported posttranslationally. The mitochondrial intermediate presequence protease MIP/Oct1, which carries out precursor processing, has not yet been established to have a role in human disease. Whole exome sequencing was performed on four unrelated probands with left ventricular non-compaction (LVNC), developmental delay (DD), seizures, and severe hypotonia. Proposed pathogenic variants were confirmed by Sanger sequencing or array comparative genomic hybridization. Functional analysis of the identified MIP variants was performed using the model organism Saccharomyces cerevisiae as the protein and its functions are highly conserved from yeast to human. Biallelic single nucleotide variants (SNVs) or copy number variants (CNVs) in MIPEP, which encodes MIP, were present in all four probands, three of whom had infantile/childhood death. Two patients had compound heterozygous SNVs (p.L582R/p.L71Q and p.E602*/p.L306F) and one patient from a consanguineous family had a homozygous SNV (p.K343E). The fourth patient, identified through the GeneMatcher tool, a part of the Matchmaker Exchange Project, was found to have inherited a paternal SNV (p.H512D) and a maternal CNV (1.4-Mb deletion of 13q12.12) that includes MIPEP. All amino acids affected in the patients' missense variants are highly conserved from yeast to human and therefore S. cerevisiae was employed for functional analysis (for p.L71Q, p.L306F, and p.K343E). The mutations p.L339F (human p.L306F) and p.K376E (human p.K343E) resulted in a severe decrease of Oct1 protease activity and accumulation of non-processed Oct1 substrates and consequently impaired viability under respiratory growth conditions. The p.L83Q (human p.L71Q) failed to localize to the mitochondria. Our findings reveal for the first time the role of the mitochondrial intermediate peptidase in

  13. MIPEP recessive variants cause a syndrome of left ventricular non-compaction, hypotonia, and infantile death

    Directory of Open Access Journals (Sweden)

    Mohammad K. Eldomery


    Full Text Available Abstract Background Mitochondrial presequence proteases perform fundamental functions as they process about 70 % of all mitochondrial preproteins that are encoded in the nucleus and imported posttranslationally. The mitochondrial intermediate presequence protease MIP/Oct1, which carries out precursor processing, has not yet been established to have a role in human disease. Methods Whole exome sequencing was performed on four unrelated probands with left ventricular non-compaction (LVNC, developmental delay (DD, seizures, and severe hypotonia. Proposed pathogenic variants were confirmed by Sanger sequencing or array comparative genomic hybridization. Functional analysis of the identified MIP variants was performed using the model organism Saccharomyces cerevisiae as the protein and its functions are highly conserved from yeast to human. Results Biallelic single nucleotide variants (SNVs or copy number variants (CNVs in MIPEP, which encodes MIP, were present in all four probands, three of whom had infantile/childhood death. Two patients had compound heterozygous SNVs (p.L582R/p.L71Q and p.E602*/p.L306F and one patient from a consanguineous family had a homozygous SNV (p.K343E. The fourth patient, identified through the GeneMatcher tool, a part of the Matchmaker Exchange Project, was found to have inherited a paternal SNV (p.H512D and a maternal CNV (1.4-Mb deletion of 13q12.12 that includes MIPEP. All amino acids affected in the patients’ missense variants are highly conserved from yeast to human and therefore S. cerevisiae was employed for functional analysis (for p.L71Q, p.L306F, and p.K343E. The mutations p.L339F (human p.L306F and p.K376E (human p.K343E resulted in a severe decrease of Oct1 protease activity and accumulation of non-processed Oct1 substrates and consequently impaired viability under respiratory growth conditions. The p.L83Q (human p.L71Q failed to localize to the mitochondria. Conclusions Our findings reveal for the first

  14. Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants.

    Directory of Open Access Journals (Sweden)

    Mengmeng Du

    Full Text Available Genome-wide association studies (GWAS have identified many common single nucleotide polymorphisms (SNPs associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs. We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33. We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s.

  15. Unusual variant of Cantrell′s pentalogy?

    Directory of Open Access Journals (Sweden)

    Kumar Basant


    Full Text Available A 12-hour-old male infant presented with prolapsed abdominal content through a defect on left side of chest wall with respiratory distress. A thorough clinical examination suggested absence of ectopia cordis, abdominal wall defect, and any bony anomaly. The child expired after 6 hours of admission because of respiratory distress and electrolyte imbalance. Is congenital defect of chest wall associated with diaphragmatic hernia without ectopia cordis and omphalocele, an unusual variant of Cantrell′s pentalogy?

  16. International Prices and Exchange Rates


    Gopinath, Gita; Burstein, Ariel


    We survey the recent empirical and theoretical developments in the literature on the relation between prices and exchange rates. After updating some of the major findings in the empirical literature we present a simple framework to interpret this evidence. We review theoretical models that generate insensitivity of prices to exchange rate changes through variable markups, both under flexible prices and nominal rigidities, first in partial equilibrium and then in general equilibrium.

  17. Exchange rate determination in Vietnam


    Thai-Ha Le


    This study investigates the determinants of the exchange rate in Vietnam and suggests policy implications. Gregory-Hansen cointegration tests and generalised variance decomposition (VDC) analysis were applied to monthly data from July 2004 to December 2013. The model was built based on the three popular approaches to exchange rate determination, which are purchasing power parity (PPP) approach, balance of payment (BOP) approach, and monetary and portfolio approach. This study finds that the p...

  18. Shared Year Exchange in Nursing

    DEFF Research Database (Denmark)

    Vedsegaard, Helle Wendner; Wederkinck, Elisabeth


    Beskrivelse af Shared Year Exchange in Nursing, et udviklingsporjekt omhandlende udvikling, beskrivelse og implementering af et fælles studieår for sygeplejerskestuderende ved Metropol og La Trobe University Australien.......Beskrivelse af Shared Year Exchange in Nursing, et udviklingsporjekt omhandlende udvikling, beskrivelse og implementering af et fælles studieår for sygeplejerskestuderende ved Metropol og La Trobe University Australien....

  19. Novel RNA variants in colorectal cancers. (United States)

    Hoff, Andreas M; Johannessen, Bjarne; Alagaratnam, Sharmini; Zhao, Sen; Nome, Torfinn; Løvf, Marthe; Bakken, Anne C; Hektoen, Merete; Sveen, Anita; Lothe, Ragnhild A; Skotheim, Rolf I


    With an annual estimated incidence of 1.4 million, and a five-year survival rate of 60%, colorectal cancer (CRC) is a major clinical burden. To identify novel RNA variants in CRC, we analyzed exon-level microarray expression data from a cohort of 202 CRCs. We nominated 25 genes with increased expression of their 3' parts in at least one cancer sample each. To efficiently investigate underlying transcript structures, we developed an approach using rapid amplification of cDNA ends followed by high throughput sequencing (RACE-seq). RACE products from the targeted genes in 23 CRC samples were pooled together and sequenced. We identified VWA2-TCF7L2, DHX35-BPIFA2 and CASZ1-MASP2 as private fusion events, and novel transcript structures for 17 of the 23 other candidate genes. The high-throughput approach facilitated identification of CRC specific RNA variants. These include a recurrent read-through fusion transcript between KLK8 and KLK7, and a splice variant of S100A2. Both of these were overrepresented in CRC tissue and cell lines from external RNA-seq datasets.

  20. [Dandy-Walker variant: Case report]. (United States)

    Cueva-Núñez, José E; Lozano-Bustillo, Alejandra; Irias-Álvarez, Merlyn S; Vásquez-Montes, Raúl F; Varela-González, Douglas M

    Dandy Walker variant is defined by a variable hypoplasia of the cerebellar vermix with or without posterior fossa increase and without tentorium elevation. describe the case of a rare disease and emphasise the need to clarify the aetiology of prenatal malformations, as well as its multidisciplinary management. A male patient, 8 years of age, with a history of Infantile Cerebral Palsy and epilepsy, who was admitted with a history of tonic-clonic seizures. He was admitted due to psycho-motor developmental delay. During his hospitalisation, he had multiple seizure episodes, controlled with anticonvulsants. A computerized tomography was performed, in which communication was observed between the cisterna magna and fourth ventricle (the latter increased in size). In addition, the cerebellar vermix showed a partial hypoplasia. All these findings were compatible with a variant of the Dandy Walker syndrome. Dandy Walker variant may be asymptomatic and the images found may not indicate them as the cause of developmental disorders, due to its association with multiple syndromes and chromosomal abnormalities. Clinical presentation and prognosis depends on the related disorders, and a multidisciplinary approach is important, because the treatment depends on the symptoms presented. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Splicing analysis of 14 BRCA1 missense variants classifies nine variants as pathogenic

    DEFF Research Database (Denmark)

    Ahlborn, Lise B; Dandanell, Mette; Steffensen, Ane Y


    needed to classify whether these uncertain variants are pathogenic or benign. In this study, we investigated 14 BRCA1 variants by in silico splicing analysis and mini-gene splicing assay. All 14 alterations were missense variants located within the BRCT domain of BRCA1 and had previously been examined...... by functional analysis at the protein level. Results from a validated mini-gene splicing assay indicated that nine BRCA1 variants resulted in splicing aberrations leading to truncated transcripts and thus can be considered pathogenic (c.4987A>T/p.Met1663Leu, c.4988T>A/p.Met1663Lys, c.5072C>T/p.Thr1691Ile, c...... to have no or an uncertain effect on the protein level, whereas one variant (c.5072C>T/p.Thr1691Ile) were shown to have a strong effect on the protein level as well. In conclusion, our study emphasizes that in silico splicing prediction and mini-gene splicing analysis are important for the classification...

  2. Microsatellite Instability Use in Mismatch Repair Gene Sequence Variant Classification

    Directory of Open Access Journals (Sweden)

    Bryony A. Thompson


    Full Text Available Inherited mutations in the DNA mismatch repair genes (MMR can cause MMR deficiency and increased susceptibility to colorectal and endometrial cancer. Microsatellite instability (MSI is the defining molecular signature of MMR deficiency. The clinical classification of identified MMR gene sequence variants has a direct impact on the management of patients and their families. For a significant proportion of cases sequence variants of uncertain clinical significance (also known as unclassified variants are identified, constituting a challenge for genetic counselling and clinical management of families. The effect on protein function of these variants is difficult to interpret. The presence or absence of MSI in tumours can aid in determining the pathogenicity of associated unclassified MMR gene variants. However, there are some considerations that need to be taken into account when using MSI for variant interpretation. The use of MSI and other tumour characteristics in MMR gene sequence variant classification will be explored in this review.

  3. Investigating alpha-globin structural variants: a retrospective review of 135,000 Brazilian individuals

    Directory of Open Access Journals (Sweden)

    Elza Miyuki Kimura


    Full Text Available Background: Brazil has a multiethnic population with a high diversity of hemoglobinopathies. While screenings for beta-globin mutations are far more common, alterations affecting alpha-globin genes are usually more silent and less well known. The aim of this study was to describe the results of a screening program for alpha-globin gene mutations in a representative sample of the Southeastern Brazilian population. Methods: A total of 135,000 individuals, including patients with clinical suspicion of hemoglobinopathies and their family members, randomly chosen individuals submitted to blood tests and blood donors who were abnormal hemoglobin carriers were analyzed. The variants were screened by alkaline and acid electrophoreses, isoelectric focusing and cation-exchange high performance liquid chromatography (HPLC and the abnormal chains were investigated by reverse-phase high performance liquid chromatography (RP-HPLC. Mutations were identified by molecular analyses, and the oxygen affinity, heme-heme cooperativity and Bohr effect of the variants were evaluated by functional tests. Results: Four new and 22 rare variants were detected in 98 families. Some of these variants were found in co-inheritance with other hemoglobinopathies. Of the rare hemoglobins, Hasharon, Stanleyville II and J-Rovigo were the most common, the first two being S-like and associated with alpha-thalassemia. Conclusion: The variability of alpha-globin alterations reflects the high degree of racial miscegenation and an intense internal migratory flow between different Brazilian regions. This diversity highlights the importance of programs for diagnosing hemoglobinopathies and preventing combinations that may lead to important clinical manifestations in multiethnic populations.

  4. Common coding variant in SERPINA1 increases the risk for large artery stroke. (United States)

    Malik, Rainer; Dau, Therese; Gonik, Maria; Sivakumar, Anirudh; Deredge, Daniel J; Edeleva, Evgeniia V; Götzfried, Jessica; van der Laan, Sander W; Pasterkamp, Gerard; Beaufort, Nathalie; Seixas, Susana; Bevan, Steve; Lincz, Lisa F; Holliday, Elizabeth G; Burgess, Annette I; Rannikmäe, Kristiina; Minnerup, Jens; Kriebel, Jennifer; Waldenberger, Melanie; Müller-Nurasyid, Martina; Lichtner, Peter; Saleheen, Danish; Rothwell, Peter M; Levi, Christopher; Attia, John; Sudlow, Cathie L M; Braun, Dieter; Markus, Hugh S; Wintrode, Patrick L; Berger, Klaus; Jenne, Dieter E; Dichgans, Martin


    Large artery atherosclerotic stroke (LAS) shows substantial heritability not explained by previous genome-wide association studies. Here, we explore the role of coding variation in LAS by analyzing variants on the HumanExome BeadChip in a total of 3,127 cases and 9,778 controls from Europe, Australia, and South Asia. We report on a nonsynonymous single-nucleotide variant in serpin family A member 1 (SERPINA1) encoding alpha-1 antitrypsin [AAT; p.V213A; P = 5.99E-9, odds ratio (OR) = 1.22] and confirm histone deacetylase 9 (HDAC9) as a major risk gene for LAS with an association in the 3'-UTR (rs2023938; P = 7.76E-7, OR = 1.28). Using quantitative microscale thermophoresis, we show that M1 (A213) exhibits an almost twofold lower dissociation constant with its primary target human neutrophil elastase (NE) in lipoprotein-containing plasma, but not in lipid-free plasma. Hydrogen/deuterium exchange combined with mass spectrometry further revealed a significant difference in the global flexibility of the two variants. The observed stronger interaction with lipoproteins in plasma and reduced global flexibility of the Val-213 variant most likely improve its local availability and reduce the extent of proteolytic inactivation by other proteases in atherosclerotic plaques. Our results indicate that the interplay between AAT, NE, and lipoprotein particles is modulated by the gate region around position 213 in AAT, far away from the unaltered reactive center loop (357-360). Collectively, our findings point to a functionally relevant balance between lipoproteins, proteases, and AAT in atherosclerosis.

  5. Performance Assessment of 239 Series Sub-cooling Heat Exchangers for the Large Hadron Collider

    CERN Document Server

    Riddone, G; Roussel, P; Moracchioli, R; Tavian, L


    Helium sub-cooling heat exchangers of the counter-flow type are used to minimize the vapor fraction produced in the final expansion of the 1.9 K distributed cooling loops used for cooling the superconducting magnets of the Large Hadron Collider (LHC). These components are of compact design, featuring low-pressure drop and handling very low pressure vapor at low temperature. Following a qualification phase of prototypes, a contract has been placed in European industry for the supply of 239 heat exchanger units. Different levels of extracted heat load require three different variants of heat exchangers. This paper will describe the manufacturing phase with emphasis on the main difficulties encountered to keep the production quality after a brief recall of the prototype phase. Finally, the acceptance tests performed at room temperature and at the nominal cryogenic condition at the factory and at CEA-Grenoble will be presented.

  6. Melanoma risk associated with MC1R gene variants in Latvia and the functional analysis of rare variants. (United States)

    Ozola, Aija; Azarjana, Kristīne; Doniņa, Simona; Proboka, Guna; Mandrika, Ilona; Petrovska, Ramona; Cēma, Ingrīda; Heisele, Olita; Eņģele, Ludmila; Streinerte, Baiba; Pjanova, Dace


    To evaluate the association of melanocortin 1 receptor gene (MC1R) variants with melanoma risk in a Latvian population, the MC1R gene was sequenced in 200 melanoma patients and 200 control persons. A functional study of previously uncharacterized, rare MC1R variants was also performed. In total, 26 different MC1R variants, including two novel variants Val165Ile and Val188Ile, were detected. The highest risk of melanoma was associated with the Arg151Cys variant (odds ratio (OR) 4.47, 95% confidence interval (CI) 2.19-9.14, PMC1R variants revealed that a subset of them is functionally relevant. Our results support the contribution of MC1R variants to a genetic predisposition to melanoma in Latvia. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Fair Exchange in Strand Spaces

    Directory of Open Access Journals (Sweden)

    Joshua D. Guttman


    Full Text Available Many cryptographic protocols are intended to coordinate state changes among principals. Exchange protocols coordinate delivery of new values to the participants, e.g. additions to the set of values they possess. An exchange protocol is fair if it ensures that delivery of new values is balanced: If one participant obtains a new possession via the protocol, then all other participants will, too. Fair exchange requires progress assumptions, unlike some other protocol properties. The strand space model is a framework for design and verification of cryptographic protocols. A strand is a local behavior of a single principal in a single session of a protocol. A bundle is a partially ordered global execution built from protocol strands and adversary activities. The strand space model needs two additions for fair exchange protocols. First, we regard the state as a multiset of facts, and we allow strands to cause changes in this state via multiset rewriting. Second, progress assumptions stipulate that some channels are resilient-and guaranteed to deliver messages-and some principals are assumed not to stop at certain critical steps. This method leads to proofs of correctness that cleanly separate protocol properties, such as authentication and confidentiality, from invariants governing state evolution. G. Wang's recent fair exchange protocol illustrates the approach.

  8. Pu Anion Exchange Process Intensification

    Energy Technology Data Exchange (ETDEWEB)

    Taylor-Pashow, Kathryn M. L. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)


    This research is focused on improving the efficiency of the anion exchange process for purifying plutonium. While initially focused on plutonium, the technology could also be applied to other ion-exchange processes. Work in FY17 focused on the improvement and optimization of porous foam columns that were initially developed in FY16. These foam columns were surface functionalized with poly(4-vinylpyridine) (PVP) to provide the Pu specific anion-exchange sites. Two different polymerization methods were explored for maximizing the surface functionalization with the PVP. The open-celled polymeric foams have large open pores and large surface areas available for sorption. The fluid passes through the large open pores of this material, allowing convection to be the dominant mechanism by which mass transport takes place. These materials generally have very low densities, open-celled structures with high cell interconnectivity, small cell sizes, uniform cell size distributions, and high structural integrity. These porous foam columns provide advantages over the typical porous resin beads by eliminating the slow diffusion through resin beads, making the anion-exchange sites easily accessible on the foam surfaces. The best performing samples exceeded the Pu capacity of the commercially available resin, and also offered the advantage of sharper elution profiles, resulting in a more concentrated product, with less loss of material to the dilute heads and tails cuts. An alternate approach to improving the efficiency of this process was also explored through the development of a microchannel array system for performing the anion exchange.

  9. Electrically Switched Cesium Ion Exchange

    Energy Technology Data Exchange (ETDEWEB)

    JPH Sukamto; ML Lilga; RK Orth


    This report discusses the results of work to develop Electrically Switched Ion Exchange (ESIX) for separations of ions from waste streams relevant to DOE site clean-up. ESIX combines ion exchange and electrochemistry to provide a selective, reversible method for radionuclide separation that lowers costs and minimizes secondary waste generation typically associated with conventional ion exchange. In the ESIX process, an electroactive ion exchange film is deposited onto. a high surface area electrode, and ion uptake and elution are controlled directly by modulating the potential of the film. As a result, the production of secondary waste is minimized, since the large volumes of solution associated with elution, wash, and regeneration cycles typical of standard ion exchange are not needed for the ESIX process. The document is presented in two parts: Part I, the Summary Report, discusses the objectives of the project, describes the ESIX concept and the approach taken, and summarizes the major results; Part II, the Technology Description, provides a technical description of the experimental procedures and in-depth discussions on modeling, case studies, and cost comparisons between ESIX and currently used technologies.


    Directory of Open Access Journals (Sweden)

    Anatoly Beletsky


    Full Text Available The methods of construction of matrix formation the secret protocols legalized subscribers of public communications networks encryption keys. Based key exchange protocols laid asymmetric cryptography algorithms. The solution involves the calculation of one-way functions and is based on the use of generalized Galois arrays of isomorphism relationship with forming elements, and depending on the selected irreducible polynomial generating matrix. A simple method for constructing generalized Galois matrix by the method of filling the diagonal. In order to eliminate the isomorphism of Galois arrays and their constituent elements, limiting the possibility of building one-way functions, Galois matrix subjected to similarity transformation carried out by means of permutation matrices. The variant of the organization of the algebraic attacks on encryption keys sharing protocols and discusses options for easing the consequences of an attack.

  11. Research progress of behavioral variant frontotemporal dementia

    Directory of Open Access Journals (Sweden)

    Xiao-hua GU


    Full Text Available There is no epidemiological data of frontotemporal dementia (FTD in China. The application of updated diagnostic criteria, publishing of frontotemporal lobar degeneration (FTLD consensus in China, development of multimodal imaging and biomarkers promote the clinical understanding on behavioral variant frontotemporal dementia (bvFTD. There is still no drugs treating FTD approved by U.S. Food and Drug Administration (FDA. Multidisciplinary intervention may delay the progression of bvFTD. DOI: 10.3969/j.issn.1672-6731.2015.07.006

  12. Space-variant polarized Airy beam

    CERN Document Server

    Chen, Hao


    We experimentally generate an Airy beam with polarization structure while keeping its original amplitude and phase profile intact. This class of Airy beam preserves the acceleration properties. By monitoring their initial polarization structure we have provided insight concerning the self-healing mechanism of Airy beams. We investigate both theoretically and experimentally the self-healing polarization properties of the space-variant polarized Airy beams. Amplitude as well as the polarization structure tends to reform during propagation in spite of the severe truncation of the beam by finite apertures.

  13. Sex steroids and variants of gender identity. (United States)

    Meyer-Bahlburg, Heino F L


    This article summarizes for the practicing endocrinologist the current literature on the psychobiology of the development of gender identity and its variants in individuals with disorders of sex development (DSD) or with non-DSD transgenderism. Gender reassignment remains the treatment of choice for strong and persistent gender dysphoria in both categories, but more research is needed on the short-term and long-term effects of puberty-suppressing medications and cross-sex hormones on brain and behavior. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Multisystem altruistic metadynamics—Well-tempered variant (United States)

    Hošek, Petr; Kříž, Pavel; Toulcová, Daniela; Spiwok, Vojtěch


    Metadynamics method has been widely used to enhance sampling in molecular simulations. Its original form suffers two major drawbacks, poor convergence in complex (especially biomolecular) systems and its serial nature. The first drawback has been addressed by introduction of a convergent variant known as well-tempered metadynamics. The second was addressed by introduction of a parallel multisystem metadynamics referred to as altruistic metadynamics. Here, we combine both approaches into well-tempered altruistic metadynamics. We provide mathematical arguments and trial simulations to show that it accurately predicts free energy surfaces.

  15. Multisystem altruistic metadynamics-Well-tempered variant. (United States)

    Hošek, Petr; Kříž, Pavel; Toulcová, Daniela; Spiwok, Vojtěch


    Metadynamics method has been widely used to enhance sampling in molecular simulations. Its original form suffers two major drawbacks, poor convergence in complex (especially biomolecular) systems and its serial nature. The first drawback has been addressed by introduction of a convergent variant known as well-tempered metadynamics. The second was addressed by introduction of a parallel multisystem metadynamics referred to as altruistic metadynamics. Here, we combine both approaches into well-tempered altruistic metadynamics. We provide mathematical arguments and trial simulations to show that it accurately predicts free energy surfaces.

  16. Genetic variants associated with lung function

    DEFF Research Database (Denmark)

    Thyagarajan, Bharat; Wojczynski, Mary; Minster, Ryan L


    BACKGROUND: Reduced forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) are strong predictors of mortality and lung function is higher among individuals with exceptional longevity. However, genetic factors associated with lung function in individuals...... with exceptional longevity have not been identified. METHOD: We conducted a genome wide association study (GWAS) to identify novel genetic variants associated with lung function in the Long Life Family Study (LLFS) (n = 3,899). Replication was performed using data from the CHARGE/SpiroMeta consortia...

  17. Performance comparison of various time variant filters

    Energy Technology Data Exchange (ETDEWEB)

    Kuwata, M. [JEOL Engineering Co. Ltd., Akishima, Tokyo (Japan); Husimi, K.


    This paper describes the advantage of the trapezoidal filter used in semiconductor detector system comparing with the other time variant filters. The trapezoidal filter is the compose of a rectangular pre-filter and a gated integrator. We indicate that the best performance is obtained by the differential-integral summing type rectangular pre-filter. This filter is not only superior in performance, but also has the useful feature that the rising edge of the output waveform is linear. We introduce an example of this feature used in a high-energy experiment. (author)

  18. Oral fibrolipoma: A rare histological variant

    Directory of Open Access Journals (Sweden)

    Treville Pereira


    Full Text Available Lipomas are benign soft tissue mesenchymal neoplasms. Fibrolipoma is a histological variant of lipoma that mostly affects the buccal mucosa and causes functional and cosmetic disabilities. The diagnosis and differentiation of fibrolipoma with clinically similar lesions such as fibroma and pleomorphic adenoma is very essential for a correct treatment plan and complete follow-up. This article presents a case of a 35-year-old female with a fibrolipoma on the lingual marginal gingiva of the mandibular left third molar.

  19. Pervaporation with ion exchange membranes

    Energy Technology Data Exchange (ETDEWEB)

    Boeddeker, K.W.; Wenzlaff, A.


    Sorption and pervaporation of aqueous-organic solvent systems (water-ethanol; water-carboxylic acids) with commercial ion exchange membranes are compared to obtain information on polymersolvent interaction vs. coupling. Close agreement between sorption selectivity and pervaporation selectivity indicates coupling. If pervaporation is less selective than sorption, polymer-solvent interaction overtakes coupling, the limit of de-coupling being phase separation within the sorbate as signaled by a sudden increase in permeability of the lesser interacting component. As long as sorption and pervaporation operate in parallel, favoring enrichment of the same component, coupling enhances the separation effect. If pervaporation counteracts sorption, coupling is detrimental to the separation effect. Potential applications include the dehydration of pre-concentrated water-ethanol using anion exchange membranes, and the enrichment of acetic acid from dilute aqueous solution by pervaporative removal of water through cation exchange membranes.

  20. Oscillating-Coolant Heat Exchanger (United States)

    Scotti, Stephen J.; Blosser, Max L.; Camarda, Charles J.


    Devices useful in situations in which heat pipes inadequate. Conceptual oscillating-coolant heat exchanger (OCHEX) transports heat from its hotter portions to cooler portions. Heat transported by oscillation of single-phase fluid, called primary coolant, in coolant passages. No time-averaged flow in tubes, so either heat removed from end reservoirs on every cycle or heat removed indirectly by cooling sides of channels with another coolant. Devices include leading-edge cooling devices in hypersonic aircraft and "frost-free" heat exchangers. Also used in any situation in which heat pipe used and in other situations in which heat pipes not usable.


    Directory of Open Access Journals (Sweden)



    Full Text Available The experience of recentyears showsthat it hasa fundamentalroleformation mechanismof the exchange rateinmacroeconomic stabilization. Global economiccrises, oil shockshave shownthe difficultyoffloatingsustainabilitybyparticipants in the system. EuropeanMonetary System, focused onconcertedfloatingcurrenciestoECU, was formedunder the conditionsin which somecountries have adoptedregional monetaryarrangements(EU countries, with suchbasescurrencyregimeshybridthat combinesspecific mechanismsto those offixedratefree floating. This paperaims to demonstratethe important role thatithasthe choice ofexchange rateregimeas abasic elementin thefoundationofmacroeconomic stabilizationinstruments. Consideredan expression of thestateof the domestic economyandinternationalcompetitiveness, the exchange rate is determined bya complex set ofexternal factorsorinternalstabilityisa prerequisite forthe crisis.

  2. Proton exchange membrane fuel cells

    CERN Document Server

    Qi, Zhigang


    Preface Proton Exchange Membrane Fuel CellsFuel CellsTypes of Fuel CellsAdvantages of Fuel CellsProton Exchange Membrane Fuel CellsMembraneCatalystCatalyst LayerGas Diffusion MediumMicroporous LayerMembrane Electrode AssemblyPlateSingle CellStackSystemCell Voltage Monitoring Module (CVM)Fuel Supply Module (FSM)Air Supply Module (ASM)Exhaust Management Module (EMM)Heat Management Module (HMM)Water Management Module (WMM)Internal Power Supply Module (IPM)Power Conditioning Module (PCM)Communications Module (COM)Controls Module (CM)SummaryThermodynamics and KineticsTheoretical EfficiencyVoltagePo

  3. Association between MTHFR variant and diabetic neuropathy. (United States)

    Kakavand Hamidi, Armita; Radfar, Mania; Amoli, Mahsa M


    Methylene-tetrahydrofolate reductase (MTHFR) gene variant may play an important role in the pathophysiology of diabetes and its complications due to its influence on plasma homocysteine levels and also its effect on scavenging peroxynitrite radicals. Diabetic peripheral neuropathy (DPN) is one of the most common diabetic chronic complications. The aim of this study was to investigate the relationship between diabetic neuropathy and MTHFR gene C677T and 1298A ⁄C polymorphisms. Patients with type 2 diabetes N=248 were enrolled in the study, consisting of patients with neuropathy (N=141) and patients without neuropathy (N=107). MTHFR C677T polymorphism was analyzed using polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) of genomic DNA for genotyping of samples. 1298A/C polymorphism was evaluated using ARMS-PCR. There was a significant difference in MTHFR polymorphism between the groups with and without neuropathy. Our results suggest that MTHFR 677 variant confer risk for diabetic neuropathy among Iranian patients with type 2 diabetes. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  4. A TIMP-1 splice variant transcript

    DEFF Research Database (Denmark)

    Øbro, Nina Friesgård; Lademann, Ulrik Axel; Birkenkamp-Demtroder, Karin


    A splice variant of tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA lacking exon 2 (TIMP-1-v2) has been identified in human cancer cells and in colorectal and breast cancer tumors. The purpose of this study was (1) to study the level of full length TIMP-1 and TIMP-1-v2 transcripts in color...... of TIMP-1 pre-mRNA to TIMP-1-v2 mRNA might be involved in regulating TIMP-1 expression.......A splice variant of tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA lacking exon 2 (TIMP-1-v2) has been identified in human cancer cells and in colorectal and breast cancer tumors. The purpose of this study was (1) to study the level of full length TIMP-1 and TIMP-1-v2 transcripts...... in colorectal tumors; (2) to investigate if TIMP-1-v2 is translated to protein. Full length TIMP-1 and TIMP-1-v2 mRNA levels were compared between colorectal tumors and normal mucosa by Q-PCR. Both full length TIMP-1 and TIMP-1-v2 transcripts were upregulated in tumor tissue. However, the level of TIMP-1-v2...

  5. COMT gene locus: new functional variants (United States)

    Meloto, Carolina B.; Segall, Samantha K.; Smith, Shad; Parisien, Marc; Shabalina, Svetlana A.; Rizzatti-Barbosa, Célia M.; Gauthier, Josée; Tsao, Douglas; Convertino, Marino; Piltonen, Marjo H.; Slade, Gary Dmitri; Fillingim, Roger B.; Greenspan, Joel D.; Ohrbach, Richard; Knott, Charles; Maixner, William; Zaykin, Dmitri; Dokholyan, Nikolay V.; Reenilä, Ilkka; Männistö, Pekka T.; Diatchenko, Luda


    Abstract Catechol-O-methyltransferase (COMT) metabolizes catecholaminergic neurotransmitters. Numerous studies have linked COMT to pivotal brain functions such as mood, cognition, response to stress, and pain. Both nociception and risk of clinical pain have been associated with COMT genetic variants, and this association was shown to be mediated through adrenergic pathways. Here, we show that association studies between COMT polymorphic markers and pain phenotypes in 2 independent cohorts identified a functional marker, rs165774, situated in the 3′ untranslated region of a newfound splice variant, (a)-COMT. Sequence comparisons showed that the (a)-COMT transcript is highly conserved in primates, and deep sequencing data demonstrated that (a)-COMT is expressed across several human tissues, including the brain. In silico analyses showed that the (a)-COMT enzyme features a distinct C-terminus structure, capable of stabilizing substrates in its active site. In vitro experiments demonstrated not only that (a)-COMT is catalytically active but also that it displays unique substrate specificity, exhibiting enzymatic activity with dopamine but not epinephrine. They also established that the pain-protective A allele of rs165774 coincides with lower COMT activity, suggesting contribution to decreased pain sensitivity through increased dopaminergic rather than decreased adrenergic tone, characteristic of reference isoforms. Our results provide evidence for an essential role of the (a)-COMT isoform in nociceptive signaling and suggest that genetic variations in (a)-COMT isoforms may contribute to individual variability in pain phenotypes. PMID:26207649

  6. Anatomic variants in Dandy-Walker complex. (United States)

    Jurcă, Maria Claudia; Kozma, Kinga; Petcheşi, CodruŢa Diana; Bembea, Marius; Pop, Ovidiu Laurean; MuŢiu, Gabriela; Coroi, Mihaela Cristiana; Jurcă, Alexandru Daniel; Dobjanschi, Luciana


    Dandy-Walker complex (DWC) is a malformative association of the central nervous system. DWC includes four different types: Dandy-Walker malformation (vermis agenesis or hypoplasia, cystic dilatation of the fourth ventricle and a large posterior fossa); Dandy-Walker variant (vermis hypoplasia, cystic dilatation of the fourth ventricle, normal posterior fossa); mega cysterna magna (large posterior fossa, normal vermis and fourth ventricle) and posterior fossa arachnoid cyst. We present and discuss four cases with different morphological and clinical forms of the Dandy-Walker complex. In all four cases, diagnosis was reached by incorporation of clinical (macrocephaly, seizures) and imaging [X-ray, computed tomography (CT), magnetic resonance imaging (MRI)] data. Two patients were diagnosed with Dandy-Walker complex, one patient was diagnosed with Dandy-Walker variant in a rare association with neurofibromatosis and one patient was diagnosed with a posterior fossa arachnoid cyst associated with left-sided Claude Bernard-Horner syndrome, congenital heart disease (coarctation of the aorta, mitral stenosis) and gastroesophageal reflux. In all forms of DWC, the clinical, radiological and functional manifestations are variable and require adequate diagnostic and therapeutic measures.

