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Sample records for huntingtin amino-terminal region

  1. Structure of antigenetic determinants in the amino-terminal region of bovine fibrinogen Aα chain

    International Nuclear Information System (INIS)

    Tanswell, P.; Reiter, H.; Timpl, R.

    1978-01-01

    A radioimmunoassay was developed for peptide F-CB1α from the amino of bovine fibrinogen Aα chain, isolated after reduction and carboxymethylation of the multichain disulfide-linked cyanogen bromide peptide F-CB1. Seven out of twelve different rabbit antisera produced against fibrinogen, peptide F-CB1 or Aα chain showed distinct binding to 125 I-labelled F-CB1α. Thrombin cleavage of F-CB1α yielded two fragments: fibrinopeptide A (residues 1-19) and the carboxy-terminal fragment Th2 (residues 20-54). Antisera could be classified into three groups according to whether they recognized antigenic determinants on fibrinopeptide A, on peptide Th2 or as they showed diminished reactions with both fragments. Only little or no cross-reaction was observed with the amino-terminal cyanogen bromide peptides of Bβ and γ chain. Proteolytic fragments of fibrinopeptide A were isolated and tested for inhibitory activity with two antisera. One antiserum contained anitbodies binding selectively to the amino-terminal sequence (residues 4-11) and did not cross-react with human fibrinopeptide A. Another antiserum showed a specific binding restricted to the carboxy-terminal sequence (residues 11-18) and cross-reacted completely with human fibrinopeptide A. These results correlate well with the primary structures of the two fibrinopeptides. The antigenic activity of the peptide fragment Th2 was localized on a 15-residue tryptic peptide derived from the central portion of the sequence. These and further data indicate that at least six different antigenic determinants are present in peptide F-CB1α. (orig.) 891 AJ [de

  2. Amino Terminal Region of Dengue Virus NS4A Cytosolic Domain Binds to Highly Curved Liposomes

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    Yu-Fu Hung

    2015-07-01

    Full Text Available Dengue virus (DENV is an important human pathogen causing millions of disease cases and thousands of deaths worldwide. Non-structural protein 4A (NS4A is a vital component of the viral replication complex (RC and plays a major role in the formation of host cell membrane-derived structures that provide a scaffold for replication. The N-terminal cytoplasmic region of NS4A(1–48 is known to preferentially interact with highly curved membranes. Here, we provide experimental evidence for the stable binding of NS4A(1–48 to small liposomes using a liposome floatation assay and identify the lipid binding sequence by NMR spectroscopy. Mutations L6E;M10E were previously shown to inhibit DENV replication and to interfere with the binding of NS4A(1–48 to small liposomes. Our results provide new details on the interaction of the N-terminal region of NS4A with membranes and will prompt studies of the functional relevance of the curvature sensitive membrane anchor at the N-terminus of NS4A.

  3. Sequence of the amino-terminal region of rat liver ribosomal proteins S4, S6, S8, L6, L7a, L18, L27, L30, L37, L37a, and L39.

    Science.gov (United States)

    Wittmann-Liebold, B; Geissler, A W; Lin, A; Wool, I G

    1979-01-01

    The sequence of the amino-terminal region of eleven rat liver ribosomal proteins--S4, S6, S8, L6, L7a, L18, L27, L30, L37a, and L39--was determined. The analysis confirmed the homogeneity of the proteins and suggests that they are unique, since no extensive common sequences were found. The N-terminal regions of the rat liver proteins were compared with amino acid sequences in Saccharomyces cerevisiae and in Escherichia coli ribosomal proteins. It seems likely that the proteins L37 from rat liver and Y55 from yeast ribosomes are homologous. It is possible that rat liver L7a or L37a or both are related to S cerevisiae Y44, although the similar sequences are at the amino-terminus of the rat liver proteins and in an internal region of Y44. A number of similarities in the sequences of rat liver and E coli ribosomal proteins have been found; however, it is not yet possible to say whether they connote a common ancestry.

  4. Nucleotide sequence of a cDNA coding for the amino-terminal region of human prepro. alpha. 1(III) collagen

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    Toman, P D; Ricca, G A [Rorer Biotechnology, Inc., Springfield, VA (USA); de Crombrugghe, B [National Institutes of Health, Bethesda, MD (USA)

    1988-07-25

    Type III Collagen is synthesized in a variety of tissues as a precursor macromolecule containing a leader sequence, a N-propeptide, a N-telopeptide, the triple helical region, a C-telopeptide, and C-propeptide. To further characterize the human type III collagen precursor, a human placental cDNA library was constructed in gt11 using an oligonucleotide derived from a partial cDNA sequence corresponding to the carboxy-terminal part of the 1(III) collagen. A cDNA was identified which contains the leader sequence, the N-propeptide and N-telopeptide regions. The DNA sequence of these regions are presented here. The triple helical, C-telopeptide and C-propeptide amino acid sequence for human type III collagen has been determined previously. A comparison of the human amino acid sequence with mouse, chicken, and calf sequence shows 81%, 81%, and 92% similarity, respectively. At the DNA level, the sequence similarity between human and mouse or chicken type III collagen sequences in this area is 82% and 77%, respectively.

  5. Functional interactions of the AF-2 activation domain core region of the human androgen receptor with the amino-terminal domain and with the transcriptional coactivator TIF2 (transcriptional intermediary factor2)

    NARCIS (Netherlands)

    C.A. Berrevoets (Cor); P. Doesburg (Paul); K. Steketee (Karine); J. Trapman (Jan); A.O. Brinkmann (Albert)

    1998-01-01

    textabstractPrevious studies in yeast and mammalian cells showed a functional interaction between the amino-terminal domain and the carboxy-terminal, ligand-binding domain (LBD) of the human androgen receptor (AR). In the present study, the AR subdomains involved in

  6. Assessment of the PrPc Amino-Terminal Domain in Prion Species Barriers.

    Science.gov (United States)

    Davenport, Kristen A; Henderson, Davin M; Mathiason, Candace K; Hoover, Edward A

    2016-12-01

    Chronic wasting disease (CWD) in cervids and bovine spongiform encephalopathy (BSE) in cattle are prion diseases that are caused by the same protein-misfolding mechanism, but they appear to pose different risks to humans. We are interested in understanding the differences between the species barriers of CWD and BSE. We used real-time, quaking-induced conversion (RT-QuIC) to model the central molecular event in prion disease, the templated misfolding of the normal prion protein, PrP c , to a pathogenic, amyloid isoform, scrapie prion protein, PrP Sc We examined the role of the PrP c amino-terminal domain (N-terminal domain [NTD], amino acids [aa] 23 to 90) in cross-species conversion by comparing the conversion efficiency of various prion seeds in either full-length (aa 23 to 231) or truncated (aa 90 to 231) PrP c We demonstrate that the presence of white-tailed deer and bovine NTDs hindered seeded conversion of PrP c , but human and bank vole NTDs did the opposite. Additionally, full-length human and bank vole PrP c s were more likely to be converted to amyloid by CWD prions than were their truncated forms. A chimera with replacement of the human NTD by the bovine NTD resembled human PrP c The requirement for an NTD, but not for the specific human sequence, suggests that the NTD interacts with other regions of the human PrP c to increase promiscuity. These data contribute to the evidence that, in addition to primary sequence, prion species barriers are controlled by interactions of the substrate NTD with the rest of the substrate PrP c molecule. We demonstrate that the amino-terminal domain of the normal prion protein, PrP c , hinders seeded conversion of bovine and white-tailed deer PrP c s to the prion forms, but it facilitates conversion of the human and bank vole PrP c s to the prion forms. Additionally, we demonstrate that the amino-terminal domain of human and bank vole PrP c s requires interaction with the rest of the molecule to facilitate conversion by CWD

  7. AAV-mediated delivery of the transcription factor XBP1s into the striatum reduces mutant Huntingtin aggregation in a mouse model of Huntington’s disease

    International Nuclear Information System (INIS)

    Zuleta, Amparo; Vidal, Rene L.; Armentano, Donna; Parsons, Geoffrey; Hetz, Claudio

    2012-01-01

    Highlights: ► The contribution of ER stress to HD has not been directly addressed. ► Expression of XBP1s using AAVs decreases Huntingtin aggregation in vivo. ► We describe a new in vivo model of HD based on the expression of a large fragment of mHtt-RFP. -- Abstract: Huntington’s disease (HD) is caused by mutations that expand a polyglutamine region in the amino-terminal domain of Huntingtin (Htt), leading to the accumulation of intracellular inclusions and progressive neurodegeneration. Recent reports indicate the engagement of endoplasmic reticulum (ER) stress responses in human HD post mortem samples and animal models of the disease. Adaptation to ER stress is mediated by the activation of the unfolded protein response (UPR), an integrated signal transduction pathway that attenuates protein folding stress by controlling the expression of distinct transcription factors including X-Box binding protein 1 (XBP1). Here we targeted the expression of XBP1 on a novel viral-based model of HD. We delivered an active form of XBP1 locally into the striatum of adult mice using adeno-associated vectors (AAVs) and co-expressed this factor with a large fragment of mutant Htt as a fusion protein with RFP (Htt588 Q95 -mRFP) to directly visualize the accumulation of Htt inclusions in the brain. Using this approach, we observed a significant reduction in the accumulation of Htt588 Q95 -mRFP intracellular inclusion when XBP1 was co-expressed in the striatum. These results contrast with recent findings indicating a protective effect of XBP1 deficiency in neurodegeneration using knockout mice, and suggest a potential use of gene therapy strategies to manipulate the UPR in the context of HD.

  8. Fate of circulating amino-terminal propeptide of type III procollagen in conscious pigs

    DEFF Research Database (Denmark)

    Jensen, L T; Henriksen, Jens Henrik Sahl; Risteli, J

    1993-01-01

    The amino-terminal propeptide of type III procollagen (PIIINP, M(r) 42,000) is a promising marker for the formation of type III collagen of granulation tissue in experimental and clinical studies. The disposal kinetics of circulating PIIINP is, however, almost unknown. In conscious pigs with a th......The amino-terminal propeptide of type III procollagen (PIIINP, M(r) 42,000) is a promising marker for the formation of type III collagen of granulation tissue in experimental and clinical studies. The disposal kinetics of circulating PIIINP is, however, almost unknown. In conscious pigs...... of the plasma disappearance curve originated from the formation and disappearance of a high and a low molecular weight (MW) fraction as part of the degradation of PIIINP. The high MW fraction (approximately M(r) 90,000) was similar to a previously described, but not further characterized, PIIINP immunoreactive...

  9. Targeted amino-terminal acetylation of recombinant proteins in E. coli.

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    Matthew Johnson

    2010-12-01

    Full Text Available One major limitation in the expression of eukaryotic proteins in bacteria is an inability to post-translationally modify the expressed protein. Amino-terminal acetylation is one such modification that can be essential for protein function. By co-expressing the fission yeast NatB complex with the target protein in E.coli, we report a simple and widely applicable method for the expression and purification of functional N-terminally acetylated eukaryotic proteins.

  10. Amino-terminal pro-B-type natriuretic peptides: testing in general populations

    DEFF Research Database (Denmark)

    Lemos, J.A. de; Hildebrandt, P.

    2008-01-01

    Screening of general populations with amino-terminal pro-B-type natriuretic peptides (NT-proBNP) holds promise for the detection of significant underlying cardiac structural and functional abnormalities, as well as for the early detection of the propensity to develop future cardiovascular events....... In comparative studies to date, NT-proBNP performs at least as well as BNP in the detection of heart disease and prognostication in the general population. In some studies and subgroups, NT-proBNP appears to outperform BNP in population screening. More needs to be learned about noncardiac sources of NT...

  11. NMR assignments for the amino-terminal residues of trp repressor and their role in DNA binding

    International Nuclear Information System (INIS)

    Arrowsmith, C.H.; Carey, J.; Treat-Clemons, L.; Jardetzky, O.

    1989-01-01

    The trp repressor of Escherichia coli specifically binds to operator DNAs in three operons involved in tryptophan metabolism. The NMR spectra of repressor and a chymotryptic fragment lacking the six amino-terminal residues are compared. Two-dimensional J-correlated spectra of the two forms of the protein are superimposable except for cross-peaks that are associated with the N-terminal region. The chemical shifts and relaxation behavior of the N-terminal resonances suggest mobile arms. Spin-echo experiments on a ternary complex of repressor with L-tryptophan and operator DNA indicate that the termini are also disordered in the complex, although removal of the arms reduces the DNA binding energy. Relaxation measurements on the armless protein show increased mobility for several residues, probably due to helix fraying in the newly exposed N-terminal region. DNA binding by the armless protein does not reduce the mobility of these residues. Thus, it appears that the arms serve to stabilize the N-terminal helix but that this structural role does not explain their contribution to the DNA binding energy. These results suggest that the promiscuous DNA binding by the arms seen in the X-ray crystal structure is found in solution as well

  12. Structural organization of intercellular channels II. Amino terminal domain of the connexins: sequence, functional roles, and structure.

    Science.gov (United States)

    Beyer, Eric C; Lipkind, Gregory M; Kyle, John W; Berthoud, Viviana M

    2012-08-01

    The amino terminal domain (NT) of the connexins consists of their first 22-23 amino acids. Site-directed mutagenesis studies have demonstrated that NT amino acids are determinants of gap junction channel properties including unitary conductance, permeability/selectivity, and gating in response to transjunctional voltage. The importance of this region has also been emphasized by the identification of multiple disease-associated connexin mutants affecting amino acid residues in the NT region. The first part of the NT is α-helical. The structure of the Cx26 gap junction channel shows that the NT α-helix localizes within the channel, and lines the wall of the pore. Interactions of the amino acid residues in the NT with those in the transmembrane helices may be critical for holding the channel open. The predicted sites of these interactions and the applicability of the Cx26 structure to the NT of other connexins are considered. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics. Copyright © 2011. Published by Elsevier B.V.

  13. Modulation of the functional association between the HIV-1 intasome and the nucleosome by histone amino-terminal tails.

    Science.gov (United States)

    Benleulmi, Mohamed S; Matysiak, Julien; Robert, Xavier; Miskey, Csaba; Mauro, Eric; Lapaillerie, Delphine; Lesbats, Paul; Chaignepain, Stéphane; Henriquez, Daniel R; Calmels, Christina; Oladosu, Oyindamola; Thierry, Eloïse; Leon, Oscar; Lavigne, Marc; Andreola, Marie-Line; Delelis, Olivier; Ivics, Zoltán; Ruff, Marc; Gouet, Patrice; Parissi, Vincent

    2017-11-28

    Stable insertion of the retroviral DNA genome into host chromatin requires the functional association between the intasome (integrase·viral DNA complex) and the nucleosome. The data from the literature suggest that direct protein-protein contacts between integrase and histones may be involved in anchoring the intasome to the nucleosome. Since histone tails are candidates for interactions with the incoming intasomes we have investigated whether they could participate in modulating the nucleosomal integration process. We show here that histone tails are required for an optimal association between HIV-1 integrase (IN) and the nucleosome for efficient integration. We also demonstrate direct interactions between IN and the amino-terminal tail of human histone H4 in vitro. Structure/function studies enabled us to identify amino acids in the carboxy-terminal domain of IN that are important for this interaction. Analysis of the nucleosome-binding properties of catalytically active mutated INs confirmed that their ability to engage the nucleosome for integration in vitro was affected. Pseudovirus particles bearing mutations that affect the IN/H4 association also showed impaired replication capacity due to altered integration and re-targeting of their insertion sites toward dynamic regions of the chromatin with lower nucleosome occupancy. Collectively, our data support a functional association between HIV-1 IN and histone tails that promotes anchoring of the intasome to nucleosomes and optimal integration into chromatin.

  14. Adsorption behavior of oxidized galactomannans onto amino terminated surfaces and their interaction with bovine serum albumin

    International Nuclear Information System (INIS)

    Sierakowski, M.-R; Silva, Maria R.V. da; Freitas, R.A.; Moreira, Jose S.R.; Fujimoto, J.; Petri, D.F.S.; Cordeiro, Paulo R.D.; Andrade, Fabiana D.

    2001-01-01

    A galactomannan (CF) extracted from Cassia fastuosa seeds was purified and oxidized with (2,2,6,6- tetramethylpiperidine-1-oxyl) to form a uronic acid-containing polysaccharide (CFOX) with a degree of oxidation (DO) of 0.22. The chemical structures of CF and CFOX were characterized. The adsorption behavior of CF and CFOX onto amino-terminated surfaces was studied by means of ellipsometric measurements. The influence of p H and ionic strength on the adsorption was also investigated. At p H 4, there was a maximum in the adsorbed amount caused by strong electrostatic attraction between the substrate and the oxidized galactomannans. There was no ionic strength effect on the adsorption behavior. The immobilization of bovine serum albumin onto CF and CFOX was studied as a function of p H. At the isoelectric point a maximum in the adsorbed amount was found. (author)

  15. Adsorption behavior of oxidized galactomannans onto amino terminated surfaces and their interaction with bovine serum albumin

    Energy Technology Data Exchange (ETDEWEB)

    Sierakowski, M.-R; Silva, Maria R.V. da [Universidade Federal do Parana, Curitiba, PR (Brazil). Dept. de Quimica. Lab. de Biopolimeros]. E-mail: mrbiopol@quimica.ufpr.br; Freitas, R.A.; Moreira, Jose S.R. [Universidade Federal do Parana, Curitiba, PR (Brazil). Dept. de Bioquimica; Fujimoto, J.; Petri, D.F.S.; Cordeiro, Paulo R.D. [Sao Paulo Univ., SP (Brazil). Inst. de Quimica]. E-mail: dfsp@quim.iq.usp.br; Andrade, Fabiana D

    2001-07-01

    A galactomannan (CF) extracted from Cassia fastuosa seeds was purified and oxidized with (2,2,6,6- tetramethylpiperidine-1-oxyl) to form a uronic acid-containing polysaccharide (CFOX) with a degree of oxidation (DO) of 0.22. The chemical structures of CF and CFOX were characterized. The adsorption behavior of CF and CFOX onto amino-terminated surfaces was studied by means of ellipsometric measurements. The influence of p H and ionic strength on the adsorption was also investigated. At p H 4, there was a maximum in the adsorbed amount caused by strong electrostatic attraction between the substrate and the oxidized galactomannans. There was no ionic strength effect on the adsorption behavior. The immobilization of bovine serum albumin onto CF and CFOX was studied as a function of p H. At the isoelectric point a maximum in the adsorbed amount was found. (author)

  16. Radioimmunoassay of Pro-. gamma. -melanotropin, the amino-terminal fragment of proopiolipomelanocortin. [Swine

    Energy Technology Data Exchange (ETDEWEB)

    Ekman, R.; Hakanson, R.; Larsson, I.; Sundler, F.; Thorell, J.I.

    1982-08-01

    A RIA has been developed for natural porcine pro-..gamma..-MSH, the 103-amino acid peptide that represents the amino-terminal part of proopiolipomelanocortin. Rabbits were immunized with the purified peptide polymerized with glutaraldehyde. The antiserum is directed against the amino-terminial end of the antigen and does not cross-react with corticotropin, ..beta..-lipotropin, ..beta..-endorphin, ..gamma../sub 3/MSH, or ..gamma../sub 2/MSH. The minimum detectable concentration is 0.15 ng/ml standard pro-..gamma..MSH (15 pg/tube). Pro-..gamma..MSH-like immunoreactivity was detected in plasma and extracts of the hypothalamus and pituitary of pigs. Gel chromatography of these extracts revealed at least three immunoreactive peaks in the anterior and neurointermediate lobes of the pituitary, wheras two immunoreactive peaks were found in extracts of the hypothalalmus. (Endocrinology 111:578,1982)

  17. Preferential assembly of heteromeric kainate and AMPA receptor amino terminal domains.

    Science.gov (United States)

    Zhao, Huaying; Lomash, Suvendu; Chittori, Sagar; Glasser, Carla; Mayer, Mark L; Schuck, Peter

    2017-10-23

    Ion conductivity and the gating characteristics of tetrameric glutamate receptor ion channels are determined by their subunit composition. Competitive homo- and hetero-dimerization of their amino-terminal domains (ATDs) is a key step controlling assembly. Here we measured systematically the thermodynamic stabilities of homodimers and heterodimers of kainate and AMPA receptors using fluorescence-detected sedimentation velocity analytical ultracentrifugation. Measured affinities span many orders of magnitude, and complexes show large differences in kinetic stabilities. The association of kainate receptor ATD dimers is generally weaker than the association of AMPA receptor ATD dimers, but both show a general pattern of increased heterodimer stability as compared to the homodimers of their constituents, matching well physiologically observed receptor combinations. The free energy maps of AMPA and kainate receptor ATD dimers provide a framework for the interpretation of observed receptor subtype combinations and possible assembly pathways.

  18. Amino-terminal domain of classic cadherins determines the specificity of the adhesive interactions

    DEFF Research Database (Denmark)

    Klingelhöfer, Jörg; Troyanovsky, R B; Laur, O Y

    2000-01-01

    Classic cadherins are transmembrane receptors involved in cell type-specific calcium-dependent intercellular adhesion. The specificity of adhesion is mediated by homophilic interactions between cadherins extending from opposing cell surfaces. In addition, classic cadherins can self-associate form......Classic cadherins are transmembrane receptors involved in cell type-specific calcium-dependent intercellular adhesion. The specificity of adhesion is mediated by homophilic interactions between cadherins extending from opposing cell surfaces. In addition, classic cadherins can self....... To study lateral and adhesive intercadherin interactions, we examined interactions between two classic cadherins, E- and P-cadherins, in epithelial A-431 cells co-producing both proteins. We showed that these cells exhibited heterocomplexes consisting of laterally assembled E- and P....... The specificity of adhesive interaction was localized to the amino-terminal (EC1) domain of both cadherins. Thus, EC1 domain of classic cadherins exposes two determinants responsible for nonspecific lateral and cadherin type-specific adhesive dimerization....

  19. Repression of HNF1α-mediated transcription by amino-terminal enhancer of split (AES)

    Energy Technology Data Exchange (ETDEWEB)

    Han, Eun Hee [Section of Structural Biology, Hormel Institute, University of Minnesota, Austin, MN 55912 (United States); Gorman, Amanda A. [Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536 (United States); Singh, Puja [Section of Structural Biology, Hormel Institute, University of Minnesota, Austin, MN 55912 (United States); Chi, Young-In, E-mail: ychi@hi.umn.edu [Section of Structural Biology, Hormel Institute, University of Minnesota, Austin, MN 55912 (United States)

    2015-12-04

    HNF1α (Hepatocyte Nuclear Factor 1α) is one of the master regulators in pancreatic beta-cell development and function, and the mutations in Hnf1α are the most common monogenic causes of diabetes mellitus. As a member of the POU transcription factor family, HNF1α exerts its gene regulatory function through various molecular interactions; however, there is a paucity of knowledge in their functional complex formation. In this study, we identified the Groucho protein AES (Amino-terminal Enhancer of Split) as a HNF1α-specific physical binding partner and functional repressor of HNF1α-mediated transcription, which has a direct link to glucose-stimulated insulin secretion in beta-cells that is impaired in the HNF1α mutation-driven diabetes. - Highlights: • We identified AES as a transcriptional repressor for HNF1α in pancreatic beta-cell. • AES's repressive activity was HNF1α-specific and was not observed with HNF1β. • AES interacts with the transactivation domain of HNF1α. • Small molecules can be designed or discovered to disrupt this interaction and improve insulin secretion and glucose homeostasis.

  20. Repression of HNF1α-mediated transcription by amino-terminal enhancer of split (AES)

    International Nuclear Information System (INIS)

    Han, Eun Hee; Gorman, Amanda A.; Singh, Puja; Chi, Young-In

    2015-01-01

    HNF1α (Hepatocyte Nuclear Factor 1α) is one of the master regulators in pancreatic beta-cell development and function, and the mutations in Hnf1α are the most common monogenic causes of diabetes mellitus. As a member of the POU transcription factor family, HNF1α exerts its gene regulatory function through various molecular interactions; however, there is a paucity of knowledge in their functional complex formation. In this study, we identified the Groucho protein AES (Amino-terminal Enhancer of Split) as a HNF1α-specific physical binding partner and functional repressor of HNF1α-mediated transcription, which has a direct link to glucose-stimulated insulin secretion in beta-cells that is impaired in the HNF1α mutation-driven diabetes. - Highlights: • We identified AES as a transcriptional repressor for HNF1α in pancreatic beta-cell. • AES's repressive activity was HNF1α-specific and was not observed with HNF1β. • AES interacts with the transactivation domain of HNF1α. • Small molecules can be designed or discovered to disrupt this interaction and improve insulin secretion and glucose homeostasis.

  1. Functions of huntingtin in germ layer specification and organogenesis.

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    Giang D Nguyen

    Full Text Available Huntington's disease (HD is a neurodegenerative disease caused by abnormal polyglutamine expansion in the huntingtin protein (Htt. Although both Htt and the HD pathogenic mutation (mHtt are implicated in early developmental events, their individual involvement has not been adequately explored. In order to better define the developmental functions and pathological consequences of the normal and mutant proteins, respectively, we employed embryonic stem cell (ESC expansion, differentiation and induction experiments using huntingtin knock-out (KO and mutant huntingtin knock-in (Q111 mouse ESC lines. In KO ESCs, we observed impairments in the spontaneous specification and survival of ectodermal and mesodermal lineages during embryoid body formation and under inductive conditions using retinoic acid and Wnt3A, respectively. Ablation of BAX improves cell survival, but failed to correct defects in germ layer specification. In addition, we observed ensuing impairments in the specification and maturation of neural, hepatic, pancreatic and cardiomyocyte lineages. These developmental deficits occurred in concert with alterations in Notch, Hes1 and STAT3 signaling pathways. Moreover, in Q111 ESCs, we observed differential developmental stage-specific alterations in lineage specification and maturation. We also observed changes in Notch/STAT3 expression and activation. Our observations underscore essential roles of Htt in the specification of ectoderm, endoderm and mesoderm, in the specification of neural and non-neural organ-specific lineages, as well as cell survival during early embryogenesis. Remarkably, these developmental events are differentially deregulated by mHtt, raising the possibility that HD-associated early developmental impairments may contribute not only to region-specific neurodegeneration, but also to non-neural co-morbidities.

  2. Interfering amino terminal peptides and functional implications for heteromeric gap junction formation

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    Richard David Veenstra

    2013-05-01

    Full Text Available Connexin43 (Cx43 is widely expressed in many different tissues of the human body. In cells of some organs, Cx43 is co-expressed with other connexins (Cx, including Cx46 and Cx50 in lens, Cx40 in atrium, Purkinje fibers, and the blood vessel wall, Cx45 in heart, and Cx37 in the ovary. Interactions with the co-expressed connexins may have profound functional implications. The abilities of Cx37, Cx45, Cx46, and Cx50 to function in heteromeric gap junction combinations with Cx43 are well documented. Different studies disagree regarding the ability of Cx43 and Cx40 to produce functional heteromeric gap junctions with each other. We review previous studies regarding the heteromeric interactions of Cx43. The possibility of negative functional interactions between the cytoplasmic pore-forming amino terminal (NT domains of these connexins was assessed using pentameric connexin sequence-specific NT domain (iNT peptides applied to cells expressing homomeric Cx40, Cx37, Cx45, Cx46, and Cx50 gap junctions. A Cx43 iNT peptide corresponding to amino acids 9 to 13 (Ac-KLLDK-NH2 specifically inhibited the electrical coupling of Cx40 gap junctions in a transjunctional (Vj voltage-dependent manner without affecting the function of homologous Cx37, Cx46, Cx50, and Cx45 gap junctions. A Cx40 iNT (Ac-EFLEE-OH peptide counteracted the Vj-dependent block of Cx40 gap junctions, whereas a similarly charged Cx50 iNT (Ac-EEVNE-OH peptide did not, suggesting that these NT domain interactions are not solely based on electrostatics. These data are consistent with functional Cx43 heteromeric gap junction formation with Cx37, Cx45, Cx46, and Cx50 and suggest that Cx40 uniquely experiences functional suppressive interactions with a Cx43 NT domain sequence. These findings present unique functional implications about the heteromeric interactions between Cx43 and Cx40 that may influence cardiac conduction in atrial myocardium and the specialized conduction system.

  3. SUMO-2 and PIAS1 Modulate Insoluble Mutant Huntingtin Protein Accumulation

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    Jacqueline Gire O’Rourke

    2013-07-01

    Full Text Available A key feature in Huntington disease (HD is the accumulation of mutant Huntingtin (HTT protein, which may be regulated by posttranslational modifications. Here, we define the primary sites of SUMO modification in the amino-terminal domain of HTT, show modification downstream of this domain, and demonstrate that HTT is modified by the stress-inducible SUMO-2. A systematic study of E3 SUMO ligases demonstrates that PIAS1 is an E3 SUMO ligase for both HTT SUMO-1 and SUMO-2 modification and that reduction of dPIAS in a mutant HTT Drosophila model is protective. SUMO-2 modification regulates accumulation of insoluble HTT in HeLa cells in a manner that mimics proteasome inhibition and can be modulated by overexpression and acute knockdown of PIAS1. Finally, the accumulation of SUMO-2-modified proteins in the insoluble fraction of HD postmortem striata implicates SUMO-2 modification in the age-related pathogenic accumulation of mutant HTT and other cellular proteins that occurs during HD progression.

  4. Uniform 15N- and 15N/13C-labeling of proteins in mammalian cells and solution structure of the amino terminal fragment of u-PA

    International Nuclear Information System (INIS)

    Hansen, A.P.; Petros, A.M.; Meadows, R.P.; Mazar, A.P.; Nettesheim, D.G.; Pederson, T.M.; Fesik, S.W.

    1994-01-01

    Urokinase-type plasminogen activator (u-PA) is a 54-kDa glycoprotein that catalyzes the conversion of plasminogen to plasmin, a broad-specificity protease responsible for the degradation of fibrin clots and extracellular matrix components. The u-PA protein consists of three individual modules: a growth factor domain (GFD), a kringle, and a serine protease domain. The amino terminal fragment (ATF) includes the GFD-responsible for u-PA binding to its receptor-and the kringle domains. This protein was expressed and uniformly 15 N-and 15 N/ 13 C-labeled in mammalian cells by methods that will be described. In addition, we present the three-dimensional structure of ATF that was derived from 1299 NOE-derived distance restraints along with the φ angle and hydrogen bonding restraints. Although the individual domains in the structures were highly converged, the two domains are structurally independent. The overall structures of the individual domains are very similar to the structures of homologous proteins. However, important structural differences between the growth factor domain of u-PA and other homologous proteins were observed in the region that has been implicated in binding the urokinase receptor. These results may explain, in part, why other growth factors show no appreciable affinity for the urokinase receptor

  5. Quantitation of some amino-terminal residues in proteins using 3H-labelled dansyl chloride and 14C labelled amino acids

    International Nuclear Information System (INIS)

    Flengsrud, R.

    1979-01-01

    A method for quantitation of amino-terminal residues in proteins is presented. The method is a modification of a double isotope-labelling technique, using 3 H-labelled dansyl chloride and 14 C-labelled amino acids as internal standards. The method is demonstrated on human fibrinogen, horse myoglobin and on mouse myoloma IgA. A linear relationship between the ratio 3 H/ 14 C in the separated amino-terminal amino acid of the protein and the amount of protein added in the labelling mixture was obtained with standard deviations of +- 7.4%, +-3.4% and +-10.3%, respectively. An application of the method is demonstrated by measuring the increase in amino-terminal glycine in fibrinogen following the proteolytic action of thrombin. The method seems to be useful when 0.1 nmol or more of protein is used. (author)

  6. Antisense downregulation of mutant huntingtin in a cell model

    DEFF Research Database (Denmark)

    Hasholt, L.; Abell, K.; Norremolle, A.

    2003-01-01

    or by addition to the culture medium. Results Expression of the fusion protein containing the mutant huntingtin fragment resulted in diffuse green fluorescence in the cytoplasm and formation of aggregates in some of the NT2 cells and NT2-N neurons. We obtained antisense sequence-specific inhibition of expression...... of the fusion protein and/or suppression of the aggregate formation in both cell types. In the NT2 cells the antisense effect was dependent on the way of administration of the oligo. Conclusions The PS-antisense oligo is effective in downregulation of mutant huntingtin, and the reduction of aggregate formation...... is a sensitive biological marker. The findings suggest that antisense knockdown of huntingtin could be a useful strategy for treatment of HD, and could also be suitable for studies of the normal and pathological function of huntingtin in different cellular model systems....

  7. The value of use of amino-terminal brain naturitic peptide as marker in cases of pleural effusion of different etiologies

    Directory of Open Access Journals (Sweden)

    Laila A. Banawan

    2013-10-01

    Conclusion: The results support the feasibility of using the pleural fluid amino terminal proBNP measurement in thoracentesis that would enhance discrimination among the different causes of pleural effusion especially for heart failure patients. Serum and pleural fluid levels of NT-pro BNP were closely correlated and measurement of NT-pro BNP in serum showed equally good diagnostic properties.

  8. Natural variation of the amino-terminal glutamine-rich domain in Drosophila argonaute2 is not associated with developmental defects.

    Directory of Open Access Journals (Sweden)

    Daniel Hain

    2010-12-01

    Full Text Available The Drosophila argonaute2 (ago2 gene plays a major role in siRNA mediated RNA silencing pathways. Unlike mammalian Argonaute proteins, the Drosophila protein has an unusual amino-terminal domain made up largely of multiple copies of glutamine-rich repeats (GRRs. We report here that the ago2 locus produces an alternative transcript that encodes a putative short isoform without this amino-terminal domain. Several ago2 mutations previously reported to be null alleles only abolish expression of the long, GRR-containing isoform. Analysis of drop out (dop mutations had previously suggested that variations in GRR copy number result in defects in RNAi and embryonic development. However, we find that dop mutations genetically complement transcript-null alleles of ago2 and that ago2 alleles with variant GRR copy numbers support normal development. In addition, we show that the assembly of the central RNAi machinery, the RISC (RNA induced silencing complex, is unimpaired in embryos when GRR copy number is altered. In fact, we find that GRR copy number is highly variable in natural D. melanogaster populations as well as in laboratory strains. Finally, while many other insects share an extensive, glutamine-rich Ago2 amino-terminal domain, its primary sequence varies drastically between species. Our data indicate that GRR variation does not modulate an essential function of Ago2 and that the amino-terminal domain of Ago2 is subject to rapid evolution.