  7. Flavonoids as Inhibitors of Human Butyrylcholinesterase Variants

    Directory of Open Access Journals (Sweden)

    Maja Katalinić


    Full Text Available The inhibition of butyrylcholinesterase (BChE, EC appears to be of interest in treating diseases with symptoms of reduced neurotransmitter levels, such as Alzheimer’s disease. However, BCHE gene polymorphism should not be neglected in research since it could have an effect on the expected outcome. Several well-known cholinergic drugs (e.g. galantamine, huperzine and rivastigmine originating from plants, or synthesised as derivatives of plant compounds, have shown that herbs could serve as a source of novel target-directed compounds. We focused our research on flavonoids, biologically active polyphenolic compounds found in many plants and plant-derived products, as BChE inhibitors. All of the tested flavonoids: galangin, quercetin, fisetin and luteolin reversibly inhibited usual, atypical, and fluoride-resistant variants of human BChE. The inhibition potency increased in the following order, identically for all three BChE variants: luteolin

  8. BBCAnalyzer: a visual approach to facilitate variant calling


    Sandmann, S.; Graaf, A.O. de; Dugas, M.


    Background Deriving valid variant calling results from raw next-generation sequencing data is a particularly challenging task, especially with respect to clinical diagnostics and personalized medicine. However, when using classic variant calling software, the user usually obtains nothing more than a list of variants that pass the corresponding caller?s internal filters. Any expected mutations (e.g. hotspot mutations), that have not been called by the software, need to be investigated manually...

  9. Copy number variants in patients with short stature


    van Duyvenvoorde, Hermine A.; Lui, Julian C.; Kant, Sarina G; Oostdijk, Wilma; Gijsbers, Antoinet CJ; Hoffer, Mariëtte JV; Karperien, Marcel; Walenkamp, Marie JE; Noordam, Cees; Voorhoeve, Paul G; Mericq, Verónica; Alberto M. Pereira; Claahsen-van der Grinten, Hedi L.; van Gool, Sandy A; Breuning, Martijn H


    Height is a highly heritable and classic polygenic trait. Recent genome-wide association studies (GWAS) have revealed that at least 180 genetic variants influence adult height. However, these variants explain only about 10% of the phenotypic variation in height. Genetic analysis of short individuals can lead to the discovery of novel rare gene defects with a large effect on growth. In an effort to identify novel genes associated with short stature, genome-wide analysis for copy number variant...

  10. Exchange asymmetry in experimental settings (United States)

    Thomas C. Brown; Mark D. Morrison; Jacob A. Benfield; Gretchen Nurse Rainbolt; Paul A. Bell


    We review past trading experiments and present 11 new experiments designed to show how the trading rate responds to alterations of the experimental procedure. In agreement with earlier studies, results show that if the trade decision is converted to one resembling a choice between goods the exchange asymmetry disappears, but otherwise the asymmetry is...


    Directory of Open Access Journals (Sweden)



    Full Text Available Using spectral analysis is very common in technical areas but rather unusual in economics and finance, where ARIMA and GARCH modeling are much more in use. To show that spectral analysis can be useful in determining hidden periodic components for high-frequency finance data as well, we use the example of foreign exchange rates

  12. Our International Art Exchange Project. (United States)

    Cocciolone, Kathy R.


    Discusses an international art exchange project designed to teach fifth-grade students that the culture of a country is reflected in its art and that art is a universal language. Describes the contributions from Scotland, Mexico, Saudi Arabia, Egypt, Japan, and India. Points out ways to use materials in schools. (KO)

  13. Milk fouling in heat exchangers

    NARCIS (Netherlands)

    Jeurnink, T.J.M.


    The mechanisms of fouling of heat exchangers by milk were studied. Two major fouling mechanisms were indentified during the heat treatment of milk: (i) the formation and the subsequent deposition of activated serum protein molecules as a result of the heat denaturation; (ii) the

  14. Update of telephone exchange switches

    CERN Multimedia


    Within the scope of the CERN phone services improvement, a software update will be done on exchange switches on Wednesday 27 october from 7.00 pm to 12.00 pm. Disturbances or even interruptions of telephony services may occur during this intervention. We appology in advance for any inconveniences that may occur.

  15. Maintenance of CERN telephone exchanges

    CERN Multimedia


    A maintenance of CERN telephone exchanges will be performed on 21st, 22nd, 23rd, 24th of September from 7 p.m. to 9 p.m. Disturbances or even interruptions of telephony services may occur during this lapse of time. We apology in advance for any inconveniences that this may cause.

  16. The Commodity and its Exchange

    DEFF Research Database (Denmark)

    Høst, Jeppe Engset


    and the value of the quota are examined through the concrete exchange of fishing rights, and it is explained why quota trade can give rise to speculation and monopolies. In the final part of the chapter, it is argued that the value of transferable fishing quotas rely on a social relation between owners...... and nonowners of quota, as a form of monopoly rent....

  17. Baltic Exchange teper v Tallinne

    Index Scriptorium Estoniae


    Viimane osa merekonteineritesse kokkupakitud Londoni laevandus- ja merebörsi Baltic Exchange'i endise peakorteri detailidest jõudis 2007. a. juunis Tallinna. Hoone detailid ostnud ärimehed Heiti Hääl ja Eerik-Niiles Kross plaanivad leida hoonele koha Tallinna kesklinnas. E.-N. Krossi kommentaar

  18. Energy Exchange NASA Opening Plenary (United States)

    Marrs, Rick


    Rick Marrs, Deputy Assistant Administrator Office of Strategic Infrastructure NASA Headquarters will be speaking during the 2017 Energy Exchange opening plenary. His presentation showcases the NASA mission, sustainability at NASA, NASA's strategic Sustainability Performance Plan, Existing PV Partnerships, and NASA funded Solar Initiatives at KSC.

  19. Homans on Exchange: Hedonism Revived (United States)

    Abrahamsson, Bengt


    George C. Homan's theory on social exchange is critically examined and found to have serious shortcomings with regard to its deductive and inductive aspects. An expecially prominent shortcoming concerns the tautological character of his concept of reward," which makes his theory deductively unclear and empirically untestable. Homan's critique…

  20. Common knowledge in email exchanges

    NARCIS (Netherlands)

    Sietsma, F.; Apt, K.R.; van Eijck, D.J.N.; Verbrugge, R.


    We consider a framework in which a group of agents communicates by means of emails, with the possibility of replies, forwards and blind carbon copies (BCC). We study the epistemic consequences of such email exchanges by introducing an appropriate epistemic language and semantics. This allows us to

  1. Knowledge Exchange with Sistema Scotland (United States)

    Allan, Julie; Moran, Nikki; Duffy, Celia; Loening, Gica


    This paper reports on a knowledge exchange project, funded by the Scottish Funding Council and undertaken by a group of researchers from three higher education institutions in Scotland and the project partner, Sistema Scotland. This newly established charity is attempting to implement a major programme of social change, developed in Venezuela,…

  2. Inflationary trispectrum from graviton exchange

    DEFF Research Database (Denmark)

    Seery, David; Sloth, Martin Snoager; Vernizzi, Filippo


    We compute the connected four-point correlation function of the primordial curvature perturbation generated during inflation with standard kinetic terms, where the correlation is established via exchange of a graviton between two pairs of scalar fluctuations. Any such correlation yields a contrib...

  3. A unified phylogeny-based nomenclature for histone variants. (United States)

    Talbert, Paul B; Ahmad, Kami; Almouzni, Geneviève; Ausió, Juan; Berger, Frederic; Bhalla, Prem L; Bonner, William M; Cande, W Zacheus; Chadwick, Brian P; Chan, Simon W L; Cross, George A M; Cui, Liwang; Dimitrov, Stefan I; Doenecke, Detlef; Eirin-López, José M; Gorovsky, Martin A; Hake, Sandra B; Hamkalo, Barbara A; Holec, Sarah; Jacobsen, Steven E; Kamieniarz, Kinga; Khochbin, Saadi; Ladurner, Andreas G; Landsman, David; Latham, John A; Loppin, Benjamin; Malik, Harmit S; Marzluff, William F; Pehrson, John R; Postberg, Jan; Schneider, Robert; Singh, Mohan B; Smith, M Mitchell; Thompson, Eric; Torres-Padilla, Maria-Elena; Tremethick, David John; Turner, Bryan M; Waterborg, Jakob Harm; Wollmann, Heike; Yelagandula, Ramesh; Zhu, Bing; Henikoff, Steven


    Histone variants are non-allelic protein isoforms that play key roles in diversifying chromatin structure. The known number of such variants has greatly increased in recent years, but the lack of naming conventions for them has led to a variety of naming styles, multiple synonyms and misleading homographs that obscure variant relationships and complicate database searches. We propose here a unified nomenclature for variants of all five classes of histones that uses consistent but flexible naming conventions to produce names that are informative and readily searchable. The nomenclature builds on historical usage and incorporates phylogenetic relationships, which are strong predictors of structure and function. A key feature is the consistent use of punctuation to represent phylogenetic divergence, making explicit the relationships among variant subtypes that have previously been implicit or unclear. We recommend that by default new histone variants be named with organism-specific paralog-number suffixes that lack phylogenetic implication, while letter suffixes be reserved for structurally distinct clades of variants. For clarity and searchability, we encourage the use of descriptors that are separate from the phylogeny-based variant name to indicate developmental and other properties of variants that may be independent of structure.

  4. A unified phylogeny-based nomenclature for histone variants

    Directory of Open Access Journals (Sweden)

    Talbert Paul B


    Full Text Available Abstract Histone variants are non-allelic protein isoforms that play key roles in diversifying chromatin structure. The known number of such variants has greatly increased in recent years, but the lack of naming conventions for them has led to a variety of naming styles, multiple synonyms and misleading homographs that obscure variant relationships and complicate database searches. We propose here a unified nomenclature for variants of all five classes of histones that uses consistent but flexible naming conventions to produce names that are informative and readily searchable. The nomenclature builds on historical usage and incorporates phylogenetic relationships, which are strong predictors of structure and function. A key feature is the consistent use of punctuation to represent phylogenetic divergence, making explicit the relationships among variant subtypes that have previously been implicit or unclear. We recommend that by default new histone variants be named with organism-specific paralog-number suffixes that lack phylogenetic implication, while letter suffixes be reserved for structurally distinct clades of variants. For clarity and searchability, we encourage the use of descriptors that are separate from the phylogeny-based variant name to indicate developmental and other properties of variants that may be independent of structure.

  5. Population structure analysis using rare and common functional variants

    Directory of Open Access Journals (Sweden)

    Ding Lili


    Full Text Available Abstract Next-generation sequencing technologies now make it possible to genotype and measure hundreds of thousands of rare genetic variations in individuals across the genome. Characterization of high-density genetic variation facilitates control of population genetic structure on a finer scale before large-scale genotyping in disease genetics studies. Population structure is a well-known, prevalent, and important factor in common variant genetic studies, but its relevance in rare variants is unclear. We perform an extensive population structure analysis using common and rare functional variants from the Genetic Analysis Workshop 17 mini-exome sequence. The analysis based on common functional variants required 388 principal components to account for 90% of the variation in population structure. However, an analysis based on rare variants required 532 significant principal components to account for similar levels of variation. Using rare variants, we detected fine-scale substructure beyond the population structure identified using common functional variants. Our results show that the level of population structure embedded in rare variant data is different from the level embedded in common variant data and that correcting for population structure is only as good as the level one wishes to correct.

  6. Exchange Rate Expectations and the Current Exchange Rate: A Test of the Monetarist Approach


    V S Somanath


    The monetarist model of the exchange rate includes expectations of the future exchange rate as a determinant of the current exchange rate. This paper investigates whether expectations are a significant determinant of the exchange rate. An expectations process that is consistent with a basic monetarist exchange rate model is considered. Alternative measures of expectations are generated using this process. In the empirical tests, while the standard forward exchange premium measure of expectati...

  7. Phase exposure-dependent exchange (United States)

    Ginn, T. R.; Schreyer, L. G.; Zamani, K.


    Solutes and suspended material often experience delays during exchange between phases one of which may be moving. Consequently transport often exhibits combined effects of advection/dispersion, and delays associated with exchange between phases. Such processes are ubiquitous and include transport in porous/fractured media, watersheds, rivers, forest canopies, urban infrastructure systems, and networks. Upscaling approaches often treat the transport and delay mechanisms together, yielding macroscopic "anomalous transport" models. When interaction with the immobile phase is responsible for the delays, it is not the transport that is anomalous, but the lack of it, due to delays. We model such exchanges with a simple generalization of first-order kinetics completely independent of transport. Specifically, we introduce a remobilization rate coefficient that depends on the time in immobile phase. Memory-function formulations of exchange (with or without transport) can be cast in this framework, and can represent practically all time-nonlocal mass balance models including multirate mass transfer and its equivalent counterparts in the continuous time random walk and time-fractional advection dispersion formalisms, as well as equilibrium exchange. Our model can address delayed single-/multievent remobilizations as in delay-differential equations and periodic remobilizations that may be useful in sediment transport modeling. It is also possible to link delay mechanisms with transport if so desired, or to superpose an additional source of nonlocality through the transport operator. This approach allows for mechanistic characterization of the mass transfer process with measurable parameters, and the full set of processes representable by these generalized kinetics is a new open question.

  8. Foreign Exchange Reserves: Bangladesh Perspective

    Directory of Open Access Journals (Sweden)

    Md Zahangir Alam


    Full Text Available This study is about foreign exchangereserves of Bangladesh. The mainpurpose of this study is to the influence of exchange rates on foreign exchangereserves to the Bangladesh context.  Both the primary and secondary data has been used inthis study. The primary data has been collected through a structuredquestionnaire from 50 respondents. The secondary data, namely Bangladeshforeign exchange reserves (FER, Bangladesh current account balance (CAB,Bangladesh capital andfinancial account balance (CFAB, and BDT/USD exchange rates (ER.  This study covers yearly data from July 01,1996 to June 30, 2005 and quarterly data from July 01, 2005 to June 30, 2012. Findingsof this study shows that out of the selected 16 factors affecting foreignexchange reserves, exchange rates occupy the first position, weighted averagescore (WAS being 4.56. Foreign exchange reserves (FER and current accountbalance (CAB have increased by 502.9087% and 1451.218%,whereas capital and financial account (CFAB has decreased by -649.024% on June30, 2012 compared to June 30, 1997. The influence of other factors heldconstant, as ER changes by 285.6894 units due to one unit change in FER, onaverage in the same direction which represents that ER has positive effect on theFER and this relationship is statistically significant.  62.1526 percentof the variation in FER is explained by ER. The outcomes of Breusch-Godfrey test (LM test, ARCHtest, and the Normality test are that there is a serial correlation among residuals, the variance of residuals is notconstant, and the residuals are not normally distributed.

  9. Compact Ceramic Microchannel Heat Exchangers

    Energy Technology Data Exchange (ETDEWEB)

    Lewinsohn, Charles [Ceramatec, Inc., Salt Lake City, UT (United States)


    The objective of the proposed work was to demonstrate the feasibility of a step change in power plant efficiency at a commercially viable cost, by obtaining performance data for prototype, compact, ceramic microchannel heat exchangers. By performing the tasks described in the initial proposal, all of the milestones were met. The work performed will advance the technology from Technology Readiness Level 3 (TRL 3) to Technology Readiness Level 4 (TRL 4) and validate the potential of using these heat exchangers for enabling high efficiency solid oxide fuel cell (SOFC) or high-temperature turbine-based power plants. The attached report will describe how this objective was met. In collaboration with The Colorado School of Mines (CSM), specifications were developed for a high temperature heat exchanger for three commercial microturbines. Microturbines were selected because they are a more mature commercial technology than SOFC, they are a low-volume and high-value target for market entry of high-temperature heat exchangers, and they are essentially scaled-down versions of turbines used in utility-scale power plants. Using these specifications, microchannel dimensions were selected to meet the performance requirements. Ceramic plates were fabricated with microchannels of these dimensions. The plates were tested at room temperature and elevated temperature. Plates were joined together to make modular, heat exchanger stacks that were tested at a variety of temperatures and flow rates. Although gas flow rates equivalent to those in microturbines could not be achieved in the laboratory environment, the results showed expected efficiencies, robust operation under significant temperature gradients at high temperature, and the ability to cycle the stacks. Details of the methods and results are presented in this final report.

  10. A rabies virus vampire bat variant shows increased neuroinvasiveness in mice when compared to a carnivore variant. (United States)

    Mesquita, Leonardo Pereira; Gamon, Thais Helena Martins; Cuevas, Silvia Elena Campusano; Asano, Karen Miyuki; Fahl, Willian de Oliveira; Iamamoto, Keila; Scheffer, Karin Correa; Achkar, Samira Maria; Zanatto, Dennis Albert; Mori, Cláudia Madalena Cabrera; Maiorka, Paulo César; Mori, Enio


    Rabies is one of the most important zoonotic diseases and is caused by several rabies virus (RABV) variants. These variants can exhibit differences in neurovirulence, and few studies have attempted to evaluate the neuroinvasiveness of variants derived from vampire bats and wild carnivores. The aim of this study was to evaluate the neuropathogenesis of infection with two Brazilian RABV street variants (variant 3 and crab-eating fox) in mice. BALB/c mice were inoculated with RABV through the footpad, with the 50% mouse lethal dose (LD50) determined by intracranial inoculation. The morbidity of rabies in mice infected with variant 3 and the crab-eating fox strain was 100% and 50%, respectively, with an incubation period of 7 and 6 days post-inoculation (dpi), respectively. The clinical disease in mice was similar with both strains, and it was characterized initially by weight loss, ruffled fur, hunched posture, and hind limb paralysis progressing to quadriplegia and recumbency at 9 to 12 dpi. Histological lesions within the central nervous system (CNS) characterized by nonsuppurative encephalomyelitis with neuronal degeneration and necrosis were observed in mice infected with variant 3 and those infected with the crab-eating fox variant. However, lesions and the presence of RABV antigen, were more widespread within the CNS of variant-3-infected mice, whereas in crab-eating fox-variant-infected mice, RABV antigens were more restricted to caudal areas of the CNS, such as the spinal cord and brainstem. In conclusion, the results shown here demonstrate that the RABV vampire bat strain (variant 3) has a higher potential for neuroinvasiveness than the carnivore variant.


    Directory of Open Access Journals (Sweden)

    Josip Arnerić


    Full Text Available Time series models that are commonly used in econometric modeling are autoregressive stochastic linear models (AR and models of moving averages (MA. Mentioned models by their structure are actually stochastic difference equations. Therefore, the objective of this paper is to estimate difference equations containing stochastic (random component. Estimated models of time series will be used to forecast observed data in the future. Namely, solutions of difference equations are closely related to conditions of stationary time series models. Based on the fact that volatility is time varying in high frequency data and that periods of high volatility tend to cluster, the most successful and popular models in modeling time varying volatility are GARCH type models and their variants. However, GARCH models will not be analyzed because the purpose of this research is to predict the value of the exchange rate in the levels within conditional mean equation and to determine whether the observed variable has a stable or explosive time path. Based on the estimated difference equation it will be examined whether Croatia is implementing a stable policy of exchange rates.

  12. Aequorin variants with improved bioluminescence properties. (United States)

    Dikici, E; Qu, X; Rowe, L; Millner, L; Logue, C; Deo, S K; Ensor, M; Daunert, S


    The photoprotein aequorin has been widely used as a bioluminescent label in immunoassays, for the determination of calcium concentrations in vivo, and as a reporter in cellular imaging. It is composed of apoaequorin (189 amino acid residues), the imidazopyrazine chromophore coelenterazine and molecular oxygen. The emission characteristics of aequorin can be changed by rational design of the protein to introduce mutations in its structure, as well as by substituting different coelenterazine analogues to yield semi-synthetic aequorins. Variants of aequorin were created by mutating residues His16, Met19, Tyr82, Trp86, Trp108, Phe113 and Tyr132. Forty-two aequorin mutants were prepared and combined with 10 different coelenterazine analogues in a search for proteins with different emission wavelengths, altered decay kinetics and improved stability. This spectral tuning strategy resulted in semi-synthetic photoprotein mutants with significantly altered bioluminescent properties.

  13. A compendium of genetic variant data

    DEFF Research Database (Denmark)

    Cardoso, Joao; Schöning, Lars Yannik; Herrgard, Markus


    Laboratory strains are genetically unstable if exposed to selective pressure as encountered, for example, during molecular cloning, fermentation, or adaptive laboratory evolution experiments. This genetic variation is the consequence of an adaptation process of the microorganism to stress conditi...... obtained from distinct experiments. This compendium of genetic variant is a critical step to develop approaches to automatically and systematically characterize mutated strains in the future.......Laboratory strains are genetically unstable if exposed to selective pressure as encountered, for example, during molecular cloning, fermentation, or adaptive laboratory evolution experiments. This genetic variation is the consequence of an adaptation process of the microorganism to stress...... conditions, e.g., high pressure or temperature, nutrient limitation, or toxic byproduct concentrations. The evolved strains display then new phenotypes: tolerance to a toxic byproduct or higher temperature, improved production rate of a byproduct, or higher uptake rates of nutrients. To understand...

  14. A look-ahead variant of TFQMR

    Energy Technology Data Exchange (ETDEWEB)

    Freund, R.W. [AT& T Bell Labs., Murray Hill, NJ (United States); Nachtigal, N.M. [Oak Ridge National Lab., TN (United States)


    Recently, Freund proposed a Krylov subspace iteration, the transpose-free quasi-minimal residual method (TFQMR), for solving general nonsingular non-Hermitian linear systems. The algorithm relies on a version of the squared Lanczos process to generate the basis vectors for the underlying Krylov subspace. It then constructs iterates defined by a quasi-minimization property, which leads to a smooth and nearly monotone convergence behavior. The authors investigate a variant of TFQMR that uses look-ahead to avoid some of the problems associated with breakdowns in the underlying squared Lanczos procedure. They also present some numerical examples that illustrate the properties of the new method, as compared to the original TFQMR algorithm.

  15. Sturge -Weber Syndrome - Three Classic variants

    Directory of Open Access Journals (Sweden)

    R S Sathawane


    Full Text Available Sturge-Weber syndrome (SWS, also known as encephalotrigeminal angiomatosis, a sporadic, non-familial, congenital disorder consists of congenital hamartomatous malformations that may affect the eye, skin and central nervous system at different times. Sturge-Weber syndrome is classified as 1 Complete trisymptomatic: - when all three organ systems i.e. eye, skin and CNS are involved 2 Incomplete bisymptomatic:- when the involvement is either oculocutaneous or neurocutaneous, and 3 Incomplete monosymptomatic: when there is only neural or cutaneous involvement. Failure of proper vascular development is believed to be the most likely cause of this condition. The malformed blood vessels or hemangiomas may lead to port-wine stain, epilepsy and glaucoma depending on its location. Three classic variants with typical findings are discussed.


    Directory of Open Access Journals (Sweden)

    Jera Jeruc


    Full Text Available Background. Clinicopathological studies indicate that Alzheimer’s disease (AD is the most common neurodegenerative cause of dementia, the other frequent causes are AD combined with diffuse Lewy bodies and dementia with Lewy bodies (DLB by itself. When histological features of AD and DLB are found together in one brain we speak about Lewy body variant of AD (LBVAD. Beside global cognitive impairment LBVAD patients show signs of subcortical dementia and mild extrapiramidal signs.Methods and results. We present two patients with post-mortem diagnosis of LBVAD. Clinical and pathomorphological characteristics of the disease are discussed.Conclusions. Post-mortem studies show that LBVAD is the second most common cause of dementia, following AB.

  17. Current conveyors variants, applications and hardware implementations

    CERN Document Server

    Senani, Raj; Singh, A K


    This book serves as a single-source reference to Current Conveyors and their use in modern Analog Circuit Design. The authors describe the various types of current conveyors discovered over the past 45 years, details of all currently available, off-the-shelf integrated circuit current conveyors, and implementations of current conveyors using other, off-the-shelf IC building blocks. Coverage includes prominent bipolar/CMOS/Bi-CMOS architectures of current conveyors, as well as all varieties of starting from third generation current conveyors to universal current conveyors, their implementations and applications. •Describes all commercially available off-the-shelf IC current conveyors, as well as hardware implementations of current conveyors using other off-the-shelf ICs; • Describes numerous variants of current conveyors evolved over the past forty five years; • Describes a number of Bipolar/CMOS/Bi-CMOS architectures of current conveyors, along with their characteristic features; • Includes a comprehe...

  18. Genetic variants in periodontal health and disease

    Energy Technology Data Exchange (ETDEWEB)

    Dumitrescu, Alexandrina L. [Tromsoe Univ. (Norway). Inst. of Clinical Dentistry; Kobayashi, Junya [Kyoto Univ. (Japan). Dept. of Genome Repair Dynamics


    Periodontitis is a complex, multifactorial disease and its susceptibility is genetically determined. The present book systematically reviews the evidence of the association between the genetic variants and periodontitis progression and/or treatment outcomes. Genetic syndromes known to be associated with periodontal disease, the candidate gene polymorphisms investigated in relation to periodontitis, the heritability of chronic and aggressive periodontitis, as well as common guidelines for association studies are described. This growing understanding of the role of genetic variation in inflammation and periodontal chronic disease presents opportunities to identify healthy persons who are at increased risk of disease and to potentially modify the trajectory of disease to prolong healthy aging. The book represents a new concept in periodontology with its pronounced focus on understanding through knowledge rather than presenting the presently valid answers. Connections between genetics and periodontology are systematically reviewed and covered in detail. (orig.)

  19. Multicentric variant of peripheral ossifying fibroma

    Directory of Open Access Journals (Sweden)

    Srikanth A Choudary


    Full Text Available Peripheral ossifying fibroma (POF is a solitary over growth of the gingiva known to arise from the cells of the periodontal ligament. The lesions usually start as a painless overgrowth of the interdental papilla unless associated with trauma and gradually involve the other counter parts of the gingiva. The lesion is more considered to be an inflammatory or reactive process rather than to be neoplastic. Here, the authors present a unique case of multiple POF in a young male adult aged 24 years where surgical excision was carried out quadrant wise. The biopsy specimen from multiple sites revealed similar histopathologic features consistent with POF, but also with the multicentric presentation of POF, which is a unique phenomenon. Multicentric variant of POF is indeed a rare case being only the second case so far which has been documented. Management of such case needs a multidisciplinary approach to prevent the recurrence along with regular long time follow-up.

  20. Modular Heat Exchanger With Integral Heat Pipe (United States)

    Schreiber, Jeffrey G.


    Modular heat exchanger with integral heat pipe transports heat from source to Stirling engine. Alternative to heat exchangers depending on integrities of thousands of brazed joints, contains only 40 brazed tubes.

  1. Flexible Exchange of Farming Device Data

    DEFF Research Database (Denmark)

    Iftikhar, Nadeem; Pedersen, Torben Bach


    A new trend in the farming business is to replace conventional farming devices with computerized farming devices. Accordingly, numerous computer-based farming devices for logging, processing and exchanging data have recently been installed on moving farm machinery such as tractors. The exchange...... of data generally takes place between the devices and farming systems, mostly installed at the premises of farmers, contractors, advisory services etc. In most cases, data exchange is based on farming data exchange standards and is bi-directional. Bi-directional data exchange allows different devices...... and systems to exchange data based on a predefined set of rules. In consequence, many hand-coded data exchange solutions have been developed in the farming business. Although efforts regarding incorporating data exchange standards have been made, their actual usage so far has been limited, due to the fact...

  2. Characterization of the basic charge variants of a human IgG1 (United States)

    Lu, Franklin; Derfus, Gayle; Kluck, Brian; Nogal, Bartek; Emery, Craig; Summers, Christie; Zheng, Kai; Bayer, Robert; Amanullah, Ashraf


    We report a case study of an IgG1 with a unique basic charge variant profile caused by C-terminal proline amidation on either one or two heavy chains. The proline amidation was sensitive to copper ion concentration in the production media during cell culture: the higher the Cu2+ ion concentration, the higher the level of proline amidation detected. This conclusion was supported by the analysis of samples that revealed direct correlation between the proline amidation level observed from peptide maps and the level of basic peaks measured by imaged capillary isoelectric focusing and a pH gradient ion-exchange chromatography method. The importance of these observations to therapeutic antibody production is discussed. PMID:22123059

  3. Treatment of spelling variants in Setswana monolingual dictionaries

    African Journals Online (AJOL)


    Abstract: This paper argues that the Setswana language is characterised by spelling variants which are a consequence of ... be pronunciation variants, as those found, for instance, in words such as data. (deɪtə or dɑ:tə), ...... idiom is "an independent lexical item having an opaque meaning" (Svensén. 2009: 194). Treatment ...

  4. Growth differentiation factor 9 gene variants in Sudanese desert ...

    African Journals Online (AJOL)

    Certain variants in the growth differentiation factor 9 (GDF9) gene have major effects on the ovulation rate in sheep. The aim of this study was to analyse GDF9 variability in the Sudanese desert sheep ecotypes Ashgar, Dubasi and Watish, and to test identified variants for association with litter size. For this purpose, ewes of ...

  5. Association analysis identifies ZNF750 regulatory variants in psoriasis

    Directory of Open Access Journals (Sweden)

    Birnbaum Ramon Y


    Full Text Available Abstract Background Mutations in the ZNF750 promoter and coding regions have been previously associated with Mendelian forms of psoriasis and psoriasiform dermatitis. ZNF750 encodes a putative zinc finger transcription factor that is highly expressed in keratinocytes and represents a candidate psoriasis gene. Methods We examined whether ZNF750 variants were associated with psoriasis in a large case-control population. We sequenced the promoter and exon regions of ZNF750 in 716 Caucasian psoriasis cases and 397 Caucasian controls. Results We identified a total of 47 variants, including 38 rare variants of which 35 were novel. Association testing identified two ZNF750 haplotypes associated with psoriasis (p ZNF750 promoter and 5' UTR variants displayed a 35-55% reduction of ZNF750 promoter activity, consistent with the promoter activity reduction seen in a Mendelian psoriasis family with a ZNF750 promoter variant. However, the rare promoter and 5' UTR variants identified in this study did not strictly segregate with the psoriasis phenotype within families. Conclusions Two haplotypes of ZNF750 and rare 5' regulatory variants of ZNF750 were found to be associated with psoriasis. These rare 5' regulatory variants, though not causal, might serve as a genetic modifier of psoriasis.

  6. Exact solutions for nonlinear variants of Kadomtsev–Petviashvili (n ...

    Indian Academy of Sciences (India)

    Exact solutions for nonlinear variants of Kadomtsev–Petviashvili (, ) equation using functional variable method. M Mirzazadeh M Eslami. Volume 81 Issue ... The functional variable method is used to establish compactons, solitons, solitary patterns and periodic solutions for these variants. This method is a powerful tool for ...

  7. Prevalence of haemoglobin variants among the Ika ethnic nationality ...

    African Journals Online (AJOL)

    Background: Haemoglobin genotype is an important blood component that determines haemoglobinopathies. Distribution of haemoglobin variants was investigated among the Ika ethnic nationality of Delta State, Nigeria. Aim: The resent study was conducted to determine the prevalence of haemoglobin variants and also to ...

  8. Genetic polymorphism of milk protein variants and their association ...

    African Journals Online (AJOL)

    To the best of our knowledge, this is the first detailed study involving frequency distribution of genetic variants and their effects on milk yield in Bos indicus Sahiwal cattle of Pakistan. Keywords: Genetic variant, milk protein genes, Sahiwal cattle. African Journal of Biotechnology, Vol. 13(4), pp. 555-565, 22 January, 2014 ...

  9. Managing Process Variants in the Process Life Cycle

    NARCIS (Netherlands)

    Hallerbach, A.; Bauer, Th.; Reichert, M.U.


    When designing process-aware information systems, often variants of the same process have to be specified. Each variant then constitutes an adjustment of a particular process to specific requirements building the process context. Current Business Process Management (BPM) tools do not adequately

  10. Detecting rare variants in case-parents association studies.

    Directory of Open Access Journals (Sweden)

    Kuang-Fu Cheng

    Full Text Available Despite the success of genome-wide association studies (GWASs in detecting common variants (minor allele frequency ≥0.05 many suggested that rare variants also contribute to the genetic architecture of diseases. Recently, researchers demonstrated that rare variants can show a strong stratification which may not be corrected by using existing methods. In this paper, we focus on a case-parents study and consider methods for testing group-wise association between multiple rare (and common variants in a gene region and a disease. All tests depend on the numbers of transmitted mutant alleles from parents to their diseased children across variants and hence they are robust to the effect of population stratification. We use extensive simulation studies to compare the performance of four competing tests: the largest single-variant transmission disequilibrium test (TDT, multivariable test, combined TDT, and a likelihood ratio test based on a random-effects model. We find that the likelihood ratio test is most powerful in a wide range of settings and there is no negative impact to its power performance when common variants are also included in the analysis. If deleterious and protective variants are simultaneously analyzed, the likelihood ratio test was generally insensitive to the effect directionality, unless the effects are extremely inconsistent in one direction.

  11. Isolation and characterization of human rhinovirus antigenic variants

    Energy Technology Data Exchange (ETDEWEB)

    Watson, D.G.


    Isolation of antigenic variants of human rhinovirus types 2, 14, and 17 was attempted by plaquing untreated virus (P-isolates), selecting variants in the presence of homologous antiserum (C-isolates), and by selecting variants in the presence of antibody following 5-fluorouracil mutagenesis (M-isolates). All viruses were triple-plaque purified and purity neutralization tested prior to isolate selection. Based on a fourfold reduction in neutralizing antibody titer to homologous antiserum, no antigenic variation was found in P-isolates from the three serotypes examined. Antigenic variants of all three serotypes could be isolated by the antiserum selection method (C-isolates). However, antigenic variants of RV17 were isolated at a much higher frequency and showed a larger degree of variation than those of RV2 and RV14. At least two of the variants selected, RV17 (C301) and RV2 (M803), failed to be neutralized by the known 89 rhinovirus antiserum. SDS-polyacrylamide gel electrophoresis of (/sup 35/S) methionine-labelled virion polypeptides revealed that each serotype had a characteristic pattern and that selected RV2 and RV17 isolates had patterns identical to those of the prototype strains. By isoelectric focusing an antigenic variant of RV2 was shown to contain altered virion polypeptides VP1 and VP2 whereas two RV17 antigenic variants demonstrated alterations only in the VP1 polypeptide.

  12. Copy number variants in patients with short stature

    NARCIS (Netherlands)

    Duyvenvoorde, H.A. van; Lui, J.C.; Kant, S.G.; Oostdijk, W.; Gijsbers, A.C.; Hoffer, M.J.V.; Karperien, M.; Walenkamp, M.J.; Noordam, C.; Voorhoeve, P.G.; Mericq, V.; Pereira, A.M.; Claahsen-van der Grinten, H.L.; Gool, S.A. van; Breuning, M.H.; Losekoot, M.; Baron, J.; Ruivenkamp, C.A.; Wit, J.M.


    Height is a highly heritable and classic polygenic trait. Recent genome-wide association studies (GWAS) have revealed that at least 180 genetic variants influence adult height. However, these variants explain only about 10% of the phenotypic variation in height. Genetic analysis of short individuals

  13. Hepatitis E Virus Variant in Farmed Mink, Denmark

    DEFF Research Database (Denmark)

    Krog, Jesper Schak; Breum, Solvej Østergaard; Jensen, Trine Hammer


    Hepatitis E virus (HEV) is a zoonotic virus for which pigs are the primary animal reservoir. To investigate whether HEV occurs in mink in Denmark, we screened feces and tissues from domestic and wild mink. Our finding of a novel HEV variant supports previous findings of HEV variants in a variety...

  14. Treatment of Spelling Variants in Setswana Monolingual Dictionaries

    African Journals Online (AJOL)

    This paper argues that the Setswana language is characterised by spelling variants which are a consequence of multiple factors. It considers spelling variants found amongst individual words as well as those found in multi-word expressions (MWEs). It argues that spelling variation may be a result of historical fissions and ...

  15. Assessment of Functional Effects of Unclassified Genetic Variants

    NARCIS (Netherlands)

    Couch, Fergus J.; Rasmussen, Lene Juel; Hofstra, Robert; Monteiro, Alvaro N. A.; Greenblatt, Marc S.; de Wind, Niels


    Inherited predisposition to disease is often linked to reduced activity of a disease associated gene product. Thus, quantitation of the influence of inherited variants on gene function can potentially be used to predict the disease relevance of these variants. While many disease genes have been

  16. Phenotypes and genotypes in individuals with SMC1A variants

    DEFF Research Database (Denmark)

    Huisman, Sylvia; Mulder, Paul A; Redeker, Egbert


    SMC1A encodes one of the proteins of the cohesin complex. SMC1A variants are known to cause a phenotype resembling Cornelia de Lange syndrome (CdLS). Exome sequencing has allowed recognizing SMC1A variants in individuals with encephalopathy with epilepsy who do not resemble CdLS. We performed an ...

  17. Expression and secretion of defined cutinase variants by Aspergillus awamori

    NARCIS (Netherlands)

    Gemeren, I.A. van; Beijersbergen, A.; Hondel, C.A.M.J.J. van den; Verrips, C.T.


    Several cutinase variants derived by molecular modelling and site- directed mutagenesis of a cutinase gene from Fusarium solani pisi are poorly secreted by Saccharomyces cerevisiae. The majority of these variants are successfully produced by the filamentous fungus Aspergillus awamori. However, the

  18. Variant Anatomy of the External Jugular Vein | Olabu | Anatomy ...

    African Journals Online (AJOL)

    Variant anatomy of the external jugular vein is important when performing invasive procedures in the neck. Although there are a number of case reports on some of these variations, there are few descriptive cross-sectional regarding the same. This study therefore aimed at describing the variant anatomy of the external ...

  19. Rethinking exchange market models as optimization algorithms (United States)

    Luquini, Evandro; Omar, Nizam


    The exchange market model has mainly been used to study the inequality problem. Although the human society inequality problem is very important, the exchange market models dynamics until stationary state and its capability of ranking individuals is interesting in itself. This study considers the hypothesis that the exchange market model could be understood as an optimization procedure. We present herein the implications for algorithmic optimization and also the possibility of a new family of exchange market models

  20. Latin American foreign exchange intervention - Updated


    Da Silva, Sergio; Nunes, Mauricio


    We examine Latin American foreign exchange intervention in a framework where the exchange rate regime is endogenous and there exists an inefficient, equilibrium foreign exchange intervention bias. The model suggests that greater central bank independence is associated with lesser intervention in the foreign exchange market, and also with leaning-against-the-wind intervention. Both results are confirmed by data from 13 Latin American countries.

  1. How to stabilize the currency exchange rate


    BLINOV, Sergey


    In 2015, many countries had to deal with the weakening of their currencies. Issues regarding exchange rate management by the Central Banks have again become the focal point of heated debate. For example, the Russian Ruble exchange rate has been fluctuating hugely. The problem now is not so much the Ruble's weakness as instability of its exchange rate, volatility. The management of the Central Bank claims that stabilization of the Ruble exchange rate is not possible though it is the respons...

  2. Heat exchanger and related methods (United States)

    Turner, Terry D.; McKellar, Michael G.


    Heat exchangers include a housing having an inlet and an outlet and forming a portion of a transition chamber. A heating member may form another portion of the transition chamber. The heating member includes a first end having a first opening and a second end having a second opening larger than the first opening. Methods of conveying a fluid include supplying a first fluid into a transition chamber of a heat exchanger, supplying a second fluid into the transition chamber, and altering a state of a portion of the first fluid with the second fluid. Methods of sublimating solid particles include conveying a first fluid comprising a material in a solid state into a transition chamber, heating the material to a gaseous state by directing a second fluid through a heating member and mixing the first fluid and the second fluid.

  3. The picture exchange communication system. (United States)

    Bondy, A S; Frost, L A


    The Picture Exchange Communication System (PECS) was developed as a means to teach children with autism and related developmental disabilities a rapidly acquired, self-initiating, functional communication system. Its theoretical roots combine principles from applied behavior analysis and guidelines established within the field of alternative and augmentative communication. This approach has several potential advantages relative to imitation-based strategies (both vocal and gestural) and symbol selection strategies. The system begins with the exchange of simple icons but rapidly builds "sentence" structure. The system also emphasizes developing the request function prior to developing responding to simple questions and commenting. The development of requesting with a sentence structure also permits the rapid development of attributes more traditionally taught within a receptive mode. The relationship between the introduction of PECS and various other behavioral issues (i.e., social approach and behavior management) as well as its relationship to the codevelopment of speech are reviewed.

  4. Analysis of Leader Member Exchange

    Directory of Open Access Journals (Sweden)

    Adi Santoso


    Full Text Available This research aims to find out how the relationship of superiors and subordinates works or we call it, LEADER MEMBER EXCHANGE (LMX in another term. The object of this research is an Integrated Nursing Home for Impaired Speech and Hearing (INISPH, ''Meohai” Kendari, with 5 superiors and subordinates of this institution as the research informants. The method used in this research is descriptive qualitative analysis. The research found that the relationship of superiors and subordinates or Leader Member Exchange (LMX, has been well-intertwined, based on the affection, loyalty, enormous contribution, and respect one another toward the profession done in creating a close relationship to achieve the goal.DOI: 10.15408/etk.v15i2.3244

  5. Value Appropriation in Business Exchange

    DEFF Research Database (Denmark)

    Ellegaard, Chris; Medlin, Christopher J.; Geersbro, Jens


    master the difficult balance between value creation and appropriation. This review has provided an overview of the many managerial options for value appropriation and created knowledge on the effects of the various appropriation mechanisms enabling managers to secure company rents while not jeopardizing......Purpose – Value appropriation is a central, yet neglected aspect in business exchange research. The purpose of the paper is to generate an overview of research on active value appropriation in business exchange and provide the foundation for further research into value appropriation, as well...... as some initial guidance for managers. Design/methodology/approach – Literatures investigating value appropriation were identified by the means of a systematic review of the overall management literature. Findings – The authors provide an overview and comparison of the literatures and find that they apply...

  6. High Temperature Composite Heat Exchangers (United States)

    Eckel, Andrew J.; Jaskowiak, Martha H.


    High temperature composite heat exchangers are an enabling technology for a number of aeropropulsion applications. They offer the potential for mass reductions of greater than fifty percent over traditional metallics designs and enable vehicle and engine designs. Since they offer the ability to operate at significantly higher operating temperatures, they facilitate operation at reduced coolant flows and make possible temporary uncooled operation in temperature regimes, such as experienced during vehicle reentry, where traditional heat exchangers require coolant flow. This reduction in coolant requirements can translate into enhanced range or system payload. A brief review of the approaches and challengers to exploiting this important technology are presented, along with a status of recent government-funded projects.

  7. Groundwater–Surface Water Exchange

    DEFF Research Database (Denmark)

    Karan, Sachin

    The exchange of groundwater-surface water has been invetigated in the western part of Denmark. Holtum AA provides the framework for all the performed investigations. Several methods are used, primarily eld based measurements ombined with numerical models to achieve insight to the governing...... processes of interaction between groundwater and surface water. By using heat as a tracer it has been possible to use temperature directly as calibrationtargets in a groundwater and heat transport model. Thus, it is possible to use heat investigate the change in groundwater discharge in dynamic conditions...... by using simple temperature devices along a stream to delineate the areas of interest in regard to GW{SW exchange. Thus, at several locations in a stream a temperature data logger was placed in the water column and right at the streambed-water interface. By looking at the correlation of streambed...

  8. Electrically controlled cesium ion exchange

    Energy Technology Data Exchange (ETDEWEB)

    Lilga, M. [Pacific Northwest Lab., Richland, WA (United States)


    Several sites within the DOE complex (Savannah River, Idaho, Oak Ridge and Hanford) have underground storage tanks containing high-level waste resulting from nuclear engineering activities. To facilitate final disposal of the tank waste, it is advantageous to separate and concentrate the radionuclides for final immobilization in a vitrified glass matrix. This task proposes a new approach for radionuclide separation by combining ion exchange (IX) and electrochemistry to provide a selective and economic separation method.

  9. Value-Added Exchange Rates


    Rudolfs Bems; Robert C. Johnson


    This paper updates the conceptual foundations for measuring real effective exchange rates (REERs) to allow for vertical specialization in trade. We derive a value-added REER describing how demand for the value added that a country produces changes as the price of its value added changes relative to competitors. We then compute this index for 42 countries from 1970-2009 using trade measured in value added terms and GDP deflators. There are substantial differences between value-added and conven...

  10. Exchange, phenomenology and the Self


    Galonska, Deniece; Yener, Efe Can; Sørensen, Karen Mallya; Olesen, Tine Lautrup


    The research project aims to investigate the ‘Self’ concerning the experience of being an international exchange student. As the research approaches the three participants as unique individuals, phenomenology provided a foundation regarding the ontological stance and a method. The philosophy of phenomenology and its different interview methods will be discussed, in relation to perspectives by Edmund Husserl and Martin Heidegger, with attention aimed at the question whether or not objectiv...

  11. Review of Fractal Heat Exchangers


    Huang, Zhiwei; Hwang, Yunho; Aute, Vikrant; Radermacher, Reinhard


    Nature has inspired many scientists and engineers to solve problems through observation and mimicry. One such example is heat transfer enhancement. The enormous natural heat and mass transfer phenomena have led engineers to seek solutions to heat transfer enhancement problems from nature. Fractal geometries are found in respiratory and vascular systems of plants and animals, such as blood vessels, human lungs, leaves, coastlines, etc. Inspired by this, fractal heat exchangers have been develo...

  12. Prison needle exchange programs work. (United States)


    On 27 October 2004 the Canadian HIV/AIDS Legal Network and the Ontario Medical Association (OMA) released reports recommending that needle exchange programs (NEPs) be implemented in prisons, based on evidence that such programs promote and protect the health of both prisoners and prison staff. At the same time, the Scottish Prison Service announced that it was looking at providing such programs, and an Iranian physician reported on a pilot project in his country.

  13. Ion-exchange chromatographic protein refolding

    NARCIS (Netherlands)

    Freydell, E.; Wielen, van der L.; Eppink, M.H.M.; Ottens, M.


    The application of ion-exchange (IEX) chromatography to protein refolding (IExR) has been successfully proven, as supported by various studies using different model proteins, ion-exchange media and flow configurations. Ion-exchange refolding offers a relatively high degree of process

  14. Monetary and Exchange Rate Policy in Slovenia


    Gonzalo Caprirolo; Vladimir Lavrac


    The paper is divided in three sections presenting some stylized facts concerning monetary and exchange rate policy framework in Slovenia. Three periods are covered: Money-based Stabilization Policy (1991-1995), Price and Real Exchange Rate Stability Dual Targeting Policy (1996-2001), and Exchange Rate Based Stabilization Policy and Accession to ERM2 (2001-).

  15. 78 FR 38203 - Refunds and Exchanges (United States)


    ... Service through the manager, Payment Technology, USPS Headquarters. Subsequently, as part of this final... from the manager, Payment Technology (see 608.8.1 for address). * * * * * 9.0 Exchanges and Refunds... Not Exchangeable The following postage items cannot be exchanged: a. Adhesive stamps, unless mistakes...

  16. Cryogenic Heat Exchanger with Turbulent Flows (United States)

    Amrit, Jay; Douay, Christelle; Dubois, Francis; Defresne, Gerard


    An evaporator-type cryogenic heat exchanger is designed and built for introducing fluid-solid heat exchange phenomena to undergraduates in a practical and efficient way. The heat exchanger functions at liquid nitrogen temperature and enables cooling of N[subscript 2] and He gases from room temperatures. We present first the experimental results of…

  17. The magic of knowledge exchange

    CERN Multimedia

    CERN Bulletin


    “If you have an apple and I have an apple and we exchange these apples then you and I will still each have one apple. But if you have an idea and I have an idea and we exchange these ideas, then each of us will have two ideas”. (George Bernard Shaw). The CERN Global Network is a new, ideal place for past and present members of the CERN community to share ideas and create new links.   On 29 April, CERN’s Knowledge and Technology Transfer (KTT) Group launched the CERN Global Network, a tool whose aim is to facilitate knowledge exchanges inside and outside CERN. "Among the greatest ambassadors of knowledge are people who have been trained and educated at CERN and also at other institutes: here is where the Global Network comes into play", says Rolf Heuer, CERN Director General. “During the first phase, the Network will be open to current and former members of the CERN personnel, that is, staff, fellows, apprentices, associates, students a...


    Energy Technology Data Exchange (ETDEWEB)

    Bunge, A.L.; Klein, G.; Radke, C.J.


    Exchange of hardness ions is important in enhanced oil recovery with chemical additives. In both micellar-polymer and caustic flooding processes, multivalent ions released from rock surfaces can interact with anionic surfactants, rendering them preferentially oil soluble and/or insoluble in water. Because hardness cations are sparingly soluble and precipitate in alkaline solutions, such solutions may be more efficient as surfactant flood preflushes than are softened brines. Multivalent ion precipitation may also occur in alkaline waterflooding. To permit design of such processes, this paper presents a chromatographic theory for simultaneous ion exchange with precipitation of divalent ions. Theoretical effluent histories and concentration profiles are presented for the cases of finite pulses and continuous injection of hydroxide ions into linear cores. Complete capture of the insoluble salt particles is assumed. Results are given for the case of instantaneous equilibration of the solution with the precipitate, as well for the case of complete nonequilibrium, in which the solid precipitate does not redissolve. The efficiency of alklaine preflushing is shown to depend on the exchange isotherm, initial divalent loading of the rock, injected pH and salinity, the solubility product of the precipitated salt, and pulse size. The effect of slug size on complete equilibrium removal of hardness ions is reduced efficiency with increasing size until a critical volume approximating continuous injection is reached. Increasing injected pH and salinity provides a more favorable response. Experimental data for Berea sandstone and an argillaceous sand compare favorably with the proposed theory.


    Energy Technology Data Exchange (ETDEWEB)

    Boltz, J.C. (ed.)


    This report discusses the following topics on computer environments: Releasing computer software outside EG G Idaho; Ilford digital photo imager; mandatory upgrade of PC ORPS software; ORPS host computer upgrade; EROB computer users see network change; password expiration notice; big iron still has place in HPC market; handy scripts to copy and move files; more on workstation password expiration; training center course schedule for April 1993; Microsoft Word Version 5.1a- button bar; file attributes can provide you greater flexibility; constructing a personal WordPerfect dictionary; and Windows shortcuts.

  20. Heterozygote Hemoglobin G-Coushatta as the Cause of a Falsely Decreased Hemoglobin A1C in an Ion-Exchange HPLC Method

    Directory of Open Access Journals (Sweden)

    Kurtoğlu Ayşegül Uğur


    Full Text Available Glycated hemoglobin (HbA1c is used for the assessment of glycemic control in patients with diabetes. The presence of genetic variants of hemoglobin can profoundly affect the accuracy of HbA1c measurement. Here, we report two cases of Hemoglobin G-Coushatta (HBB:c.68A>C variant that interferes in the measurement of HbA1c by a cation-exchange HPLC (CE-HPLC method. HbA1c was measured by a CE-HPLC method in a Tosoh HLC-723 G7 instrument. The HbA1c levels were 2.9% and 4%. These results alerted us to a possible presence of hemoglobinopathy. In the hemoglobin variant analysis, HbA2 levels were detected as 78.3% and 40.7% by HPLC using the short program for the Biorad Variant II. HbA1c levels were measured by an immunoturbidimetric assay in a Siemens Dimension instrument. HbA1c levels were reported as 5.5% and 5.3%. DNA mutation analysis was performed to detect the abnormal hemoglobin variant. Presence of Hemoglobin G-Coushatta variant was detected in the patients. The Hb G-Coushatta variants have an impact on the determination of glycated hemoglobin levels using CEHPLC resulting in a false low value. Therefore, it is necessary to use another measurement method.

  1. Correlation between leukoaraiosis volume and circle of Willis variants. (United States)

    Saba, Luca; Raz, Eytan; Fatterpekar, Girish; Montisci, Roberto; di Martino, Michele; Bassareo, Pier Paolo; Piga, Mario


    The Circle of Willis (COW) is the main collateral system between the bilateral carotid systems and the posterior circulation. COW normal variants are encountered in up to 62% of subjects. We hypothesize that, in patients with carotid artery stenosis, the presence of COW variants is a risk factor for leukoaraiosis. Forty-seven patients (mean age 72.1 ± 9 years, males = 39) with carotid artery stenosis admitted for carotid endarterectomy were included and underwent an admission brain MRI/MRA. Two neuroradiologists evaluated the COW variants. FLAIR-leukoaraiosis lesion-volume was performed using a semiautomated segmentation technique. Mann-Whitney and Pearson correlations were conducted to identify the correlation between the FLAIR-leukoaraiosis lesion-volume and the COW variants. ROC analysis was performed to evaluate the AUC of FLAIR-leukoaraiosis lesion-volume and presence/absence of COW variants. Pearson correlation demonstrated that the leukoaraiosis lesion-volume is significantly associated with the COW variants number (rho = .358, P = .0215). When patients were dicotomized in two subgroups, with and without COW variants, the lesion-volume was significantly higher in the variants group (P = .0405). The ROC curve analysis showed an AUC of .688 (SE = .083, 95%CI = .525-.823) with a statistically significant P = .0225, between the presence of COW variants and the FLAIR-leukoaraiosis lesion-volume. The presence and the number of COW variants are associated with a higher leukoaraiosis volume in patients with significant internal carotid artery stenosis. Copyright © 2014 by the American Society of Neuroimaging.

  2. Bayesian detection of causal rare variants under posterior consistency.

    KAUST Repository

    Liang, Faming


    Identification of causal rare variants that are associated with complex traits poses a central challenge on genome-wide association studies. However, most current research focuses only on testing the global association whether the rare variants in a given genomic region are collectively associated with the trait. Although some recent work, e.g., the Bayesian risk index method, have tried to address this problem, it is unclear whether the causal rare variants can be consistently identified by them in the small-n-large-P situation. We develop a new Bayesian method, the so-called Bayesian Rare Variant Detector (BRVD), to tackle this problem. The new method simultaneously addresses two issues: (i) (Global association test) Are there any of the variants associated with the disease, and (ii) (Causal variant detection) Which variants, if any, are driving the association. The BRVD ensures the causal rare variants to be consistently identified in the small-n-large-P situation by imposing some appropriate prior distributions on the model and model specific parameters. The numerical results indicate that the BRVD is more powerful for testing the global association than the existing methods, such as the combined multivariate and collapsing test, weighted sum statistic test, RARECOVER, sequence kernel association test, and Bayesian risk index, and also more powerful for identification of causal rare variants than the Bayesian risk index method. The BRVD has also been successfully applied to the Early-Onset Myocardial Infarction (EOMI) Exome Sequence Data. It identified a few causal rare variants that have been verified in the literature.

  3. Incorporating Non-Coding Annotations into Rare Variant Analysis.

    Directory of Open Access Journals (Sweden)

    Tom G Richardson

    Full Text Available The success of collapsing methods which investigate the combined effect of rare variants on complex traits has so far been limited. The manner in which variants within a gene are selected prior to analysis has a crucial impact on this success, which has resulted in analyses conventionally filtering variants according to their consequence. This study investigates whether an alternative approach to filtering, using annotations from recently developed bioinformatics tools, can aid these types of analyses in comparison to conventional approaches.We conducted a candidate gene analysis using the UK10K sequence and lipids data, filtering according to functional annotations using the resource CADD (Combined Annotation-Dependent Depletion and contrasting results with 'nonsynonymous' and 'loss of function' consequence analyses. Using CADD allowed the inclusion of potentially deleterious intronic variants, which was not possible when filtering by consequence. Overall, different filtering approaches provided similar evidence of association, although filtering according to CADD identified evidence of association between ANGPTL4 and High Density Lipoproteins (P = 0.02, N = 3,210 which was not observed in the other analyses. We also undertook genome-wide analyses to determine how filtering in this manner compared to conventional approaches for gene regions. Results suggested that filtering by annotations according to CADD, as well as other tools known as FATHMM-MKL and DANN, identified association signals not detected when filtering by variant consequence and vice versa.Incorporating variant annotations from non-coding bioinformatics tools should prove to be a valuable asset for rare variant analyses in the future. Filtering by variant consequence is only possible in coding regions of the genome, whereas utilising non-coding bioinformatics annotations provides an opportunity to discover unknown causal variants in non-coding regions as well. This should allow

  4. Porphyromonas gingivalis Uses Specific Domain Rearrangements and Allelic Exchange to Generate Diversity in Surface Virulence Factors (United States)

    Dashper, Stuart G.; Mitchell, Helen L.; Seers, Christine A.; Gladman, Simon L.; Seemann, Torsten; Bulach, Dieter M.; Chandry, P. Scott; Cross, Keith J.; Cleal, Steven M.; Reynolds, Eric C.


    Porphyromonas gingivalis is a keystone pathogen of chronic periodontitis. The virulence of P. gingivalis is reported to be strain related and there are currently a number of strain typing schemes based on variation in capsular polysaccharide, the major and minor fimbriae and adhesin domains of Lys-gingipain (Kgp), amongst other surface proteins. P. gingivalis can exchange chromosomal DNA between strains by natural competence and conjugation. The aim of this study was to determine the genetic variability of P. gingivalis strains sourced from international locations over a 25-year period and to determine if variability in surface virulence factors has a phylogenetic basis. Whole genome sequencing was performed on 13 strains and comparison made to 10 previously sequenced strains. A single nucleotide polymorphism-based phylogenetic analysis demonstrated a shallow tri-lobed phylogeny. There was a high level of reticulation in the phylogenetic network, demonstrating extensive horizontal gene transfer between the strains. Two highly conserved variants of the catalytic domain of the major virulence factor the Kgp proteinase (KgpcatI and KgpcatII) were found. There were three variants of the fourth Kgp C-terminal cleaved adhesin domain. Specific variants of the cell surface proteins FimA, FimCDE, MfaI, RagAB, Tpr, and PrtT were also identified. The occurrence of all these variants in the P. gingivalis strains formed a mosaic that was not related to the SNP-based phylogeny. In conclusion P. gingivalis uses domain rearrangements and genetic exchange to generate diversity in specific surface virulence factors. PMID:28184216


    Directory of Open Access Journals (Sweden)

    L. V. Borukhava


    Full Text Available The paper considers reasons of internal air parameter mismatch in warm season of the year for public building premises having large area of translucent structures. The main reason of uncomfortable air environment is an underestimated value of air supply volume due to air exchange calculation according to multiplicity factor or air exchange rate per one person which are determinative values only for cold period and transient conditions. In other words multiplicity factor and air exchange rate do not take into account equipment abundance in modern offices and heat input of the office equipment is rather significant value. The paper contains an analysis and comparison of the existing air exchange rates for the Republic of Belarus, Russian Federation, European countries and USA. Calculation of heat input and air exchange for public building premises during warm season of the year for assimilation of evident heat excess has been made at various orientations of curtain walls. The paper provides structure of heat input into premises. The required rate of air supply volume per one person has been determined on the basis of air exchange and it has been compared with the existing air exchange rate. The required rate averagely exceeds the standard one by 12-fold. But this does not mean that there is necessity to increase the rate in such a way because it entails an increase in capital and operational costs. In this connection the paper reviews variants for improvement of micro-climate in the building premises with large area of translucent structures: automatic regulation of heat transfer in heating appliances during cold period of the year; usage of air conditioning and increase in temperature difference of input and output air during warm period.

  6. HIV-1 genetic variants in Kyrgyzstan

    Directory of Open Access Journals (Sweden)

    V Laga


    Full Text Available Objectives: During the last two decades, HIV-1 has been spreading rapidly in former Soviet Union republics including Kyrgyzstan. The current molecular monitoring of HIV-infection epidemic is carried out in Russia only with no or limited data from the other FSU countries. The aim of this work was to investigate the prevalence of HIV-1 genetic variants circulating in Kyrgyzstan. Methods: Blood collection from the HIV-infected patients was carried out by local specialists with the informed consent and the questionnaire was answered by each of the patients. The total number of samples was 100. The washed cell pellets were transferred to Moscow following with proviral DNA extraction, PCR amplification and gag, pol and env genes sequencing. The phylogenetic analysis of nucleotide sequences using neighbor-joining method was carried out by MEGA 3 program. The preliminary data were obtained in 22 samples isolated from PBMC of HIV-infected patients from Kyrgyzstan. Results: Among the samples studied 6 (27.3% samples belonged to a subtype CRF02_AG, 16 samples - to subtype A (A1. One of the samples belonging to CRF02_AG, probably, is a recombinant between CRF02_AG and A1. There was no major drug resistance mutations in the samples studied. The minor mutations were presented in small proportions: 1 in PR (L10I, 6 in RT (A62V - in 3 samples, V108G, E138A, Y181F, M184I, L210M - on one sample and 1 in IN (L74M. It was impossible to associate the distribution of mutations with HIV-1 genetic variant. The V3 loop (env gene in 17 samples was analyzed for tropism using geno2pheno program; all samples were found to be R5-viruses. Conclusion: The HIV-1 subtype A seems to dominate in Kyrgyzstan like in other FSU countries. The recombinant CRF02_AG epidemiologically linked to Uzbekistan is quite widespread. The rest of Kyrgyzstan collection is under investigation and the data will be refined soon.

  7. Variants of polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Sweeney, Matt; Wogulis, Mark


    The present invention relates to polypeptide having cellulolytic enhancing activity variants. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the variants.

  8. The determinants of exchange rate in Croatia

    Directory of Open Access Journals (Sweden)

    Manuel BENAZIC


    Full Text Available The dilemma for every country with an independent monetary policy is which kind of exchange rate arrangement should be applied. Through the exchange rate policy, countries can influence their economies, i.e. price stability and export competiveness. Croatia is a new EU member state, it has its own monetary policy and currency but it is on the way to euro introduction. Regarding the experiences from the beginning of the 1990s when Croatia was faced with serious monetary instabilities and hyperinflation, the goal of Croatian National Bank (CNB is to ensure price stability and one way to do so is through exchange rate policy. Croatia, as a small and open economy, has applied a managed floating exchange rate regime. The exchange rate is determined primarily by the foreign exchange supply and demand on the foreign exchange market, with occasional market interventions by the CNB. Therefore, in order to maintain exchange rate stability, policymakers must be able to recognize how changes in these factors affect changes in the exchange rate. This research aims to find a relationship among the main sources of foreign currency inflow and outflow and the level of exchange rate in Croatia. The analysis is carried out by using the bounds testing (ARDL approach for co-integration. The results indicate the existence of a stable co-integration relationship between the observed variables, whereby an increase in the majority of variables leads to an exchange rate appreciation.

  9. Effects of deficit irrigation and straw mulching on gas exchange of cucumber plants (Cucumis sativus L.

    Directory of Open Access Journals (Sweden)

    František Hnilička


    Full Text Available Leaves gas exchange were studied in one cucumber (Cucumis sativus L. cultivar Harriet F1 grown under control conditions (C, deficit irrigation (S and straw mulch (M, as well as under control or deficit irrigation conditions and straw mulch in combination (CM or SM. Cucumber plants were grown in loose soil, foil tunnel. The photosynthesis rate (PN and transpiration rate (E were measured in the leaves in situ using the portable gas exchange system LCpro+. It follows from the results obtained that water deficit (PN was 11.88 μmol CO2.m−2.s−1 and E was 1.83 mmol H2O.m−2.s−1 provably decreases the gas exchange rate in cucumber plants in comparison with the irrigated control group (average value of PN - 15.03 μmol CO2.m−2.s−1 and E – 2.16 mmol H2O.m−2.s−1. The application of mulch in the control and stresses plants statistically insignificantly reduced the photosynthesis rates −14.91 μmol CO2.m−2.s−1 and 11.86 μmol CO2.m−2.s−1, respectively. However, after the application of the mulch to the plants growing in the variant of deficit irrigation and control conditions with mulch, the transpiration rate increased. The rate of transpiration (E by plants from control and deficit irrigation with mulch was 2.28 mmol H2O.m−2.s−1 and 2.24 mmol H2O.m−2.s−1, respectively. Photosynthesis and transpiration rate is also influenced by stomatal conductance (gs. The obtained values ​of the coefficient of determination (r2 is evident no stomatal inhibition of gas exchange for variants C (r2 = 0.1404 – PN; 0.2352 – E and CM (r2 = 0.2656 – PN; 0.2483 – E. No stomatal inhibition of photosynthesis was observed in SM variant (r2 = 0.2867, too. However, stomatal inhibition of photosynthesis and transpiration rate was based on the coefficient of determination found in plants with limited irrigation (PN – r2 = 0.5222 and E – r2 = 0.7191 and in SM variant (r2 = 0.8972.

  10. A Review of Industrial Heat Exchange Optimization (United States)

    Yao, Junjie


    Heat exchanger is an energy exchange equipment, it transfers the heat from a working medium to another working medium, which has been wildly used in petrochemical industry, HVAC refrigeration, aerospace and so many other fields. The optimal design and efficient operation of the heat exchanger and heat transfer network are of great significance to the process industry to realize energy conservation, production cost reduction and energy consumption reduction. In this paper, the optimization of heat exchanger, optimal algorithm and heat exchanger optimization with different objective functions are discussed. Then, optimization of the heat exchanger and the heat exchanger network considering different conditions are compared and analysed. Finally, all the problems discussed are summarized and foresights are proposed.