  9. Detection of ubiquitinated huntingtin species in intracellular aggregates

    Directory of Open Access Journals (Sweden)

    Katrin eJuenemann

    2015-01-01

    Full Text Available Protein conformation diseases, including polyglutamine diseases, result from the accumulation and aggregation of misfolded proteins. Huntington’s disease is one of nine diseases caused by an expanded polyglutamine repeat within the affected protein and is hallmarked by intracellular inclusion bodies composed of aggregated N-terminal huntingtin fragments and other sequestered proteins. Fluorescence microscopy and filter trap assay are conventional methods to study protein aggregates, but cannot be used to analyze the presence and levels of post-translational modifications of aggregated huntingtin such as ubiquitination. Ubiquitination of proteins can be a signal for degradation and intracellular localization, but also affects protein activity and protein-protein interactions. The function of ubiquitination relies on its mono- and polymeric isoforms attached to protein substrates. Studying the ubiquitination pattern of aggregated huntingtin fragments offers an important possibility to understand huntingtin degradation and aggregation processes within the cell. For the identification of aggregated huntingtin and its ubiquitinated species, solubilization of the cellular aggregates is mandatory. Here we describe methods to identify post-translational modifications such as ubiquitination of aggregated mutant huntingtin. This approach is specifically described for use with mammalian cell culture and is suitable to study other disease-related proteins prone to aggregate.

  10. Surface characterization on binary nano/micro-domain composed of alkyl- and amino-terminated self-assembled monolayer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, S.H. [Faculty of Engineering, Shinshu University, 4-17-1 Wakasato, Nagano 380-8553 (Japan); Ishizaki, T. [Materials Research Institute for Sustainable Development, National Institute of Advanced Industrial Science and Technology, 2266-98 Anagahora, Shimo-Shidami, Moriyama-ku, Nagoya 463-8560 (Japan); Saito, N. [Department of Molecular Design and Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa, Nagano 464-8603 (Japan)], E-mail: hiro@eco-t.esi.nagoya-u.ac.jp; Takai, O. [EcoTopia Science Institute, Nagoya University, Furo-cho, Chikusa, Nagoya 464-8603 (Japan)

    2008-09-15

    The binary alkyl- and amino-terminated self-assembled monolayers (SAMs) composed of nano/micro-sized domains was prepared though a self-assembly technique. In addition, the wetting and electrostatic property of the binary SAMs was investigated by the analysis of the static and dynamic water contact angle and zeta-potentials measurement. The binary SAMs were also characterized by atomic force microscope (AFM), Kelvin probe force microscope (KPFM) and X-ray photoelectron spectroscopy (XPS). The domains on the binary SAMs were observed in topographic and surface potential images. The height of domain and the surface potential between octadecyltrichlorosilanes (OTS)-domain and n-(6-aminohexl)aminopropyl-trimethoxysilane (AHAPS)-SAM were about 1.1 nm and -30 mV. These differences of height and surface potential correspond to the ones between OTS and AHAPS. In XPS N 1s spectra, we confirmed the formation of binary SAMs by an amino peak observed at 399.15 eV. The dynamic and the static water contact angles indicated that the wetting property of the binary SAMs was depended on the OTS domain size. In addition, static water contact angles were measured under the conditions of different pH water and zeta-potential also indicated that the electrostatic property of the binary SAMs depended on OTS domain size. Thus, these results showed that the wetting and electrostatic property on the binary SAMs could be regulated by controlling the domain size.

  11. Functional roles of the amino terminal domain in determining biophysical properties of Cx50 gap junction channels

    Directory of Open Access Journals (Sweden)

    Li eXin

    2013-12-01

    Full Text Available Communication through gap junction channels is essential for synchronized and coordinated cellular activities. The gap junction channel pore size, its switch control for opening/closing, and the modulations by chemicals can be different depending on the connexin subtypes that compose the channel. Recent structural and functional studies provide compelling evidence that the amino terminal (NT domains of several connexins line the pore of gap junction channels and play an important role in single channel conductance (γj and transjunctional voltage-dependent gating (Vj-gating. This article reviews recent studies conducted on a series of mutations/chimeras in the NT domain of connexin50 (Cx50. Functional examination of the gap junction channels formed by these mutants/chimeras shows the net charge number at the NT domain to be an important factor in γj and in Vj-gating. Furthermore, with an increase in the net negative charge at the NT domain, we observed an increase in the γj, as well as changes in the parameters of the Boltzmann fit of the normalized steady-state conductance and Vj relationship. Our data are consistent with a structural model where the NT domain of Cx50 lines the gap junction pore and plays an important role in sensing Vj and in the subsequent conformational changes leading to gating, as well as in limiting the rate of ion permeation.

  12. Procollagen type III amino terminal peptide and myocardial fibrosis: A study in hypertensive patients with and without left ventricular hypertrophy.

    Science.gov (United States)

    dos Santos Moreira, Carlos; Serejo, Fátima; Alcântara, Paula; Ramalhinho, Vítor; Braz Nogueira, J

    2015-05-01

    An exaggerated accumulation of type I and type III fibrillar collagens occurs throughout the free wall and interventricular septum of patients with primary hypertension and left ventricular hypertrophy (LVH). In the present study the serum concentration of procollagen type III amino terminal peptide (PIIIP) was measured to determine the value of this peptide as a potential marker of ventricular fibrosis in hypertensive patients, particularly those with LVH. The study population consisted of patients with never-treated mild to moderate essential hypertension and 30 normotensive control subjects. Clinical, echocardiographic, electrocardiographic and biochemical parameters were assessed in all patients. Heart rate, body mass index and levels of blood pressure were increased in hypertensives, particularly those with LVH, compared to normotensive controls. Posterior wall thickness, left ventricular (LV) mass and LV mass index, and serum PIIIP concentration were also increased in hypertensives, with significant differences between the two hypertensive groups. The ratio between maximal early and late transmitral flow velocity measured during diastole was lower in hypertensives, particularly those with LVH, than in normotensive controls. The increase in PIIIP indicates that type III collagen synthesis increases in hypertensives, particularly those with LVH, implying that alterations in the heart in hypertension are the result not solely of hypertrophied LV muscle, but also of increased collagen deposition within the ventricular wall and around the coronary vessels. Thus, measurement of serum PIIIP could be a practical and useful tool in the non-invasive assessment of myocardial remodeling in hypertension. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  13. Alteration of the mode of antibacterial action of a defensin by the amino-terminal loop substitution

    International Nuclear Information System (INIS)

    Gao, Bin; Zhu, Shunyi

    2012-01-01

    Highlights: ► Al-M is an engineered fungal defensin with the n-loop of an insect defensin. ► Al-M adopts a native defensin-like structure with high antibacterial potency. ► Al-M kills bacteria through a membrane disruptive mechanism. ► This work sheds light on the functional evolution of CSαβ-type defensins. -- Abstract: Ancient invertebrate-type and classical insect-type defensins (AITDs and CITDs) are two groups of evolutionarily related antimicrobial peptides (AMPs) that adopt a conserved cysteine-stabilized α-helical and β-sheet (CSαβ) fold with a different amino-terminal loop (n-loop) size and diverse modes of antibacterial action. Although they both are identified as inhibitors of cell wall biosynthesis, only CITDs evolved membrane disruptive ability by peptide oligomerization to form pores. To understand how this occurred, we modified micasin, a fungus-derived AITDs with a non-membrane disruptive mechanism, by substituting its n-loop with that of an insect-derived CITDs. After air oxidization, the synthetic hybrid defensin (termed Al-M) was structurally identified by circular dichroism (CD) and functionally evaluated by antibacterial and membrane permeability assays and electronic microscopic observation. Results showed that Al-M folded into a native-like defensin structure, as determined by its CD spectrum that is similar to that of micasin. Al-M was highly efficacious against the Gram-positive bacterium Bacillus megaterium with a lethal concentration of 1.76 μM. As expected, in contrast to micasin, Al-M killed the bacteria through a membrane disruptive mechanism of action. The alteration in modes of action supports a key role of the n-loop extension in assembling functional surface of CITDs for membrane disruption. Our work provides mechanical evidence for evolutionary relationship between AITDs and CITDs.

  14. Alteration of the mode of antibacterial action of a defensin by the amino-terminal loop substitution

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Bin [Group of Animal Innate Immunity, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, 100101 Beijing (China); Zhu, Shunyi, E-mail: Zhusy@ioz.ac.cn [Group of Animal Innate Immunity, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, 100101 Beijing (China)

    2012-10-05

    Highlights: Black-Right-Pointing-Pointer Al-M is an engineered fungal defensin with the n-loop of an insect defensin. Black-Right-Pointing-Pointer Al-M adopts a native defensin-like structure with high antibacterial potency. Black-Right-Pointing-Pointer Al-M kills bacteria through a membrane disruptive mechanism. Black-Right-Pointing-Pointer This work sheds light on the functional evolution of CS{alpha}{beta}-type defensins. -- Abstract: Ancient invertebrate-type and classical insect-type defensins (AITDs and CITDs) are two groups of evolutionarily related antimicrobial peptides (AMPs) that adopt a conserved cysteine-stabilized {alpha}-helical and {beta}-sheet (CS{alpha}{beta}) fold with a different amino-terminal loop (n-loop) size and diverse modes of antibacterial action. Although they both are identified as inhibitors of cell wall biosynthesis, only CITDs evolved membrane disruptive ability by peptide oligomerization to form pores. To understand how this occurred, we modified micasin, a fungus-derived AITDs with a non-membrane disruptive mechanism, by substituting its n-loop with that of an insect-derived CITDs. After air oxidization, the synthetic hybrid defensin (termed Al-M) was structurally identified by circular dichroism (CD) and functionally evaluated by antibacterial and membrane permeability assays and electronic microscopic observation. Results showed that Al-M folded into a native-like defensin structure, as determined by its CD spectrum that is similar to that of micasin. Al-M was highly efficacious against the Gram-positive bacterium Bacillus megaterium with a lethal concentration of 1.76 {mu}M. As expected, in contrast to micasin, Al-M killed the bacteria through a membrane disruptive mechanism of action. The alteration in modes of action supports a key role of the n-loop extension in assembling functional surface of CITDs for membrane disruption. Our work provides mechanical evidence for evolutionary relationship between AITDs and CITDs.

  15. Human dermatosparaxis: a form of Ehlers-Danlos syndrome that results from failure to remove the amino-terminal propeptide of type I procollagen.

    OpenAIRE

    Smith, L T; Wertelecki, W; Milstone, L M; Petty, E M; Seashore, M R; Braverman, I M; Jenkins, T G; Byers, P H

    1992-01-01

    Dermatosparaxis is a recessively inherited connective-tissue disorder that results from lack of the activity of type I procollagen N-proteinase, the enzyme that removes the amino-terminal propeptides from type I procollagen. Initially identified in cattle more than 20 years ago, the disorder was subsequently characterized in sheep, cats, and dogs. Affected animals have fragile skin, lax joints, and often die prematurely because of sepsis following avulsion of portions of skin. We recently ide...

  16. Human dermatosparaxis: a form of Ehlers-Danlos syndrome that results from failure to remove the amino-terminal propeptide of type I procollagen.

    Science.gov (United States)

    Smith, L T; Wertelecki, W; Milstone, L M; Petty, E M; Seashore, M R; Braverman, I M; Jenkins, T G; Byers, P H

    1992-08-01

    Dermatosparaxis is a recessively inherited connective-tissue disorder that results from lack of the activity of type I procollagen N-proteinase, the enzyme that removes the amino-terminal propeptides from type I procollagen. Initially identified in cattle more than 20 years ago, the disorder was subsequently characterized in sheep, cats, and dogs. Affected animals have fragile skin, lax joints, and often die prematurely because of sepsis following avulsion of portions of skin. We recently identified two children with soft, lax, and fragile skin, which, when examined by transmission electron microscopy, contained the twisted, ribbon-like collagen fibrils characteristic of dermatosparaxis. Skin extracts from one child contained collagen precursors with amino-terminal extensions. Cultured fibroblasts from both children failed to cleave the amino-terminal propeptides from the pro alpha 1(I) and pro alpha 2(I) chains in type I procollagen molecules. Extracts of normal cells cleaved to collagen, the type I procollagen synthesized by cells from both children, demonstrating that the enzyme, not the substrate, was defective. These findings distinguish dermatosparaxis from Ehlers-Danlos syndrome type VII, which results from substrate mutations that prevent proteolytic processing of type I procollagen molecules.

  17. Functional evidence for the critical amino-terminal conserved domain and key amino acids of Arabidopsis 4-HYDROXY-3-METHYLBUT-2-ENYL DIPHOSPHATE REDUCTASE.

    Science.gov (United States)

    Hsieh, Wei-Yu; Sung, Tzu-Ying; Wang, Hsin-Tzu; Hsieh, Ming-Hsiun

    2014-09-01

    The plant 4-HYDROXY-3-METHYLBUT-2-ENYL DIPHOSPHATE REDUCTASE (HDR) catalyzes the last step of the methylerythritol phosphate pathway to synthesize isopentenyl diphosphate and its allyl isomer dimethylallyl diphosphate, which are common precursors for the synthesis of plastid isoprenoids. The Arabidopsis (Arabidopsis thaliana) genomic HDR transgene-induced gene-silencing lines are albino, variegated, or pale green, confirming that HDR is essential for plants. We used Escherichia coli isoprenoid synthesis H (Protein Data Bank code 3F7T) as a template for homology modeling to identify key amino acids of Arabidopsis HDR. The predicted model reveals that cysteine (Cys)-122, Cys-213, and Cys-350 are involved in iron-sulfur cluster formation and that histidine (His)-152, His-241, glutamate (Glu)-242, Glu-243, threonine (Thr)-244, Thr-312, serine-379, and asparagine-381 are related to substrate binding or catalysis. Glu-242 and Thr-244 are conserved only in cyanobacteria, green algae, and land plants, whereas the other key amino acids are absolutely conserved from bacteria to plants. We used site-directed mutagenesis and complementation assay to confirm that these amino acids, except His-152 and His-241, were critical for Arabidopsis HDR function. Furthermore, the Arabidopsis HDR contains an extra amino-terminal domain following the transit peptide that is highly conserved from cyanobacteria, and green algae to land plants but not existing in the other bacteria. We demonstrated that the amino-terminal conserved domain was essential for Arabidopsis and cyanobacterial HDR function. Further analysis of conserved amino acids in the amino-terminal conserved domain revealed that the tyrosine-72 residue was critical for Arabidopsis HDR. These results suggest that the structure and reaction mechanism of HDR evolution have become specific for oxygen-evolving photosynthesis organisms and that HDR probably evolved independently in cyanobacteria versus other prokaryotes. © 2014

  18. Aliphatic semisynthetic amino terminal variants of myoglobin: enrichment with carbon-13, determination and interpretation of terminal pK values and motions

    International Nuclear Information System (INIS)

    Busch, M.R.

    1985-01-01

    The synthesis of a series of myoglobins substituted in the amino terminal residue to provide variation in the aliphatic nature of the side chain and enrichment in 13 C was accomplished by semisynthetic methods. The replacements of valine, the native first residue, included 13 C enriched glycine, alanine, valine, leucine, and isoleucine. The products were extensively characterized and found to be virtually indistinguishable by most physical methods. 13 C NMR spectroscopy showed significant differences in the amino terminal pK value, ranging from 7.72 for myoglobin to 7.15 for myoglobin. Consideration of the electrostatic effects of the charge array indicated a balance of interactions at this site not significantly altered by variations in the side chain. By examination of the crystal structure, consideration of earlier work regarding the interactions of the side chain of Leu-2, and data regarding the motions of the terminal residue, it was concluded that the interaction of the side chain of the first residue with the hydrophobic cluster formed primarily by close contact of invariant residues Leu-2 and Leu-137 was the primary cause for the reduction in the terminal pK values seen for the larger aliphatics. By restricting the freedom of the residue, this interaction limits the available hydration volume, and consequently favors the unprotonated form of the amine. The concurrent observation of both functional elements in the series of α amino terminal residues brings out the interrelated consequences for the two categories of solvent interactions controlling structural and functional properties in a graded way

  19. Nuclear uptake of an amino-terminal fragment of apolipoprotein E4 promotes cell death and localizes within microglia of the Alzheimer's disease brain.

    Science.gov (United States)

    Love, Julia E; Day, Ryan J; Gause, Justin W; Brown, Raquel J; Pu, Xinzhu; Theis, Dustin I; Caraway, Chad A; Poon, Wayne W; Rahman, Abir A; Morrison, Brad E; Rohn, Troy T

    2017-01-01

    Although harboring the apolipoprotein E4 ( APOE4 ) allele is a well known risk factor in Alzheimer's disease (AD), the mechanism by which it contributes to disease risk remains elusive. To investigate the role of proteolysis of apoE4 as a potential mechanism, we designed and characterized a site-directed cleavage antibody directed at position D151 of the mature form of apoE4 and E3. Characterization of this antibody indicated a high specificity for detecting synthesized recombinant proteins corresponding to the amino acid sequences 1-151 of apoE3 and E4 that would generate the 17 kDa (p17) fragment. In addition, this antibody also detected a ~17 kDa amino-terminal fragment of apoE4 following incubation with collagenase and matrix metalloproteinase-9 (MMP-9), but did not react with full-length apoE4. Application of this amino-terminal apoE cleavage-fragment (nApoECFp17) antibody, revealed nuclear labeling within glial cells and labeling of a subset of neurofibrillary tangles in the human AD brain. A quantitative analysis indicated that roughly 80% of labeled nuclei were microglia. To confirm these findings, cultured BV2 microglia cells were incubated with the amino-terminal fragment of apoE4 corresponding to the cleavage site at D151. The results indicated efficient uptake of this fragment and trafficking to the nucleus that also resulted in significant cell death. In contrast, a similarly designed apoE3 fragment showed no toxicity and primarily localized within the cytoplasm. These data suggest a novel cleavage event by which apoE4 is cleaved by the extracellular proteases, collagenase and MMP-9, generating an amino-terminal fragment that is then taken up by microglia, traffics to the nucleus and promotes cell death. Collectively, these findings provide important mechanistic insights into the mechanism by which harboring the APOE4 allele may elevate dementia risk observed in AD.