  11. The Clinical Significance of Unknown Sequence Variants in BRCA Genes

    Energy Technology Data Exchange (ETDEWEB)

    Calò, Valentina; Bruno, Loredana; Paglia, Laura La; Perez, Marco; Margarese, Naomi [Department of Surgery and Oncology, Regional Reference Center for the Biomolecular Characterization and Genetic Screening of Hereditary Tumors, University of Palermo, Via del Vespro 127, 90127 Palermo (Italy); Gaudio, Francesca Di [Department of Medical Biotechnologies and Legal Medicine, University of Palermo, Palermo (Italy); Russo, Antonio, E-mail: [Department of Surgery and Oncology, Regional Reference Center for the Biomolecular Characterization and Genetic Screening of Hereditary Tumors, University of Palermo, Via del Vespro 127, 90127 Palermo (Italy)


    Germline mutations in BRCA1/2 genes are responsible for a large proportion of hereditary breast and/or ovarian cancers. Many highly penetrant predisposition alleles have been identified and include frameshift or nonsense mutations that lead to the translation of a truncated protein. Other alleles contain missense mutations, which result in amino acid substitution and intronic variants with splicing effect. The discovery of variants of uncertain/unclassified significance (VUS) is a result that can complicate rather than improve the risk assessment process. VUSs are mainly missense mutations, but also include a number of intronic variants and in-frame deletions and insertions. Over 2,000 unique BRCA1 and BRCA2 missense variants have been identified, located throughout the whole gene (Breast Cancer Information Core Database (BIC database)). Up to 10–20% of the BRCA tests report the identification of a variant of uncertain significance. There are many methods to discriminate deleterious/high-risk from neutral/low-risk unclassified variants (i.e., analysis of the cosegregation in families of the VUS, measure of the influence of the VUSs on the wild-type protein activity, comparison of sequence conservation across multiple species), but only an integrated analysis of these methods can contribute to a real interpretation of the functional and clinical role of the discussed variants. The aim of our manuscript is to review the studies on BRCA VUS in order to clarify their clinical relevance.

  12. NECTAR: a database of codon-centric missense variant annotations. (United States)

    Gong, Sungsam; Ware, James S; Walsh, Roddy; Cook, Stuart A


    NECTAR (Non-synonymous Enriched Coding muTation ARchive; is a database and web application to annotate disease-related and functionally important amino acids in human proteins. A number of tools are available to facilitate the interpretation of DNA variants identified in diagnostic or research sequencing. These typically identify previous reports of DNA variation at a given genomic location, predict its effects on transcript and protein sequence and may predict downstream functional consequences. Previous reports and functional annotations are typically linked by the genomic location of the variant observed. NECTAR collates disease-causing variants and functionally important amino acid residues from a number of sources. Importantly, rather than simply linking annotations by a shared genomic location, NECTAR annotates variants of interest with details of previously reported variation affecting the same codon. This provides a much richer data set for the interpretation of a novel DNA variant. NECTAR also identifies functionally equivalent amino acid residues in evolutionarily related proteins (paralogues) and, where appropriate, transfers annotations between them. As well as accessing these data through a web interface, users can upload batches of variants in variant call format (VCF) for annotation on-the-fly. The database is freely available to download from the ftp site:

  13. A pathway-centric approach to rare variant association analysis (United States)

    Richardson, Tom G; Timpson, Nicholas J; Campbell, Colin; Gaunt, Tom R


    Current endeavours in rare variant analysis are typically underpowered when investigating association signals from individual genes. We undertook an approach to rare variant analysis which utilises biological pathway information to analyse functionally relevant genes together. Conventional filtering approaches for rare variant analysis are based on variant consequence and are therefore confined to coding regions of the genome. Therefore, we undertook a novel approach to this process by obtaining functional annotations from the Combined Annotation Dependent Depletion (CADD) tool, which allowed potentially deleterious variants from intronic regions of genes to be incorporated into analyses. This work was undertaken using whole-genome sequencing data from the UK10K project. Rare variants from the KEGG pathway for arginine and proline metabolism were collectively associated with systolic blood pressure (P=3.32x10−5) based on analyses using the optimal sequence kernel association test. Variants along this pathway also showed evidence of replication using imputed data from the Avon Longitudinal Study of Parents and Children cohort (P=0.02). Subsequent analyses found that the strength of evidence diminished when analysing genes in this pathway individually, suggesting that they would have been overlooked in a conventional gene-based analysis. Future studies that adopt similar approaches to investigate polygenic effects should yield value in better understanding the genetic architecture of complex disease. PMID:27577545

  14. Whole-Exome Sequencing Identifies Novel Variants for Tooth Agenesis. (United States)

    Dinckan, N; Du, R; Petty, L E; Coban-Akdemir, Z; Jhangiani, S N; Paine, I; Baugh, E H; Erdem, A P; Kayserili, H; Doddapaneni, H; Hu, J; Muzny, D M; Boerwinkle, E; Gibbs, R A; Lupski, J R; Uyguner, Z O; Below, J E; Letra, A


    Tooth agenesis is a common craniofacial abnormality in humans and represents failure to develop 1 or more permanent teeth. Tooth agenesis is complex, and variations in about a dozen genes have been reported as contributing to the etiology. Here, we combined whole-exome sequencing, array-based genotyping, and linkage analysis to identify putative pathogenic variants in candidate disease genes for tooth agenesis in 10 multiplex Turkish families. Novel homozygous and heterozygous variants in LRP6, DKK1, LAMA3, and COL17A1 genes, as well as known variants in WNT10A, were identified as likely pathogenic in isolated tooth agenesis. Novel variants in KREMEN1 were identified as likely pathogenic in 2 families with suspected syndromic tooth agenesis. Variants in more than 1 gene were identified segregating with tooth agenesis in 2 families, suggesting oligogenic inheritance. Structural modeling of missense variants suggests deleterious effects to the encoded proteins. Functional analysis of an indel variant (c.3607+3_6del) in LRP6 suggested that the predicted resulting mRNA is subject to nonsense-mediated decay. Our results support a major role for WNT pathways genes in the etiology of tooth agenesis while revealing new candidate genes. Moreover, oligogenic cosegregation was suggestive for complex inheritance and potentially complex gene product interactions during development, contributing to improved understanding of the genetic etiology of familial tooth agenesis.

  15. Identification of copy number variants in horses

    KAUST Repository

    Doan, R.


    Copy number variants (CNVs) represent a substantial source of genetic variation in mammals. However, the occurrence of CNVs in horses and their subsequent impact on phenotypic variation is unknown. We performed a study to identify CNVs in 16 horses representing 15 distinct breeds (Equus caballus) and an individual gray donkey (Equus asinus) using a whole-exome tiling array and the array comparative genomic hybridization methodology. We identified 2368 CNVs ranging in size from 197 bp to 3.5 Mb. Merging identical CNVs from each animal yielded 775 CNV regions (CNVRs), involving 1707 protein- and RNA-coding genes. The number of CNVs per animal ranged from 55 to 347, with median and mean sizes of CNVs of 5.3 kb and 99.4 kb, respectively. Approximately 6% of the genes investigated were affected by a CNV. Biological process enrichment analysis indicated CNVs primarily affected genes involved in sensory perception, signal transduction, and metabolism. CNVs also were identified in genes regulating blood group antigens, coat color, fecundity, lactation, keratin formation, neuronal homeostasis, and height in other species. Collectively, these data are the first report of copy number variation in horses and suggest that CNVs are common in the horse genome and may modulate biological processes underlying different traits observed among horses and horse breeds.

  16. Numerical calculation of spatially variant anisotropic metamaterials (United States)

    Gulib, Asad Ullah Hil

    3D printing, or additive manufacturing, is rapidly evolving into a mainstream manufacturing technology that is creating new opportunities for electromagnetics and circuits. 3D printing permits circuits to fully utilize the third dimension allowing more functions in the same amount of space and allows the devices to have arbitrary form factors. 3D printing is letting us discover new physics that is not possible in standard 2D circuits and devices. However, evolving electromagnetics and circuits into three dimensions introduces some serious problems like thermal management, interference, and mutual coupling between the components which degrades performance and hurts signal integrity. Metamaterials are engineered composites that exhibit extreme electromagnetic properties and allow extraordinary control over electromagnetic fields. The EM Lab is developing spatially-variant anisotropic metamaterials (SVAMs) as a solution to mitigate mutual coupling between components. The concept of SVAMs is to electrically stretch the space between components to reduce mutual coupling. To do this, alternating layers of different dielectric must bisect adjacent components. However, the overall dielectric fill must also conform around dozens of electrical components and be smooth, continuous, and defect free. The research described here is the first prototype of an algorithm which generates a SVAM infill between all of the electrical components of a circuit in order to reduce the mutual coupling.

  17. Functional characterization of 21 allelic variants of dihydropyrimidinase. (United States)

    Hishinuma, Eiji; Akai, Fumika; Narita, Yoko; Maekawa, Masamitsu; Yamaguchi, Hiroaki; Mano, Nariyasu; Oda, Akifumi; Hirasawa, Noriyasu; Hiratsuka, Masahiro


    Dihydropyrimidinase (DHP, EC, encoded by the gene DPYS, is the second enzyme in the catabolic pathway of pyrimidine and of fluoropyrimidine drugs such as 5-fluorouracil, which are commonly used in anticancer treatment; DHP catalyzes the hydrolytic ring opening of dihydrouracil and dihydro-5-fluorouracil. DPYS mutations are known to contribute to interindividual variations in the toxicity of fluoropyrimidine drugs, but the functional characterization of DHP allelic variants remains inadequate. In this study, in vitro analysis was performed on 22 allelic variants of DHP by transiently expressing wild-type DHP and 21 DHP variants in 293FT cells and characterizing their enzymatic activities by using dihydrouracil and dihydro-5-fluorouracil as substrates. DHP expression levels and oligomeric forms were determined using immunoblotting and blue native PAGE, respectively, and the stability of the DHP variants was assessed by examining the proteins in variant-transfected cells treated with cycloheximide or bortezomib. Moreover, three kinetic parameters, Km, Vmax, and intrinsic clearance (Vmax/Km), for the hydrolysis of dihydrouracil and dihydro-5-fluorouracil were determined. We found that 5/21 variants showed significantly decreased intrinsic clearance as compared to wild-type DHP, and that 9/21 variants were expressed at low levels and were inactive due to proteasome-mediated degradation. The band patterns observed in the immunoblotting of blue native gels corresponded to DHP activity, and, notably, 18/21 DHP variants exhibited decreased or null enzymatic activity and these variants also showed a drastically reduced ability to form large oligomers. Thus, detection of DPYS genetic polymorphisms might facilitate the prediction severe adverse effects of fluoropyrimidine-based treatments. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Robust and Powerful Affected Sibpair Test for Rare Variant Association. (United States)

    Lin, Keng-Han; Zöllner, Sebastian


    Advances in DNA sequencing technology facilitate investigating the impact of rare variants on complex diseases. However, using a conventional case-control design, large samples are needed to capture enough rare variants to achieve sufficient power for testing the association between suspected loci and complex diseases. In such large samples, population stratification may easily cause spurious signals. One approach to overcome stratification is to use a family-based design. For rare variants, this strategy is especially appropriate, as power can be increased considerably by analyzing cases with affected relatives. We propose a novel framework for association testing in affected sibpairs by comparing the allele count of rare variants on chromosome regions shared identical by descent to the allele count of rare variants on nonshared chromosome regions, referred to as test for rare variant association with family-based internal control (TRAFIC). This design is generally robust to population stratification as cases and controls are matched within each sibpair. We evaluate the power analytically using general model for effect size of rare variants. For the same number of genotyped people, TRAFIC shows superior power over the conventional case-control study for variants with summed risk allele frequency f < 0.05; this power advantage is even more substantial when considering allelic heterogeneity. For complex models of gene-gene interaction, this power advantage depends on the direction of interaction and overall heritability. In sum, we introduce a new method for analyzing rare variants in affected sibpairs that is robust to population stratification, and provide freely available software. © 2015 WILEY PERIODICALS, INC.

  19. Hemoglobin Variants in Northern Thailand: Prevalence, Heterogeneity and Molecular Characteristics. (United States)

    Panyasai, Sitthichai; Fucharoen, Goonnapa; Fucharoen, Supan


    There are limited data on hemoglobin (Hb) variants among peoples of northern Thailand. Hence, we determined the prevalence of Hb variants among a large cohort from this region. A study was done on 23,914 subjects recruited from eight provinces during June 2012-January 2014. Hb was analyzed by high performance liquid chromatography (HPLC) and capillary electrophoresis, and corresponding mutations were identified by polymerase chain reaction. Among 23,914 subjects examined, 211 (0.88%) were found to carry 14 different Hb variants. Five α-globin chain variants were identified: Hb Q-Thailand (n = 40; 19.0%), Hb Hekinan (n = 8, 3.8%), Hb Siam (n = 2, 0.9%), Hb Beijing (n = 1, 0.5%), and Hb Kawachi (n = 1, 0.5%), not previously described in the Thai population. Seven β-globin variants, including Hb Hope, Hb Tak, Hb S, Hb J-Bangkok, Hb G-Makassar, Hb C, and Hb Korle-Bu, were found in 115 (54.5%), 30 (14.2%), 3 (1.4%), 3 (1.4%), 1 (0.5%), 1 (0.5%), and 1 (0.5%) subjects, respectively. The remaining five subjects (2.4%) were carriers of two different δ-globin chain variants. A different spectrum and frequencies of Hb variants were noted compared to other geographical areas. Haplotype analysis demonstrated multiple origins for Hbs Hope and Tak and confirmed a non-African origin of Hb C. Several genetic interactions between these variants with other hemoglobinopathies were encountered. Associated hematological phenotypes and novel Hb derivatives formed were presented. The prevalence and molecular heterogeneities of the Hb variants found in this large cohort of the northern Thai people's should prove useful in developing a screening program, and for the performance of additional population genetics studies of hemoglobinopathy in the region.

  20. Heat exchanger with oscillating flow (United States)

    Scotti, Stephen J. (Inventor); Blosser, Max L. (Inventor); Camarda, Charles J. (Inventor)


    Various heat exchange apparatuses are described in which an oscillating flow of primary coolant is used to dissipate an incident heat flux. The oscillating flow may be imparted by a reciprocating piston, a double action twin reciprocating piston, fluidic oscillators or electromagnetic pumps. The oscillating fluid flows through at least one conduit in either an open loop or a closed loop. A secondary flow of coolant may be used to flow over the outer walls of at least one conduit to remove heat transferred from the primary coolant to the walls of the conduit.

  1. Information exchanges in cournot duopolies

    Directory of Open Access Journals (Sweden)

    Faíña Medín J. Andrés


    Full Text Available In this paper we analyze the profitability of information sharing among Cournot oligopolists receiving private information about random demand. We model the random demand as a linear demand having, 1 an unknown intercept, and 2 an unknown slope. In each of these two scenarios, firms observe private signals about the unknown parameter. We show that in the scenario-1, if the private signal observed by firms is accurate enough, information exchange is profitable and in the scenario-2, if there is a sufficiently large variation in the demand slope and private signals are accurate enough, firms earn strictly higher profits by sharing their information rather than keeping it private.



    V. L. Dobin; V. G. Demikhov; M. P. Zharikova


    The review analyzes the major foreign publications on the iron exchange in mycobacteria for the recent years. The issues of iron absorption by tuberculous mycobacteria, its preservation and regulation of their metabolism have been reviewed. Deeper and more detail description of the above process will provide new opportunities for therapeutic interventions into it and assist in development of new tuberculosis treatment techniques.


    Directory of Open Access Journals (Sweden)

    V. L. Dobin


    Full Text Available The review analyzes the major foreign publications on the iron exchange in mycobacteria for the recent years. The issues of iron absorption by tuberculous mycobacteria, its preservation and regulation of their metabolism have been reviewed. Deeper and more detail description of the above process will provide new opportunities for therapeutic interventions into it and assist in development of new tuberculosis treatment techniques.

  4. EPR of exchange coupled systems

    CERN Document Server

    Bencini, Alessandro


    From chemistry to solid state physics to biology, the applications of Electron Paramagnetic Resonance (EPR) are relevant to many areas. This unified treatment is based on the spin Hamiltonian approach and makes extensive use of irreducible tensor techniques to analyze systems in which two or more spins are magnetically coupled. This edition contains a new Introduction by coauthor Dante Gatteschi, a pioneer and scholar of molecular magnetism.The first two chapters review the foundations of exchange interactions, followed by examinations of the spectra of pairs and clusters, relaxation in oligon

  5. Conformational analysis of HAMLET, the folding variant of human alpha-lactalbumin associated with apoptosis. (United States)

    Casbarra, Annarita; Birolo, Leila; Infusini, Giuseppe; Dal Piaz, Fabrizio; Svensson, Malin; Pucci, Piero; Svanborg, Catharina; Marino, Gennaro


    A combination of hydrogen/deuterium (H/D) exchange and limited proteolysis experiments coupled to mass spectrometry analysis was used to depict the conformation in solution of HAMLET, the folding variant of human alpha-lactalbumin, complexed to oleic acid, that induces apoptosis in tumor and immature cells. Although near- and far-UV CD and fluorescence spectroscopy were not able to discriminate between HAMLET and apo-alpha-lactalbumin, H/D exchange experiments clearly showed that they correspond to two distinct conformational states, with HAMLET incorporating a greater number of deuterium atoms than the apo and holo forms. Complementary proteolysis experiments revealed that HAMLET and apo are both accessible to proteases in the beta-domain but showed substantial differences in accessibility to proteases at specific sites. The overall results indicated that the conformational changes associated with the release of Ca2+ are not sufficient to induce the HAMLET conformation. Metal depletion might represent the first event to produce a partial unfolding in the beta-domain of alpha-lactalbumin, but some more unfolding is needed to generate the active conformation HAMLET, very likely allowing the protein to bind the C18:1 fatty acid moiety. On the basis of these data, a putative binding site of the oleic acid, which stabilizes the HAMLET conformation, is proposed.

  6. Identification of a novel alpha1-antitrypsin variant

    Directory of Open Access Journals (Sweden)

    Camille de Seynes


    We report the identification of a novel alpha1-antitrypsin variant in a 64-year old woman presenting with dyspnea on exertion. Imaging revealed bilateral bronchiectasis associated with moderate panacinar emphysema. The pulmonary function tests (PFTs were subnormal but hypoxemia was noticed and A1AT quantitative analysis revealed a severe deficiency. DNA sequencing showed compound heterozygosity for the PIZ variant and a novel missense variant p.Phe232Leu (p.Phe208Leu. No specific treatment was proposed since PFTs were within the normal range at this stage of the disease. Close follow-up of pulmonary and hepatic parameters was recommended.

  7. De Novo Coding Variants Are Strongly Associated with Tourette Disorder

    DEFF Research Database (Denmark)

    Willsey, A Jeremy; Fernandez, Thomas V; Yu, Dongmei


    Whole-exome sequencing (WES) and de novo variant detection have proven a powerful approach to gene discovery in complex neurodevelopmental disorders. We have completed WES of 325 Tourette disorder trios from the Tourette International Collaborative Genetics cohort and a replication sample of 186...... trios from the Tourette Syndrome Association International Consortium on Genetics (511 total). We observe strong and consistent evidence for the contribution of de novo likely gene-disrupting (LGD) variants (rate ratio [RR] 2.32, p = 0.002). Additionally, de novo damaging variants (LGD and probably...

  8. Variante de Dandy Walker: relato de caso = Dandy Walker variant: a case report

    Directory of Open Access Journals (Sweden)

    Khan, Richard Lester et al.


    Full Text Available Objetivos: relatar o caso de um paciente com variante de Dandy Walker, chamando atenção para a importância da suspeita, investigação e manejo das repercussões clínicas. Descrição do caso: é relatado o caso de um paciente do sexo masculino, com quadro clínico e radiológico típico da Variante de Dandy Walker. Durante o pré-natal, através de ecografia obstétrica com 23 semanas e 3 dias, apresentou alterações sugestivas de Síndrome de Dandy Walker. Ao nascimento apresentou exame físico com fenda palatina, criptorquidia à direita, hexodactilia em ambos os pés. Apresentava ainda ecocardiograma com forame oval patente e persistência do canal arterial. O diagnóstico foi estabelecido através da ressonância magnética realizada após o nascimento, que evidenciava hipoplasia do vermis cerebelar, alargamento da fossa posterior e leve dilatação ventricular. Conclusões: este artigo procura caracterizar a variante de Dandy Walker, que é uma malformação congênita do sistema nervoso central e é o tipo mais comum da Síndrome de Dandy Walker. Seu fenótipo é variável, devendo-se sempre pesquisar malformações tanto intra quanto extracranianas, visto que o risco de mortalidade pós-natal aumenta quando existe esta associação. O tratamento envolve equipe multidisciplinar e o prognóstico é reservado, variando conforme o fenótipo.

  9. Hierarchical generalized linear models for multiple groups of rare and common variants: jointly estimating group and individual-variant effects.

    Directory of Open Access Journals (Sweden)

    Nengjun Yi


    Full Text Available Complex diseases and traits are likely influenced by many common and rare genetic variants and environmental factors. Detecting disease susceptibility variants is a challenging task, especially when their frequencies are low and/or their effects are small or moderate. We propose here a comprehensive hierarchical generalized linear model framework for simultaneously analyzing multiple groups of rare and common variants and relevant covariates. The proposed hierarchical generalized linear models introduce a group effect and a genetic score (i.e., a linear combination of main-effect predictors for genetic variants for each group of variants, and jointly they estimate the group effects and the weights of the genetic scores. This framework includes various previous methods as special cases, and it can effectively deal with both risk and protective variants in a group and can simultaneously estimate the cumulative contribution of multiple variants and their relative importance. Our computational strategy is based on extending the standard procedure for fitting generalized linear models in the statistical software R to the proposed hierarchical models, leading to the development of stable and flexible tools. The methods are illustrated with sequence data in gene ANGPTL4 from the Dallas Heart Study. The performance of the proposed procedures is further assessed via simulation studies. The methods are implemented in a freely available R package BhGLM (

  10. Hierarchical generalized linear models for multiple groups of rare and common variants: jointly estimating group and individual-variant effects. (United States)

    Yi, Nengjun; Liu, Nianjun; Zhi, Degui; Li, Jun


    Complex diseases and traits are likely influenced by many common and rare genetic variants and environmental factors. Detecting disease susceptibility variants is a challenging task, especially when their frequencies are low and/or their effects are small or moderate. We propose here a comprehensive hierarchical generalized linear model framework for simultaneously analyzing multiple groups of rare and common variants and relevant covariates. The proposed hierarchical generalized linear models introduce a group effect and a genetic score (i.e., a linear combination of main-effect predictors for genetic variants) for each group of variants, and jointly they estimate the group effects and the weights of the genetic scores. This framework includes various previous methods as special cases, and it can effectively deal with both risk and protective variants in a group and can simultaneously estimate the cumulative contribution of multiple variants and their relative importance. Our computational strategy is based on extending the standard procedure for fitting generalized linear models in the statistical software R to the proposed hierarchical models, leading to the development of stable and flexible tools. The methods are illustrated with sequence data in gene ANGPTL4 from the Dallas Heart Study. The performance of the proposed procedures is further assessed via simulation studies. The methods are implemented in a freely available R package BhGLM (

  11. 31 CFR 515.325 - National securities exchange. (United States)


    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false National securities exchange. 515.325... Definitions § 515.325 National securities exchange. The term national securities exchange shall mean an exchange registered as a national securities exchange under section 6 of the Securities Exchange Act of...

  12. 31 CFR 500.325 - National securities exchange. (United States)


    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false National securities exchange. 500.325... Definitions § 500.325 National securities exchange. The term national securities exchange shall mean an exchange registered as a national securities exchange under section 6 of the Securities Exchange Act of...

  13. Inorganic ion exchangers for nuclear waste remediation

    Energy Technology Data Exchange (ETDEWEB)

    Clearfield, A.; Bortun, A.; Bortun, L.; Behrens, E. [Texas A& M Univ., College Station, TX (United States)


    The objective of this work is to provide a broad spectrum of inorganic ion exchangers that can be used for a range of applications and separations involving remediation of groundwater and tank wastes. The authors intend to scale-up the most promising exchangers, through partnership with AlliedSignal Inc., to provide samples for testing at various DOE sites. While much of the focus is on exchangers for removal of Cs{sup +} and Sr{sup 2+} from highly alkaline tank wastes, especially at Hanford, the authors have also synthesized exchangers for acid wastes, alkaline wastes, groundwater, and mercury, cobalt, and chromium removal. These exchangers are now available for use at DOE sites. Many of the ion exchangers described here are new, and others are improved versions of previously known exchangers. They are generally one of three types: (1) layered compounds, (2) framework or tunnel compounds, and (3) amorphous exchangers in which a gel exchanger is used to bind a fine powder into a bead for column use. Most of these exchangers can be regenerated and used again.

  14. How did China's foreign exchange reform affect the efficiency of foreign exchange market? (United States)

    Ning, Ye; Wang, Yiming; Su, Chi-wei


    This study compares the market efficiency of China's onshore and offshore foreign exchange markets before and after the foreign exchange reform on August 11, 2015. We use the multifractal detrended fluctuation analysis of the onshore and offshore RMB/USD spot exchange rate series as basis. We then find that the onshore foreign exchange market before the reform has the lowest market efficiency, which increased after the reform. The offshore foreign exchange market before the reform has the highest market efficiency, which dropped after the reform. This finding implies the increased efficiency of the onshore foreign exchange market and the loss of efficiency in the offshore foreign exchange market. We also find that the offshore foreign exchange market is more efficient than the onshore market and that the gap shrank after the reform. Changes in intervention of the People's Bank of China since the reform is a possible explanation for the changes in the efficiency of the foreign exchange market.

  15. Phase-exchange thermoacoustic engine (United States)

    Offner, Avshalom; Meir, Avishai; Ramon, Guy Z.; WET Lab Team


    Phase-exchange thermoacoustic engines are reliable machines holding great promise in converting heat from low grade heat sources to mechanical or electrical power. In these engines the working fluid is a gas mixture containing one condensable component, decreasing the temperature difference required for ignition and steady state operation. Our experimental setup consists of a vertical acoustic resonator containing a mixture of air-water vapor. Water evaporates near the heat source, condenses at the heat sink and is drawn back down by gravity and capillary forces where it re-evaporates, sustaining a steady state closed thermodynamic cycle. We investigated the stability limit, namely the critical point at which temperature difference in the engine enables onset of self-excited oscillations, and the steady state of the engine. A simple theoretical model was derived, describing mechanisms of irreversible entropy generation and production of acoustic power in such engines. This model captures the essence in the differences between regular and phase-exchange thermoacoustic engines, and shows good agreement with experimental results of stability limit. Steady state results reveal not only a dramatic decrease in temperature difference, but also an increase in engine performances. The authors acknowledge the support from the Nancy and Stephen Grand Technion Energy Program (GTEP).

  16. Dipole-induced exchange bias. (United States)

    Torres, Felipe; Morales, Rafael; Schuller, Ivan K; Kiwi, Miguel


    The discovery of dipole-induced exchange bias (EB), switching from negative to positive sign, is reported in systems where the antiferromagnet and the ferromagnet are separated by a paramagnetic spacer (AFM-PM-FM). The magnitude and sign of the EB is determined by the cooling field strength and the PM thickness. The same cooling field yields negative EB for thin spacers, and positive EB for thicker ones. The EB decay profile as a function of the spacer thickness, and the change of sign, are attributed to long-ranged dipole coupling. Our model, which accounts quantitatively for the experimental results, ignores the short range interfacial exchange interactions of the usual EB theories. Instead, it retains solely the long range dipole field that allows for the coupling of the FM and AFM across the PM spacer. The experiments allow for novel switching capabilities of long range EB systems, while the theory allows description of the structures where the FM and AFM are not in atomic contact. The results provide a new approach to design novel interacting heterostructures.

  17. Exchange of astronomy teaching experiences (United States)

    Ros, Rosa M.

    The Working Group of the European Association for Astronomy Education responsible for Teacher Training organises an annual Summer School for teachers under expert guidance. For a week the teachers participating can exchange experiences, increase their knowledge and discuss different ideas and perspectives. In general, the instructors are professional astronomers, professors and teachers from different countries. The papers presented offer very practical activities, paying special attention to didactic aspects, and take the form of general lectures to all 40 participants and workshops to reduced groups of 20 participants. There are also day and night observations, without expensive equipment or complicated procedures, that are easy to set up and based on topics that it is possible to use in the classroom. The Summer Schools promote a scientific astronomical education at all levels of astronomy teaching, reinforce the link between professional astronomers and teachers with experience of teaching astronomy, allow debates among the participants on their pedagogical activities already carried out in their own classroom and help them to organise activities outside it. Astronomy teachers need special training, access to specific research, to new educational materials and methods and the opportunity to exchange experiences. All these things are provided by the Summer School.

  18. Three-dimensional spatial analysis of missense variants in RTEL1 identifies pathogenic variants in patients with Familial Interstitial Pneumonia. (United States)

    Sivley, R Michael; Sheehan, Jonathan H; Kropski, Jonathan A; Cogan, Joy; Blackwell, Timothy S; Phillips, John A; Bush, William S; Meiler, Jens; Capra, John A


    Next-generation sequencing of individuals with genetic diseases often detects candidate rare variants in numerous genes, but determining which are causal remains challenging. We hypothesized that the spatial distribution of missense variants in protein structures contains information about function and pathogenicity that can help prioritize variants of unknown significance (VUS) and elucidate the structural mechanisms leading to disease. To illustrate this approach in a clinical application, we analyzed 13 candidate missense variants in regulator of telomere elongation helicase 1 (RTEL1) identified in patients with Familial Interstitial Pneumonia (FIP). We curated pathogenic and neutral RTEL1 variants from the literature and public databases. We then used homology modeling to construct a 3D structural model of RTEL1 and mapped known variants into this structure. We next developed a pathogenicity prediction algorithm based on proximity to known disease causing and neutral variants and evaluated its performance with leave-one-out cross-validation. We further validated our predictions with segregation analyses, telomere lengths, and mutagenesis data from the homologous XPD protein. Our algorithm for classifying RTEL1 VUS based on spatial proximity to pathogenic and neutral variation accurately distinguished 7 known pathogenic from 29 neutral variants (ROC AUC = 0.85) in the N-terminal domains of RTEL1. Pathogenic proximity scores were also significantly correlated with effects on ATPase activity (Pearson r = -0.65, p = 0.0004) in XPD, a related helicase. Applying the algorithm to 13 VUS identified from sequencing of RTEL1 from patients predicted five out of six disease-segregating VUS to be pathogenic. We provide structural hypotheses regarding how these mutations may disrupt RTEL1 ATPase and helicase function. Spatial analysis of missense variation accurately classified candidate VUS in RTEL1 and suggests how such variants cause disease. Incorporating

  19. Myostatin: genetic variants, therapy and gene doping

    Directory of Open Access Journals (Sweden)

    André Katayama Yamada


    Full Text Available Since its discovery, myostatin (MSTN has been at the forefront of muscle therapy research because intrinsic mutations or inhibition of this protein, by either pharmacological or genetic means, result in muscle hypertrophy and hyperplasia. In addition to muscle growth, MSTN inhibition potentially disturbs connective tissue, leads to strength modulation, facilitates myoblast transplantation, promotes tissue regeneration, induces adipose tissue thermogenesis and increases muscle oxidative phenotype. It is also known that current advances in gene therapy have an impact on sports because of the illicit use of such methods. However, the adverse effects of these methods, their impact on athletic performance in humans and the means of detecting gene doping are as yet unknown. The aim of the present review is to discuss biosynthesis, genetic variants, pharmacological/genetic manipulation, doping and athletic performance in relation to the MSTN pathway. As will be concluded from the manuscript, MSTN emerges as a promising molecule for combating muscle wasting diseases and for triggering wide-ranging discussion in view of its possible use in gene doping.Desde sua descoberta, a miostatina (MSTN entrou na linha de frente em pesquisas relacionadas às terapias musculares porque mutações intrínsecas ou inibição desta proteína tanto por abordagens farmacológicas como genéticas resultam em hipertrofia muscular e hiperplasia. Além do aumento da massa muscular, a inibição de MSTN potencialmente prejudica o tecido conectivo, modula a força muscular, facilita o transplante de mioblastos, promove regeneração tecidual, induz termogênese no tecido adiposo e aumenta a oxidação na musculatura esquelética. É também sabido que os atuais avanços em terapia gênica têm uma relação com o esporte devido ao uso ilícito de tal método. Os efeitos adversos de tal abordagem, seus efeitos no desempenho de atletas e métodos para detectar doping genético s

  20. Two variants of minimum discarded fill ordering

    Energy Technology Data Exchange (ETDEWEB)

    D' Azevedo, E.F. (Oak Ridge National Lab., TN (USA)); Forsyth, P.A.; Tang, Wei-Pai (Waterloo Univ., ON (Canada). Dept. of Computer Science)


    It is well known that the ordering of the unknowns can have a significant effect on the convergence of Preconditioned Conjugate Gradient (PCG) methods. There has been considerable experimental work on the effects of ordering for regular finite difference problems. In many cases, good results have been obtained with preconditioners based on diagonal, spiral or natural row orderings. However, for finite element problems having unstructured grids or grids generated by a local refinement approach, it is difficult to define many of the orderings for more regular problems. A recently proposed Minimum Discarded Fill (MDF) ordering technique is effective in finding high quality Incomplete LU (ILU) preconditioners, especially for problems arising from unstructured finite element grids. Testing indicates this algorithm can identify a rather complicated physical structure in an anisotropic problem and orders the unknowns in the preferred'' direction. The MDF technique may be viewed as the numerical analogue of the minimum deficiency algorithm in sparse matrix technology. At any stage of the partial elimination, the MDF technique chooses the next pivot node so as to minimize the amount of discarded fill. In this work, two efficient variants of the MDF technique are explored to produce cost-effective high-order ILU preconditioners. The Threshold MDF orderings combine MDF ideas with drop tolerance techniques to identify the sparsity pattern in the ILU preconditioners. These techniques identify an ordering that encourages fast decay of the entries in the ILU factorization. The Minimum Update Matrix (MUM) ordering technique is a simplification of the MDF ordering and is closely related to the minimum degree algorithm. The MUM ordering is especially for large problems arising from Navier-Stokes problems. Some interesting pictures of the orderings are presented using a visualization tool. 22 refs., 4 figs., 7 tabs.