  20. The amino-terminal 200 amino acids of the plasma membrane Na+,K+-ATPase alpha subunit confer ouabain sensitivity on the sarcoplasmic reticulum Ca(2+)-ATPase.

    OpenAIRE

    Ishii, T; Takeyasu, K

    1993-01-01

    Cardiac glycosides such as G-strophanthin (ouabain) bind to and inhibit the plasma membrane Na+,K(+)-ATPase but not the sarcoplasmic reticulum (SR) Ca(2+)-ATPase, whereas thapsigargin specifically blocks the SR Ca(2+)-ATPase. The chimera [n/c]CC, in which the amino-terminal amino acids Met1 to Asp162 of the SR Ca(2+)-ATPase (SERCA1) were replaced with the corresponding portion of the Na+,K(+)-ATPase alpha 1 subunit (Met1 to Asp200), retained thapsigargin- and Ca(2+)-sensitive ATPase activity,...

  1. An amino-terminal segment of hantavirus nucleocapsid protein presented on hepatitis B virus core particles induces a strong and highly cross-reactive antibody response in mice

    International Nuclear Information System (INIS)

    Geldmacher, Astrid; Skrastina, Dace; Petrovskis, Ivars; Borisova, Galina; Berriman, John A.; Roseman, Alan M.; Crowther, R. Anthony; Fischer, Jan; Musema, Shamil; Gelderblom, Hans R.; Lundkvist, Aake; Renhofa, Regina; Ose, Velta; Krueger, Detlev H.; Pumpens, Paul; Ulrich, Rainer

    2004-01-01

    Previously, we have demonstrated that hepatitis B virus (HBV) core particles tolerate the insertion of the amino-terminal 120 amino acids (aa) of the Puumala hantavirus nucleocapsid (N) protein. Here, we demonstrate that the insertion of 120 amino-terminal aa of N proteins from highly virulent Dobrava and Hantaan hantaviruses allows the formation of chimeric core particles. These particles expose the inserted foreign protein segments, at least in part, on their surface. Analysis by electron cryomicroscopy of chimeric particles harbouring the Puumala virus (PUUV) N segment revealed 90% T = 3 and 10% T = 4 shells. A map computed from T = 3 shells shows additional density splaying out from the tips of the spikes producing the effect of an extra shell of density at an outer radius compared with wild-type shells. The inserted Puumala virus N protein segment is flexibly linked to the core spikes and only partially icosahedrally ordered. Immunisation of mice of two different haplotypes (BALB/c and C57BL/6) with chimeric core particles induces a high-titered and highly cross-reactive N-specific antibody response in both mice strains

  2. Identification of a direct interaction between residue 19 in the helical portion of calcitonin and the amino-terminal domain of the calcitonin receptor from photoaffinity cross-linking and mutational studies

    International Nuclear Information System (INIS)

    Pham, V.; Wade, J.; McDowall, S.G.; Quiza, M.; Sexton, P.M.

    2001-01-01

    Full text: Calcitonins (CTs) are 32 amino acid hormones with both peripheral and central actions mediated via specific cell surface receptors, which belong to the superfamily of class II G-protein coupled receptors. Chimeric receptor and mutational data suggested that the helical portion (residues 8-22) of salmon CT (sCT) is important for high affinity binding to the amino-terminal extracellular domain of the human CT receptor (hCTR). In this study, we have developed photoactive sCT analogues [Arg 11, 18 , Bpa 19 ]sCT and [Arg 11 , 18 , Bpa 19 ]sCT(8-32) that incorporate a photolabile Bpa (p-benzoyl-L-phenylalanine) into position 19 of the helical domain of the ligand and used this to determine a specific receptor fragment proximate to it. These analogues saturably bound to the CTR with high affinity (IC 50 = 3 nM) which was similar to that of the natural sCT and its antagonist (IC 50 = 2 nM and 20 nM, respectively). Upon photolysis, radioiodinated 125 I-[Arg 11, 18 , Bpa 19 ]sCT and 125 I-[Arg 11,18 , Bpa 19 ]sCT(8-32) efficiently and specifically cross-linked to hCTR stably expressed in baby hamster kidney cells (Hollexl cells, ∼ 800,000 receptors per cell), generating a single radiolabeled band of ∼ 72-kDa on SDS/PAGE autoradiography. To identify the 'contact domain' within CTR involved in binding of 125 I-[Arg1 1 , 18 , Bpa 19 ]sCT and 125 I-[Arg 11, 18 , Bpa 19 ]sCT(8-32), the radiolabeled band containing the ligand-receptor conjugate was subjected to chemical and enzymatic cleavage. Cyanogen bromide cleavage of the native receptor yielded a radiolabeled fragment of apparent Mr ∼ 31-kDa that shifted to Mr ∼ 14 kDa after deglycosylation. This receptor domain corresponded to amino acids 59-134 of the hCTR, located at the amino-terminal extracellular region of the receptor. These results provide the first direct demonstration of a contact domain between calcitonin and its receptor, and will contribute towards the modelling of CT-CTR interface. Copyright

  3. Mutated Huntingtin Causes Testicular Pathology in Transgenic Minipig Boars

    Czech Academy of Sciences Publication Activity Database

    Mačáková, Monika; Bohuslavová, Božena; Vochozková, Petra; Pavlok, Antonín; Sedláčková, M.; Vidinská, Daniela; Vochyánová, Klára; Lišková, Irena; Valeková, Ivona; Baxa, Monika; Ellederová, Zdeňka; Klíma, Jiří; Juhás, Štefan; Juhásová, Jana; Kloučková, J.; Haluzík, M.; Klempíř, J.; Hansíková, H.; Spáčilová, J.; Collins, R.; Blumenthal, I.; Talkowski, M.; Gusella, J. F.; Howland, D. S.; DiFiglia, M.; Motlík, Jan

    2016-01-01

    Roč. 16, 3-4 (2016), s. 245-259 ISSN 1660-2854 R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) LO1609; GA MŠk(CZ) 7F14308 Institutional support: RVO:67985904 Keywords : Huntington´s disease * pig model * mutant huntingtin Subject RIV: FH - Neurology Impact factor: 2.842, year: 2016

  4. Uniform {sup 15}N- and {sup 15}N/{sup 13}C-labeling of proteins in mammalian cells and solution structure of the amino terminal fragment of u-PA

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, A.P.; Petros, A.M.; Meadows, R.P.; Mazar, A.P.; Nettesheim, D.G.; Pederson, T.M.; Fesik, S.W. [Abbott Laboratories, Abbott Park, IL (United States)

    1994-12-01

    Urokinase-type plasminogen activator (u-PA) is a 54-kDa glycoprotein that catalyzes the conversion of plasminogen to plasmin, a broad-specificity protease responsible for the degradation of fibrin clots and extracellular matrix components. The u-PA protein consists of three individual modules: a growth factor domain (GFD), a kringle, and a serine protease domain. The amino terminal fragment (ATF) includes the GFD-responsible for u-PA binding to its receptor-and the kringle domains. This protein was expressed and uniformly {sup 15}N-and {sup 15}N/{sup 13}C-labeled in mammalian cells by methods that will be described. In addition, we present the three-dimensional structure of ATF that was derived from 1299 NOE-derived distance restraints along with the {phi} angle and hydrogen bonding restraints. Although the individual domains in the structures were highly converged, the two domains are structurally independent. The overall structures of the individual domains are very similar to the structures of homologous proteins. However, important structural differences between the growth factor domain of u-PA and other homologous proteins were observed in the region that has been implicated in binding the urokinase receptor. These results may explain, in part, why other growth factors show no appreciable affinity for the urokinase receptor.

  5. Measurement of amino terminal propeptide of type III procollagen (PIIINP) employing the ADVIA Centaur platform. Validation, reference interval and comparison to UniQ RIA

    DEFF Research Database (Denmark)

    Knudsen, Cindy Soendersoe; Heickendorff, Lene; Nexo, Ebba

    2014-01-01

    Background: Recently, measurement of amino terminal propeptide of type III procollagen (PIIINP) was introduced as a part of the hepatic cirrhotic marker enhanced liver fibrosis™ test on the automated ADVIA Centaur® immunoassay platform (Siemens Healthcare Diagnostics Inc., Tarrytown, NY, USA...... UniQ PIIINP RIA assay (Orion Diagnostica, Espoo, Finland) using 55 patient samples (range=3.7-43.3 µg/L). Furthermore, we established a reference interval based on samples from 287 blood donors. Results: In the concentration range 2.5-11.9 µg/L, the total imprecision was below 8%. Comparison...... PIIINP assay is suitable for routine use with our newly defined reference interval. The results obtained by Centaur correlates well with those obtained by the previously employed RIA, though the absolute values are higher....

  6. Relationship between serum amino-terminal propeptide of type III procollagen and changes of left ventricular function after acute myocardial infarction

    DEFF Research Database (Denmark)

    Poulsen, S H; Høst, N B; Jensen, S E

    2000-01-01

    BACKGROUND: The amino-terminal propeptide of type III procollagen (PIIINP) is a marker of type III collagen synthesis, which has previously been shown to correlate with infarct size in nonthrombolyzed myocardial infarction (MI) and to provide prognostic information after MI. METHODS AND RESULTS......: The relationship between PIIINP and changes of left ventricular (LV) function was studied in 47 consecutive patients with first acute MI and 16 control subjects. Serum PIIINP analysis was measured daily during hospitalization and on days 90, 180, and 360. LV function was assessed by echocardiography on days 1, 5......, 90, and 360. Patients with MI were stratified according to their serum PIIINP value at day 4 (group A, 5.0 microg/L). On arrival, LV function and size were comparable between groups A (n=31) and B (n=16). LV ejection fraction, initially depressed (day 1: group A, 47...

  7. Frequency of nuclear mutant huntingtin inclusion formation in neurons and glia is cell-type-specific

    NARCIS (Netherlands)

    Jansen, Anne H. P.; van Hal, Maurik; Op den Kelder, Ilse C.; Meier, Romy T.; de Ruiter, Anna-Aster; Schut, Menno H.; Smith, Donna L.; Grit, Corien; Brouwer, Nieske; Kamphuis, Willem; Boddeke, H. W. G. M.; den Dunnen, Wilfred F. A.; van Roon, Willeke M. C.; Bates, Gillian P.; Hol, Elly M.; Reits, Eric A.

    2017-01-01

    Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder that is caused by a CAG expansion in the Huntingtin (HTT) gene, leading to HTT inclusion formation in the brain. The mutant huntingtin protein (mHTT) is ubiquitously expressed and therefore nuclear inclusions

  8. Frequency of Nuclear Mutant Huntingtin Inclusion Formation in Neurons and Glia is Cell-Type-Specific

    NARCIS (Netherlands)

    Jansen, Anne H P; van Hal, Maurik; op den Kelder, Ilse C.; Meier, Romy T.; de Ruiter, Anna-Aster; Schut, Menno H.; Smith, Donna L.; Grit, Corien; Brouwer, Nieske; Kamphuis, Willem; Boddeke, H. W. G. M.; den Dunnen, Wilfred F. A.; van Roon, Willeke M. C.; Bates, Gillian P.; Hol, Elly M.; Reits, Eric A.

    Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder that is caused by a CAG expansion in the Huntingtin (HTT) gene, leading to HTT inclusion formation in the brain. The mutant huntingtin protein (mHTT) is ubiquitously expressed and therefore nuclear inclusions

  9. Perturbation with intrabodies reveals that calpain cleavage is required for degradation of huntingtin exon 1.

    Directory of Open Access Journals (Sweden)

    Amber L Southwell

    2011-01-01

    Full Text Available Proteolytic processing of mutant huntingtin (mHtt, the protein that causes Huntington's disease (HD, is critical for mHtt toxicity and disease progression. mHtt contains several caspase and calpain cleavage sites that generate N-terminal fragments that are more toxic than full-length mHtt. Further processing is then required for the degradation of these fragments, which in turn, reduces toxicity. This unknown, secondary degradative process represents a promising therapeutic target for HD.We have used intrabodies, intracellularly expressed antibody fragments, to gain insight into the mechanism of mutant huntingtin exon 1 (mHDx-1 clearance. Happ1, an intrabody recognizing the proline-rich region of mHDx-1, reduces the level of soluble mHDx-1 by increasing clearance. While proteasome and macroautophagy inhibitors reduce turnover of mHDx-1, Happ1 is still able to reduce mHDx-1 under these conditions, indicating Happ1-accelerated mHDx-1 clearance does not rely on these processes. In contrast, a calpain inhibitor or an inhibitor of lysosomal pH block Happ1-mediated acceleration of mHDx-1 clearance. These results suggest that mHDx-1 is cleaved by calpain, likely followed by lysosomal degradation and this process regulates the turnover rate of mHDx-1. Sequence analysis identifies amino acid (AA 15 as a potential calpain cleavage site. Calpain cleavage of recombinant mHDx-1 in vitro yields fragments of sizes corresponding to this prediction. Moreover, when the site is blocked by binding of another intrabody, V(L12.3, turnover of soluble mHDx-1 in living cells is blocked.These results indicate that calpain-mediated removal of the 15 N-terminal AAs is required for the degradation of mHDx-1, a finding that may have therapeutic implications.

  10. Amino-terminal pro-brain natriuretic peptide as a predictor of outcome in patients admitted to intensive care. A prospective observational study.

    Science.gov (United States)

    De Geer, Lina; Fredrikson, Mats; Oscarsson, Anna

    2012-06-01

    Amino-terminal pro-brain-type natriuretic peptide is known to predict outcome in patients with heart failure, but its role in an intensive care setting is not yet fully established. To assess the incidence of elevated amino-terminal pro-brain natriuretic peptide (NT-pro-BNP) on admission to intensive care and its relation to death in the ICU and within 30 days. Prospective, observational cohort study. A mixed non-cardiothoracic tertiary ICU in Sweden. NT-pro-BNP was collected from 481 consecutive patients on admission to intensive care, in addition to data on patient characteristics and outcome. A receiver-operating characteristic curve was used to identify a discriminatory level of significance, a stepwise logistic regression analysis to correct for other clinical factors and a Kaplan-Meier analysis to assess survival. The correlation between Simplified Acute Physiology Score (SAPS) 3, Sequential Organ Failure Assessment score (SOFA) and NT-pro-BNP was analysed using Spearman's correlation test. Quartiles of NT-pro-BNP elevation were compared for baseline data and outcome using a logistic regression model. An NT-pro-BNP more than 1380 ng -l on admission was an independent predictor of death in the ICU and within 30 days [odds ratio (OR) 2.6; 95% confidence interval (CI), 1.5 to 4.4] and was present in 44% of patients. Thirty-three percent of patients with NT-pro-BNP more than 1380 ng -1, and 14.6% of patients below that threshold died within 30 days (log rank P=0.005). NT-pro-BNP correlated moderately with SAPS 3 and with SOFA on admission (Spearman's ρ 0.5552 and 0.5129, respectively). In quartiles of NT-pro-BNP elevation on admission, severity of illness and mortality increased significantly (30-day mortality 36.1%; OR 3.9; 95% CI, 2.0 to 7.3 in the quartile with the highest values, vs. 12.8% in the lowest quartile). We conclude that NT-pro-BNP is commonly elevated on admission to intensive care, that it increases with severity of illness and that it is an

  11. Amino-terminal domain of the v-fms oncogene product includes a functional signal peptide that directs synthesis of a transforming glycoprotein in the absence of feline leukemia virus gag sequences

    International Nuclear Information System (INIS)

    Wheeler, E.F.; Roussel, M.F.; Hampe, A.; Walker, M.H.; Fried, V.A.; Look, A.T.; Rettenmier, C.W.; Sherr, C.J.

    1986-01-01

    The nucleotide sequence of a 5' segment of the human genomic c-fms proto-oncogene suggested that recombination between feline leukemia virus and feline c-fms sequences might have occurred in a region encoding the 5' untranslated portion of c-fms mRNA. The polyprotein precursor gP180/sup gag-fms/ encoded by the McDonough strain of feline sarcoma virus was therefore predicted to contain 34 v-fms-coded amino acids derived from sequences of the c-fms gene that are not ordinarily translated from the proto-oncogene mRNA. The (gP180/sup gag-fms/) polyprotein was cotranslationally cleaved near the gag-fms junction to remove its gag gene-coded portion. Determination of the amino-terminal sequence of the resulting v-fms-coded glycoprotein, gp120/sup v-fms/, showed that the site of proteolysis corresponded to a predicted signal peptidase cleavage site within the c-fms gene product. Together, these analyses suggested that the linked gag sequences may not be necessary for expression of a biologically active v-fms gene product. The gag-fms sequences of feline sarcoma virus strain McDonough and the v-fms sequences alone were inserted into a murine retroviral vector containing a neomycin resistance gene. The authors conclude that a cryptic hydrophobic signal peptide sequence in v-fms was unmasked by gag deletion, thereby allowing the correct orientation and transport of the v-fms was unmasked by gag deletion, thereby allowing the correct orientation and transport of the v-fms gene product within membranous organelles. It seems likely that the proteolytic cleavage of gP180/gag-fms/ is mediated by signal peptidase and that the amino termini of gp140/sup v-fms/ and the c-fms gene product are identical

  12. Amino-terminal domain of the v-fms oncogene product includes a functional signal peptide that directs synthesis of a transforming glycoprotein in the absence of feline leukemia virus gag sequences

    Energy Technology Data Exchange (ETDEWEB)

    Wheeler, E.F.; Roussel, M.F.; Hampe, A.; Walker, M.H.; Fried, V.A.; Look, A.T.; Rettenmier, C.W.; Sherr, C.J.