  1. DHE (downhole heat exchangers). [Downhole Heat Exchangers (DHE)

    Energy Technology Data Exchange (ETDEWEB)

    Culver, G.


    The use of downhole heat exchangers (DHE) for residential or commercial space and domestic water heating and other applications has several desirable features. Systems are nearly or completely passive -- that is, no or very little geothermal water or steam is produced from the well either reducing or completely eliminating surface environmental concerns and the need for disposal systems or injection wells. Initial cost of pumps and installation are eliminated or reduced along with pumping power costs and maintenance costs associated with pumping often corrosive geothermal fluids. Many residential and small commercial systems do not require circulating pumps because the density difference in the incoming and outgoing sides of the loop are sufficient to overcome circulating friction losses in the entire system. The major disadvantage of DHEs is their dependence on natural heat flow. In areas where geological conditions provide high permeability and a natural hydraulic gradient, DHEs can provide a substantial quantity of heat. A single 500-ft (152 m) well in Klamath Falls, Oregon, supplies over one megawatt thermal and output is apparently limited by the surface area of pipe that can be installed in the well bore. In contrast, DHEs used in conjunction with heat pumps may supply less than 8 KW from a well of similar depth. Here output is limited by conductive heat flow with perhaps a small contribution from convection near the well bore. The highest capacity DHE reported to date, in Turkey, supplies 6 MW thermal from an 820-ft (250 m) well. There were two main goals for this project. The first was to gather, disseminate and exchange internationally information on DHES. The second was to perform experiments that would provide insight into well bore/aquifer interaction and thereby provide more information on which to base DHE designs. 27 refs., 31 figs., 3 tabs.

  2. Structure of chymotrypsin variant B from Atlantic cod, Gadus morhua

    DEFF Research Database (Denmark)

    Leth-Larsen, Rikke; Asgeirsson, B; Thórólfsson, M


    The amino-acid sequence of chymotrypsin variant B isolated from the pyloric caeca of Atlantic cod has been elucidated. The characterization of the primary structure is based on N-terminal Edman degradation and mass spectrometry of the native protein and enzymatically derived peptides. Chymotrypsin...... variant B showed 72% sequence identity with the A-variant and 64% and 62%, respectively, with the bovine counterparts A and B, all consisting of 245 amino acids. This new sequence contains a higher proportion of charged residues compared with bovine chymotrypsin but fewer polar hydrogen-bond forming...... side-chains may contribute to the maintenance of flexibility at low temperatures. Several amino-acid sequence differences adjacent to the catalytic site are observed in the two cod chymotrypsin variants which also differ in kinetic properties. Unlike the mammalian chymotrypsins, which contain several...

  3. Common Gene Variants Account for Most Genetic Risk for Autism (United States)

    ... gene variants account for most genetic risk for autism Roles of heritability, mutations, environment estimated – NIH-funded study. The bulk of risk, or liability, for autism spectrum disorders (ASD) was traced to inherited variations ...

  4. Infectious Bronchitis Virus Variants: Molecular Analysis and Pathogenicity Investigation

    Directory of Open Access Journals (Sweden)

    Shu-Yi Lin


    Full Text Available Infectious bronchitis virus (IBV variants constantly emerge and pose economic threats to poultry farms worldwide. Numerous studies on the molecular and pathogenic characterization of IBV variants have been performed between 2007 and 2017, which we have reviewed herein. We noted that viral genetic mutations and recombination events commonly gave rise to distinct IBV genotypes, serotypes and pathotypes. In addition to characterizing the S1 genes, full viral genomic sequencing, comprehensive antigenicity, and pathogenicity studies on emerging variants have advanced our understanding of IBV infections, which is valuable for developing countermeasures against IBV field outbreaks. This review of IBV variants provides practical value for understanding their phylogenetic relationships and epidemiology from both regional and worldwide viewpoints.

  5. cyvcf2: fast, flexible variant analysis with Python. (United States)

    Pedersen, Brent S; Quinlan, Aaron R


    Variant call format (VCF) files document the genetic variation observed after DNA sequencing, alignment and variant calling of a sample cohort. Given the complexity of the VCF format as well as the diverse variant annotations and genotype metadata, there is a need for fast, flexible methods enabling intuitive analysis of the variant data within VCF and BCF files. We introduce cyvcf2 , a Python library and software package for fast parsing and querying of VCF and BCF files and illustrate its speed, simplicity and utility. or cyvcf2 is available from under the MIT license and from common python package managers. Detailed documentation is available at

  6. Genotype and phenotype spectrum of NRAS germline variants

    NARCIS (Netherlands)

    Altmuller, F.; Lissewski, C.; Bertola, D.; Flex, E.; Stark, Z.; Spranger, S.; Baynam, G.; Buscarilli, M.; Dyack, S.; Gillis, J.; Yntema, H.G.; Pantaleoni, F.; Loon, R.L. van; MacKay, S.; Mina, K.; Schanze, I.; Tan, T.Y.; Walsh, M.; White, S.M.; Niewisch, M.R.; Garcia-Minaur, S.; Plaza, D.; Ahmadian, M.R.; Cave, H.; Tartaglia, M.; Zenker, M.


    RASopathies comprise a group of disorders clinically characterized by short stature, heart defects, facial dysmorphism, and varying degrees of intellectual disability and cancer predisposition. They are caused by germline variants in genes encoding key components or modulators of the highly

  7. Genotype and phenotype spectrum of NRAS germline variants

    National Research Council Canada - National Science Library

    Altmuller, F; Lissewski, C; Bertola, D; Flex, E; Stark, Z; Spranger, S; Baynam, G; Buscarilli, M; Dyack, S; Gillis, J; Yntema, H.G; Pantaleoni, F; Loon, R.L. van; MacKay, S; Mina, K; Schanze, I; Tan, T.Y; Walsh, M; White, S.M; Niewisch, M.R; Garcia-Minaur, S; Plaza, D; Ahmadian, M.R; Cave, H; Tartaglia, M; Zenker, M


    .... Germline changes in the genes encoding members of the RAS subfamily of GTPases are rare and associated with variable phenotypes of the RASopathy spectrum, ranging from Costello syndrome (HRAS variants...

  8. variant formula for predicting peak expiratory flow rate in pregnant ...

    African Journals Online (AJOL)


    Accepted: November, 2009. VARIANT FORMULA FOR PREDICTING PEAK EXPIRATORY FLOW RATE IN. PREGNANT WOMEN IN KURA LOCAL GOVERNMENT AREA, KANO STATE,. NIGERIA. A. I. Salisu. Department of Human Physiology, Faculty of Medicine, Bayero University, Kano;.

  9. Leapfrog variants of iterative methods for linear algebra equations (United States)

    Saylor, Paul E.


    Two iterative methods are considered, Richardson's method and a general second order method. For both methods, a variant of the method is derived for which only even numbered iterates are computed. The variant is called a leapfrog method. Comparisons between the conventional form of the methods and the leapfrog form are made under the assumption that the number of unknowns is large. In the case of Richardson's method, it is possible to express the final iterate in terms of only the initial approximation, a variant of the iteration called the grand-leap method. In the case of the grand-leap variant, a set of parameters is required. An algorithm is presented to compute these parameters that is related to algorithms to compute the weights and abscissas for Gaussian quadrature. General algorithms to implement the leapfrog and grand-leap methods are presented. Algorithms for the important special case of the Chebyshev method are also given.

  10. HD-CNV: hotspot detector for copy number variants

    National Research Council Canada - National Science Library

    Butler, Jenna L; Osborne Locke, Marjorie Elizabeth; Hill, Kathleen A; Daley, Mark


    ... (hotspot detector for copy number variants) is a tool for downstream analysis of previously identified CNV regions from multiple samples, and it detects recurrent regions by finding cliques in an interval graph generated from the input...

  11. vipR: variant identification in pooled DNA using R

    National Research Council Canada - National Science Library

    Altmann, Andre; Weber, Peter; Quast, Carina; Rex-Haffner, Monika; Binder, Elisabeth B; Müller-Myhsok, Bertram


    .... Thus, recently, screens for rare sequence variants were carried out in samples of pooled DNA, in which equimolar amounts of DNA from multiple individuals are mixed prior to sequencing with HTS...

  12. Method of generating ploynucleotides encoding enhanced folding variants

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, Andrew M.; Kiss, Csaba; Waldo, Geoffrey S.


    The invention provides directed evolution methods for improving the folding, solubility and stability (including thermostability) characteristics of polypeptides. In one aspect, the invention provides a method for generating folding and stability-enhanced variants of proteins, including but not limited to fluorescent proteins, chromophoric proteins and enzymes. In another aspect, the invention provides methods for generating thermostable variants of a target protein or polypeptide via an internal destabilization baiting strategy. Internally destabilization a protein of interest is achieved by inserting a heterologous, folding-destabilizing sequence (folding interference domain) within DNA encoding the protein of interest, evolving the protein sequences adjacent to the heterologous insertion to overcome the destabilization (using any number of mutagenesis methods), thereby creating a library of variants. The variants in the library are expressed, and those with enhanced folding characteristics selected.

  13. Anatomic variant of the median nerve in the carpal tunnel. (United States)

    Steinberg, E L; Luger, E; Taitz, C; Arensburg, B


    Forty-six hands of 23 cadavers (15 female and 8 male) were dissected to observe the patterns of distribution of the median nerve. The findings showed that in 33 hands the median nerve had a normal distribution of its branches. Also identified was the commonly recognized transligamentous variant, where the recurrent branch pierces the carpal ligament 2 to 4 mm proximal to the distal end of the carpal tunel. This latter variant occurred in 13 hands. The current study focused on the presence of an additional variant, not previously identified, that occurred in 10 hands. This branch, considered sensory, was approximately 1 mm wide and pierced the lateral carpal ligament 3 to 6 mm distal to the proximal edge of the tunnel. The importance of recognition of variants of median nerve distribution in surgery of the carpal tunnel is emphasized.

  14. Pharyngeal-Cervical-Brachial Variant of Guillain-Barre Syndrome


    J Gordon Millichap; John J Millichap


    Investigators from National University Hospital, Singapore, review the clinical features of 13 cases of pharyngeal-cervical-brachial (PCB) variant of Guillain-Barre syndrome (GBS) and outline new diagnostic criteria.

  15. Disintegrating perineal disease: A variant of watering-can perineum


    N. Abrol; Devasia, A.


    Watering-can perineum is a known complication of inflammatory urethral stricture disease. We report a case of disintegrating perineal disease, a fulminant variant of watering-can perineum, in an immunocompetent patient.

  16. Genetic variant as a marker for bladder cancer therapy (United States)

    Patients who have inherited a specific common genetic variant develop bladder cancer tumors that strongly express a protein known as prostate stem cell antigen (PSCA), which is also expressed in many pancreatic and prostate tumors, according to research a

  17. Association of Genetic Variants of Milk Proteins with Milk Production ...

    African Journals Online (AJOL)


    Aschaffenburg & Drewry,. 1955; 1957) researchers have become interested in the genetic polymorphism of milk proteins. It is known today that there are at least 39 genetic variants of six milk protein fractions (Eigel et al., 1984; Bouniol et al.,.

  18. Detection of combined genomic variants in a Jordanian family with ...

    Indian Academy of Sciences (India)

    TSHR) gene was performed by direct sequencing of genomic DNA extracted from peripheral blood leukocytes of all family members. The sequence analysis of all TSHR gene exons and intron borders revealed two genomic variants. The first ...

  19. Variant Plasmodium ovale isolated from a patient infected in Ghana

    Directory of Open Access Journals (Sweden)

    Petersen Eskild


    Full Text Available Abstract Recent data have found that Plasmodium ovale can be separated in two distinct species: classic and variant P. ovale based on multilocus typing of different genes. This study presents a P. ovale isolate from a patient infected in Ghana together with an analysis of the small subunit RNA, cytochrome b, cytochrome c oxidase I, cysteine protease and lactate dehydrogenase genes, which show that the sample is a variant P. ovale and identical or highly similar to variant P. ovale isolated from humans in South-East Asia and Africa, and from a chimpanzee in Cameroon. The split between the variant and classic P. ovale is estimated to have occurred 1.7 million years ago.

  20. Investigating the effects of liquidity and exchange rate on Tehran Stock Exchange

    Directory of Open Access Journals (Sweden)

    Younos Vakil Alroaia


    Full Text Available This paper presents an empirical investigation to study the effects of two macroeconomic factors; namely exchange rate and liquidity on stock index. The proposed study was applied in Iran and on major index of Tehran Stock Exchange over the period 2001-2011. They reported that the currency exchange maintained negative impact on stock exchange for the period of investigation. This is due to the fact that when currency devalued, working capital decreases and firms did not enough money to purchase raw materials, pay wages, etc. In addition, liquidity marinated a direct and positive relationship with exchange index. However, the impact of liquidity seems to be bigger than currency exchange.

  1. Prevalence of Titin Truncating Variants in General Population.

    Directory of Open Access Journals (Sweden)

    Oyediran Akinrinade

    Full Text Available Truncating titin (TTN mutations, especially in A-band region, represent the most common cause of dilated cardiomyopathy (DCM. Clinical interpretation of these variants can be challenging, as these variants are also present in reference populations. We carried out systematic analyses of TTN truncating variants (TTNtv in publicly available reference populations, including, for the first time, data from Exome Aggregation Consortium (ExAC. The goal was to establish more accurate estimate of prevalence of different TTNtv to allow better clinical interpretation of these findings.Using data from 1000 Genomes Project, Exome Sequencing Project (ESP and ExAC, we estimated the prevalence of TTNtv in the population. In the three population datasets, 52-54% of TTNtv were not affecting all TTN transcripts. The frequency of truncations affecting all transcripts in ExAC was 0.36% (0.32% - 0.41%, 95% CI and 0.19% (0.16% - 0.23%, 95% CI for those affecting the A-band. In the A-band region, the prevalences of frameshift, nonsense and essential splice site variants were 0.057%, 0.090%, and 0.047% respectively. Cga/Tga (arginine/nonsense-R/* transitional change at CpG mutation hotspots was the most frequent type of TTN nonsense mutation accounting for 91.3% (21/23 of arginine residue nonsense mutation (R/* at TTN A-band region. Non-essential splice-site variants had significantly lower proportion of private variants and higher proportion of low-frequency variants compared to essential splice-site variants (P = 0.01; P = 5.1 X 10-4, respectively.A-band TTNtv are more rare in the general population than previously reported. Based on this analysis, one in 500 carries a truncation in TTN A-band suggesting the penetrance of these potentially harmful variants is still poorly understood, and some of these variants do not manifest as autosomal dominant DCM. This calls for caution when interpreting TTNtv in individuals and families with no history of DCM. Considering the

  2. Needs Assessment for Exchange Students in Taiwan

    Directory of Open Access Journals (Sweden)

    Kentei Takaya


    Full Text Available With the growing mobility of international students in Asia and the Pacific, Taiwan has become actively involved in promoting international academic exchange. This research investigates the experience of exchange students from the Philippines and mainland China and examines their needs while studying in Taiwan. Qualitative in-depth interviews were conducted with exchange students from the Philippines and mainland China. The findings suggest that while exchange students from the Philippines and mainland China both encountered difficulties during their study in Taiwan, exchange students from the Philippines were inclined to encounter more difficulties compared to those from mainland China due to language difficulties. Based on the findings of this study, suggested support services for future exchange students in Taiwan are outlined to match the needs of students from both Chinese and non-Chinese-speaking backgrounds.

  3. Listening to agent agendas in student exchanges

    DEFF Research Database (Denmark)

    Tarp, Gertrud


    The paper is based upon a research study of short-term student exchanges. The study took place from 1996-2000, and comprises seven classes of students from six Danish business schools. Short-term student exchanges in terms of EU funded exchanges and local school exchanges are means to develop...... the students’ understanding of their own cultural background and of foreign cultures. The research study is an attempt to look at internationalisation and student exchanges from a student perspective. Thus the structural aim and the structural framework are considered given elements. The study is based upon...... institutional scepticism and placed within the theoretical framework of symbolic interactionism. The methodology applied is qualitative, grounded theory, and the data originate from diaries, semi-structured interviews and semi-open questionnaires. The findings show that the students have their own exchange...

  4. Androgen Receptor Splice Variants and Resistance to Taxane Chemotherapy (United States)


    AWARD NUMBER: W81XWH-14-1-0480 TITLE: Androgen Receptor Splice Variants and Resistance to Taxane Chemotherapy PRINCIPAL INVESTIGATOR...Splice Variants and Resistance to Taxane Chemotherapy 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0480 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...During this reporting period, we have obtained approval for a no-cost extension of this award and change of research focus in the final year. This

  5. HIV-1 genetic variants in the Russian Far East. (United States)

    Kazennova, Elena; Laga, Vita; Lapovok, Ilya; Glushchenko, Nataliya; Neshumaev, Dmitry; Vasilyev, Alexander; Bobkova, Marina


    A molecular analysis of HIV-1 subtypes and recombinants circulating in cities in the Russian Far East was performed. The study included samples from 201 outpatients from Vladivostok, Khabarovsk, and Blagoveshchensk. In most parts of Russia, patients are infected with HIV-1 subtype A, known as the IDU-A variant. Subtype B, including the IDU-B variant, is rare in Russia but widespread in the Ukraine, and the CRF02_AG is prevalent in Central Asian countries and Siberia, Russia. One of the challenges of this study in the Far East was to determine whether the molecular landscape of HIV infection in this region is influenced by the bordering countries, including China and Japan, where a distinct set of HIV subtypes is circulating, such as B', C, and CRF01_AE. The distribution of HIV-1 genetic variants in the cities studied was as follows: subtype A (IDU-A), 55.7%; subtype B, 25.3% (IDU-B variant-24.3%); subtype C, 10.0%; CRF02_AG, 1.5%; and CRF63_02A1, 7.5%. A phylogenetic analysis confirmed the relationship of subtype A viruses with the IDU-A variant predominating in Ukraine, Russia and other former Soviet Union (FSU) countries, of subtype B viruses with IDU-B in the Ukraine and of CRF02_AG variants with variants in Uzbekistan, Russia, and other former USSR countries. Subtype C sequences were not uniform, and most clustered between each other and HIV-1 sequences originating from Africa; there was only one sample possibly related to Chinese variants. Thus, despite close cultural and commercial relationships among Russia, China, and Japan, the distribution of HIV-1 subtypes in the Russian Far East is still primarily influenced by contacts with the countries of the former USSR.

  6. Histone variant innovation in a rapidly evolving chordate lineage

    Directory of Open Access Journals (Sweden)

    Jansen Pascal WTC


    Full Text Available Abstract Background Histone variants alter the composition of nucleosomes and play crucial roles in transcription, chromosome segregation, DNA repair, and sperm compaction. Modification of metazoan histone variant lineages occurs on a background of genome architecture that shows global similarities from sponges to vertebrates, but the urochordate, Oikopleura dioica, a member of the sister group to vertebrates, exhibits profound modification of this ancestral architecture. Results We show that a histone complement of 47 gene loci encodes 31 histone variants, grouped in distinct sets of developmental expression profiles throughout the life cycle. A particularly diverse array of 15 male-specific histone variants was uncovered, including a testes-specific H4t, the first metazoan H4 sequence variant reported. Universal histone variants H3.3, CenH3, and H2A.Z are present but O. dioica lacks homologs of macroH2A and H2AX. The genome encodes many H2A and H2B variants and the repertoire of H2A.Z isoforms is expanded through alternative splicing, incrementally regulating the number of acetylatable lysine residues in the functionally important N-terminal "charge patch". Mass spectrometry identified 40 acetylation, methylation and ubiquitylation posttranslational modifications (PTMs and showed that hallmark PTMs of "active" and "repressive" chromatin were present in O. dioica. No obvious reduction in silent heterochromatic marks was observed despite high gene density in this extraordinarily compacted chordate genome. Conclusions These results show that histone gene complements and their organization differ considerably even over modest phylogenetic distances. Substantial innovation among all core and linker histone variants has evolved in concert with adaptation of specific life history traits in this rapidly evolving chordate lineage.

  7. Stress Induced Cardiomyopathy with Midventricular Ballooning: A Rare Variant


    Muhammad Umer Siddiqui; Michael C. Desiderio; Nicholas Ricculli; Arthur Rusovici


    Stress cardiomyopathy (SCM) also referred to as the ?broken heart syndrome? is a condition in which intense emotional or physical stress can cause fulminant and reversible cardiac muscle weakness. SCM most commonly involves the apical segment of left ventricle but newer and rare variants have recently been seen reported. We here report a case of rare midventricular variant of stress related cardiomyopathy. A 72-year-old female with past medical history, only significant for SVT, presented wit...

  8. Development and Testing of a Refractory Millimeter-Wave Absorbent Heat Exchanger (United States)

    Lambot, Thomas; Myrabo, Leik; Murakami, David; Parkin, Kevin


    Central to the Millimeter-Wave Thermal Launch System (MTLS) is the millimeter-wave absorbent heat exchanger. We have developed metallic and ceramic variants, with the key challenge being the millimeter-wave absorbent coatings for each. The ceramic heat exchanger came to fruition first, demonstrating for the first time 1800 K peak surface temperatures under illumination by a 110 GHz Gaussian beam. Absorption efficiencies of up to 80 are calculated for mullite heat exchanger tubes and up to 50 are calculated for alumina tubes. These are compared with estimates based on stratified layer and finite element analyses. The problem of how to connect the 1800 K end of the ceramic tubes to a graphite outlet manifold and nozzle is solved by press fitting, or by threading the ends of the ceramic tubes and screwing them into place. The problem of how to connect the ceramic tubes to a metallic or nylon inlet pipe is solved by using soft compliant PTFE and PVC tubes that accommodate thermal deformations of the ceramic tubes during startup and operation. We show the resulting heat exchangers in static tests using argon and helium as propellants.

  9. Incentives and Information Exchange in International Taxation


    Keen, M.; Ligthart, J.E.


    The exchange of taxpayer-specific information between national tax authorities has recently emerged as a key and controversial topic in international tax policy discussions, most notably with the OECD s harmful tax practices project and the EU s savings tax initiative.This paper analyses the effects of information exchange and withholding taxes, recognizing that countries which agree to exchange information do not forfeit the ability to levy withholding taxes, and also focusing in particular ...

  10. Development of nursing students during international exchange


    Varusk, Inge


    The purpose of the study was to gather information about the experiences which nursing exchange students have had when they have been abroad. This aim of this literature review was to evaluates and presents the most current and relevant information of the topic as possible. The findings were divided into two themes – how nursing exchange students had evolved on a personal and on a professional level. Most of the findings were about how the nursing exchange students had evolved on a person...

  11. [Plasma exchange in nephrology: Indications and technique]. (United States)

    Ridel, Christophe; Kissling, Sébastien; Mesnard, Laurent; Hertig, Alexandre; Rondeau, Éric


    Plasma exchange is a non-selective apheresis technique that can be performed by filtration or centrifugation allowing rapid purification of high molecular weight pathogens. An immunosuppressive treatment is generally associated to reduce the rebound effect of the purified substance. Substitution solutes such as human albumin and macromolecules are needed to compensate for plasma extraction. Compensation by viro-attenuated plasma is reserved solely for the treatment of thrombotic microangiopathies or when there is a risk of bleeding, because this product is very allergenic and expensive. The treatment goal for a plasma exchange session should be between one and one and one-half times the patient's plasma volume estimated at 40 mL/kg body weight. The anticoagulation is best ensured by the citrate. Complications of plasma exchange are quite rare according to the French hemapheresis registry. The level of evidence of efficacy of plasma exchange in nephrology varies from one pathology to another. Main indications of plasma exchange in nephrology are Goodpasture syndrome, antineutrophil cytoplasmic antibody vasculitis when plasma creatinine is greater than 500 μmol/L, and thrombotic microangiopathies. During renal transplantation, plasma exchange may be proposed in the context of human leukocyte antigen (HLA) desensitization protocols or ABO-incompatible graft. After renal transplantation, plasma exchange is indicated as part of the treatment of acute humoral rejection or recurrent focal segmental glomerulosclerosis on the graft. Plasma exchanges are also proposed in the management of cryoglobulinemia or polyarteritis nodosa. Hemodialysis with membranes of very high permeability tends to replace plasma exchange for myeloma nephropathy. The benefit from plasma exchange has not been formally demonstrated for the treatment of severe lupus or antiphospholipid antibody syndrome. There is no indication of plasma exchange in the treatment of scleroderma or nephrogenic

  12. Electric control of exchange bias training. (United States)

    Echtenkamp, W; Binek, Ch


    Voltage-controlled exchange bias training and tunability are introduced. Isothermal voltage pulses are used to reverse the antiferromagnetic order parameter of magnetoelectric Cr(2)O(3), and thus continuously tune the exchange bias of an adjacent CoPd film. Voltage-controlled exchange bias training is initialized by tuning the antiferromagnetic interface into a nonequilibrium state incommensurate with the underlying bulk. Interpretation of these hitherto unreported effects contributes to new understanding in electrically controlled magnetism.

  13. China: Exchange Rate Policy and Asian Trade


    Alicia García-Herrero; Tuuli Koivu


    This paper shows empirically that China s trade balance is sensitive to fluctuations in the renminbi real effective exchange rate. However, the current size of the trade surplus is such that exchange rate policy, alone, will probably not be able to address the imbalance. The reduction in the trade surplus is limited mainly because Chinese imports do not react as expected to exchange rate appreciation. In fact, they tend to fall rather than increase. By estimating bilateral import equations fo...

  14. Variants affecting exon skipping contribute to complex traits.

    Directory of Open Access Journals (Sweden)

    Younghee Lee

    Full Text Available DNA variants that affect alternative splicing and the relative quantities of different gene transcripts have been shown to be risk alleles for some Mendelian diseases. However, for complex traits characterized by a low odds ratio for any single contributing variant, very few studies have investigated the contribution of splicing variants. The overarching goal of this study is to discover and characterize the role that variants affecting alternative splicing may play in the genetic etiology of complex traits, which include a significant number of the common human diseases. Specifically, we hypothesize that single nucleotide polymorphisms (SNPs in splicing regulatory elements can be characterized in silico to identify variants affecting splicing, and that these variants may contribute to the etiology of complex diseases as well as the inter-individual variability in the ratios of alternative transcripts. We leverage high-throughput expression profiling to 1 experimentally validate our in silico predictions of skipped exons and 2 characterize the molecular role of intronic genetic variations in alternative splicing events in the context of complex human traits and diseases. We propose that intronic SNPs play a role as genetic regulators within splicing regulatory elements and show that their associated exon skipping events can affect protein domains and structure. We find that SNPs we would predict to affect exon skipping are enriched among the set of SNPs reported to be associated with complex human traits.

  15. Prebiotic Competition between Information Variants, With Low Error Catastrophe Risks

    Directory of Open Access Journals (Sweden)

    Radu Popa


    Full Text Available During competition for resources in primitive networks increased fitness of an information variant does not necessarily equate with successful elimination of its competitors. If variability is added fast to a system, speedy replacement of pre-existing and less-efficient forms of order is required as novel information variants arrive. Otherwise, the information capacity of the system fills up with information variants (an effect referred as “error catastrophe”. As the cost for managing the system’s exceeding complexity increases, the correlation between performance capabilities of information variants and their competitive success decreases, and evolution of such systems toward increased efficiency slows down. This impasse impedes the understanding of evolution in prebiotic networks. We used the simulation platform Biotic Abstract Dual Automata (BiADA to analyze how information variants compete in a resource-limited space. We analyzed the effect of energy-related features (differences in autocatalytic efficiency, energy cost of order, energy availability, transformation rates and stability of order on this competition. We discuss circumstances and controllers allowing primitive networks acquire novel information with minimal “error catastrophe” risks. We present a primitive mechanism for maximization of energy flux in dynamic networks. This work helps evaluate controllers of evolution in prebiotic networks and other systems where information variants compete.

  16. Update on lichen planus and its clinical variants. (United States)

    Weston, Gillian; Payette, Michael


    Lichen planus (LP) is an inflammatory skin condition with characteristic clinical and histopathological findings. Classic LP typically presents as pruritic, polygonal, violaceous flat-topped papules and plaques; many variants in morphology and location also exist, including oral, nail, linear, annular, atrophic, hypertrophic, inverse, eruptive, bullous, ulcerative, lichen planus pigmentosus, lichen planopilaris, vulvovaginal, actinic, lichen planus-lupus erythematosus overlap syndrome, and lichen planus pemphigoides. Clinical presentation of the rarer variant lesions may be largely dissimilar to classic LP and therefore difficult to diagnose based solely on clinical examination. However, histopathological examination of LP and LP-variant lesions reveal similar features, aiding in the proper diagnosis of the disease. Management of LP and LP variants aims to control symptoms and to decrease time from onset to resolution; it often involves topical corticosteroids, but varies depending on the severity and location of the lesion. The literature contains an array of reports on the variations in presentation and successful management of LP and its variants. A familiarity with LP and its variants is important in achieving timely recognition and management of the disease.

  17. [Hemoglobin variants in Colombian patients referred to discard hemoglobinopathies]. (United States)

    Romero-Sánchez, Consuelo; Gómez Gutiérrez, Alberto; Duarte, Yurani; Amazo, Constanza; Manosalva, Clara; Chila M, Lorena; Casas-Gómez, María Consuelo; Briceño Balcázar, Ignacio


    Oxygen transport is altered in hemoglobinopathies. To study the distribution of hemoglobinopathies in Andean subjects without African ancestry. We analyzed blood samples of 1,407 subjects aged 18 to 59 years (58% females), living in the central Andean region of Colombia, referred to discard hemoglobinopathies. The frequency and type of hemoglobinopathy was established by capillary and agarose gel electrophoresis. The frequency of hemoglobinopathies was 34.5% and higher among females. The structural variants found were: AS-heterozygous hemoglobin (8.1%), homozygous SS (3.7%), heterozygous SC (2.2%), AC heterozygotes (0.5%) and heterozygous AE (0.3%). Quantitative variants found were Hb A-Beta thalassemia (13.91%) and Hb H (0.06%), Beta-thalassemia heterozygotes C (0.88%), S-Beta thalassemia heterozygotes (6.07%) and compound heterozygous SC/Beta thalassemia (0.25%), with a persistence of fetal hemoglobin 0. Composite thalassemia was also found in 31%. All techniques showed good correlation and capillary electrophoresis demonstrated a greater detection of hemoglobin variants. The frequency of hemoglobin variants in the analyzed population was high, which is an important public health indicator. The most common hemoglobin variant was HbA/Increased structural Hb A2 and the mos frequent structural hemoglobinopathy was sickle cell trait. Capillary electrophoresis can discern any Hb variants present in the population.

  18. Lightning-fast genome variant detection with GROM. (United States)

    Smith, Sean D; Kawash, Joseph K; Grigoriev, Andrey


    Current human whole genome sequencing projects produce massive amounts of data, often creating significant computational challenges. Different approaches have been developed for each type of genome variant and method of its detection, necessitating users to run multiple algorithms to find variants. We present Genome Rearrangement OmniMapper (GROM), a novel comprehensive variant detection algorithm accepting aligned read files as input and finding SNVs, indels, structural variants (SVs), and copy number variants (CNVs). We show that GROM outperforms state-of-the-art methods on 7 validated benchmarks using 2 whole genome sequencing (WGS) data sets. Additionally, GROM boasts lightning-fast run times, analyzing a 50× WGS human data set (NA12878) on commonly available computer hardware in 11 minutes, more than an order of magnitude (up to 72 times) faster than tools detecting a similar range of variants. Addressing the needs of big data analysis, GROM combines in 1 algorithm SNV, indel, SV, and CNV detection, providing superior speed, sensitivity, and precision. GROM is also able to detect CNVs, SNVs, and indels in non-paired-read WGS libraries, as well as SNVs and indels in whole exome or RNA sequencing data sets. © The Authors 2017. Published by Oxford University Press.

  19. An Efficient Multiple Variants Coordination Framework for Differential Evolution. (United States)

    Zhang, Sheng Xin; Zheng, Shao Yong; Zheng, Li Ming


    Differential evolution (DE) is recognized as a simple but powerful algorithm in the family of evolutionary algorithms. Over the past two decades, many advanced DE variants with significantly improved performance have been proposed. However, the variants may only achieve the best performance on a certain type of functions. Moreover, a specific optimizer may not always be suitable for the whole optimization process. To overcome these weaknesses, this paper proposes a multiple variants coordination (MVC) framework with two mechanisms, namely, the multiple variants adaptive selecting mechanism and the multiple variants adaptive solutions preserving mechanisms (MV-APM). In MVC, the evolution process is divided into nonoverlap segments with equal numbers of generations. Each segment includes the learning generations (LGs) and executing generations (EGs). In LG, all the candidate DE optimizers are utilized independently. The best performing optimizer is determined and then utilized in EG in the same segment. Furthermore, MV-APM maintains the population by adaptively preserving promising solutions generated by multiple optimizers. Numerical experiments on the CEC2014 benchmark suit show that the proposed MVC framework can significantly improve the performance of the baseline algorithms and the resulted algorithm significantly outperform the start-of-the-art and up-to-date DEs. Moreover, as a general framework, MVC can also be applied to coordinate multiple improved DE variants to further enhance their performance.