    1986-08-01

    The nucleotide sequence of a 5' segment of the human genomic c-fms proto-oncogene suggested that recombination between feline leukemia virus and feline c-fms sequences might have occurred in a region encoding the 5' untranslated portion of c-fms mRNA. The polyprotein precursor gP180/sup gag-fms/ encoded by the McDonough strain of feline sarcoma virus was therefore predicted to contain 34 v-fms-coded amino acids derived from sequences of the c-fms gene that are not ordinarily translated from the proto-oncogene mRNA. The (gP180/sup gag-fms/) polyprotein was cotranslationally cleaved near the gag-fms junction to remove its gag gene-coded portion. Determination of the amino-terminal sequence of the resulting v-fms-coded glycoprotein, gp120/sup v-fms/, showed that the site of proteolysis corresponded to a predicted signal peptidase cleavage site within the c-fms gene product. Together, these analyses suggested that the linked gag sequences may not be necessary for expression of a biologically active v-fms gene product. The gag-fms sequences of feline sarcoma virus strain McDonough and the v-fms sequences alone were inserted into a murine retroviral vector containing a neomycin resistance gene. The authors conclude that a cryptic hydrophobic signal peptide sequence in v-fms was unmasked by gag deletion, thereby allowing the correct orientation and transport of the v-fms was unmasked by gag deletion, thereby allowing the correct orientation and transport of the v-fms gene product within membranous organelles. It seems likely that the proteolytic cleavage of gP180/gag-fms/ is mediated by signal peptidase and that the amino termini of gp140/sup v-fms/ and the c-fms gene product are identical.

  13. Structure of the Paramyxovirus Parainfluenza Virus 5 Nucleoprotein in Complex with an Amino-Terminal Peptide of the Phosphoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Aggarwal, Megha; Leser, George P.; Kors, Christopher A.; Lamb, Robert A.; Sundquist, Wesley I.

    2017-12-13

    Parainfluenza virus 5 (PIV5) belongs to the familyParamyxoviridae, which consists of enveloped viruses with a nonsegmented negative-strand RNA genome encapsidated by the nucleoprotein (N). Paramyxovirus replication is regulated by the phosphoprotein (P) through protein-protein interactions with N and the RNA polymerase (L). The chaperone activity of P is essential to maintain the unassembled RNA-free form of N in order to prevent nonspecific RNA binding and premature N oligomerization. Here, we determined the crystal structure of unassembled PIV5 N in complex with a P peptide (N0P) derived from the N terminus of P (P50) at 2.65 Å. The PIV5 N0P consists of two domains: an N-terminal domain (NTD) and a C-terminal domain (CTD) separated by a hinge region. The cleft at the hinge region of RNA-bound PIV5 N was previously shown to be an RNA binding site. The N0P structure shows that the P peptide binds to the CTD of N and extends toward the RNA binding site to inhibit N oligomerization and, hence, RNA binding. Binding of P peptide also keeps the PIV5 N in the open form. A molecular dynamics (MD) analysis of both the open and closed forms of N shows the flexibility of the CTD and the preference of the N protein to be in an open conformation. The gradual opening of the hinge region, to release the RNA, was also observed. Together, these results advance our knowledge of the conformational swapping of N required for the highly regulated paramyxovirus replication.

    IMPORTANCEParamyxovirus replication is regulated by the interaction of P with N and L proteins. Here, we report the crystal structure of unassembled parainfluenza virus 5 (PIV5) N chaperoned with P peptide. Our results provide a detailed understanding of the binding of P to N. The conformational switching of N between closed and open forms during its initial interaction with P, as well as

  14. Establishment of the enzyme-linked immunosorbent assay system to detect the amino terminal secretory form of rat Erc/Mesothelin.

    Science.gov (United States)

    Nakaishi, Masayuki; Kajino, Kazunori; Ikesue, Masahiro; Hagiwara, Yoshiaki; Kuwahara, Maki; Mitani, Hiroaki; Horikoshi-Sakuraba, Yuko; Segawa, Tatsuya; Kon, Shigeyuki; Maeda, Masahiro; Wang, Tegexibaiyin; Abe, Masaaki; Yokoyama, Masayoshi; Hino, Okio

    2007-05-01

    By representational difference analysis, we previously identified the rat Erc (Expressed in renal carcinoma) gene that was more abundantly expressed in the renal carcinoma tissues of Eker rats than in the rat normal kidney. In this study, we raised antibodies against the amino-terminal portion of the rat Erc, and demonstrated the existence of a approximately 30-kDa secretory form in the supernatant of cultured cells derived from rat renal carcinoma. The enzyme-linked immunosorbent assay (ELISA) system using these antibodies detected high concentrations of this form in the sera of Eker rats bearing renal carcinomas, and in the sera of rats transplanted with mesothelioma cells. Mesothelin, a human homolog of the rat Erc, was recently reported to be a serum marker of malignant mesothelioma. The prognosis of mesothelioma is poor and there is no effective treatment at present. There are several rat model systems of mesothelioma that may be promising tools in the development of an antimesothelioma treatment. We hope our ELISA to detect the soluble form of rat Erc/Mesothelin is useful in the rat model system to exploit the antimesothelioma therapy to be used in human cases.

  15. Conserved cell cycle regulatory properties within the amino terminal domain of the Epstein-Barr virus nuclear antigen 3C

    International Nuclear Information System (INIS)

    Sharma, Nikhil; Knight, Jason S.; Robertson, Erle S.

    2006-01-01

    The gammaherpesviruses Rhesus lymphocryptovirus (LCV) and Epstein-Barr virus (EBV) are closely related phylogenetically. Rhesus LCV efficiently immortalizes Rhesus B cells in vitro. However, despite a high degree of conservation between the Rhesus LCV and EBV genomes, Rhesus LCV fails to immortalize human B cells in vitro. This species restriction may, at least in part, be linked to the EBV nuclear antigens (EBNAs) and latent membrane proteins (LMPs), known to be essential for B cell transformation. We compared specific properties of EBNA3C, a well-characterized and essential EBV protein, with its Rhesus counterpart to determine whether EBNA3C phenotypes which contribute to cell cycle regulation are conserved in the Rhesus LCV. We show that both EBNA3C and Rhesus EBNA3C bind to a conserved region of mammalian cyclins, regulate pRb stability, and modulate SCF Skp2 -dependent ubiquitination. These results suggest that Rhesus LCV restriction from human B cell immortalization is independent of the conserved cell cycle regulatory functions of the EBNA3C protein

  16. The cryo-electron microscopy structure of huntingtin

    Science.gov (United States)

    Guo, Qiang; Bin Huang; Cheng, Jingdong; Seefelder, Manuel; Engler, Tatjana; Pfeifer, Günter; Oeckl, Patrick; Otto, Markus; Moser, Franziska; Maurer, Melanie; Pautsch, Alexander; Baumeister, Wolfgang; Fernández-Busnadiego, Rubén; Kochanek, Stefan

    2018-03-01

    Huntingtin (HTT) is a large (348 kDa) protein that is essential for embryonic development and is involved in diverse cellular activities such as vesicular transport, endocytosis, autophagy and the regulation of transcription. Although an integrative understanding of the biological functions of HTT is lacking, the large number of identified HTT interactors suggests that it serves as a protein-protein interaction hub. Furthermore, Huntington’s disease is caused by a mutation in the HTT gene, resulting in a pathogenic expansion of a polyglutamine repeat at the amino terminus of HTT. However, only limited structural information regarding HTT is currently available. Here we use cryo-electron microscopy to determine the structure of full-length human HTT in a complex with HTT-associated protein 40 (HAP40; encoded by three F8A genes in humans) to an overall resolution of 4 Å. HTT is largely α-helical and consists of three major domains. The amino- and carboxy-terminal domains contain multiple HEAT (huntingtin, elongation factor 3, protein phosphatase 2A and lipid kinase TOR) repeats arranged in a solenoid fashion. These domains are connected by a smaller bridge domain containing different types of tandem repeats. HAP40 is also largely α-helical and has a tetratricopeptide repeat-like organization. HAP40 binds in a cleft and contacts the three HTT domains by hydrophobic and electrostatic interactions, thereby stabilizing the conformation of HTT. These data rationalize previous biochemical results and pave the way for improved understanding of the diverse cellular functions of HTT.

  17. Transfer of the amino-terminal nuclear envelope targeting domain of human MX2 converts MX1 into an HIV-1 resistance factor.

    Science.gov (United States)

    Goujon, Caroline; Moncorgé, Olivier; Bauby, Hélène; Doyle, Tomas; Barclay, Wendy S; Malim, Michael H

    2014-08-01

    The myxovirus resistance 2 (MX2) protein of humans has been identified recently as an interferon (IFN)-inducible inhibitor of human immunodeficiency virus type 1 (HIV-1) that acts at a late postentry step of infection to prevent the nuclear accumulation of viral cDNA (C. Goujon et al., Nature 502:559-562, 2013, http://dx.doi.org/10.1038/nature12542; M. Kane et al., Nature 502:563-566, 2013, http://dx.doi.org/10.1038/nature12653; Z. Liu et al., Cell Host Microbe 14:398-410, 2013, http://dx.doi.org/10.1016/j.chom.2013.08.015). In contrast, the closely related human MX1 protein, which suppresses infection by a range of RNA and DNA viruses (such as influenza A virus [FluAV]), is ineffective against HIV-1. Using a panel of engineered chimeric MX1/2 proteins, we demonstrate that the amino-terminal 91-amino-acid domain of MX2 confers full anti-HIV-1 function when transferred to the amino terminus of MX1, and that this fusion protein retains full anti-FluAV activity. Confocal microscopy experiments further show that this MX1/2 fusion, similar to MX2 but not MX1, can localize to the nuclear envelope (NE), linking HIV-1 inhibition with MX accumulation at the NE. MX proteins are dynamin-like GTPases, and while MX1 antiviral function requires GTPase activity, neither MX2 nor MX1/2 chimeras require this attribute to inhibit HIV-1. This key discrepancy between the characteristics of MX1- and MX2-mediated viral resistance, together with previous observations showing that the L4 loop of the stalk domain of MX1 is a critical determinant of viral substrate specificity, presumably reflect fundamental differences in the mechanisms of antiviral suppression. Accordingly, we propose that further comparative studies of MX proteins will help illuminate the molecular basis and subcellular localization requirements for implementing the noted diversity of virus inhibition by MX proteins. Interferon (IFN) elicits an antiviral state in cells through the induction of hundreds of IFN

  18. Amino-Terminal proB-Type Natriuretic Peptide Levels in the Umbilical Cord Blood of Neonates Differ According to the Type of Prenatally Diagnosed Congenital Heart Disease.

    Science.gov (United States)

    Bae, Jin Young; Cha, Hyun-Hwa; Seong, Won Joon

    2015-12-01

    The aim of this study was to investigate differences in amino-terminal proB-type natriuretic peptide (NT-proBNP) levels in the cord blood of neonates according to the type of congenital heart disease (CHD) and to evaluate the usefulness of NT-proBNP as a prognostic marker. We included 76 neonates with prenatally diagnosed CHD and 45 controls without CHD. Neonates were classified into five groups based on echocardiographic findings. The levels of NT-proBNP in the cord blood were examined and analyzed according to the neonatal outcomes. The levels of NT-proBNP were significantly elevated in the cord blood of neonates with CHD compared with that in the cord blood of controls. The levels of NT-proBNP in the group with right ventricular outflow tract obstruction without a ventricular septal defect were significantly increased compared to that in the other groups. The neonates that required acute surgical correction had higher levels of NT-proBNP in the cord blood, though they were not statistically significant. Meanwhile, NT-proBNP levels in the cord blood of neonates with functional single ventricle were significantly higher than that in the cord blood of those with functional biventricles. Significant differences in the levels of NT-proBNP between survivors and nonsurvivors were observed within 1 year of birth. In this study, we found that the levels of NT-proBNP in the cord blood of neonates with CHD were higher than the levels in controls. This finding was striking in the group with right ventricular outflow tract obstruction, and it was associated with surgery for functional single ventricle and 1-year survival.

  19. Nontruncated amino-terminal parathyroid hormone overproduction in two patients with parathyroid carcinoma: a possible link to HRPT2 gene inactivation.

    Science.gov (United States)

    Caron, Philippe; Simonds, William F; Maiza, Jean-Christophe; Rubin, Mishaela; Cantor, Tom; Rousseau, Louise; Bilezikian, John P; Souberbielle, Jean-Claude; D'Amour, Pierre

    2011-06-01

    Some patients with parathyroid carcinoma present with an over-production of nontruncated amino-terminal (NT-N) parathyroid hormone (PTH), a post-transcriptionally modified form of PTH(1-84). This is usually picked up on an elevated whole (W) PTH (third-generation)/total (T) (second-generation) PTH assay ratio (N > 0·8). Two parathyroid cancer patients with several episodes of hypercalcaemia and multiple surgeries are described. In both patients, W-PTH, T-PTH and circulating PTH molecular forms separated by high-pressure liquid chromatography (HPLC) were measured with the same assays. qPCR was used to study HRPT2 gene mutation. The first patient had total calcium of 3·8 and 3·22 mmol/l before the fourth and fifth surgeries, and third/second-generation PTH ratios of 2·95 and 3·6, respectively. After the fourth surgery, the ratio remained normal for 1 year and increased progressively to 3·6 over 15 months. This preceded hypercalcaemia by 6 months. The ratio became normal after the fifth surgery. HPLC analysis disclosed an over-expression of NT-N PTH to 82·2% (N < 10%) relative to hPTH(1-84) before the fifth surgery. A deletion of all the tested exons of the HRPT2 gene was identified. In the second patient, W-PTH/T-PTH ratio was 0·89 when serum calcium was 3·3 mmol/l. NT-N PTH was also over-expressed at 51·9%. An inactivating mutation of the HRPT2 gene was also identified. This may suggest that a progressive rise in third/second-generation ratio may have possible clinical utility to monitor parathyroid cancer recurrence. A possible association between NT-N PTH overproduction and HRPT2 gene inactivation is also suggested. © 2011 Blackwell Publishing Ltd.

  20. Inhibition of Cartilage Acidic Protein 1 Reduces Ultraviolet B Irradiation Induced-Apoptosis through P38 Mitogen-Activated Protein Kinase and Jun Amino-Terminal Kinase Pathways

    Directory of Open Access Journals (Sweden)

    Yinghong Ji

    2016-11-01

    Full Text Available Background/Aims: Ultraviolet B (UVB irradiation can easily induce apoptosis in human lens epithelial cells (HLECs and further lead to various eye diseases including cataract. Here for the first time, we investigated the role of cartilage acidic protein 1 (CRTAC1 gene in UVB irradiation induced-apoptosis in HLECs. Methods: Three groups of HLECs were employed including model group, empty vector group, and CRTAC1 interference group. Results: After UVB irradiation, the percentage of primary apoptotic cells was obviously fewer in CRTAC1 interference group. Meanwhile, inhibition of CRTAC1 also reduced both reactive oxygen species (ROS production and intracellular Ca2+ concentration, but the level of mitochondrial membrane potential (Δψm was increased in HLECs. Further studies indicated that superoxide dismutase (SOD activity and total antioxidative (T-AOC level were significantly increased in CRTAC1-inhibited cells, while the levels of malondialdehyde (MDA and lactate dehydrogenase (LDH were significantly decreased. ELISA analysis of CRTAC1-inhibited cells showed that the concentrations of tumor necrosis factor-α (TNF-α and interleukin-6 (IL-6 were significantly decreased, but the concentration of interleukin-10 (IL-10 was significantly increased. Western blot analyses of eight apoptosis-associated proteins including Bax, Bcl-2, p38, phospho-p38 (p-p38, Jun amino-terminal kinases (JNK1/2, phospho-JNK1/2 (p-JNK1/2, calcium-sensing receptor (CasR, and Ca2+/calmodulin-dependent protein kinase II (CaMKII indicated that the inhibition of CRTAC1 alleviated oxidative stress and inflammation response, inactivated calcium-signaling pathway, p38 and JNK1/2 signal pathways, and eventually reduced UVB irradiation induced-apoptosis in HLECs. Conclusion: These results provided new insights into the mechanism of cataract development, and demonstrated that CRTAC1 could be a potentially novel target for cataract treatment.

  1. Inhibition of Cartilage Acidic Protein 1 Reduces Ultraviolet B Irradiation Induced-Apoptosis through P38 Mitogen-Activated Protein Kinase and Jun Amino-Terminal Kinase Pathways.

    Science.gov (United States)

    Ji, Yinghong; Rong, Xianfang; Li, Dan; Cai, Lei; Rao, Jun; Lu, Yi

    2016-01-01

    Ultraviolet B (UVB) irradiation can easily induce apoptosis in human lens epithelial cells (HLECs) and further lead to various eye diseases including cataract. Here for the first time, we investigated the role of cartilage acidic protein 1 (CRTAC1) gene in UVB irradiation induced-apoptosis in HLECs. Three groups of HLECs were employed including model group, empty vector group, and CRTAC1 interference group. After UVB irradiation, the percentage of primary apoptotic cells was obviously fewer in CRTAC1 interference group. Meanwhile, inhibition of CRTAC1 also reduced both reactive oxygen species (ROS) production and intracellular Ca2+ concentration, but the level of mitochondrial membrane potential (Δψm) was increased in HLECs. Further studies indicated that superoxide dismutase (SOD) activity and total antioxidative (T-AOC) level were significantly increased in CRTAC1-inhibited cells, while the levels of malondialdehyde (MDA) and lactate dehydrogenase (LDH) were significantly decreased. ELISA analysis of CRTAC1-inhibited cells showed that the concentrations of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were significantly decreased, but the concentration of interleukin-10 (IL-10) was significantly increased. Western blot analyses of eight apoptosis-associated proteins including Bax, Bcl-2, p38, phospho-p38 (p-p38), Jun amino-terminal kinases (JNK1/2), phospho-JNK1/2 (p-JNK1/2), calcium-sensing receptor (CasR), and Ca2+/calmodulin-dependent protein kinase II (CaMKII) indicated that the inhibition of CRTAC1 alleviated oxidative stress and inflammation response, inactivated calcium-signaling pathway, p38 and JNK1/2 signal pathways, and eventually reduced UVB irradiation induced-apoptosis in HLECs. These results provided new insights into the mechanism of cataract development, and demonstrated that CRTAC1 could be a potentially novel target for cataract treatment. © 2016 The Author(s) Published by S. Karger AG, Basel.

  2. Measurement of Urinary Amino-Terminal Pro-Brain Natriuretic Peptide in Childhood Lower Respiratory Tract Infections: An Indicator of Clinical Severity?

    Directory of Open Access Journals (Sweden)

    Nisa Eda Çullas İlarslan

    2017-12-01

    Full Text Available Aim: Prompt diagnosis and determination of the clinical severity and intervention of lower respiratory tract infections (LRTI is essential for the prevention and management of life-threatening complications. Laboratory tests do not serve as accurate indicators of clinical severity. Our aim was to evaluate the contribution of urinary amino-terminal pro-brain natriuretic peptide (NT-ProBNP concentrations in children with LRTI to clinical assessment in terms of determining clinical severity and the necessity of hospitalization. Materials and Methods: This prospective non-randomised study included a total of 160 patients, aged 0-6 years, diagnosed with LRTI [(group 1=outpatient group (n=108, and (group 2=hospitalized patients (n=52]. The control group (group 3 was comprised of 46 healthy children. Urinary NT-ProBNP level of each participant was measured by ELISA method. Results: Although not significant, the mean urinary NT-ProBNP level of all patients was higher than that of the control group (p=0.322. When we compared the three groups separately, the highest levels belonged to outpatients whereas hospitalized patients showed slightly lower levels than the control group without any statistical significance (p=0.128. As for newborns (n=16, patients showed higher levels than the controls (p=0.041. P value <0.05 was considered significant. Conclusion: Although urinary NT-ProBNP level tends to increase to some extent in childhood LRTI, this alteration does not seem to be valuable in the prediction of the severity of the disease. We believe that the establishment of further studies including larger series of patients, especially neonates, is warranted.

  3. Sequestration of Sup35 by aggregates of huntingtin fragments causes toxicity of [PSI+] yeast.

    Science.gov (United States)

    Zhao, Xiaohong; Park, Yang-Nim; Todor, Horia; Moomau, Christine; Masison, Daniel; Eisenberg, Evan; Greene, Lois E

    2012-07-06

    Expression of huntingtin fragments with 103 glutamines (HttQ103) is toxic in yeast containing either the [PIN(+)] prion, which is the amyloid form of Rnq1, or [PSI(+)] prion, which is the amyloid form of Sup35. We find that HttQP103, which has a polyproline region at the C-terminal end of the polyQ repeat region, is significantly more toxic in [PSI(+)] yeast than in [PIN(+)], even though HttQP103 formed multiple aggregates in both [PSI(+)] and [PIN(+)] yeast. This toxicity was only observed in the strong [PSI(+)] variant, not the weak [PSI(+)] variant, which has more soluble Sup35 present than the strong variant. Furthermore, expression of the MC domains of Sup35, which retains the C-terminal domain of Sup35, but lacks the N-terminal prion domain, almost completely rescued HttQP103 toxicity, but was less effective in rescuing HttQ103 toxicity. Therefore, the toxicity of HttQP103 in yeast containing the [PSI(+)] prion is primarily due to sequestration of the essential protein, Sup35.

  4. Disposable amperometric magnetoimmunosensor for the sensitive detection of the cardiac biomarker amino-terminal pro-B-type natriuretic peptide in human serum

    Energy Technology Data Exchange (ETDEWEB)

    Esteban-Fernández de Ávila, Berta, E-mail: berta.efa@quim.ucm.es; Escamilla-Gómez, Vanessa, E-mail: vaneeg@quim.ucm.es; Campuzano, Susana, E-mail: susanacr@quim.ucm.es; Pedrero, María, E-mail: mpedrero@quim.ucm.es; Pingarrón, José M., E-mail: pingarro@quim.ucm.es

    2013-06-19

    Graphical abstract: -- Highlights: •Novel and sensitive amperometric magnetoimmunosensor for NT-proBNP detection. •Indirect competitive immunoassay onto HOOC-MBs and Au/SPEs as transducers. •Excellent analytical performance at levels clinically relevant in human serum. •Useful in clinical diagnosis and prognosis of cardiac diseases. -- Abstract: A novel amperometric magnetoimmunosensor using an indirect competitive format is developed for the sensitive detection of the amino-terminal pro-B-type natriuretic peptide (NT-proBNP). The immunosensor design involves the covalent immobilization of the antigen onto carboxylic-modified magnetic beads (HOOC-MBs) activated with N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDC) and N-hydroxysulfosuccinimide (sulfo-NHS), and further incubation in a mixture solution containing variable concentrations of the antigen and a fixed concentration of an HRP-labeled detection antibody. Accordingly, the target NT-proBNP in the sample and that immobilized on the MBs compete for binding to a fixed amount of the specific HRP-labeled secondary antibody. The immunoconjugate-bearing MBs are captured by a magnet placed under the surface of a disposable gold screen-printed electrode (Au/SPE). The amperometric responses measured at –0.10 V (vs. a Ag pseudo-reference electrode), upon addition of 3,3′,5,5′-tetramethylbenzidine (TMB) as electron transfer mediator and H{sub 2}O{sub 2} as the enzyme substrate, are used to monitor the affinity reaction. The developed magnetoimmunosensor provides attractive analytical characteristics in 10-times diluted human serum samples, exhibiting a linear range of clinical usefulness (0.12–42.9 ng mL{sup −1}) and a detection limit of 0.02 ng mL{sup −1}, which can be used in clinical diagnosis of chronic heart failure in the elderly and for classifying patients at risk of death after heart transplantation. The magnetoimmunosensor was successfully applied to the analysis of spiked human serum

  5. Prognostic utility of the Seattle Heart Failure Score and amino terminal pro B-type natriuretic peptide in varying stages of systolic heart failure.

    Science.gov (United States)

    Adlbrecht, Christopher; Hülsmann, Martin; Neuhold, Stephanie; Strunk, Guido; Pacher, Richard

    2013-05-01

    Cardiac transplantation represents the best procedure to improve long-term clinical outcome in advanced chronic heart failure (CHF), if pre-selection criteria are sufficient to outweigh the risk of the failing heart over the risk of transplantation. Although the cornerstone of success, risk assessment in heart transplant candidates is still under-investigated. Amino terminal pro B-type natriuretic peptide (NT-proBNP) is regarded as the best predictor of outcome in CHF, and the Seattle Heart Failure Score (SHFS), including clinical markers, is widely used if NT-proBNP is unavailable. The present study assessed the predictive value for all-cause death of the SHFS in CHF patients and compared it with NT-proBNP in a multivariate model including established baseline parameters known to predict survival. A total of 429 patients receiving stable HF-specific pharmacotherapy were included and monitored for 53.4 ± 20.6 months. Of these, 133 patients (31%) died during follow-up. Several established predictors of death on univariate analysis proved significant for the total study cohort. Systolic pulmonary arterial pressure (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.02-1.05); p < 0.001, Wald 15.1), logNT-proBNP (HR, 1.51; 95% CI, 1.22-1.86; p < 0.001, Wald 14.9), and the SHFS (HR, 0.99; 95% CI, 0.99-1.00; p < 0.001, Wald 12.6) remained within the stepwise multivariate Cox regression model as independent predictors of all-cause death. Receiver operating characteristic curve analysis revealed an area under the curve of 0.802 for logNT-proBNP and 0.762 for the SHFS. NT-proBNP is a more potent marker to identify patients at the highest risk. If the NT-proBNP measurement is unavailable, the SHFS may serve as an adequate clinical surrogate to predict all-cause death. Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  6. Length and sequence dependence in the association of Huntingtin protein with lipid membranes

    Science.gov (United States)

    Jawahery, Sudi; Nagarajan, Anu; Matysiak, Silvina

    2013-03-01

    There is a fundamental gap in our understanding of how aggregates of mutant Huntingtin protein (htt) with overextended polyglutamine (polyQ) sequences gain the toxic properties that cause Huntington's disease (HD). Experimental studies have shown that the most important step associated with toxicity is the binding of mutant htt aggregates to lipid membranes. Studies have also shown that flanking amino acid sequences around the polyQ sequence directly affect interactions with the lipid bilayer, and that polyQ sequences of greater than 35 glutamine repeats in htt are a characteristic of HD. The key steps that determine how flanking sequences and polyQ length affect the structure of lipid bilayers remain unknown. In this study, we use atomistic molecular dynamics simulations to study the interactions between lipid membranes of varying compositions and polyQ peptides of varying lengths and flanking sequences. We find that overextended polyQ interactions do cause deformation in model membranes, and that the flanking sequences do play a role in intensifying this deformation by altering the shape of the affected regions.

  7. Unbiased gene expression analysis implicates the huntingtin polyglutamine tract in extra-mitochondrial energy metabolism.

    Directory of Open Access Journals (Sweden)

    Jong-Min Lee

    2007-08-01

    Full Text Available The Huntington's disease (HD CAG repeat, encoding a polymorphic glutamine tract in huntingtin, is inversely correlated with cellular energy level, with alleles over approximately 37 repeats leading to the loss of striatal neurons. This early HD neuronal specificity can be modeled by respiratory chain inhibitor 3-nitropropionic acid (3-NP and, like 3-NP, mutant huntingtin has been proposed to directly influence the mitochondrion, via interaction or decreased PGC-1alpha expression. We have tested this hypothesis by comparing the gene expression changes due to mutant huntingtin accurately expressed in STHdh(Q111/Q111 cells with the changes produced by 3-NP treatment of wild-type striatal cells. In general, the HD mutation did not mimic 3-NP, although both produced a state of energy collapse that was mildly alleviated by the PGC-1alpha-coregulated nuclear respiratory factor 1 (Nrf-1. Moreover, unlike 3-NP, the HD CAG repeat did not significantly alter mitochondrial pathways in STHdh(Q111/Q111 cells, despite decreased Ppargc1a expression. Instead, the HD mutation enriched for processes linked to huntingtin normal function and Nf-kappaB signaling. Thus, rather than a direct impact on the mitochondrion, the polyglutamine tract may modulate some aspect of huntingtin's activity in extra-mitochondrial energy metabolism. Elucidation of this HD CAG-dependent pathway would spur efforts to achieve energy-based therapeutics in HD.

  8. Assembly of Huntingtin headpiece into α-helical bundles.

    Science.gov (United States)

    Ozgur, Beytullah; Sayar, Mehmet

    2017-05-24

    Protein aggregation is a hallmark of neurodegenerative disorders. In this group of brain-related disorders, a disease-specific "host" protein or fragment misfolds and adopts a metastatic, aggregate-prone conformation. Often, this misfolded conformation is structurally and thermodynamically different from its native state. Intermolecular contacts, which arise in this non-native state, promote aggregation. In this regard, understanding the molecular principles and mechanisms that lead to the formation of such a non-native state and further promote the formation of the critical nucleus for fiber growth is essential. In this study, the authors analyze the aggregation propensity of Huntingtin headpiece (htt NT ), which is known to facilitate the polyQ aggregation, in relation to the helix mediated aggregation mechanism proposed by the Wetzel group. The authors demonstrate that even though htt NT displays a degenerate conformational spectrum on its own, interfaces of macroscopic or molecular origin can promote the α-helix conformation, eliminating all other alternatives in the conformational phase space. Our findings indicate that htt NT molecules do not have a strong orientational preference for parallel or antiparallel orientation of the helices within the aggregate. However, a parallel packed bundle of helices would support the idea of increased polyglutamine concentration, to pave the way for cross-β structures.

  9. Normal aging modulates the neurotoxicity of mutant huntingtin.

    Directory of Open Access Journals (Sweden)

    Elsa Diguet

    Full Text Available Aging likely plays a role in neurodegenerative disorders. In Huntington's disease (HD, a disorder caused by an abnormal expansion of a polyglutamine tract in the protein huntingtin (Htt, the role of aging is unclear. For a given tract length, the probability of disease onset increases with age. There are mainly two hypotheses that could explain adult onset in HD: Either mutant Htt progressively produces cumulative defects over time or "normal" aging renders neurons more vulnerable to mutant Htt toxicity. In the present study, we directly explored whether aging affected the toxicity of mutant Htt in vivo. We studied the impact of aging on the effects produced by overexpression of an N-terminal fragment of mutant Htt, of wild-type Htt or of a beta-Galactosidase (beta-Gal reporter gene in the rat striatum. Stereotaxic injections of lentiviral vectors were performed simultaneously in young (3 week and old (15 month rats. Histological evaluation at different time points after infection demonstrated that the expression of mutant Htt led to pathological changes that were more severe in old rats, including an increase in the number of small Htt-containing aggregates in the neuropil, a greater loss of DARPP-32 immunoreactivity and striatal neurons as assessed by unbiased stereological counts.The present results support the hypothesis that "normal" aging is involved in HD pathogenesis, and suggest that age-related cellular defects might constitute potential therapeutic targets for HD.

  10. Huntingtin is critical both pre- and postsynaptically for long-term learning-related synaptic plasticity in Aplysia.

    Directory of Open Access Journals (Sweden)

    Yun-Beom Choi

    Full Text Available Patients with Huntington's disease exhibit memory and cognitive deficits many years before manifesting motor disturbances. Similarly, several studies have shown that deficits in long-term synaptic plasticity, a cellular basis of memory formation and storage, occur well before motor disturbances in the hippocampus of the transgenic mouse models of Huntington's disease. The autosomal dominant inheritance pattern of Huntington's disease suggests the importance of the mutant protein, huntingtin, in pathogenesis of Huntington's disease, but wild type huntingtin also has been shown to be important for neuronal functions such as axonal transport. Yet, the role of wild type huntingtin in long-term synaptic plasticity has not been investigated in detail. We identified a huntingtin homolog in the marine snail Aplysia, and find that similar to the expression pattern in mammalian brain, huntingtin is widely expressed in neurons and glial cells. Importantly the expression of mRNAs of huntingtin is upregulated by repeated applications of serotonin, a modulatory transmitter released during learning in Aplysia. Furthermore, we find that huntingtin expression levels are critical, not only in presynaptic sensory neurons, but also in the postsynaptic motor neurons for serotonin-induced long-term facilitation at the sensory-to-motor neuron synapse of the Aplysia gill-withdrawal reflex. These results suggest a key role for huntingtin in long-term memory storage.

  11. Huntingtin interacting proteins are genetic modifiers of neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Linda S Kaltenbach

    2007-05-01

    Full Text Available Huntington's disease (HD is a fatal neurodegenerative condition caused by expansion of the polyglutamine tract in the huntingtin (Htt protein. Neuronal toxicity in HD is thought to be, at least in part, a consequence of protein interactions involving mutant Htt. We therefore hypothesized that genetic modifiers of HD neurodegeneration should be enriched among Htt protein interactors. To test this idea, we identified a comprehensive set of Htt interactors using two complementary approaches: high-throughput yeast two-hybrid screening and affinity pull down followed by mass spectrometry. This effort led to the identification of 234 high-confidence Htt-associated proteins, 104 of which were found with the yeast method and 130 with the pull downs. We then tested an arbitrary set of 60 genes encoding interacting proteins for their ability to behave as genetic modifiers of neurodegeneration in a Drosophila model of HD. This high-content validation assay showed that 27 of 60 orthologs tested were high-confidence genetic modifiers, as modification was observed with more than one allele. The 45% hit rate for genetic modifiers seen among the interactors is an order of magnitude higher than the 1%-4% typically observed in unbiased genetic screens. Genetic modifiers were similarly represented among proteins discovered using yeast two-hybrid and pull-down/mass spectrometry methods, supporting the notion that these complementary technologies are equally useful in identifying biologically relevant proteins. Interacting proteins confirmed as modifiers of the neurodegeneration phenotype represent a diverse array of biological functions, including synaptic transmission, cytoskeletal organization, signal transduction, and transcription. Among the modifiers were 17 loss-of-function suppressors of neurodegeneration, which can be considered potential targets for therapeutic intervention. Finally, we show that seven interacting proteins from among 11 tested were able to

  12. Scalable production in human cells and biochemical characterization of full-length normal and mutant huntingtin.

    Directory of Open Access Journals (Sweden)

    Bin Huang

    Full Text Available Huntingtin (Htt is a 350 kD intracellular protein, ubiquitously expressed and mainly localized in the cytoplasm. Huntington's disease (HD is caused by a CAG triplet amplification in exon 1 of the corresponding gene resulting in a polyglutamine (polyQ expansion at the N-terminus of Htt. Production of full-length Htt has been difficult in the past and so far a scalable system or process has not been established for recombinant production of Htt in human cells. The ability to produce Htt in milligram quantities would be a prerequisite for many biochemical and biophysical studies aiming in a better understanding of Htt function under physiological conditions and in case of mutation and disease. For scalable production of full-length normal (17Q and mutant (46Q and 128Q Htt we have established two different systems, the first based on doxycycline-inducible Htt expression in stable cell lines, the second on "gutless" adenovirus mediated gene transfer. Purified material has then been used for biochemical characterization of full-length Htt. Posttranslational modifications (PTMs were determined and several new phosphorylation sites were identified. Nearly all PTMs in full-length Htt localized to areas outside of predicted alpha-solenoid protein regions. In all detected N-terminal peptides methionine as the first amino acid was missing and the second, alanine, was found to be acetylated. Differences in secondary structure between normal and mutant Htt, a helix-rich protein, were not observed in our study. Purified Htt tends to form dimers and higher order oligomers, thus resembling the situation observed with N-terminal fragments, although the mechanism of oligomer formation may be different.