  20. Fluid to fluid contact heat exchanger (United States)

    Clark, W. E.


    Heat transfer and pressure drop test results for a fluid to fluid contact heat exchanger are reported. The heat exchanger, fabricated and tested to demonstrate one method of transferring heat between structures in space, had a total contact area of 0.18 sq m. It utilized contact surfaces which were flexible and conformed to the mating contact surfaces upon pressurization of the fluid circulating within the heat exchanger. During proof-of-concept performance tests, the heat exchanger was operated in a typical earth environment. It demonstrated a contact conductance of 3.8 kW/sq m C at contact pressures in the 15 to 70 kPa range.

  1. Essential Specification Elements for Heat Exchanger Replacement

    Energy Technology Data Exchange (ETDEWEB)

    Bower, L.


    Performance upgrade and equipment degradation are the primary impetuses for a nuclear power plant to engage in the large capital cost project of heat exchanger replacement. Along with attention to these issues, consideration of heat exchanger Codes and Standards, material improvements, thermal redesign, and configuration are essential for developing User’s Design Specifications for successful replacement projects. The User’s Design Specification is the central document in procuring ASME heat exchangers. Properly stated objectives for the heat exchanger replacement are essential for obtaining the materials, configurations and thermal designs best suited for the nuclear power plant. Additionally, the code of construction required and the applied manufacturing standard (TEMA or HEI) affects how the heat exchanger may be designed or configured to meet the replacement goals. Knowledge of how Codes and Standards affect design and configuration details will aid in writing the User’s Design Specification. Joseph Oat Corporation has designed and fabricated many replacement heat exchangers for the nuclear power industry. These heat exchangers have been constructed per ASME Section III to various Code-Years or ASME Section VIII-1 to the current Code-Year also in accordance with TEMA and HEI. These heat exchangers have been a range of like-for-like replacement to complete thermal, material and configuration redesigns. Several examples of these heat exchangers with their Code, Standard and specification implications are presented. (Author.

  2. Ion Exchange and Liquid Column Chromatography. (United States)

    Walton, Harold F.


    Emphasizes recent advances in principles and methodology in ion exchange and chromatography. Two tables list representative examples for inorganic ions and organic compounds. Cites 544 references. (CS)

  3. Entropy exchange for infinite-dimensional systems. (United States)

    Duan, Zhoubo; Hou, Jinchuan


    In this paper the entropy exchange for channels and states in infinite-dimensional systems are defined and studied. It is shown that, this entropy exchange depends only on the given channel and the state. An explicit expression of the entropy exchange in terms of the state and the channel is proposed. The generalized Klein's inequality, the subadditivity and the triangle inequality about the entropy including infinite entropy for the infinite-dimensional systems are established, and then, applied to compare the entropy exchange with the entropy change.

  4. Micro tube heat exchangers for Space Project (United States)

    National Aeronautics and Space Administration — Mezzo fabricates micro tube heat exchangers for a variety of applications, including aerospace, automotive racing, Department of Defense ground vehicles, economizers...

  5. Foreign Exchange Risk in International Transactions

    Directory of Open Access Journals (Sweden)

    Florentina-Olivia Balu


    In this article we will focus on forward and futures contracts for managing foreign exchange risk. A forward is a contract to buy or sell currency at an agreed upon exchange rate at a specific date in the future. Futures are similar to forwards except that they’re traded on exchanges which specify settlement dates. Also we make some recommendations related to the foreign exchange risk-management practices that are useful for companies involved in international trade and for financial institutions interested in providing hedging products to these companies.

  6. Data Exchange Management Information System (DEMIS) (United States)

    Social Security Administration — DEMIS combines a database (Operational Data Store - ODS) of data exchange-related Management Information (MI) with the agency's querying and reporting utility, the...

  7. Health and sexual behaviour among exchange students. (United States)

    Petersson, Carina; Peterson, Ulla; Swahnberg, Katarina; Oscarsson, Marie


    The objective was to describe the exchange students' health and sexual behaviour associated with their exchange studies, and examine the extent to which they had received preventive efforts against human immunodeficiency virus (HIV)/sexually transmitted infection (STI) and safer sex before departure. A cross-sectional study was conducted based on a web survey with questions about sexual behaviour, self-esteem and psychological well-being. Data were analysed using descriptive and analytical statistics. A total of 136 outgoing exchange students from a Swedish University participated. Most of the exchange students rated their health as good, had psychological well-being and rated their self-esteem as being high. Approximately half of the exchange students had sex with a new partner during the exchange semester, and 87% of them had sexually risky behaviour. More than half (61%) of the exchange students had received preventive efforts before departure. No statistically significant difference regarding preventive information was found between those who reported sexually risky behaviour and those who did not. The group that had sexually risky behaviour desired free condoms and access to clinics for sexual health. CONCLUSIONS EXCHANGE STUDENTS RATED THEIR HEALTH AS GOOD, AND THE MAJORITY OF THEM PARTICIPATED IN INFORMATION SESSIONS THAT ADDRESSED PREVENTIVE EFFORTS ON HIV/STI AND SAFER SEX BEFORE DEPARTURE SEXUALLY RISKY BEHAVIOUR DURING EXCHANGE STUDIES WAS REPORTED AND HIGHLIGHTS THE NEED FOR MORE EFFECTIVE PREVENTIVE MEASURES; FOR EXAMPLE, A RECOLLECTION OF READING STI INFORMATION. © Author(s) 2016.

  8. Exchange effects in a cold plasma

    CERN Document Server

    Ekman, Robin; Brodin, Gert


    We have studied the exchange corrections to linear electrostatic wave propagation in a plasma using a quantum kinetic formalism. Specifically we have considered the zero temperature limit. In order to simplify the calculations we have focused on the long wavelength limit, i.e. wavelengths much longer than the de Broglie wavelength. For the case of ion-acoustic waves we have calculated the exchange correction both to the damping rate and the real part of the frequency. For Langmuir waves the frequency shift due to exchange effects is found. Our results are compared with the frequency shifts deduced from commonly used exchange potentials which are computed from density functional theory.

  9. Algorithms for Lightweight Key Exchange. (United States)

    Alvarez, Rafael; Caballero-Gil, Cándido; Santonja, Juan; Zamora, Antonio


    Public-key cryptography is too slow for general purpose encryption, with most applications limiting its use as much as possible. Some secure protocols, especially those that enable forward secrecy, make a much heavier use of public-key cryptography, increasing the demand for lightweight cryptosystems that can be implemented in low powered or mobile devices. This performance requirements are even more significant in critical infrastructure and emergency scenarios where peer-to-peer networks are deployed for increased availability and resiliency. We benchmark several public-key key-exchange algorithms, determining those that are better for the requirements of critical infrastructure and emergency applications and propose a security framework based on these algorithms and study its application to decentralized node or sensor networks.

  10. Monetary Exchange with Multilateral Matching

    DEFF Research Database (Denmark)

    Julien, Benoît; Kennes, John; King, Ian

    This paper analyzes monetary exchange in a search model allowing for multilateral matches to be formed, according to a standard urn-ballprocess. We consider three physical environments: indivisible goods and money, divisible goods and indivisible money, and divisible goods and money. We compare....... In particular, surplus maximization can be achieved in this setting, in equilibrium, with a positive money supply. Moreover, with flexible prices and directed search, the first best allocation can be attained through price posting or through auctions with lotteries, but not through auctions without lotteries....... Finally, analysis of the case of divisible goods and money can be performed without the assumption of large families (as in Shi (1997)) or the day and night structure of Lagos and Wright (2005)....

  11. Educational Exchanges Across the Equator (United States)

    Norman, D. J.; Walker, C. E.; Smith, M.; Pompea, S. M.; Orellana, D.


    What is color? What is light? How can we use a spectrometer to help students understand the answers to these questions? Even half a world apart and between people of different languages and cultures, how to teach these ideas to students can be a lively subject for discussion. And it is! Aided by Internet 2-based videoconferencing, NOAO North and South have sponsored three teacher professional development videoconference workshops, dubbed ASTRO-Chile, linking teachers in Tucson, AZ, and La Serena, Chile. The teachers exchange methods and ideas about how to explain and demonstrate physical concepts, important to the study of astronomy, to students of various ages. The workshops are conducted in Spanish with four bilingual science teachers from the Tucson area discussing pedagogical approaches with their teaching counterparts in Chile. Demonstrations and project presentations, from both sites, are included as part of each workshop. This work is supported, in part, through funding from the NSF Astronomy and Astrophysics Postdoctoral Fellowship.

  12. Exchanger system for anhydrite pipeline

    Energy Technology Data Exchange (ETDEWEB)

    Penet, A.


    This paper deals with the problem of roadway behaviour affecting airways, bottom roads and top roads in advancing faces in the HBNPC area. The support work in these zones used to be undertaken manually and involved a lot of man hours. These operations are now mechanized in the form of pneumatic stowing with anhydrite. The latter is delivered by pipeline using compressed air. The 'exchanger' is a sort of branching system in the pipeline enabling the flow to be switched from the top end of the face to the bottom end and vice versa (diagram). The associated operations can be undertaken with ease. The effect the system has on costs will soon be known. (In French)

  13. Genetic risk variants for social anxiety. (United States)

    Stein, Murray B; Chen, Chia-Yen; Jain, Sonia; Jensen, Kevin P; He, Feng; Heeringa, Steven G; Kessler, Ronald C; Maihofer, Adam; Nock, Matthew K; Ripke, Stephan; Sun, Xiaoying; Thomas, Michael L; Ursano, Robert J; Smoller, Jordan W; Gelernter, Joel


    Social anxiety is a neurobehavioral trait characterized by fear and reticence in social situations. Twin studies have shown that social anxiety has a heritable basis, shared with neuroticism and extraversion, but genetic studies have yet to demonstrate robust risk variants. We conducted genomewide association analysis (GWAS) of subjects within the Army Study To Assess Risk and Resilience in Servicemembers (Army STARRS) to (i) determine SNP-based heritability of social anxiety; (ii) discern genetic risk loci for social anxiety; and (iii) determine shared genetic risk with neuroticism and extraversion. GWAS were conducted within ancestral groups (EUR, AFR, LAT) using linear regression models for each of the three component studies in Army STARRS, and then meta-analyzed across studies. SNP-based heritability for social anxiety was significant (h2g  = 0.12, P = 2.17 × 10-4 in EUR). One meta-analytically genomewide significant locus was seen in each of EUR (rs708012, Chr 6: BP 36965970, P = 1.55 × 10-8 ; beta = 0.073) and AFR (rs78924501, Chr 1: BP 88406905, P = 3.58 × 10-8 ; beta = 0.265) samples. Social anxiety in Army STARRS was significantly genetically correlated (negatively) with extraversion (rg  = -0.52, se = 0.22, P = 0.02) but not with neuroticism (rg  = 0.05, se = 0.22, P = 0.81) or with an anxiety disorder factor score (rg  = 0.02, se = 0.32, P = 0.94) from external GWAS meta-analyses. This first GWAS of social anxiety confirms a genetic basis for social anxiety, shared with extraversion but possibly less so with neuroticism. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  14. Psychosis in behavioral variant frontotemporal dementia

    Directory of Open Access Journals (Sweden)

    Gossink FT


    Full Text Available Flora T Gossink,1,2 Everard GB Vijverberg,2,3 Welmoed Krudop,2 Philip Scheltens,2 Max L Stek,1 Yolande AL Pijnenburg,1,2 Annemiek Dols1,2 1Department of Old Age Psychiatry, GGZinGeest, 2Alzheimer Center & Department of Neurology, VU University Medical Center, Amsterdam, 3Department of Neurology, HagaZiekenhuis, The Hague, the Netherlands Background: Dementia is generally characterized by cognitive impairment that can be accompanied by psychotic symptoms; for example, visual hallucinations are a core feature of dementia with Lewy bodies, and delusions are often seen in Alzheimer’s disease. However, for behavioral variant of frontotemporal dementia (bvFTD, studies on the broad spectrum of psychotic symptoms are still lacking. The aim of this study was to systematically and prospectively subtype the wide spectrum of psychotic symptoms in probable and definite bvFTD.Methods: In this study, a commonly used and validated clinical scale that quantifies the broad spectrum of psychotic symptoms (Positive and Negative Symptom Scale was used in patients with probable and definite bvFTD (n=22 and with a primary psychiatric disorder (n=35 in a late-onset frontal lobe cohort. Median symptom duration was 2.8 years, and the patients were prospectively followed for 2 years.Results: In total, 22.7% of bvFTD patients suffered from delusions, hallucinatory behavior, and suspiciousness, although the majority of the patients exhibited negative psychotic symptoms such as social and emotional withdrawal and blunted affect (95.5% and formal thought disorders (81.8%. “Difficulty in abstract thinking” and “stereotypical thinking” (formal thought disorders differentiated bvFTD from psychiatric disorders. The combined predictors difficulty in abstract thinking, stereotypical thinking, “anxiety”, “guilt feelings,” and “tension” explained 75.4% of variance in the diagnosis of bvFTD versus psychiatric diagnoses (P<0.001.Conclusion: Delusions

  15. Alternative Technical Summary Report: Electrometallurgical Treatment Variant

    Energy Technology Data Exchange (ETDEWEB)

    Gray, L.W.


    Immobilization is the fixation of the surplus fissile materials in an acceptable matrix such as glass or ceramics to create an environmentally benign form for disposal in a repository. In addition to the traditional characteristics required of an immobilization form to achieve isolation of the fissile material from the biosphere over geologic times, the immobilization form for the Fissile Materials Disposition Program (FMDP) must also possess the property that it is inherently as unattractive and inaccessible as the fissile material from commercial spent fuel. This latter requirement is similar to the wording of the ''spent fuel standard'' invoked in the National Academy of Sciences (NAS) study on plutonium disposition. High-level wastes (HLW) or separated cesium ({sup 137}Cs), can be added with the fissile material into the waste form to create a radiation field that increases the proliferation resistance and decreases reuse by the host nation in the following ways: (1) Plutonium will be diluted with elements that must be removed by extensive chemical processing to return it to weapons-usable purity; (2) The immobilized plutonium canisters will contain approximately 2 tonnes (2000 kg; 2.2 tons) of mass, thereby forcing the use of heavy equipment to move the canisters; (3) A gamma radiation barrier will be added to the immobilized plutonium canisters; the present concept is to add a radiation barrier that is greater than 1 Gy (100 rad) per hour at 1 m (3 ft) 30 years after fabrication; (4) These canisters will then be sealed in casks and emplaced into drifts in a federal repository where they will be monitored for 100 years before the repository is sealed. This immobilization process is shown conceptually in Figure 1. In the electrometallurgical treatment (ET) variant, plutonium-rich residues are shipped to existing Argonne National Laboratory-West (ANL-W) facilities where the plutonium is converted to plutonium chloride, dissolved in a molten

  16. Exchange Rate Policy in Morocco and Persistence of Real Exchange Rate Misalignments

    National Research Council Canada - National Science Library

    Mohamed Bouzahzah; Radouane Bachar


    .... The objective of this article is to highlight the persistent nature of misalignments of the real exchange rate of the Dirham, especially since the adoption by Morocco of a policy exchange rate based...

  17. Preferential accumulation of severe variants of Citrus tristeza virus in plants co-inoculated with mild and severe variants. (United States)

    Sambade, A; Ambrós, S; López, C; Ruiz-Ruiz, S; Hermoso de Mendoza, A; Flores, R; Guerri, J; Moreno, P


    The viral population in sweet orange plants, either healthy or pre-inoculated with the asymptomatic isolate of Citrus tristeza virus (CTV) T32, and then graft- or aphid-inoculated with the stem-pitting isolate T318, was characterized with respect to symptom expression, reaction with monoclonal antibody MCA13, single-strand conformation polymorphism (SSCP) of genes p18 and p20, bi-directional RT-PCR, and dot-blot hybridisation. All plants inoculated with T318, with or without pre-inoculation, showed stem pitting, reacted with MCA13, had the SSCP profile characteristic of this isolate, and in bi-directional RT-PCR yielded a 450-bp DNA product associated with severe isolates, indicating that T32 afforded no protection against T318. The latter isolate had two main sequence variants, the minor one of which was indistinguishable from the main T32 sequence, and both were detected in most plants that were graft-inoculated with T318. However, the T32 variant was not detected in plants that were aphid-inoculated only with T318 and also showed stem pitting. This suggested an association of symptoms with the major T318 sequence and preferential transmission of this variant by aphids. The T318-specific variant accumulated more than the T32 variant in plants in which both were replicating, suggesting a higher fitness of the former. Our results clearly emphasize the potential threat of severe CTV variants in areas where mild isolates are presently predominant.

  18. Adenosquamous variant of metaplastic carcinoma of breast - an unusual histological variant. (United States)

    Swathy, P U; Arunalatha, P; Chandramouleeswari, K; Lily, S Mary; Ramya, S


    Metaplastic carcinoma of breast refers to a heterogeneous group of neoplasms characterized by intimate admixture of adenocarcinoma with dominant areas of spindle cell, squamous cell and/ or mesenchymal differentiation. They constitute the rarest histological variant of invasive ductal carcinoma. These carcinomas have aggressive clinical behaviour and show suboptimal response to standard treatment. A 49-year-old female presented with lump in the left breast for one year. She was diagnosed as infiltrating ductal carcinoma breast with triple negative hormone status by trucut biopsy. She completed four cycles of neoadjuvant chemotherapy. Postchemotherapy, axillary nodes decreased in size but the size of the primary tumour remained the same. Hence, she underwent modified radical mastectomy and the specimen sent for histopathological examination. Grossly, there was a solitary cyst measuring 4x3cm. Histologically, cyst enclosing malignant cells which resemble mature squamous epithelial cells. Also, seen are malignant cells in glandular pattern.

  19. 76 FR 25774 - Determination of Foreign Exchange Swaps and Foreign Exchange Forwards Under the Commodity... (United States)


    ... exchange derivatives, such as foreign exchange options, currency swaps, or non-deliverable forwards (``NDFs... markets for derivative instruments. In general, the payment obligations on currency swaps, interest rate... derivatives. Foreign exchange options, currency swaps, and NDFs may not be exempted from the CEA's definition...

  20. Interest Rate Rules, Exchange Market Pressure, and Successful Exchange Rate Management

    NARCIS (Netherlands)

    Klaassen, F.; Mavromatis, K.


    Central banks with an exchange rate objective set the interest rate in response to what they call ''pressure.'' Instead, existing interest rate rules rely on the exchange rate minus its target. To stay closer to actual policy, we introduce a rule that uses exchange market pressure (EMP), the

  1. Australian Universities' Strategic Goals of Student Exchange and Participation Rates in Outbound Exchange Programmes (United States)

    Daly, Amanda; Barker, Michelle


    International student exchange programmes are acknowledged as one aspect of a broader suite of internationalisation strategies aimed at enhancing students' intercultural understanding and competence. The decision to participate in an exchange programme is dependent on both individual and contextual factors such as student exchange policies and…

  2. Exchange Studies as Actor-Networks: Following Korean Exchange Students in Swedish Higher Education (United States)

    Ahn, Song-ee


    This article explores how Korean exchange students organized their studies during exchange programs in Swedish higher education. For most students, the programs became a disordered period in relation to their education. The value of exchange studies seems mainly to be extra-curricular. Drawing upon actor network theory, the article argues that the…

  3. 77 FR 24752 - Self-Regulatory Organizations; EDGA Exchange, Inc.; EDGX Exchange, Inc.; International Securities... (United States)


    ... COMMISSION [Release No. 34-66834; File Nos. SR-EDGA-2012-08; SR-EDGX-2012-07; SR- ISE-2012-21] Self... Exchange AG Will Transfer Its Interest in ISE Holdings, Inc. to a Newly Formed Swiss Corporation, Eurex... (``EDGA''), EDGX Exchange, Inc. (``EDGX''), International Securities Exchange, LLC (``ISE'' and, with EDGA...

  4. Functionally significant, rare transcription factor variants in tetralogy of Fallot. (United States)

    Töpf, Ana; Griffin, Helen R; Glen, Elise; Soemedi, Rachel; Brown, Danielle L; Hall, Darroch; Rahman, Thahira J; Eloranta, Jyrki J; Jüngst, Christoph; Stuart, A Graham; O'Sullivan, John; Keavney, Bernard D; Goodship, Judith A


    Rare variants in certain transcription factors involved in cardiac development cause Mendelian forms of congenital heart disease. The purpose of this study was to systematically assess the frequency of rare transcription factor variants in sporadic patients with the cardiac outflow tract malformation tetralogy of Fallot (TOF). We sequenced the coding, 5'UTR, and 3'UTR regions of twelve transcription factor genes implicated in cardiac outflow tract development (NKX2.5, GATA4, ISL1, TBX20, MEF2C, BOP/SMYD1, HAND2, FOXC1, FOXC2, FOXH, FOXA2 and TBX1) in 93 non-syndromic, non-Mendelian TOF cases. We also analysed Illumina Human 660W-Quad SNP Array data for copy number variants in these genes; none were detected. Four of the rare variants detected have previously been shown to affect transactivation in in vitro reporter assays: FOXC1 p.P297S, FOXC2 p.Q444R, FOXH1 p.S113T and TBX1 p.P43_G61del PPPPRYDPCAAAAPGAPGP. Two further rare variants, HAND2 p.A25_A26insAA and FOXC1 p.G378_G380delGGG, A488_491delAAAA, affected transactivation in in vitro reporter assays. Each of these six functionally significant variants was present in a single patient in the heterozygous state; each of the four for which parental samples were available were maternally inherited. Thus in the 93 TOF cases we identified six functionally significant mutations in the secondary heart field transcriptional network. This study indicates that rare genetic variants in the secondary heart field transcriptional network with functional effects on protein function occur in 3-13% of patients with TOF. This is the first report of a functionally significant HAND2 mutation in a patient with congenital heart disease.

  5. Mendelian randomization analysis with multiple genetic variants using summarized data. (United States)

    Burgess, Stephen; Butterworth, Adam; Thompson, Simon G


    Genome-wide association studies, which typically report regression coefficients summarizing the associations of many genetic variants with various traits, are potentially a powerful source of data for Mendelian randomization investigations. We demonstrate how such coefficients from multiple variants can be combined in a Mendelian randomization analysis to estimate the causal effect of a risk factor on an outcome. The bias and efficiency of estimates based on summarized data are compared to those based on individual-level data in simulation studies. We investigate the impact of gene-gene interactions, linkage disequilibrium, and 'weak instruments' on these estimates. Both an inverse-variance weighted average of variant-specific associations and a likelihood-based approach for summarized data give similar estimates and precision to the two-stage least squares method for individual-level data, even when there are gene-gene interactions. However, these summarized data methods overstate precision when variants are in linkage disequilibrium. If the P-value in a linear regression of the risk factor for each variant is less than 1×10⁻⁵, then weak instrument bias will be small. We use these methods to estimate the causal association of low-density lipoprotein cholesterol (LDL-C) on coronary artery disease using published data on five genetic variants. A 30% reduction in LDL-C is estimated to reduce coronary artery disease risk by 67% (95% CI: 54% to 76%). We conclude that Mendelian randomization investigations using summarized data from uncorrelated variants are similarly efficient to those using individual-level data, although the necessary assumptions cannot be so fully assessed. © 2013 WILEY PERIODICALS, INC.

  6. HABP2 G534E Variant in Papillary Thyroid Carcinoma.

    Directory of Open Access Journals (Sweden)

    Jerneja Tomsic

    Full Text Available The main nonmedullary form of thyroid cancer is papillary thyroid carcinoma (PTC that accounts for 80-90% of all thyroid malignancies. Only 3-10% of PTC patients have a positive family history of PTC yet the familiality is one of the highest of all cancers as measured by case control studies. A handful of genes have been implicated accounting for a small fraction of this genetic predisposition. It was therefore of considerable interest that a mutation in the HABP2 gene was recently implicated in familial PTC. The present work was undertaken to examine the extent of HABP2 variant involvement in PTC. The HABP2 G534E variant (rs7080536 was genotyped in blood DNA from 179 PTC families (one affected individual per family, 1160 sporadic PTC cases and 1395 controls. RNA expression of HABP2 was tested by qPCR in RNA extracted from tumor and normal thyroid tissue from individuals that are homozygous wild-type or heterozygous for the variant. The variant was found to be present in 6.1% familial cases, 8.0% sporadic cases (2 individuals were homozygous for the variant and 8.7% controls. The variant did not segregate with PTC in one large and 6 smaller families in which it occurred. In keeping with data from the literature and databases the expression of HABP2 was highest in the liver, much lower in 3 other tested tissues (breast, kidney, brain but not found in thyroid. Given these results showing lack of any involvement we suggest that the putative role of variant HABP2 in PTC should be carefully scrutinized.

  7. Combined effects of thrombosis pathway gene variants predict cardiovascular events.

    Directory of Open Access Journals (Sweden)

    Kirsi Auro


    Full Text Available The genetic background of complex diseases is proposed to consist of several low-penetrance risk loci. Addressing this complexity likely requires both large sample size and simultaneous analysis of different predisposing variants. We investigated the role of four thrombosis genes: coagulation factor V (F5, intercellular adhesion molecule 1 (ICAM1, protein C (PROC, and thrombomodulin (THBD in cardiovascular diseases. Single allelic gene variants and their pair-wise combinations were analyzed in two independently sampled population cohorts from Finland. From among 14,140 FINRISK participants (FINRISK-92, n = 5,999 and FINRISK-97, n = 8,141, we selected for genotyping a sample of 2,222, including 528 incident cardiovascular disease (CVD cases and random subcohorts totaling 786. To cover all known common haplotypes (>10%, 54 single nucleotide polymorphisms (SNPs were genotyped. Classification-tree analysis identified 11 SNPs that were further analyzed in Cox's proportional hazard model as single variants and pair-wise combinations. Multiple testing was controlled by use of two independent cohorts and with false-discovery rate. Several CVD risk variants were identified: In women, the combination of F5 rs7542281 x THBD rs1042580, together with three single F5 SNPs, was associated with CVD events. Among men, PROC rs1041296, when combined with either ICAM1 rs5030341 or F5 rs2269648, was associated with total mortality. As a single variant, PROC rs1401296, together with the F5 Leiden mutation, was associated with ischemic stroke events. Our strategy to combine the classification-tree analysis with more traditional genetic models was successful in identifying SNPs-acting either in combination or as single variants--predisposing to CVD, and produced consistent results in two independent cohorts. These results suggest that variants in these four thrombosis genes contribute to arterial cardiovascular events at population level.

  8. Functionally significant, rare transcription factor variants in tetralogy of Fallot.

    Directory of Open Access Journals (Sweden)

    Ana Töpf

    Full Text Available Rare variants in certain transcription factors involved in cardiac development cause Mendelian forms of congenital heart disease. The purpose of this study was to systematically assess the frequency of rare transcription factor variants in sporadic patients with the cardiac outflow tract malformation tetralogy of Fallot (TOF.We sequenced the coding, 5'UTR, and 3'UTR regions of twelve transcription factor genes implicated in cardiac outflow tract development (NKX2.5, GATA4, ISL1, TBX20, MEF2C, BOP/SMYD1, HAND2, FOXC1, FOXC2, FOXH, FOXA2 and TBX1 in 93 non-syndromic, non-Mendelian TOF cases. We also analysed Illumina Human 660W-Quad SNP Array data for copy number variants in these genes; none were detected. Four of the rare variants detected have previously been shown to affect transactivation in in vitro reporter assays: FOXC1 p.P297S, FOXC2 p.Q444R, FOXH1 p.S113T and TBX1 p.P43_G61del PPPPRYDPCAAAAPGAPGP. Two further rare variants, HAND2 p.A25_A26insAA and FOXC1 p.G378_G380delGGG, A488_491delAAAA, affected transactivation in in vitro reporter assays. Each of these six functionally significant variants was present in a single patient in the heterozygous state; each of the four for which parental samples were available were maternally inherited. Thus in the 93 TOF cases we identified six functionally significant mutations in the secondary heart field transcriptional network.This study indicates that rare genetic variants in the secondary heart field transcriptional network with functional effects on protein function occur in 3-13% of patients with TOF. This is the first report of a functionally significant HAND2 mutation in a patient with congenital heart disease.

  9. Functionally Significant, Rare Transcription Factor Variants in Tetralogy of Fallot (United States)

    Töpf, Ana; Griffin, Helen R.; Glen, Elise; Soemedi, Rachel; Brown, Danielle L.; Hall, Darroch; Rahman, Thahira J.; Eloranta, Jyrki J.; Jüngst, Christoph; Stuart, A. Graham; O'Sullivan, John; Keavney, Bernard D.; Goodship, Judith A.


    Objective Rare variants in certain transcription factors involved in cardiac development cause Mendelian forms of congenital heart disease. The purpose of this study was to systematically assess the frequency of rare transcription factor variants in sporadic patients with the cardiac outflow tract malformation tetralogy of Fallot (TOF). Methods and Results We sequenced the coding, 5′UTR, and 3′UTR regions of twelve transcription factor genes implicated in cardiac outflow tract development (NKX2.5, GATA4, ISL1, TBX20, MEF2C, BOP/SMYD1, HAND2, FOXC1, FOXC2, FOXH, FOXA2 and TBX1) in 93 non-syndromic, non-Mendelian TOF cases. We also analysed Illumina Human 660W-Quad SNP Array data for copy number variants in these genes; none were detected. Four of the rare variants detected have previously been shown to affect transactivation in in vitro reporter assays: FOXC1 p.P297S, FOXC2 p.Q444R, FOXH1 p.S113T and TBX1 p.P43_G61del PPPPRYDPCAAAAPGAPGP. Two further rare variants, HAND2 p.A25_A26insAA and FOXC1 p.G378_G380delGGG, A488_491delAAAA, affected transactivation in in vitro reporter assays. Each of these six functionally significant variants was present in a single patient in the heterozygous state; each of the four for which parental samples were available were maternally inherited. Thus in the 93 TOF cases we identified six functionally significant mutations in the secondary heart field transcriptional network. Significance This study indicates that rare genetic variants in the secondary heart field transcriptional network with functional effects on protein function occur in 3–13% of patients with TOF. This is the first report of a functionally significant HAND2 mutation in a patient with congenital heart disease. PMID:25093829

  10. Cerivastatin, genetic variants, and the risk of rhabdomyolysis. (United States)

    Marciante, Kristin D; Durda, Jon P; Heckbert, Susan R; Lumley, Thomas; Rice, Ken; McKnight, Barbara; Totah, Rheem A; Tamraz, Bani; Kroetz, Deanna L; Fukushima, Hisayo; Kaspera, Rüdiger; Bis, Joshua C; Glazer, Nicole L; Li, Guo; Austin, Thomas R; Taylor, Kent D; Rotter, Jerome I; Jaquish, Cashell E; Kwok, Pui-Yan; Tracy, Russell P; Psaty, Bruce M


    The withdrawal of cerivastatin involved an uncommon but serious adverse reaction, rhabdomyolysis. The bimodal response, rhabdomyolysis in a small proportion of users, points to genetic factors as a potential cause. We conducted a case-control study to evaluate genetic markers for cerivastatin-associated rhabdomyolysis. This study had two components: a candidate gene study to evaluate variants in CYP2C8, UGT1A1, UGT1A3, and SLCO1B1; and a genome-wide association study to identify risk factors in other regions of the genome. A total of 185 rhabdomyolysis cases were frequency matched to statin-using controls from the Cardiovascular Health Study (n=374) and the Heart and Vascular Health Study (n=358). Validation relied on functional studies. Permutation test results suggested an association between cerivastatin-associated rhabdomyolysis and variants in SLCO1B1 (P=0.002), but not variants in CYP2C8 (P=0.073) or UGTs (P=0.523). An additional copy of the minor allele of SLCO1B1 rs4149056 (p.Val174Ala) was associated with the risk of rhabdomyolysis (odds ratio: 1.89; 95% confidence interval: 1.40-2.56). In transfected cells, this variant reduced cerivastatin transport by 40% compared with the reference transporter (P<0.001). The genome-wide association study identified an intronic variant (rs2819742) in the ryanodine receptor 2 gene (RYR2) as significant (P=1.74E-07). An additional copy of the minor allele of the RYR2 variant was associated with a reduced risk of rhabdomyolysis (odds ratio: 0.48; 95% confidence interval: 0.36-0.63). We identified modest genetic risk factors for an extreme response to cerivastatin. Disabling genetic variants in the candidate genes were not responsible for the bimodal response to cerivastatin.