  13. The common inhaled anesthetic isoflurane increases aggregation of huntingtin and alters calcium homeostasis in a cell model of Huntington's disease

    International Nuclear Information System (INIS)

    Wang Qiujun; Liang Ge; Yang Hui; Wang Shouping; Eckenhoff, Maryellen F.; Wei Huafeng

    2011-01-01

    Isoflurane is known to increase β-amyloid aggregation and neuronal damage. We hypothesized that isoflurane will have similar effects on the polyglutamine huntingtin protein and will cause alterations in intracellular calcium homeostasis. We tested this hypothesis in striatal cells from the expanded glutamine huntingtin knock-in mouse (STHdh Q111/Q111 ) and wild type (STHdh Q7/Q7 ) striatal neurons. The primary cultured neurons were exposed for 24 h to equipotent concentrations of isoflurane, sevoflurane, and desflurane in the presence or absence of extracellular calcium and with or without xestospongin C, a potent endoplasmic reticulum inositol 1,4,5-trisphosphate (InsP 3 ) receptor antagonist. Aggregation of huntingtin protein, cell viability, and calcium concentrations were measured. Isoflurane, sevoflurane, and desflurane all increased the aggregation of huntingtin in STHdh Q111/Q111 cells, with isoflurane having the largest effect. Isoflurane induced greater calcium release from the ER and relatively more cell damage in the STHdh Q111/Q111 huntingtin cells than in the wild type STHdh Q7/Q7 striatal cells. However, sevoflurane and desflurane caused less calcium release from the ER and less cell damage. Xestospongin C inhibited the isoflurane-induced calcium release from the ER, aggregation of huntingtin, and cell damage in the STHdh Q111/Q111 cells. In summary, the Q111 form of huntingtin increases the vulnerability of striatal neurons to isoflurane neurotoxicity through combined actions on the ER IP 3 receptors. Calcium release from the ER contributes to the anesthetic induced huntingtin aggregation in STHdh Q111/Q111 striatal cells.

  14. Mutant Huntingtin Gene-Dose Impacts on Aggregate Deposition, DARPP32 Expression and Neuroinflammation in HdhQ150 Mice

    Science.gov (United States)

    Young, Douglas; Mayer, Franziska; Vidotto, Nella; Schweizer, Tatjana; Berth, Ramon; Abramowski, Dorothee; Shimshek, Derya R.; van der Putten, P. Herman; Schmid, Peter

    2013-01-01

    Huntington's disease (HD) is an autosomal dominant, progressive and fatal neurological disorder caused by an expansion of CAG repeats in exon-1 of the huntingtin gene. The encoded poly-glutamine stretch renders mutant huntingtin prone to aggregation. HdhQ150 mice genocopy a pathogenic repeat (∼150 CAGs) in the endogenous mouse huntingtin gene and model predominantly pre-manifest HD. Treating early is likely important to prevent or delay HD, and HdhQ150 mice may be useful to assess therapeutic strategies targeting pre-manifest HD. This requires appropriate markers and here we demonstrate, that pre-symptomatic HdhQ150 mice show several dramatic mutant huntingtin gene-dose dependent pathological changes including: (i) an increase of neuronal intra-nuclear inclusions (NIIs) in brain, (ii) an increase of extra-nuclear aggregates in dentate gyrus, (iii) a decrease of DARPP32 protein and (iv) an increase in glial markers of neuroinflammation, which curiously did not correlate with local neuronal mutant huntingtin inclusion-burden. HdhQ150 mice developed NIIs also in all retinal neuron cell-types, demonstrating that retinal NIIs are not specific to human exon-1 R6 HD mouse models. Taken together, the striking and robust mutant huntingtin gene-dose related changes in aggregate-load, DARPP32 levels and glial activation markers should greatly facilitate future testing of therapeutic strategies in the HdhQ150 HD mouse model. PMID:24086450

  15. Determination of L-AP4-bound human mGlu8 receptor amino terminal domain structure and the molecular basis for L-AP4’s group III mGlu receptor functional potency and selectivity

    Energy Technology Data Exchange (ETDEWEB)

    Schkeryantz, Jeffery M.; Chen, Qi; Ho, Joseph D.; Atwell, Shane; Zhang, Aiping; Vargas, Michelle C.; Wang, Jing; Monn, James A.; Hao, Junliang (Lilly)

    2018-02-01

    Here, L-2-Amino-4-phosphonobutyric acid (L-AP4) is a known potent and selective agonist for the Group III mGlu receptors. However, it does not show any selectivity among the individual group III mGlu subtypes. In order to understand the molecular basis for this group selectivity, we solved the first human mGlu8 amino terminal domain (ATD) crystal structures in complex with L-glu and L-AP4. In comparison with other published L-glu-bound mGlu ATD structures, we have observed L-glu binds in a significantly different manner in mGlu1. Furthermore, these new structures provided evidence that both the electronic and steric nature of the distal phosphate of L-AP4 contribute to its exquisite Group III functional agonist potency and selectivity.

  16. Dose-Dependent Lowering of Mutant Huntingtin Using Antisense Oligonucleotides in Huntington Disease Patients.

    Science.gov (United States)

    van Roon-Mom, Willeke M C; Roos, Raymund A C; de Bot, Susanne T

    2018-04-01

    On December 11 of 2017, Ionis Pharmaceuticals published a press release announcing dose-dependent reductions of mutant huntingtin protein in their HTTRx Phase 1/2a study in Huntington disease (HD) patients. The results from this Ionis trial have gained much attention from the patient community and the oligonucleotide therapeutics field, since it is the first trial targeting the cause of HD, namely the mutant huntingtin protein, using antisense oligonucleotides (ASOs). The press release also states that the primary endpoints of the study (safety and tolerability) were met, but does not contain data. This news follows the approval of another therapeutic ASO nusinersen (trade name Spinraza) for a neurological disease, spinal muscular atrophy, by the U.S. Food and Drug Administration and European Medicines Agency, in 2016 and 2017, respectively. Combined, this offers hope for the development of the HTTRx therapy for HD patients.

  17. Expression of Huntingtons disease markers in the cornea of minipig transgenic for the human mutated huntingtin

    Czech Academy of Sciences Publication Activity Database

    Ardan, Taras; Juhás, Štefan; Motlík, Jan

    2013-01-01

    Roč. 91, č. 252 (2013), S016-S016 ISSN 1755-375X. [European Association for Vision and Eye Research EVER 2013. 18.09.2013-21.09.2013, Nice] R&D Projects: GA MŠk ED2.1.00/03.0124; GA TA ČR(CZ) TA01011466 Institutional support: RVO:67985904 Keywords : huntingtin Subject RIV: EB - Genetics ; Molecular Biology

  18. Expression of the amino-terminal half-molecule of human serum transferrin in cultured cells and characterization of the recombinant protein

    International Nuclear Information System (INIS)

    Funk, W.D.; MacGillivray, R.T.A.; Mason, A.B.; Brown, S.A.; Woodworth, R.C.

    1990-01-01

    A human liver cDNA library was screened with a synthetic oligonucleotide, complementary to the 5' region of human transferrin mRNA, as a hybridization probe. The full-length human cDNA clone isolated from this screen contained part of the 5' untranslated region, the complete coding region for the signal peptide and the two lobes of transferrin, the 3' untranslated region, and a poly(A) tail. By use of oligonucleotide-directed mutagenesis in vitro, two translational stop codons and a HindIII site were introduced after the codon for Asp-337. This fragment was inserted into two different expression vectors that were then introduced into Escherichia coli. As judged by NaDodSO 4 -polyacrylamide gel electrophoresis and Western blot analysis, however, recombinant hTF/2N was undetectable in bacteria transformed by these plasmids. Concurrently, the authors developed a plasmid vector for the expression of recombinant hTF/2N in eukaryotic cells. The recombinant hTF/2N appeared to behave identically with the proteolytically derived half-molecule, but to show a higher degree of monodispersity than the latter protein. Addition of m-fluorotyrosine to the culture medium resulted in random incorporation of this amino acid into cellular protein in lieu of tyrosine. Purified recombinant 19 F-Tyr hTF/2N gave four well-resolved 19 F NMR resonances of 20-40 Hz line width, two with suggestions of shoulders

  19. Potent and selective antisense oligonucleotides targeting single-nucleotide polymorphisms in the Huntington disease gene / allele-specific silencing of mutant huntingtin

    DEFF Research Database (Denmark)

    Carroll, Jeffrey B; Warby, Simon C; Southwell, Amber L

    2011-01-01

    Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG-expansion in the huntingtin gene (HTT) that results in a toxic gain of function in the mutant huntingtin protein (mHTT). Reducing the expression of mHTT is therefore an attractive therapy for HD. However, wild...

  20. Overproduction and secretion of a novel amino-terminal form of parathyroid hormone from a severe type of parathyroid hyperplasia in uremia.

    Science.gov (United States)

    Arakawa, Toshio; D'Amour, Pierre; Rousseau, Louise; Brossard, Jean-Hugues; Sakai, Makoto; Kasumoto, Hiroomi; Igaki, Naoya; Goto, Takeo; Cantor, Tom; Fukagawa, Masafumi

    2006-05-01

    Measurement of bioactive parathyroid hormone (PTH) is essential for optimal management of bone abnormalities in dialysis patients. This can be accomplished by PTH measurements using third-generation PTH assays, which detect more or less of the first six amino acids of the PTH structure. Such assays do not detect non-(1-84) PTH fragments, such as human PTH (7-84), which are recognized by the second-generation PTH assays that use a detection antibody that recognizes an epitope within the 13-34 region of the PTH structure. Therefore, third-generation PTH results are expected to be lower than those that are obtained with second-generation PTH assays. Rare exceptions to this rule have been reported for patients with severe primary hyperparathyroidism or parathyroid cancer. Sera and gland extracts were analyzed from a dialysis patient with high bone turnover disease and with surprising higher PTH levels by a third-generation assay than by a second-generation assay. This finding normalized after the surgical removal of an enlarged gland with a single nodule, an advanced type of nodular hyperplasia. HPLC fractionation of sera and gland extracts revealed the overproduction and secretion of a PTH molecule with an intact amino-terminus structure distinct from (1-84) PTH. This form of PTH was readily detectable by third-generation PTH assays but was poorly reactive in second-generation PTH assays. Therefore, parathyroid glands with advanced uremic nodular hyperplasia may overproduce and secrete a novel, biologically active form of PTH with an intact 1-6 region but a presumably modified 12-18 region required for the detection in second-generation PTH assays.

  1. Immunization with a dicistronic plasmid expressing a truncated form of bovine herpesvirus-1 glycoprotein D and the amino-terminal subunit of glycoprotein B results in reduced gB-specific immune responses

    International Nuclear Information System (INIS)

    Manoj, Sharmila; Babiuk, Lorne A.; Drunen Littel van-Hurk, Sylvia van den

    2003-01-01

    As an approach to create a divalent DNA vaccine, a truncated secreted version of bovine herpesvirus-1 (BHV-1) glycoprotein D (tgD) and the amino-terminal subunit of glycoprotein B (gBb) were expressed from a dicistronic plasmid, designated pSLIAtgD-IRES-gBb. Intradermal immunization of mice with pSLIAtgD-IRES-gBb or a mixture of plasmids encoding tgD (pSLIAtgD) and gBb (pSLIAgBb) by needle injection or gene gun elicited strong tgD-specific immune responses. However, a significant reduction in gBb-specific immune responses was observed upon immunization of mice with pSLIAtgD-IRES-gBb or a mixture of pSLIAtgD and pSLIAgBb in comparison to immunization with pSLIAgBb alone. This reduction in gBb-specific immune responses induced by pSLIAtgD-IRES-gBb was due to production of low amounts of gBb from pSLIAtgD-IRES-gBb, inefficient processing and transport of gBb, and possibly competition for antigen-presenting cells by tgD and gBb. These results indicate that, although divalent plasmids may be used to express different antigens, the efficacy of vaccination with such plasmids may be influenced by the plasmid design and the characteristics of the expressed antigens

  2. Crystal structure of type I ryanodine receptor amino-terminal [beta]-trefoil domain reveals a disease-associated mutation 'hot spot' loop

    Energy Technology Data Exchange (ETDEWEB)

    Amador, Fernando J.; Liu, Shuang; Ishiyama, Noboru; Plevin, Michael J.; Wilson, Aaron; MacLennan, David H.; Ikura, Mitsuhiko; (Toronto)

    2009-12-01

    Muscle contraction and relaxation is regulated by transient elevations of myoplasmic Ca{sup 2+}. Ca{sup 2+} is released from stores in the lumen of the sarco(endo)plasmic reticulum (SER) to initiate formation of the Ca{sup 2+} transient by activation of a class of Ca{sup 2+} release channels referred to as ryanodine receptors (RyRs) and is pumped back into the SER lumen by Ca{sup 2+}-ATPases (SERCAs) to terminate the Ca{sup 2+} transient. Mutations in the type 1 ryanodine receptor gene, RYR1, are associated with 2 skeletal muscle disorders, malignant hyperthermia (MH), and central core disease (CCD). The evaluation of proposed mechanisms by which RyR1 mutations cause MH and CCD is hindered by the lack of high-resolution structural information. Here, we report the crystal structure of the N-terminal 210 residues of RyR1 (RyR{sub NTD}) at 2.5 {angstrom}. The RyR{sub NTD} structure is similar to that of the suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor (IP3Rsup), but lacks most of the long helix-turn-helix segment of the 'arm' domain in IP3Rsup. The N-terminal {beta}-trefoil fold, found in both RyR and IP{sub 3}R, is likely to play a critical role in regulatory mechanisms in this channel family. A disease-associated mutation 'hot spot' loop was identified between strands 8 and 9 in a highly basic region of RyR1. Biophysical studies showed that 3 MH-associated mutations (C36R, R164C, and R178C) do not adversely affect the global stability or fold of RyRNTD, supporting previously described mechanisms whereby mutations perturb protein-protein interactions.

  3. c-Jun amino-terminal kinase-1 mediates glucose-responsive upregulation of the RNA editing enzyme ADAR2 in pancreatic beta-cells.

    Directory of Open Access Journals (Sweden)

    Liu Yang

    Full Text Available A-to-I RNA editing catalyzed by the two main members of the adenosine deaminase acting on RNA (ADAR family, ADAR1 and ADAR2, represents a RNA-based recoding mechanism implicated in a variety of cellular processes. Previously we have demonstrated that the expression of ADAR2 in pancreatic islet β-cells is responsive to the metabolic cues and ADAR2 deficiency affects regulated cellular exocytosis. To investigate the molecular mechanism by which ADAR2 is metabolically regulated, we found that in cultured β-cells and primary islets, the stress-activated protein kinase JNK1 mediates the upregulation of ADAR2 in response to changes of the nutritional state. In parallel with glucose induction of ADAR2 expression, JNK phosphorylation was concurrently increased in insulin-secreting INS-1 β-cells. Pharmacological inhibition of JNKs or siRNA knockdown of the expression of JNK1 prominently suppressed glucose-augmented ADAR2 expression, resulting in decreased efficiency of ADAR2 auto-editing. Consistently, the mRNA expression of Adar2 was selectively reduced in the islets from JNK1 null mice in comparison with that of wild-type littermates or JNK2 null mice, and ablation of JNK1 diminished high-fat diet-induced Adar2 expression in the islets from JNK1 null mice. Furthermore, promoter analysis of the mouse Adar2 gene identified a glucose-responsive region and revealed the transcription factor c-Jun as a driver of Adar2 transcription. Taken together, these results demonstrate that JNK1 serves as a crucial component in mediating glucose-responsive upregulation of ADAR2 expression in pancreatic β-cells. Thus, the JNK1 pathway may be functionally linked to the nutrient-sensing actions of ADAR2-mediated RNA editing in professional secretory cells.

  4. α-Synuclein and huntingtin exon 1 amyloid fibrils bind laterally to the cellular membrane.

    Science.gov (United States)

    Monsellier, Elodie; Bousset, Luc; Melki, Ronald

    2016-01-13

    Fibrillar aggregates involved in neurodegenerative diseases have the ability to spread from one cell to another in a prion-like manner. The underlying molecular mechanisms, in particular the binding mode of the fibrils to cell membranes, are poorly understood. In this work we decipher the modality by which aggregates bind to the cellular membrane, one of the obligatory steps of the propagation cycle. By characterizing the binding properties of aggregates made of α-synuclein or huntingtin exon 1 protein displaying similar composition and structure but different lengths to mammalian cells we demonstrate that in both cases aggregates bind laterally to the cellular membrane, with aggregates extremities displaying little or no role in membrane binding. Lateral binding to artificial liposomes was also observed by transmission electron microscopy. In addition we show that although α-synuclein and huntingtin exon 1 fibrils bind both laterally to the cellular membrane, their mechanisms of interaction differ. Our findings have important implications for the development of future therapeutic tools that aim to block protein aggregates propagation in the brain.