  11. Likelihood ratio tests in rare variant detection for continuous phenotypes. (United States)

    Zeng, Ping; Zhao, Yang; Liu, Jin; Liu, Liya; Zhang, Liwei; Wang, Ting; Huang, Shuiping; Chen, Feng


    It is believed that rare variants play an important role in human phenotypes; however, the detection of rare variants is extremely challenging due to their very low minor allele frequency. In this paper, the likelihood ratio test (LRT) and restricted likelihood ratio test (ReLRT) are proposed to test the association of rare variants based on the linear mixed effects model, where a group of rare variants are treated as random effects. Like the sequence kernel association test (SKAT), a state-of-the-art method for rare variant detection, LRT and ReLRT can effectively overcome the problem of directionality of effect inherent in the burden test in practice. By taking full advantage of the spectral decomposition, exact finite sample null distributions for LRT and ReLRT are obtained by simulation. We perform extensive numerical studies to evaluate the performance of LRT and ReLRT, and compare to the burden test, SKAT and SKAT-O. The simulations have shown that LRT and ReLRT can correctly control the type I error, and the controls are robust to the weights chosen and the number of rare variants under study. LRT and ReLRT behave similarly to the burden test when all the causal rare variants share the same direction of effect, and outperform SKAT across various situations. When both positive and negative effects exist, LRT and ReLRT suffer from few power reductions compared to the other two competing methods; under this case, an additional finding from our simulations is that SKAT-O is no longer the optimal test, and its power is even lower than that of SKAT. The exome sequencing SNP data from Genetic Analysis Workshop 17 were employed to illustrate the proposed methods, and interesting results are described. © 2014 John Wiley & Sons Ltd/University College London.

  12. Melanocortin 1 receptor variants and skin cancer risk. (United States)

    Han, Jiali; Kraft, Peter; Colditz, Graham A; Wong, Jason; Hunter, David J


    Melanocortin 1 receptor (MC1R) gene variants are associated with red hair and fair skin color. We assessed the associations of common MC1R genotypes with the risks of 3 types of skin cancer simultaneously in a nested case-control study within the Nurses' Health Study (219 melanoma, 286 squamous cell carcinoma (SCC), and 300 basal cell carcinoma (BCC) cases, and 873 controls). We found that the 151Cys, 160Trp and 294His variants were significantly associated with red hair, fair skin color and childhood tanning tendency. The MC1R variants, especially the 151Cys variant, were associated with increased risks of the 3 types of skin cancer, after controlling for hair color, skin color and other skin cancer risk factors. Carriers of the 151Cys variant had an OR of 1.65 (95% CI, 1.04-2.59) for melanoma, 1.67 (1.12-2.49) for SCC and 1.56 (1.03-2.34) for BCC. Women with medium or olive skin color carrying 1 nonred hair color allele and 1 red hair color allele had the highest risk of melanoma. A similar interaction pattern was observed for red hair and carrying at least 1 red hair color allele on melanoma risk. We also observed that the 151Cys variant contributed additional melanoma risk among red-haired women. The information on MC1R status modestly improved the risk prediction; the increase was significant for melanoma and BCC (p, 0.004 and 0.05, respectively). These findings indicated that the effects of the MC1R variants on skin cancer risk were independent from self-reported phenotypic pigmentation. Copyright 2006 Wiley-Liss, Inc.

  13. Functional PMS2 hybrid alleles containing a pseudogene-specific missense variant trace back to a single ancient intrachromosomal recombination event. (United States)

    Ganster, Christina; Wernstedt, Annekatrin; Kehrer-Sawatzki, Hildegard; Messiaen, Ludwine; Schmidt, Konrad; Rahner, Nils; Heinimann, Karl; Fonatsch, Christa; Zschocke, Johannes; Wimmer, Katharina


    Sequence exchange between PMS2 and its pseudogene PMS2CL, embedded in an inverted duplication on chromosome 7p22, has been reported to be an ongoing process that leads to functional PMS2 hybrid alleles containing PMS2- and PMS2CL-specific sequence variants at the 5'-and the 3'-end, respectively. The frequency of PMS2 hybrid alleles, their biological significance, and the mechanisms underlying their formation are largely unknown. Here we show that overall hybrid alleles account for one-third of 384 PMS2 alleles analyzed in individuals of different ethnic backgrounds. Depending on the population, 14-60% of hybrid alleles carry PMS2CL-specific sequences in exons 13-15, the remainder only in exon 15. We show that exons 13-15 hybrid alleles, named H1 hybrid alleles, constitute different haplotypes but trace back to a single ancient intrachromosomal recombination event with crossover. Taking advantage of an ancestral sequence variant specific for all H1 alleles we developed a simple gDNA-based polymerase chain reaction (PCR) assay that can be used to identify H1-allele carriers with high sensitivity and specificity (100 and 99%, respectively). Because H1 hybrid alleles harbor missense variant p.N775S of so far unknown functional significance, we assessed the H1-carrier frequency in 164 colorectal cancer patients. So far, we found no indication that the variant plays a major role with regard to cancer susceptibility. (c) 2010 Wiley-Liss, Inc.

  14. Heat Exchanger Lab for Chemical Engineering Undergraduates (United States)

    Rajala, Jonathan W.; Evans, Edward A.; Chase, George G.


    Third year chemical engineering undergraduate students at The University of Akron designed and fabricated a heat exchanger for a stirred tank as part of a Chemical Engineering Laboratory course. The heat exchanger portion of this course was three weeks of the fifteen week long semester. Students applied concepts of scale-up and dimensional…

  15. Assessing heat exchanger performance data using temperature ...

    African Journals Online (AJOL)

    To ensure operation of heat exchangers, the goal is to verify that the exchanger is performing, or will perform, at its design. This is especially relevant to coolers that typically operate at heat loads reduced from their design basis. In addition, any calculated performance acceptance criteria must also consider uncertainty and ...

  16. Identifying the weights in exchange market pressure

    NARCIS (Netherlands)

    Klaassen, F.


    Exchange market pressure (EMP) measures the pressure on a currency to depreciate, and it is particularly relevant in crisis periods. EMP adds to the actual depreciation a weighted combination of policy instruments used to ward off depreciation, such as interest rates and foreign exchange

  17. The Story of Foreign Trade and Exchange. (United States)

    Fan, Cedric

    This comic-style booklet is one of a series of educational booklets published by the Federal Reserve Bank of New York. The booklet uses everyday language and lively illustrations to explain the benefits of international trade; the effects of tariffs and quotas; the significance of foreign exchange rates; how the foreign exchange market facilities…

  18. Timing matters in foreign exchange markets (United States)

    Hirata, Yoshito; Aihara, Kazuyuki


    We show using nonlinear time series analysis that the timing of trades in foreign exchange markets has significant information. We apply a set of methods for analyzing point process data developed in neuroscience and nonlinear science. Our results imply that foreign exchange markets might be chaotic and have short-term predictability.

  19. Individual Differences in Reactions to Inequitable Exchanges. (United States)

    Ellis, Barbara B.; Penner, Louis A.


    Investigates the role of sociopathic tendencies in reactions to inequitable exchanges in 273 males and females classified as high or low in sociopathy. Subjects read narratives of inequitable exchanges and assumed the role of the exploiter and the role of the victim in each. (Author/RH)

  20. Synthesis, characterization and ion exchange properties of ...

    Indian Academy of Sciences (India)

    The material has been characterized on the basis of chemical composition, pH titration, Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis. The effect on the exchange capacity of drying the exchanger at different temperatures has been studied. The analytical importance of the material has been ...

  1. 22 CFR 41.62 - Exchange visitors. (United States)


    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Exchange visitors. 41.62 Section 41.62 Foreign Relations DEPARTMENT OF STATE VISAS VISAS: DOCUMENTATION OF NONIMMIGRANTS UNDER THE IMMIGRATION AND... intends to participate, in an exchange visitor program designated by the Bureau of Education and Cultural...

  2. Intersite Coulomb interaction and Heisenberg exchange

    NARCIS (Netherlands)

    Eder, R; van den Brink, J.; Sawatzky, G.A


    Based on exact diagonalization results for small clusters we discuss the effect of intersite Coulomb repulsion in Mott-Hubbard or charge transfers insulators. Whereas the exchange constant J for direct exchange is enhanced by intersite Coulomb interaction, that for superexchange is suppressed. The

  3. Exchange Rate Deregulation and Industrial Performance: An ...

    African Journals Online (AJOL)

    The study found that a long-run relationship exists between the industrial productivity growth rate, ration of industrial production to gross domestic product, exchange rate, interest rate and terms of trade, and that exchange rate deregulation has significant impact on industrial performance. In order to determine the short term ...

  4. Are Student Exchange Programs Worth It? (United States)

    Messer, Dolores; Wolter, Stefan C.


    The number of university students participating in exchange programs has risen sharply over the last decade. A survey of Swiss university graduates (classes of 1999 and 2001) shows that participation in student exchange programs depends significantly on the socio-economic background of students. We further analyze whether the participants benefit…

  5. 76 FR 33993 - Exchange Visitor Program (United States)


    ... due to this employment and accordingly, such students will be deemed to be in valid J-1 Exchange... Part 62 RIN 1400-ZA20 Exchange Visitor Program AGENCY: Department of State. ACTION: Notice of... Libyan students. This action is necessary to mitigate the adverse impact upon these students due to...

  6. Pan-American Teletandem Language Exchange Project (United States)

    Castillo-Scott, Aurora


    This paper describes a TeleTandem language exchange project between English speaking Spanish students at Georgia College, USA, and Spanish speaking English students at Universidad de Concepción, Chile. The aim of the project was to promote linguistic skills and intercultural competence through a TeleTandem exchange. Students used Skype and Google…

  7. Ion exchange in the nuclear industry

    Energy Technology Data Exchange (ETDEWEB)

    Bibler, J.P.


    Ion exchange is used in nearly every part of the nuclear fuel cycle -- from the purification of uranium from its ore to the final recovery of uranium and transmutation products. Ion exchange also plays a valuable role in the management of nuclear wastes generated in the fuel cycle.

  8. Ion exchange in the nuclear industry

    Energy Technology Data Exchange (ETDEWEB)

    Bibler, J.P.


    Ion exchange is used in nearly every part of the nuclear fuel cycle -- from the purification of uranium from its ore to the final recovery of uranium and transmutation products. Ion exchange also plays a valuable role in the management of nuclear wastes generated in the fuel cycle.

  9. Staff Exchange or Legal Alien Programs

    DEFF Research Database (Denmark)

    Jørgensen, Rune Nørgaard


    SRA would very much like to support the exchange of best practice between members throughout the year and the Membership Committee is presently looking into the opportunities for a Staff Exchange or Legal Alien Program. However the International Section has already had the chance to provide...

  10. Synthesis, characterization and ion exchange properties of ...

    Indian Academy of Sciences (India)

    zirconium(IV) oxychloride. Its ion exchange capacity for Na+ and K+ was found to be 2⋅20 and 2⋅35 meq g–1 dry exchanger, respectively. The material has been characterized on the basis of chemical composition, pH titration, Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis. The effect on the.

  11. Anion exchange membrane design for reverse electrodialysis

    NARCIS (Netherlands)

    Güler, E.


    Reverse electrodialysis (RED) is a clean, sustainable technology for the generation of energy from the mixing of solutions with different salinity. The ion exchange membranes are key elements in RED. Especially the study of anion exchange membranes is crucial since limited research has been done

  12. Microsoft Exchange Server PowerShell cookbook

    CERN Document Server

    Andersson, Jonas


    This book is for messaging professionals who want to build real-world scripts with Windows PowerShell 5 and the Exchange Management Shell. If you are a network or systems administrator responsible for managing and maintaining Exchange Server 2013, you will find this highly useful.

  13. Health information exchange among US hospitals. (United States)

    Adler-Milstein, Julia; DesRoches, Catherine M; Jha, Ashish K


    To determine the proportion of US hospitals engaged in health information exchange (HIE) with unaffiliated providers and to identify key hospital-level and market-level factors associated with participating in exchange. Using the 2009 American Hospital Association Information Technology survey, supplemented by Dartmouth Atlas, Area Resource File, and other national data, we examined which hospitals participated in regional efforts to electronically exchange clinical data. We used logistic regression models to determine hospital-level characteristics and market-level characteristics associated with hospitals' likelihood of participating in HIE. We found that 10.7% of US hospitals engaged in HIE with unaffiliated providers. In communities where exchange occurred, for-profit hospitals and those with a small market share were far less likely to engage in HIE than nonprofit hospitals or those with a larger market share. Hospitals in more concentrated markets were more likely to exchange and hospitals in markets with higher Medicare spending were less likely to exchange. At the start of implementation of the Health Information Technology for Economic and Clinical Health (HITECH) Act, only a small minority of US hospitals electronically exchange clinical data with unaffiliated providers. Health information exchange is a key part of reforming the healthcare system, and factors related to competitiveness may be holding some providers back.

  14. Occurrence of the Cys311 DRD2 variant in a pedigree multiply affected with panic disorder

    Energy Technology Data Exchange (ETDEWEB)

    Crawford, F.; Hoyne, J.; Diaz, P. [Univ. of South Florida, Tampa, FL (United States)] [and others


    Following the detection of the rare DRD2 codon 311 variant (Ser{yields}Cys) in an affected member from a large, multiply affected panic disorder family, we investigated the occurrence of this variant in other family members. The variant occurred in both affected and unaffected individuals. Further screening in panic disorder sib pairs unrelated to this family failed to detect the Cys311 variant. Our data suggests that this variant has no pathogenic role in panic disorder. 18 refs., 1 fig.

  15. Exchange fluctuation theorem for correlated quantum systems. (United States)

    Jevtic, Sania; Rudolph, Terry; Jennings, David; Hirono, Yuji; Nakayama, Shojun; Murao, Mio


    We extend the exchange fluctuation theorem for energy exchange between thermal quantum systems beyond the assumption of molecular chaos, and describe the nonequilibrium exchange dynamics of correlated quantum states. The relation quantifies how the tendency for systems to equilibrate is modified in high-correlation environments. In addition, a more abstract approach leads us to a "correlation fluctuation theorem". Our results elucidate the role of measurement disturbance for such scenarios. We show a simple application by finding a semiclassical maximum work theorem in the presence of correlations. We also present a toy example of qubit-qudit heat exchange, and find that non-classical behaviour such as deterministic energy transfer and anomalous heat flow are reflected in our exchange fluctuation theorem.

  16. Pseudo exchange bias due to rotational anisotropy

    Energy Technology Data Exchange (ETDEWEB)

    Ehrmann, A., E-mail: [Faculty of Engineering and Mathematics, Bielefeld University of Applied Sciences, 33619 Bielefeld (Germany); Komraus, S.; Blachowicz, T.; Domino, K. [Institute of Physics – Center for Science and Education, Silesian University of Technology, 44-100 Gliwice (Poland); Nees, M.K.; Jakobs, P.J.; Leiste, H. [Karlsruhe Nano Micro Facility (KNMF), Karlsruhe Institute of Technology (KIT), 76344 Eggenstein-Leopoldshafen (Germany); Mathes, M.; Schaarschmidt, M. [ACCESS e. V., 57072 Aachen (Germany)


    Ferromagnetic nanostructure arrays with particle dimensions between 160 nm and 400 nm were created by electron-beam lithography. The permalloy structures consist of rectangular-shaped walls around a square open space. While measuring their magnetic properties using the Magneto-Optical Kerr Effect (MOKE), in some angular regions an exchange bias (EB) seemed to appear. This paper gives an overview of possible reasons for this “pseudo exchange bias” and shows experimentally and by means of micromagnetic simulations that this effect can be attributed to unintentionally measuring minor loops. - Highlights: • Pseudo exchange bias can be found in square Py nanorings of different dimensions. • Pseudo exchange bias stems from unintentionally measuring minor loops. • New approach in explaining “real” exchange bias effect in coupled FM/AFM systems. • Theoretical base to explain other measurements of a rotational anisotropy.

  17. Fertility as a process of social exchange

    Directory of Open Access Journals (Sweden)

    Patrick Heady


    Full Text Available By marrying and raising children, parents participate in a system of gift-exchange in which the gifts in question are human lives, and the parties to the exchange are the kinship groups recognised in the society concerned. Fertility reflects the attitudes of prospective parents to their place in the existing system of reproductive exchange, and the relationships of cooperation and authority which it implies - as well as their confidence in the system's continuing viability. It is shown that this view is compatible with earlier ideas about self-regulating population systems - and that changing economic circumstances are an important source of discrepancy between existing exchange systems and the attitudes and expectations of prospective parents. The discussion is developed with reference to data on European societies, including a case-study from the Alps, and concludes with an assessment of the relevance of the anthropological theory of gift exchange to contemporary fertility patterns in Europe and beyond.

  18. Ion-exchange chromatography for the characterization of biopharmaceuticals. (United States)

    Fekete, Szabolcs; Beck, Alain; Veuthey, Jean-Luc; Guillarme, Davy


    Ion-exchange chromatography (IEX) is a historical technique widely used for the detailed characterization of therapeutic proteins and can be considered as a reference and powerful technique for the qualitative and quantitative evaluation of charge heterogeneity. The goal of this review is to provide an overview of theoretical and practical aspects of modern IEX applied for the characterization of therapeutic proteins including monoclonal antibodies (Mabs) and antibody drug conjugates (ADCs). The section on method development describes how to select a suitable stationary phase chemistry and dimensions, the mobile phase conditions (pH, nature and concentration of salt), as well as the temperature and flow rate, considering proteins isoelectric point (pI). In addition, both salt-gradient and pH-gradient approaches were critically reviewed and benefits as well as limitations of these two strategies were provided. Finally, several applications, mostly from pharmaceutical industries, illustrate the potential of IEX for the characterization of charge variants of various types of biopharmaceutical products. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Connected speech production in three variants of primary progressive aphasia. (United States)

    Wilson, Stephen M; Henry, Maya L; Besbris, Max; Ogar, Jennifer M; Dronkers, Nina F; Jarrold, William; Miller, Bruce L; Gorno-Tempini, Maria Luisa


    Primary progressive aphasia is a clinical syndrome defined by progressive deficits isolated to speech and/or language, and can be classified into non-fluent, semantic and logopenic variants based on motor speech, linguistic and cognitive features. The connected speech of patients with primary progressive aphasia has often been dichotomized simply as 'fluent' or 'non-fluent', however fluency is a multidimensional construct that encompasses features such as speech rate, phrase length, articulatory agility and syntactic structure, which are not always impacted in parallel. In this study, our first objective was to improve the characterization of connected speech production in each variant of primary progressive aphasia, by quantifying speech output along a number of motor speech and linguistic dimensions simultaneously. Secondly, we aimed to determine the neuroanatomical correlates of changes along these different dimensions. We recorded, transcribed and analysed speech samples for 50 patients with primary progressive aphasia, along with neurodegenerative and normal control groups. Patients were scanned with magnetic resonance imaging, and voxel-based morphometry was used to identify regions where atrophy correlated significantly with motor speech and linguistic features. Speech samples in patients with the non-fluent variant were characterized by slow rate, distortions, syntactic errors and reduced complexity. In contrast, patients with the semantic variant exhibited normal rate and very few speech or syntactic errors, but showed increased proportions of closed class words, pronouns and verbs, and higher frequency nouns, reflecting lexical retrieval deficits. In patients with the logopenic variant, speech rate (a common proxy for fluency) was intermediate between the other two variants, but distortions and syntactic errors were less common than in the non-fluent variant, while lexical access was less impaired than in the semantic variant. Reduced speech rate was

  20. Functional significance of rare neuroligin 1 variants found in autism.

    Directory of Open Access Journals (Sweden)

    Moe Nakanishi


    Full Text Available Genetic mutations contribute to the etiology of autism spectrum disorder (ASD, a common, heterogeneous neurodevelopmental disorder characterized by impairments in social interaction, communication, and repetitive and restricted patterns of behavior. Since neuroligin3 (NLGN3, a cell adhesion molecule at the neuronal synapse, was first identified as a risk gene for ASD, several additional variants in NLGN3 and NLGN4 were found in ASD patients. Moreover, synaptopathies are now known to cause several neuropsychiatric disorders including ASD. In humans, NLGNs consist of five family members, and neuroligin1 (NLGN1 is a major component forming a complex on excitatory glutamatergic synapses. However, the significance of NLGN1 in neuropsychiatric disorders remains unknown. Here, we systematically examine five missense variants of NLGN1 that were detected in ASD patients, and show molecular and cellular alterations caused by these variants. We show that a novel NLGN1 Pro89Leu (P89L missense variant found in two ASD siblings leads to changes in cellular localization, protein degradation, and to the impairment of spine formation. Furthermore, we generated the knock-in P89L mice, and we show that the P89L heterozygote mice display abnormal social behavior, a core feature of ASD. These results, for the first time, implicate rare variants in NLGN1 as functionally significant and support that the NLGN synaptic pathway is of importance in the etiology of neuropsychiatric disorders.

  1. Unclassified sequence variants (UVS and genetic predisposition to cancer

    Directory of Open Access Journals (Sweden)

    Yves-Jean Bignon


    Full Text Available Hereditary breast and ovarian cancers are mainly attributable to predisposition genes whose germinal mutations are responsible for the disease. The most common genes associated with breast/ovarian cancer are BRCA1 and BRCA2 but at least 20 other genes of medium of high penetrance have been associated with these types of cancer. Lifetime risk of breast cancer for BRCA mutations carriers approaches 90%. Appropriate medical follow-up is therefore essential for women carrying mutations in these genes. BRCA mutational spectrum has not been entirely characterized but not all sequence variants are pathogenic. These are classified as benign polymorphisms or unclassified variants (UV with unknown pathological potential. To date, 43,5% of over 3500 genetic variants BRCA1 and BRCA2 are reported as having uncertain clinical significance. Whether one sequence variant has or not a pathogenicity implication is often a hard decision to take, involving important consequences for diagnosis and medical follow-up. Here we present several cases of unclassified sequence variants detection and interpretation by in-silico analysis.

  2. Canine parvovirus: the worldwide occurrence of antigenic variants. (United States)

    Miranda, Carla; Thompson, Gertrude


    The most important enteric virus infecting canids is canine parvovirus type 2 (CPV-2). CPV is the aetiologic agent of a contagious disease, mainly characterized by clinical gastroenteritis signs in younger dogs. CPV-2 emerged as a new virus in the late 1970s, which could infect domestic dogs, and became distributed in the global dog population within 2 years. A few years later, the virus's original type was replaced by a new genetic and antigenic variant, called CPV-2a. Around 1984 and 2000, virus variants with the single change to Asp or Glu in the VP2 residue 426 were detected (sometimes termed CPV-2b and -2c). The genetic and antigenic changes in the variants have also been correlated with changes in their host range; in particular, in the ability to replicate in cats and also host range differences in canine and other tissue culture cells. CPV-2 variants have been circulating among wild carnivores and have been well-documented in several countries around the world. Here, we have reviewed and summarized the current information about the worldwide distribution and evolution of CPV-2 variants since they emerged, as well as the host ranges they are associated with.

  3. De Novo Coding Variants Are Strongly Associated with Tourette Disorder. (United States)

    Willsey, A Jeremy; Fernandez, Thomas V; Yu, Dongmei; King, Robert A; Dietrich, Andrea; Xing, Jinchuan; Sanders, Stephan J; Mandell, Jeffrey D; Huang, Alden Y; Richer, Petra; Smith, Louw; Dong, Shan; Samocha, Kaitlin E; Neale, Benjamin M; Coppola, Giovanni; Mathews, Carol A; Tischfield, Jay A; Scharf, Jeremiah M; State, Matthew W; Heiman, Gary A


    Whole-exome sequencing (WES) and de novo variant detection have proven a powerful approach to gene discovery in complex neurodevelopmental disorders. We have completed WES of 325 Tourette disorder trios from the Tourette International Collaborative Genetics cohort and a replication sample of 186 trios from the Tourette Syndrome Association International Consortium on Genetics (511 total). We observe strong and consistent evidence for the contribution of de novo likely gene-disrupting (LGD) variants (rate ratio [RR] 2.32, p = 0.002). Additionally, de novo damaging variants (LGD and probably damaging missense) are overrepresented in probands (RR 1.37, p = 0.003). We identify four likely risk genes with multiple de novo damaging variants in unrelated probands: WWC1 (WW and C2 domain containing 1), CELSR3 (Cadherin EGF LAG seven-pass G-type receptor 3), NIPBL (Nipped-B-like), and FN1 (fibronectin 1). Overall, we estimate that de novo damaging variants in approximately 400 genes contribute risk in 12% of clinical cases. VIDEO ABSTRACT. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. European multiple sclerosis risk variants in the south Asian population. (United States)

    Pandit, Lekha; Ban, Maria; Beecham, Ashley Harris; McCauley, Jacob L; Sawcer, Stephen; D'Cunha, Anitha; Malli, Chaitra; Malik, Omar


    In less than a decade, genomewide association studies have identified over 100 single-nucleotide variants that are associated with increased risk of developing multiple sclerosis. However, since these studies have focused almost exclusively on European populations, it is unclear what role these variants might play in determining risk in other ethnic groups. To assess the effects of European multiple sclerosis-associated risk variants in the south Asian population. Using a combination of chip-based genotyping and next-generation sequencing, we have assessed 109 European-associated variants in a total of 270 cases and 555 controls from the south Asian population. We found that two-thirds of the tested variants (72/109) showed over representation of the European risk allele in south Asian cases (p TNFSF13B, the gene for the B-cell-related protein BAFF. Our data indicate substantial overlap in genetic risk architecture between Europeans and south Asians and suggest that the aetiology of the disease may be largely independent of ethnicity. © The Author(s), 2016.

  5. [Specificities of the logopenic variant of primary progressive aphasia]. (United States)

    Magnin, E; Teichmann, M; Martinaud, O; Moreaud, O; Ryff, I; Belliard, S; Pariente, J; Moulin, T; Vandel, P; Démonet, J-F


    The logopenic variant of primary progressive aphasia is a syndrome with neuropsychological and linguistic specificities, including phonological loop impairment for which diagnosis is currently mainly based on the exclusion of the two other variants, semantic and nonfluent/agrammatic primary progressive aphasia. The syndrome may be underdiagnosed due (1) to mild language difficulties during the early stages of the disease or (2) to being mistaken for mild cognitive impairment or Alzheimer's disease when the evaluation of episodic memory is based on verbal material and (3) finally, it is not uncommon that the disorders are attributed to psychiatric co-morbidities such as, for example, anxiety. Moreover, compared to other variants of primary progressive aphasia, brain abnormalities are different. The left temporoparietal junction is initially affected. Neuropathology and biomarkers (cerebrospinal fluid, molecular amyloid nuclear imaging) frequently reveal Alzheimer's disease. Consequently this variant of primary progressive aphasia does not fall under the traditional concept of frontotemporal lobar degeneration. These distinctive features highlight the utility of correct diagnosis, classification, and use of biomarkers to show the neuropathological processes underlying logopenic primary progressive aphasia. The logopenic variant of primary progressive aphasia is a specific form of Alzheimer's disease frequently presenting a rapid decline; specific linguistic therapies are needed. Further investigation of this syndrome is needed to refine screening, improve diagnostic criteria and better understand the epidemiology and the biological mechanisms involved. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  6. Common genetic variants influence human subcortical brain structures (United States)

    Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Olde Loohuis, Loes M.; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rose, Emma J.; Salami, Alireza; Sämann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Pütz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Göring, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Mühleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Nöthen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdés Hernández, Maria C.; van ’t Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Völzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E.; Jönsson, Erik G.; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S.; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S.; Saykin, Andrew J.; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M.; Weale, Michael E.; Weinberger, Daniel R.; Adams, Hieab H. H.; Launer, Lenore J.; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L.; Becker, James T.; Yanek, Lisa; van der Lee, Sven J.; Ebling, Maritza; Fischl, Bruce; Longstreth, W. T.; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N.; van Duijn, Cornelia M.; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C.; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M. Arfan; Martin, Nicholas G.; Wright, Margaret J.; Schumann, Gunter; Franke, Barbara; Thompson, Paul M.; Medland, Sarah E.


    The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability inhuman brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. PMID:25607358

  7. [Genetic variants associated to male infertility in Mexican patients]. (United States)

    Piña-Aguilar, Raúl Eduardo; Chima-Galán, María del Carmen; Yerena-de-vega, María de la Concepción A; Regalado-Hernández, Miguel Angel; Sánchez-Guerrero, Cecilia; García-Ortiz, Liliana; Santillán-Hernández, Yuritzi; Moreno-García, Jesús Daniel


    Recently Mexican Federation of Obstetrics and Gynecology Colleges (Federación Mexicana de Colegios de Obstetricia y Ginecologia, FEMECOG) published the Mexican guideline forthe management of male infertility, which suggests performing genetic laboratory tests as part of diagnosis and management of infertile patients and states that these should receive genetic counseling. This paper reviews the genetic approach proposed by Mexican guideline. A systematic review of medical literature was performed in Pubmed and Web of Knowledge from 1980 to 2012 in order to find reports of genetic variants associated to male infertility in Mexican patients. Also it is discussed the current knowledge of these variants, their clinical implications and finally the guidelines and recommendations for their molecular diagnosis. Most genetic variants in Mexican infertile patients are chromosome abnormalities. In relation to other variants there is only a report of Y chromosome microdeletions, repeated CAG in androgen receptor and more common mutations in CFTR, and other article reporting mutations in CFTR in patients with congenital absence of vas deferens. Little is known about the genetics of Mexican infertile patients apart from chromosome abnormalities. However, the contribution of genetics as etiology of male infertility is taking more relevance and currently the consensual management of infertile male should include the screening of genetic background. This review pretends to be a quick guide for clinicians who want to know about reports of genetic variants related to male infertility in Mexican population and how to approach their diagnosis.

  8. Calretinin Variant in Hirschsprung Disease: Pretransitional Sign and Surgical Planning. (United States)

    Muller, Cecile Olivia; Hobeika, Christian; Montalva, Louise; Berrebi, Dominique; Bonnard, Arnaud


    Objectives Calretinin immunohistochemistry (IHC) with slight submucosal positivity (variant) has been reported in short forms of Hirschsprung disease (HD). The first aim of our study was to confirm this variant being a pretransitional sign. The second was to evaluate if its presence on suction rectal biopsy was reliable enough for surgical planning. Methods We performed a monocentric retrospective study of all rectosigmoid HD between 2009 and 2014. Suction rectal biopsy defined two groups of calretinin results: P- group with no staining and P+ group with slight positivity. P- group final resection specimen was retrospectively reanalyzed looking for the variant to appear within the aganglionic bowel. P+ group surgical management was analyzed in terms of initial symptoms, radiological results, type of surgery and outcome, before and after formal identification of the variant by our pathologists (2011). Results Overall, 54 patients with rectosigmoid HD were included from 2009 to 2014. In the P- group (48.2%), the variant pattern finally appeared on all surgical resection specimens, 1 cm before the transitional zone (minimum-maximum: 0-5 cm). In the P+ group, 46% of these patients had peroperative biopsies before the transanal pull through before 2011 against 10% after 2011, with 100% of ganglionic coloanal anastomosis and similar outcome. Conclusion We confirmed our hypothesis of this varied pattern of calretinin being a pretransitional sign only visible on rectal suction biopsies in short segment HD and reliable enough to plan direct transanal pull through. Georg Thieme Verlag KG Stuttgart · New York.

  9. 40 CFR 63.654 - Heat exchange systems. (United States)


    ... any one of the criteria in paragraphs (b)(1) through (2) of this section. (1) All heat exchangers that... any heat exchangers that are in organic HAP service as defined in this subpart). (c) The owner or... each heat exchanger exit line for each heat exchanger or group of heat exchangers in organic HAP...

  10. 40 CFR 63.1409 - Heat exchange system provisions. (United States)


    ... locations where the cooling water enters and exits each heat exchanger or any combination of heat exchangers.... (iii) For samples taken at the entrance and exit of each heat exchanger or any combination of heat exchangers, the entrance is the point at which the cooling water enters the individual heat exchanger or...

  11. 17 CFR 229.802 - Exchange Act industry guides. (United States)


    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Exchange Act industry guides. 229.802 Section 229.802 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION STANDARD... AND CONSERVATION ACT OF 1975-REGULATION S-K List of Industry Guides § 229.802 Exchange Act industry...

  12. Species-specific activity of HIV-1 Vpu and positive selection of tetherin transmembrane domain variants.

    Directory of Open Access Journals (Sweden)

    Matthew W McNatt


    Full Text Available Tetherin/BST-2/CD317 is a recently identified antiviral protein that blocks the release of nascent retrovirus, and other virus, particles from infected cells. An HIV-1 accessory protein, Vpu, acts as an antagonist of tetherin. Here, we show that positive selection is evident in primate tetherin sequences and that HIV-1 Vpu appears to have specifically adapted to antagonize variants of tetherin found in humans and chimpanzees. Tetherin variants found in rhesus macaques (rh, African green monkeys (agm and mice were able to inhibit HIV-1 particle release, but were resistant to antagonism by HIV-1 Vpu. Notably, reciprocal exchange of transmembrane domains between human and monkey tetherins conferred sensitivity and resistance to Vpu, identifying this protein domain as a critical determinant of Vpu function. Indeed, differences between hu-tetherin and rh-tetherin at several positions in the transmembrane domain affected sensitivity to antagonism by Vpu. Two alterations in the hu-tetherin transmembrane domain, that correspond to differences found in rh- and agm-tetherin proteins, were sufficient to render hu-tetherin completely resistant to HIV-1 Vpu. Interestingly, transmembrane and cytoplasmic domain sequences in primate tetherins exhibit variation at numerous codons that is likely the result of positive selection, and some of these changes coincide with determinants of HIV-1 Vpu sensitivity. Overall, these data indicate that tetherin could impose a barrier to viral zoonosis as a consequence of positive selection that has been driven by ancient viral antagonists, and that the HIV-1 Vpu protein has specialized to target the transmembrane domains found in human/chimpanzee tetherin proteins.

  13. The European-American exchange. (United States)

    Guerra, F


    The European-American exchange of infectious diseases was responsible for the demographic havoc of the native population in the New World after 1492. Prior to this date medical writers describe the presence in Spain of viral diseases like influenza, parotitis, smallpox, measles, poliomyelitis, and rabies; there were also rickettsiasis, diphtheria, salmonellosis, plague, tubercolosis, leprosy, malaria, scabies and tinea. In America, before European arrivals, there were no records of human viral diseases, though there were records of rickettsiasis, treponematosis--pinta, yaws and syphilis--leihsmaniasis, amibiasis and perhaps leprosy. With the discovery of America in 1492, Columbus's sailors were contaminated by yaws and spread this disease into Europe. In 1493 influenza, as a zoonosis, was introduced into Santo Domingo and was responsible for the annihilation of the natives of the Antilles in less than a quarter of a century; in 1518 smallpox was also introduced in Santo Domingo and then to the American continent by negro slaves: by the same means measles were introduced in 1531. The previous existence or introduction of other infectious diseases in America is also discussed.

  14. Therapeutic plasma exchange in Casablanca. (United States)

    Tazi, I; Merimi, F; Majd, A; Benchemsi, N


    Therapeutic plasma exchange (TPE) is an extracorporeal blood purification method for the treatment of diseases in which pathological proteins have to be eliminated. In the aim to demonstrate our single center activity, we analyzed our data since 2 years. Between years 2002 and 2005, 104 TPE procedures were performed on 42 patients. Median age and male/female ratio were 32 (range, 17-56) and 24/18, respectively. Departments those referred the majority of the TPE were neurology (n=32), nephrology (n=5) and intensive care unit (n=5). The most common indications were: polyradiculoneuropathies (53%), myasthenia gravis (17%) and Guillain-Barré syndrome (12%). The median TPE procedure per patient was 2.3 (range, 1-10). In the majority of patients, vascular access was provided by puncture of two large, durable peripheral antecubital veins. The procedures were performed with the "Haemonetic Ultralight" discontinuous flow cell separator devices. Citrate solution was used as an anticoagulant in all cases. The substitution fluids most often used in our unit are Albumin 20% solution (92 times), Albumin 4% (10 times) and fresh frozen plasma (twice). Seventy five percent of the patients showed improvement, 7% remained the same and 18% worsened. Thirteen adverse reactions were recorded. The creation of a national registry by the local society is a vital move to improve TPE practice in our country.

  15. The interplanetary exchange of photosynthesis. (United States)

    Cockell, Charles S


    Panspermia, the transfer of organisms from one planet to another, either through interplanetary or interstellar space, remains speculation. However, its potential can be experimentally tested. Conceptually, it is island biogeography on an interplanetary or interstellar scale. Of special interest is the possibility of the transfer of oxygenic photosynthesis between one planet and another, as it can initiate large scale biospheric productivity. Photosynthetic organisms, which must live near the surface of rocks, can be shown experimentally to be subject to destruction during atmospheric transit. Many of them grow as vegetative cells, which are shown experimentally to be susceptible to destruction by shock during impact ejection, although the effectiveness of this dispersal filter can be shown to be mitigated by the characteristics of the cells and their local environment. Collectively these, and other, experiments reveal the particular barriers to the cross-inoculation of photosynthesis. If oxygen biosignatures are eventually found in the atmospheres of extrasolar planets, understanding the potential for the interplanetary exchange of photosynthesis will aid in their interpretation.

  16. Update of CERN exchange network

    CERN Multimedia


    An update of the CERN exchange network will be done next April. Disturbances or even interruptions of telephony services may occur from 4th to 24th April during evenings from 18:30 to 00:00 but will not exceed more than 4 consecutive hours (see tentative planning below). In addition, the voice messaging system will be shut down on March, 26th April from 18:00 to 00:00. Calls supposed to be routed to the voice messaging system will not be possible during the shutdown. CERN divisions are invited to avoid any change requests (set-ups, move or removals) of telephones and fax machines from 4th to 25th April. Everything will be done to minimize potential inconveniences which may occur during this update. There will be no loss of telephone functionalities. CERN GSM portable phones won't be affected by this change. Should you need more details, please send us your questions by email to Date Change type Affected areas March 26 Update of the voice messaging system All CERN sites April...

  17. Update of CERN exchange network

    CERN Multimedia


    An update of the CERN exchange network will be done next April. Disturbances or even interruptions of telephony services may occur from 4th to 24th April during evenings from 18:30 to 00:00 but will not exceed more than 4 consecutive hours (see tentative planning below). In addition, the voice messaging system will be shut down on March, 26th April from 18:00 to 00:00. Calls supposed to be routed to the voice messaging system will not be possible during the shutdown. CERN divisions are invited to avoid any change requests (set-ups, move or removals) of telephones and fax machines from 4th to 25th April. Everything will be done to minimize potential inconveniences which may occur during this update. There will be no loss of telephone functionalities. CERN GSM portable phones won't be affected by this change. Should you need more details, please send us your questions by email to Date Change type Affected areas April 8 Update of switch in LHC 7 LHC 7 Point April 9 Update of...

  18. Update of CERN exchange network

    CERN Multimedia


    An update of the CERN exchange network will be done next April. Disturbances or even interruptions of telephony services may occur from 4th to 24th April during evenings from 18:30 to 00:00 but will not exceed more than 4 consecutive hours (see tentative planning below). In addition, the voice messaging system will be shut down on March, 26th April from 18:00 to 00:00. Calls supposed to be routed to the voice messaging system will not be possible during the shutdown. CERN divisions are invited to avoid any change requests (set-ups, move or removals) of telephones and fax machines from 4th to 25th April. Everything will be done to minimize potential inconveniences which may occur during this update. There will be no loss of telephone functionalities. CERN GSM portable phones won't be affected by this change. Should you need more details, please send us your questions by email to DateChange typeAffected areas March 26Update of the voice messaging systemAll CERN sites April 4Updat...

  19. Update of CERN exchange network

    CERN Multimedia


    An update of the CERN exchange network will be done next April. Disturbances or even interruptions of telephony services may occur from 4th to 24th April during evenings from 18:30 to 00:00 but will not exceed more than 4 consecutive hours (see tentative planning below). CERN divisions are invited to avoid any change requests (set-ups, move or removals) of telephones and fax machines from 4th to 25th April. Everything will be done to minimize potential inconveniences which may occur during this update. There will be no loss of telephone functionalities. CERN GSM portable phones won't be affected by this change. Should you need more details, please send us your questions by email to DateChange typeAffected areas April 11 Update of switch in LHC 4 LHC 4 Point April 14 Update of switch in LHC 5 LHC 5 Point April 15 Update of switches in LHC 3 and LHC 2 Points LHC 3 and LHC 2 April 22 Update of switch N4 Meyrin Ouest April 23 Update of switch  N6 Prévessin Site Ap...

  20. Hb A2-Konz [δ50(D1)Ser → Thr; HBD: c.151T > A]: a new δ chain hemoglobin variant characterized by mass spectrometry and high performance liquid chromatography. (United States)

    Alayi, Tchilabalo Dilezitoko; Van Dorsselaer, Alain; Epting, Thomas; Bissé, Emmanuel; Schaeffer-Reiss, Christine


    We report a new slow-moving δ chain hemoglobin (Hb) variant, named Hb A2-Konz [δ50(D1)Ser → Thr; HBD: c.151T > A]. It was detected during simultaneous measurement of Hb A1C and Hb A2 by high resolution cation exchange high performance liquid chromatography (HPLC) using a PolyCATA column. Hb A2-Konz comprised 0.8% of total Hb. This new variant was identified by peptide mapping using nanoliquid chromatography electrospray ionization-tandem mass spectrometry (nanoLC-ESI-MS/MS) as a serine to threonine substitution at δ50(D1), indicating that the variant was due to a single base change at codon 51 (TCT > ACT) of the δ-globin gene. The new mutant is clinically silent but could lead to a misdiagnosis of β-thalassemia (β-thal) based on the level of Hb A2.

  1. Ionic strength-dependent changes in tentacular ion exchangers with variable ligand density. I. Structural properties. (United States)

    Bhambure, Rahul; Gillespie, Christopher M; Phillips, Michael; Graalfs, Heiner; Lenhoff, Abraham M


    The ligand density critically affects the performance of ion-exchange resins in such measures as the adsorption capacity and transport characteristics. However, for tentacular and other polymer-modified exchangers, the mechanistic basis of the effect of ligand density on performance is not yet fully understood. In this study we map the ionic strength-dependent structural changes in tentacular cation exchangers with variable ligand densities as the basis for subsequent investigation of effects on functional properties. Inverse size-exclusion chromatography (ISEC), scanning electron microscopy (SEM) and small-angle x-ray scattering (SAXS) were used to assess the effect of ionic strength on the pore size and intraparticle architecture of resin variants with different ligand densities. Comparison of ISEC and cryo-SEM results shows a considerable reduction in average pore size with increasing ligand density; these methods also confirm an increase of average pore size at higher ionic strengths. SAXS analysis of ionic strength-dependent conformational changes in the grafted polyelectrolyte layer shows a characteristic ionomer peak at values of the scattering vector q (0.1-0.2Å(-1)) that depend on the ligand density and the ionic strength of the solution. This peak attribution reflects nanoscale changes in the structure of the grafted polyelectrolyte chains that can in turn be responsible for observed pore-size changes in the resins. Finally, salt breakthrough experiments confirm a stronger Donnan exclusion effect on pore accessibility for small ions in the high ligand density variant. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Fine-mapping CASP8 risk variants in breast cancer. (United States)

    Camp, Nicola J; Parry, Marina; Knight, Stacey; Abo, Ryan; Elliott, Graeme; Rigas, Sushilaben H; Balasubramanian, Sabapathy P; Reed, Malcolm W R; McBurney, Helen; Latif, Ayse; Newman, William G; Cannon-Albright, Lisa A; Evans, D Gareth; Cox, Angela


    Multiple genome-wide and candidate gene association studies have been conducted in search of common risk variants for breast cancer. Recent large meta analyses, consolidating evidence from these studies, have been consistent in highlighting the caspase-8 (CASP8) gene as important in this regard. To define a risk haplotype and map the CASP8 gene region with respect to underlying susceptibility variant/s, we screened four genes in the CASP8 region on 2q33-q34 for breast cancer risk. Two independent data sets from the United Kingdom and the United States, including 3,888 breast cancer cases and controls, were genotyped for 45 tagging single nucleotide polymorphisms (tSNP) in the expanded CASP8 region. SNP and haplotype association tests were carried out using Monte Carlo-based methods. We identified a three-SNP haplotype across rs3834129, rs6723097, and rs3817578 that was significantly associated with breast cancer (P breast carcinogenesis.

  3. A hierarchical particle swarm optimizer and its adaptive variant. (United States)

    Janson, Stefan; Middendorf, Martin


    A hierarchical version of the particle swarm optimization (PSO) metaheuristic is introduced in this paper. In the new method called H-PSO, the particles are arranged in a dynamic hierarchy that is used to define a neighborhood structure. Depending on the quality of their so-far best-found solution, the particles move up or down the hierarchy. This gives good particles that move up in the hierarchy a larger influence on the swarm. We introduce a variant of H-PSO, in which the shape of the hierarchy is dynamically adapted during the execution of the algorithm. Another variant is to assign different behavior to the individual particles with respect to their level in the hierarchy. H-PSO and its variants are tested on a commonly used set of optimization functions and are compared to PSO using different standard neighborhood schemes.

  4. Massively Parallel Functional Analysis of BRCA1 RING Domain Variants. (United States)

    Starita, Lea M; Young, David L; Islam, Muhtadi; Kitzman, Jacob O; Gullingsrud, Justin; Hause, Ronald J; Fowler, Douglas M; Parvin, Jeffrey D; Shendure, Jay; Fields, Stanley


    Interpreting variants of uncertain significance (VUS) is a central challenge in medical genetics. One approach is to experimentally measure the functional consequences of VUS, but to date this approach has been post hoc and low throughput. Here we use massively parallel assays to measure the effects of nearly 2000 missense substitutions in the RING domain of BRCA1 on its E3 ubiquitin ligase activity and its binding to the BARD1 RING domain. From the resulting scores, we generate a model to predict the capacities of full-length BRCA1 variants to support homology-directed DNA repair, the essential role of BRCA1 in tumor suppression, and show that it outperforms widely used biological-effect prediction algorithms. We envision that massively parallel functional assays may facilitate the prospective interpretation of variants observed in clinical sequencing. Copyright © 2015 by the Genetics Society of America.

  5. Arrhythmogenic KCNE gene variants: current knowledge and future challenges

    Directory of Open Access Journals (Sweden)

    Shawn M Crump


    Full Text Available There are twenty-five known inherited cardiac arrhythmia susceptibility genes, all of which encode either ion channel pore-forming subunits or proteins that regulate aspects of ion channel biology such as function, trafficking and localization. The human KCNE gene family comprises five potassium channel regulatory subunits, sequence variants in each of which are associated with cardiac arrhythmias. KCNE gene products exhibit promiscuous partnering and in some cases ubiquitous expression, hampering efforts to unequivocally correlate each gene to specific native potassium currents. Likewise, deducing the molecular etiology of cardiac arrhythmias in individuals harboring rare KCNE gene variants, or more common KCNE polymorphisms, can be challenging. In this review we provide an update on putative arrhythmia-causing KCNE gene variants, and discuss current thinking and future challenges in the study of molecular mechanisms of KCNE-associated cardiac rhythm disturbances.

  6. Retinal vascular nonperfusion in siblings with Dandy-Walker variant. (United States)

    Rusu, Irene; Gupta, Mrinali Patel; Patel, Samir N; Oltra, Erica; Chan, R V Paul


    We report the case of a 2-month-old girl with Dandy-Walker variant who presented with strabismus, pathologic myopia measuring -16.00 D in each eye, diffuse chorioretinal atrophy and pigment mottling in the macula of both eyes, and areas of retinal capillary nonperfusion in both eyes. The patient's brother also has Dandy-Walker variant and was found to have bilateral severe myopia, myopic fundi, tilted optic disks with peripapillary atrophy, extensive areas of white without pressure, areas of lattice degeneration, and several chronic-appearing atrophic retinal holes surrounded by pigmentation. We hypothesize that children with Dandy-Walker variant may present with refractive errors such as pathologic myopia and with diverse retinal findings, including retinal ischemia. A lower threshold for ophthalmologic examination may be considered in this population. Copyright © 2016 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

  7. Splice variants of porcine PPHLN1 encoding periphilin-1

    DEFF Research Database (Denmark)

    Larsen, Knud Erik; Momeni, Jamal; Farajzadeh, Leila


    of the periphilin-1 protein. Thus, variants Sp1 and Sp1 are the result of alternative splicing. The porcine PPHLN1 gene was mapped to chromosome 5. The porcine PPHLN1 gene was found to be differentially expressed in various porcine organs and tissues. The sequence of the porcine PPHLN1 cDNA, encoding the periphilin......The periphilin-1 protein is encoded by the PPHLN1 gene. Periphilin-1 is found in the cornified cell envelope during the terminal differentiation of keratinocyte at the outer layer of epidermis. In the current study we report on the cloning and characterization of the porcine PPHLN1 cDNA and two...... splice variants hereof. RT-PCR cloning using oligonucleotide primers derived from in silico sequences resulted in three PPHLN1 transcripts: a full-length mRNA and two transcript variant resulting in shorter proteins. The longest encoded periphilin-1, consisting of 373 amino acids, displays a high...

  8. 75 FR 55381 - Joint Industry Plan; Order Approving Amendment To Add EDGA Exchange, Inc. and EDGX Exchange, Inc... (United States)


    ... COMMISSION Joint Industry Plan; Order Approving Amendment To Add EDGA Exchange, Inc. and EDGX Exchange, Inc... participants to the Joint-SRO Plan are the American Stock Exchange LLC (n/k/a NYSE Amex, Inc.), BATS Exchange... exchange or national securities association may become a party to the Plan by: (i) Executing a copy of the...

  9. Fire Usage and Ancient Hominin Detoxification Genes: Protective Ancestral Variants Dominate While Additional Derived Risk Variants Appear in Modern Humans.

    Directory of Open Access Journals (Sweden)

    Jac M M J G Aarts

    Full Text Available Studies of the defence capacity of ancient hominins against toxic substances may contribute importantly to the reconstruction of their niche, including their diets and use of fire. Fire usage implies frequent exposure to hazardous compounds from smoke and heated food, known to affect general health and fertility, probably resulting in genetic selection for improved detoxification. To investigate whether such genetic selection occurred, we investigated the alleles in Neanderthals, Denisovans and modern humans at gene polymorphisms well-known to be relevant from modern human epidemiological studies of habitual tobacco smoke exposure and mechanistic evidence. We compared these with the alleles in chimpanzees and gorillas. Neanderthal and Denisovan hominins predominantly possess gene variants conferring increased resistance to these toxic compounds. Surprisingly, we observed the same in chimpanzees and gorillas, implying that less efficient variants are derived and mainly evolved in modern humans. Less efficient variants are observable from the first early Upper Palaeolithic hunter-gatherers onwards. While not clarifying the deep history of fire use, our results highlight the long-term stability of the genes under consideration despite major changes in the hominin dietary niche. Specifically for detoxification gene variants characterised as deleterious by epidemiological studies, our results confirm the predominantly recent appearance reported for deleterious human gene variants, suggesting substantial impact of recent human population history, including pre-Holocene expansions.

  10. Fire Usage and Ancient Hominin Detoxification Genes: Protective Ancestral Variants Dominate While Additional Derived Risk Variants Appear in Modern Humans (United States)

    Alink, Gerrit M.; Scherjon, Fulco; MacDonald, Katharine; Smith, Alison C.; Nijveen, Harm; Roebroeks, Wil


    Studies of the defence capacity of ancient hominins against toxic substances may contribute importantly to the reconstruction of their niche, including their diets and use of fire. Fire usage implies frequent exposure to hazardous compounds from smoke and heated food, known to affect general health and fertility, probably resulting in genetic selection for improved detoxification. To investigate whether such genetic selection occurred, we investigated the alleles in Neanderthals, Denisovans and modern humans at gene polymorphisms well-known to be relevant from modern human epidemiological studies of habitual tobacco smoke exposure and mechanistic evidence. We compared these with the alleles in chimpanzees and gorillas. Neanderthal and Denisovan hominins predominantly possess gene variants conferring increased resistance to these toxic compounds. Surprisingly, we observed the same in chimpanzees and gorillas, implying that less efficient variants are derived and mainly evolved in modern humans. Less efficient variants are observable from the first early Upper Palaeolithic hunter-gatherers onwards. While not clarifying the deep history of fire use, our results highlight the long-term stability of the genes under consideration despite major changes in the hominin dietary niche. Specifically for detoxification gene variants characterised as deleterious by epidemiological studies, our results confirm the predominantly recent appearance reported for deleterious human gene variants, suggesting substantial impact of recent human population history, including pre-Holocene expansions. PMID:27655273

  11. Optimization of parameters of heat exchangers vehicles

    Directory of Open Access Journals (Sweden)

    Andrei MELEKHIN


    Full Text Available The relevance of the topic due to the decision of problems of the economy of resources in heating systems of vehicles. To solve this problem we have developed an integrated method of research, which allows to solve tasks on optimization of parameters of heat exchangers vehicles. This method decides multicriteria optimization problem with the program nonlinear optimization on the basis of software with the introduction of an array of temperatures obtained using thermography. The authors have developed a mathematical model of process of heat exchange in heat exchange surfaces of apparatuses with the solution of multicriteria optimization problem and check its adequacy to the experimental stand in the visualization of thermal fields, an optimal range of managed parameters influencing the process of heat exchange with minimal metal consumption and the maximum heat output fin heat exchanger, the regularities of heat exchange process with getting generalizing dependencies distribution of temperature on the heat-release surface of the heat exchanger vehicles, defined convergence of the results of research in the calculation on the basis of theoretical dependencies and solving mathematical model.

  12. High heat flux single phase heat exchanger (United States)

    Valenzuela, Javier A.; Izenson, Michael G.


    This paper presents the results obtained to date in a program to develop a high heat flux, single-phase heat exchanger for spacecraft thermal management. The intended application is a net generation interface heat exchanger to couple the crew module water thermal bus to the two-phase ammonia main thermal bus in the Space Station Freedom. The large size of the interface heat exchanger is dictated by the relatively poor water-side heat transfer characteristics. The objective of this program is to develop a single-phase heat transfer approach which can achieve heat fluxes and heat transfer coefficients comparable to those of the evaporation ammonia side. A new heat exchanger concept has been developed to meet these objecties. The main feature of this heat exchanger is that it can achieve very high heat fluxes with a pressure drop one to two orders of magnitude lower than those of previous microchannel or jet impingement high heat flux heat exchangers. This paper describes proof-of-concept experiments performed in air and water and presents analytical model of the heat exchanger.

  13. Ion Exchange Formation via Sulfonated Bicomponent Nonwovens (United States)

    Stoughton, Hannah L.

    For many years ion exchange resins were used to: remove heavy metals from water, recover materials from wastewater, and eliminate harmful gases from the air. While use of these resin beads dominates the ion exchange industry, the beads have limitations that should be considered when decisions are made to employ them. For instance, officials must balance the inherent zero sum surface area and porosity of the materials. This series of studies investigates the use of bicomponent nonwovens as a base substrate for producing high surface area ion exchange materials for the removal of heavy metal ions. Functionalized materials were produced in a two-step process: (1) PET/PE spunbond bicomponent fibers were fractured completely, producing the high surface area nonwoven to be used as the base ion exchange material, and (2) the conditions for functionalizing the PET fibers of the nonwoven webs were investigated where an epoxy containing monomer was grafted to the surface followed by sulfonation of the monomer. The functionalization reactions of the PET fibers were monitored based on: weight gain, FTIR, TOF-SIMS, and SEM. Ion exchange properties were evaluated using titration and copper ion removal capacity from test solutions. The relationship between web structure and removal efficiency of the metal ions was defined through a comparison of the bicomponent and homocomponent nonwovens for copper ion removal efficiency. The investigation revealed that utilizing the high surface area, fractured bicomponent nonwoven ion exchange materials with capacities comparable to commercially available ion exchange resins could be produced.

  14. Searching for an Appropriate Exchange Rate Regime

    Directory of Open Access Journals (Sweden)

    Yunjong Wang


    Full Text Available This paper attempts to survey current debates on the choice of exchange rate regime in emerging market economies. The issue of choosing an appropriate exchange rate regime is being actively discussed since the recent Asian crisis. As a lesson from the recent crises, one widely shared conclusion is that soft peg exchange rate regimes are extremely vulnerable in a world of volatile capital movements. Consequently, new orthodoxy based on the impossible trinity hypothesis favours two corner solutions ― greater flexibility or credible institutional assurance, like a currency board system or dollarization. Nevertheless, questions whether such corner solutions are adequate for developing countries are rising of late. "Fear of floating" is still conspicuous in many developing countries having adopted nominally a free-floating exchange rate regime. Developing countries are sensitive to exchange rate fluctuations because the cost of exchange rate volatility is greater than the benefit when compared to developed countries. Monitoring bands is a compromise solution, but it still needs further enhancement of estimation techniques for fundamental equilibrium exchange rates in order to make those estimation results more workable in practice. Other alternatives include the creation of soft peg of the G-3 currencies. Despite counterarguments, the stability of G-3 currencies could prove to be beneficial to emerging market economies.

  15. Tear exchange and contact lenses: a review. (United States)

    Muntz, Alex; Subbaraman, Lakshman N; Sorbara, Luigina; Jones, Lyndon


    Tear exchange beneath a contact lens facilitates ongoing fluid replenishment between the ocular surface and the lens. This exchange is considerably lower during the wear of soft lenses compared with rigid lenses. As a result, the accumulation of tear film debris and metabolic by-products between the cornea and a soft contact lens increases, potentially leading to complications. Lens design innovations have been proposed, but no substantial improvement in soft lens tear exchange has been reported. Researchers have determined post-lens tear exchange using several methods, notably fluorophotometry. However, due to technological limitations, little remains known about tear hydrodynamics around the lens and, to-date, true tear exchange with contact lenses has not been shown. Further knowledge regarding tear exchange could be vital in aiding better contact lens design, with the prospect of alleviating certain adverse ocular responses. This article reviews the literature to-date on the significance, implications and measurement of tear exchange with contact lenses. Copyright © 2014 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.

  16. Research of Spined Heat-Exchanging Pipes

    Directory of Open Access Journals (Sweden)

    Akulov Kirill


    Full Text Available Work is devoted to a research of spined heat-exchanging pipes that are assumed to use in air-cooler exchangers (ACE. The proposed new geometry of finning allows intensifying heat exchange and improving the efficiency of air coolers. It is caused by the increased area of finned surface with a value of finning ratio (the ratio of the area of the smooth pipe to a finned one to 42.7, while in the commercially available ACE, the figure is 22. Besides, the geometrical arrangement of the pin fins turbulizes the airflow. It should be mentioned that an easier method of manufacturing of heat exchanging pipes is proposed to use, which will reduce their costs. The proposed heat exchange pipes are made by winding cut aluminum strip to the supporting pipe or stretching stamped blanks on it. To increase the efficiency of the heat exchange surface pin fins should be as thin and long as possible; however, their strength should be sufficient for deformation-free operation. Fins should be staggered to maximize the distance between them. Spined heat-exchange pipes are designed to operate in a commercially produced ACE and their service is carried out similarly to commercially produced transversely finned pipes.

  17. Impact of MYH6 variants in hypoplastic left heart syndrome (United States)

    Stamm, Karl D.; Mahnke, Donna K.; Kim, Min-Su; Hidestrand, Pip M.; Liang, Huan Ling; Goetsch, Mary A.; Hidestrand, Mats; Simpson, Pippa; Pelech, Andrew N.; Tweddell, James S.; Benson, D. Woodrow; Lough, John W.; Mitchell, Michael E.


    Hypoplastic left heart syndrome (HLHS) is a clinically and anatomically severe form of congenital heart disease (CHD). Although prior studies suggest that HLHS has a complex genetic inheritance, its etiology remains largely unknown. The goal of this study was to characterize a risk gene in HLHS and its effect on HLHS etiology and outcome. We performed next-generation sequencing on a multigenerational family with a high prevalence of CHD/HLHS, identifying a rare variant in the α-myosin heavy chain (MYH6) gene. A case-control study of 190 unrelated HLHS subjects was then performed and compared with the 1000 Genomes Project. Damaging MYH6 variants, including novel, missense, in-frame deletion, premature stop, de novo, and compound heterozygous variants, were significantly enriched in HLHS cases (P < 1 × 10−5). Clinical outcomes analysis showed reduced transplant-free survival in HLHS subjects with damaging MYH6 variants (P < 1 × 10−2). Transcriptome and protein expression analyses with cardiac tissue revealed differential expression of cardiac contractility genes, notably upregulation of the β-myosin heavy chain (MYH7) gene in subjects with MYH6 variants (P < 1 × 10−3). We subsequently used patient-specific induced pluripotent stem cells (iPSCs) to model HLHS in vitro. Early stages of in vitro cardiomyogenesis in iPSCs derived from two unrelated HLHS families mimicked the increased expression of MYH7 observed in vivo (P < 1 × 10−2), while revealing defective cardiomyogenic differentiation. Rare, damaging variants in MYH6 are enriched in HLHS, affect molecular expression of contractility genes, and are predictive of poor outcome. These findings indicate that the etiology of MYH6-associated HLHS can be informed using iPSCs and suggest utility in future clinical applications. PMID:27789736

  18. Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients (United States)

    Sadovnick, A. Dessa; Traboulsee, Anthony L.; Bernales, Cecily Q.; Ross, Jay P.; Forwell, Amanda L.; Yee, Irene M.; Guillot-Noel, Lena; Fontaine, Bertrand; Cournu-Rebeix, Isabelle; Alcina, Antonio; Fedetz, Maria; Izquierdo, Guillermo; Matesanz, Fuencisla; Hilven, Kelly; Dubois, Bénédicte; Goris, An; Astobiza, Ianire; Alloza, Iraide; Antigüedad, Alfredo; Vandenbroeck, Koen; Akkad, Denis A.; Aktas, Orhan; Blaschke, Paul; Buttmann, Mathias; Chan, Andrew; Epplen, Joerg T.; Gerdes, Lisa-Ann; Kroner, Antje; Kubisch, Christian; Kümpfel, Tania; Lohse, Peter; Rieckmann, Peter; Zettl, Uwe K.; Zipp, Frauke; Bertram, Lars; Lill, Christina M; Fernandez, Oscar; Urbaneja, Patricia; Leyva, Laura; Alvarez-Cermeño, Jose Carlos; Arroyo, Rafael; Garagorri, Aroa M.; García-Martínez, Angel; Villar, Luisa M.; Urcelay, Elena; Malhotra, Sunny; Montalban, Xavier; Comabella, Manuel; Berger, Thomas; Fazekas, Franz; Reindl, Markus; Schmied, Mascha C.; Zimprich, Alexander; Vilariño-Güell, Carles


    Multiple sclerosis (MS) is a prevalent neurological disease of complex etiology. Here, we describe the characterization of a multi-incident MS family that nominated a rare missense variant (p.G420D) in plasminogen (PLG) as a putative genetic risk factor for MS. Genotyping of PLG p.G420D (rs139071351) in 2160 MS patients, and 886 controls from Canada, identified 10 additional probands, two sporadic patients and one control with the variant. Segregation in families harboring the rs139071351 variant, identified p.G420D in 26 out of 30 family members diagnosed with MS, 14 unaffected parents, and 12 out of 30 family members not diagnosed with disease. Despite considerably reduced penetrance, linkage analysis supports cosegregation of PLG p.G420D and disease. Genotyping of PLG p.G420D in 14446 patients, and 8797 controls from Canada, France, Spain, Germany, Belgium, and Austria failed to identify significant association with disease (P = 0.117), despite an overall higher prevalence in patients (OR = 1.32; 95% CI = 0.93–1.87). To assess whether additional rare variants have an effect on MS risk, we sequenced PLG in 293 probands, and genotyped all rare variants in cases and controls. This analysis identified nine rare missense variants, and although three of them were exclusively observed in MS patients, segregation does not support pathogenicity. PLG is a plausible biological candidate for MS owing to its involvement in immune system response, blood-brain barrier permeability, and myelin degradation. Moreover, components of its activation cascade have been shown to present increased activity or expression in MS patients compared to controls; further studies are needed to clarify whether PLG is involved in MS susceptibility. PMID:27194806

  19. Theory of laser enhancement and suppression of cold reactions: the fermion-boson 6Li+7Li2(variant Planck's over 2pi omega0) 6Li7Li+7Li radiative collision. (United States)

    Li, Xuan; Parker, Gregory A; Brumer, Paul; Thanopulos, Ioannis; Shapiro, Moshe


    We present a nonperturbative time-dependent quantum mechanical theory of the laser catalysis and control of a bifurcating A+BC(variant Planck's over 2pi omega(0))ABC*(v)(variant Planck's over 2pi omega(0) )AB+C reaction, with ABC*(v) denoting an intermediate, electronically excited, complex of ABC in the vth vibrational state. We apply this theory to the low collision energy fermion-boson light-induced exchange reaction, (6)Li((2)S)+(7)Li(2)((3)Sigma(u)(+))(variant Planck's over 2pi omega(0))((6)Li(7)Li(7)Li)*(variant Planck's over 2pi omega(0))(6)Li(7)Li((3)Sigma(+))+(7)Li((2)S). We show that at very low collision energies and energetically narrow (approximately 0.01 cm(-1)) initial reactant wave packets, it is possible to tune the yield of the exchange reaction from 0 to near-unity (yield >or=99%) values. Controllability is somewhat reduced at collisions involving energetically wider (approximately 1 cm(-1)) initial reactant wave packets. At these energetic bandwidths, the radiative reactive control, although still impressive, is limited to the 0%-76% reactive-probabilities range.

  20. Refractive outcomes after multifocal intraocular lens exchange. (United States)

    Kim, Eric J; Sajjad, Ahmar; Montes de Oca, Ildamaris; Koch, Douglas D; Wang, Li; Weikert, Mitchell P; Al-Mohtaseb, Zaina N


    To evaluate the refractive outcomes after multifocal intraocular lens (IOL) exchange. Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, USA. Retrospective case series. Patients had multifocal IOL explantation followed by IOL implantation. Outcome measures included type of IOL, surgical indication, corrected distance visual acuity (CDVA), and refractive prediction error. The study comprised 29 patients (35 eyes). The types of IOLs implanted after multifocal IOL explantation included in-the-bag IOLs (74%), iris-sutured IOLs (6%), sulcus-fixated IOLs with optic capture (9%), sulcus-fixated IOLs without optic capture (9%), and anterior chamber IOLs (3%). The surgical indication for exchange included blurred vision (60%), photic phenomena (57%), photophobia (9%), loss of contrast sensitivity (3%), and multiple complaints (29%). The CDVA was 20/40 or better in 94% of eyes before the exchange and 100% of eyes after the exchange (P = .12). The mean refractive prediction error significantly decreased from 0.22 ± 0.81 diopter (D) before the exchange to -0.09 ± 0.53 D after the exchange (P < .05). The median absolute refractive prediction error significantly decreased from 0.43 D before the exchange to 0.23 D after the exchange (P < .05). Multifocal IOL exchange can be performed safely with good visual outcomes using different types of IOLs. A lower refractive prediction error and a higher likelihood of 20/40 or better vision can be achieved with the implantation of the second IOL compared with the original multifocal IOL, regardless of the final IOL position. Copyright © 2017 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.