  5. Inhibition of PIP4Kγ ameliorates the pathological effects of mutant huntingtin protein.

    Science.gov (United States)

    Al-Ramahi, Ismael; Panapakkam Giridharan, Sai Srinivas; Chen, Yu-Chi; Patnaik, Samarjit; Safren, Nathaniel; Hasegawa, Junya; de Haro, Maria; Wagner Gee, Amanda K; Titus, Steven A; Jeong, Hyunkyung; Clarke, Jonathan; Krainc, Dimitri; Zheng, Wei; Irvine, Robin F; Barmada, Sami; Ferrer, Marc; Southall, Noel; Weisman, Lois S; Botas, Juan; Marugan, Juan Jose

    2017-12-26

    The discovery of the causative gene for Huntington's disease (HD) has promoted numerous efforts to uncover cellular pathways that lower levels of mutant huntingtin protein (mHtt) and potentially forestall the appearance of HD-related neurological defects. Using a cell-based model of pathogenic huntingtin expression, we identified a class of compounds that protect cells through selective inhibition of a lipid kinase, PIP4Kγ. Pharmacological inhibition or knock-down of PIP4Kγ modulates the equilibrium between phosphatidylinositide (PI) species within the cell and increases basal autophagy, reducing the total amount of mHtt protein in human patient fibroblasts and aggregates in neurons. In two Drosophila models of Huntington's disease, genetic knockdown of PIP4K ameliorated neuronal dysfunction and degeneration as assessed using motor performance and retinal degeneration assays respectively. Together, these results suggest that PIP4Kγ is a druggable target whose inhibition enhances productive autophagy and mHtt proteolysis, revealing a useful pharmacological point of intervention for the treatment of Huntington's disease, and potentially for other neurodegenerative disorders.

  6. Value of Combining Left Atrial Diameter and Amino-terminal Pro-brain Natriuretic Peptide to the CHA2DS2-VASc Score for Predicting Stroke and Death in Patients with Sick Sinus Syndrome after Pacemaker Implantation.

    Science.gov (United States)

    Mo, Bin-Feng; Lu, Qiu-Fen; Lu, Shang-Biao; Xie, Yu-Quan; Feng, Xiang-Fei; Li, Yi-Gang

    2017-08-20

    The CHA2DS2-VASc score is used clinically for stroke risk stratification in patients with atrial fibrillation (AF). We sought to investigate whether the CHA2DS2-VASc score predicts stroke and death in Chinese patients with sick sinus syndrome (SSS) after pacemaker implantation and to evaluate whether the predictive power of the CHA2DS2-VASc score could be improved by combining it with left atrial diameter (LAD) and amino-terminal pro-brain natriuretic peptide (NT-proBNP). A total of 481 consecutive patients with SSS who underwent pacemaker implantation from January 2004 to December 2014 in our department were included. The CHA2DS2-VASc scores were retrospectively calculated according to the hospital medical records before pacemaker implantation. The outcome data (stroke and death) were collected by pacemaker follow-up visits and telephonic follow-up until December 31, 2015. During 2151 person-years of follow-up, 46 patients (9.6%) suffered stroke and 52 (10.8%) died. The CHA2DS2-VASc score showed a significant association with the development of stroke (hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.20-1.75, Ppacemaker implantation. The addition of LAD and NT-proBNP to the CHA2DS2-VASc score improved its predictive power for stroke and death, respectively, in this patient cohort. Future prospective studies are warranted to validate the benefit of adding LAD and NT-proBNP to the CHA2DS2-VASc score for predicting stroke and death risk in non-AF populations.

  7. [Impact of plasma pro-B-type natriuretic peptide amino-terminal and galectin-3 levels on the predictive capacity of the LIPID Clinical Risk Scale in stable coronary disease].

    Science.gov (United States)

    Higueras, Javier; Martín-Ventura, José Luis; Blanco-Colio, Luis; Cristóbal, Carmen; Tarín, Nieves; Huelmos, Ana; Alonso, Joaquín; Pello, Ana; Aceña, Álvaro; Carda, Rocío; Lorenzo, Óscar; Mahíllo-Fernández, Ignacio; Asensio, Dolores; Almeida, Pedro; Rodríguez-Artalejo, Fernando; Farré, Jerónimo; López Bescós, Lorenzo; Egido, Jesús; Tuñón, José

    2015-01-01

    At present, there is no tool validated by scientific societies for risk stratification of patients with stable coronary artery disease (SCAD). It has been shown that plasma levels of monocyte chemoattractant protein-1 (MCP-1), galectin-3 and pro-B-type natriuretic peptide amino-terminal (NT-proBNP) have prognostic value in this population. To analyze the prognostic value of a clinical risk scale published in Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study and determining its predictive capacity when combined with plasma levels of MCP-1, galectin-3 and NT-proBNP in patients with SCAD. A total of 706 patients with SCAD and a history of acute coronary syndrome (ACS) were analyzed over a follow up period of 2.2 ± 0.99 years. The primary endpoint was the occurrence of an ischemic event (any SCA, stroke or transient ischemic attack), heart failure, or death. A clinical risk scale derived from the LIPID study significantly predicted the development of the primary endpoint, with an area under the ROC curve (Receiver Operating Characteristic) of 0.642 (0.579 to 0.705); Pvalue improved with an area under the curve of 0.744 (0.684 to 0.805); P<0.001 (P=0.022 for comparison). A score greater than 21.5 had a sensitivity of 74% and a specificity of 61% for the development of the primary endpoint (P<0.001, log -rank test). Plasma levels of MCP-1, galectin -3 and NT-proBNP improve the ability of the LIPID clinical scale to predict the prognosis of patients with SCAD. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  8. In-hospital and long-term outcomes of congestive heart failure: Predictive value of B-type and amino-terminal pro-B-type natriuretic peptides and their ratio.

    Science.gov (United States)

    Dai, Yuxiang; Yang, Jun; Takagi, Atsutoshi; Konishi, Hakuoh; Miyazaki, Tetsuro; Masuda, Hiroshi; Shimada, Kazunori; Miyauchi, Katsumi; Daida, Hiroyuki

    2017-08-01

    Relative changes in B-type natriuretic peptide (BNP) and amino terminal pro-BNP (NT-proBNP) levels may help to assess the risk of congestive heart failure (CHF). However, whether these levels at the time of admission enable the prediction of outcomes with acute exacerbation remains unknown. The current study determined the abilities of BNP, NT-proBNP and their ratio to predict in-hospital and long-term outcomes of patients with CHF. Patients who were admitted to the cardiac care unit of Juntendo University Hospital (Tokyo, Japan) with acute CHF onset were consecutively enrolled into the present observational study. Serum levels of BNP and NT-proBNP were immediately measured on admission, and other biomarkers and clinical data were also investigated. Of 195 enrolled patients, 16 (8.2%) succumbed to CHF in hospital and 124 (69.3%) reached the endpoint of mortality or readmission following a median follow-up of 14 months. Multiple linear regression analysis revealed body mass index, low density lipoprotein cholesterol, hemoglobin, estimated glomerular filtration rate and C-reactive protein as independent predictors of the NT-proBNP/BNP ratio. BNP, NT-proBNP and their ratio were significantly higher among those who succumbed to CHF than in those who remained alive in hospital (P<0.05). Logistic regression analysis indicated that the ratio was an independent predictor for in-hospital mortality and long-term outcomes. In conclusion, the ratio of NT-proBNP to BNP more effectively predicts in-hospital outcomes than either factor alone and it may also help to predict outcomes among patients with acute exacerbation of HF.

  9. Hydrophobically Modified siRNAs Silence Huntingtin mRNA in Primary Neurons and Mouse Brain

    Directory of Open Access Journals (Sweden)

    Julia F Alterman

    2015-01-01

    Full Text Available Applications of RNA interference for neuroscience research have been limited by a lack of simple and efficient methods to deliver oligonucleotides to primary neurons in culture and to the brain. Here, we show that primary neurons rapidly internalize hydrophobically modified siRNAs (hsiRNAs added directly to the culture medium without lipid formulation. We identify functional hsiRNAs targeting the mRNA of huntingtin, the mutation of which is responsible for Huntington's disease, and show that direct uptake in neurons induces potent and specific silencing in vitro. Moreover, a single injection of unformulated hsiRNA into mouse brain silences Htt mRNA with minimal neuronal toxicity. Thus, hsiRNAs embody a class of therapeutic oligonucleotides that enable simple and straightforward functional studies of genes involved in neuronal biology and neurodegenerative disorders in a native biological context.

  10. Amino-terminal pro-B-type natriuretic peptide and high-sensitivity C-reactive protein but not cystatin C predict cardiovascular events in male patients with peripheral artery disease independently of ambulatory pulse pressure.

    Science.gov (United States)

    Skoglund, Per H; Arpegård, Johannes; Ostergren, Jan; Svensson, Per

    2014-03-01

    Patients with peripheral arterial disease (PAD) are at high risk for cardiovascular (CV) events. We have previously shown that ambulatory pulse pressure (APP) predicts CV events in PAD patients. The biomarkers amino-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and cystatin C are related to a worse outcome in patients with CV disease, but their predictive values have not been studied in relation to APP. Blood samples and 24-hour measurements of ambulatory blood pressure were examined in 98 men referred for PAD evaluation during 1998-2001. Patients were followed for a median of 71 months. The outcome variable was CV events defined as either CV mortality or any hospitalization for myocardial infarction, stroke, or coronary revascularization. The predictive values of log(NT-proBNP), log(hs-CRP), and log(cystatin C) alone and together with APP were assessed by multivariable Cox regression. Area under the curve (AUC) and net reclassification improvement (NRI) were calculated compared with a model containing other significant risk factors. During follow-up, 36 patients had at least 1 CV event. APP, log(NT-proBNP), and log(hs-CRP) all predicted CV events in univariable analysis, whereas log(cystatin C) did not. In multivariable analysis log(NT-proBNP) (hazard ratio (HR) = 1.62; 95% confidence interval (CI) = 1.05-2.51) and log(hs-CRP) (HR = 1.63; 95% CI = 1.19-2.24) predicted events independently of 24-hour PP. The combination of log(NT-proBNP), log(hs-CRP), and average day PP improved risk discrimination (AUC = 0.833 vs. 0.736; P < 0.05) and NRI (37%; P < 0.01) when added to other significant risk factors. NT-proBNP and hs-CRP predict CV events independently of APP and the combination of hs-CRP, NT-proBNP, and day PP improves risk discrimination in PAD patients.

  11. Different Forms of Huntingtin in the Most 
Affected Organs; Brain and Testes of Transgenic Minipigs

    Czech Academy of Sciences Publication Activity Database

    Vidinská, Daniela; Motlík, Jan; Ellederová, Zdeňka

    2015-01-01

    Roč. 78, Suppl 2 (2015), s. 66-69 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Disease s /3./. Liblice, 08.11.2015-10.11.2015] R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) 7F14308 Institutional support: RVO:67985904 Keywords : Huntington´s disease * transgenic minipig model * mutant huntingtin Subject RIV: FH - Neurology Impact factor: 0.209, year: 2015

  12. Clues to γ-secretase, huntingtin and Hirano body normal function using the model organism Dictyostelium discoideum

    Directory of Open Access Journals (Sweden)

    Myre Michael A

    2012-04-01

    Full Text Available Abstract Many neurodegenerative disorders, although related by their destruction of brain function, display remarkable cellular and/or regional pathogenic specificity likely due to a deregulated functionality of the mutant protein. However, neurodegenerative disease genes, for example huntingtin (HTT, the ataxins, the presenilins (PSEN1/PSEN2 are not simply localized to neurons but are ubiquitously expressed throughout peripheral tissues; it is therefore paramount to properly understand the earliest precipitating events leading to neuronal pathogenesis to develop effective long-term therapies. This means, in no unequivocal terms, it is crucial to understand the gene's normal function. Unfortunately, many genes are often essential for embryogenesis which precludes their study in whole organisms. This is true for HTT, the β-amyloid precursor protein (APP and presenilins, responsible for early onset Alzheimer's disease (AD. To better understand neurological disease in humans, many lower and higher eukaryotic models have been established. So the question arises: how reasonable is the use of organisms to study neurological disorders when the model of choice does not contain neurons? Here we will review the surprising, and novel emerging use of the model organism Dictyostelium discoideum, a species of soil-living amoeba, as a valuable biomedical tool to study the normal function of neurodegenerative genes. Historically, the evidence on the usefulness of simple organisms to understand the etiology of cellular pathology cannot be denied. But using an organism without a central nervous system to understand diseases of the brain? We will first introduce the life cycle of Dictyostelium, the presence of many disease genes in the genome and how it has provided unique opportunities to identify mechanisms of disease involving actin pathologies, mitochondrial disease, human lysosomal and trafficking disorders and host-pathogen interactions. Secondly, I will

  13. Overproduction of an amino-terminal form of PTH distinct from human PTH(1-84) in a case of severe primary hyperparathyroidism: influence of medical treatment and surgery.

    Science.gov (United States)

    Räkel, Agnès; Brossard, Jean-Hugues; Patenaude, Jean-Victor; Albert, Caroline; Nassif, Edgard; Cantor, Tom; Rousseau, Louise; D'Amour, Pierre

    2005-06-01

    an amino-terminal (N) form of PTH recognized by PTH assays with (1-4) or (26-32) epitopes but not by the T-PTH assay with a (12-18) epitope. This molecular form represented 50% of CA-PTH measured in this patient, but only 7% in less severe cases of primary hyperparathyroidism. It was unaffected by medical therapy and disappeared after surgery. The relationship between the overexpression of this N-PTH molecular form and severe primary hyperparathyroidism remains unclear. Further studies will be required in these rare patients to see whether N-PTH is a marker of less well differentiated parathyroid tumours and/or relates to the overproduction of C-PTH fragments in the presence of severe hypercalcaemia.

  14. Preventing mutant huntingtin proteolysis and intermittent fasting promote autophagy in models of Huntington disease.

    Science.gov (United States)

    Ehrnhoefer, Dagmar E; Martin, Dale D O; Schmidt, Mandi E; Qiu, Xiaofan; Ladha, Safia; Caron, Nicholas S; Skotte, Niels H; Nguyen, Yen T N; Vaid, Kuljeet; Southwell, Amber L; Engemann, Sabine; Franciosi, Sonia; Hayden, Michael R

    2018-03-06

    Huntington disease (HD) is caused by the expression of mutant huntingtin (mHTT) bearing a polyglutamine expansion. In HD, mHTT accumulation is accompanied by a dysfunction in basal autophagy, which manifests as specific defects in cargo loading during selective autophagy. Here we show that the expression of mHTT resistant to proteolysis at the caspase cleavage site D586 (C6R mHTT) increases autophagy, which may be due to its increased binding to the autophagy adapter p62. This is accompanied by faster degradation of C6R mHTT in vitro and a lack of mHTT accumulation the C6R mouse model with age. These findings may explain the previously observed neuroprotective properties of C6R mHTT. As the C6R mutation cannot be easily translated into a therapeutic approach, we show that a scheduled feeding paradigm is sufficient to lower mHTT levels in YAC128 mice expressing cleavable mHTT. This is consistent with a previous model, where the presence of cleavable mHTT impairs basal autophagy, while fasting-induced autophagy remains functional. In HD, mHTT clearance and autophagy may become increasingly impaired as a function of age and disease stage, because of gradually increased activity of mHTT-processing enzymes. Our findings imply that mHTT clearance could be enhanced by a regulated dietary schedule that promotes autophagy.

  15. Discovery of novel isoforms of huntingtin reveals a new hominid-specific exon.

    Directory of Open Access Journals (Sweden)

    Albert Ruzo

    Full Text Available Huntington's disease (HD is a devastating neurological disorder that is caused by an expansion of the poly-Q tract in exon 1 of the Huntingtin gene (HTT. HTT is an evolutionarily conserved and ubiquitously expressed protein that has been linked to a variety of functions including transcriptional regulation, mitochondrial function, and vesicle transport. This large protein has numerous caspase and calpain cleavage sites and can be decorated with several post-translational modifications such as phosphorylations, acetylations, sumoylations, and palmitoylations. However, the exact function of HTT and the role played by its modifications in the cell are still not well understood. Scrutiny of HTT function has been focused on a single, full length mRNA. In this study, we report the discovery of 5 novel HTT mRNA splice isoforms that are expressed in normal and HTT-expanded human embryonic stem cell (hESC lines as well as in cortical neurons differentiated from hESCs. Interestingly, none of the novel isoforms generates a truncated protein. Instead, 4 of the 5 new isoforms specifically eliminate domains and modifications to generate smaller HTT proteins. The fifth novel isoform incorporates a previously unreported additional exon, dubbed 41b, which is hominid-specific and introduces a potential phosphorylation site in the protein. The discovery of this hominid-specific isoform may shed light on human-specific pathogenic mechanisms of HTT, which could not be investigated with current mouse models of the disease.

  16. Discovery of Novel Isoforms of Huntingtin Reveals a New Hominid-Specific Exon

    Science.gov (United States)

    Popowski, Melissa; Haremaki, Tomomi; Croft, Gist F.; Deglincerti, Alessia; Brivanlou, Ali H.

    2015-01-01

    Huntington’s disease (HD) is a devastating neurological disorder that is caused by an expansion of the poly-Q tract in exon 1 of the Huntingtin gene (HTT). HTT is an evolutionarily conserved and ubiquitously expressed protein that has been linked to a variety of functions including transcriptional regulation, mitochondrial function, and vesicle transport. This large protein has numerous caspase and calpain cleavage sites and can be decorated with several post-translational modifications such as phosphorylations, acetylations, sumoylations, and palmitoylations. However, the exact function of HTT and the role played by its modifications in the cell are still not well understood. Scrutiny of HTT function has been focused on a single, full length mRNA. In this study, we report the discovery of 5 novel HTT mRNA splice isoforms that are expressed in normal and HTT-expanded human embryonic stem cell (hESC) lines as well as in cortical neurons differentiated from hESCs. Interestingly, none of the novel isoforms generates a truncated protein. Instead, 4 of the 5 new isoforms specifically eliminate domains and modifications to generate smaller HTT proteins. The fifth novel isoform incorporates a previously unreported additional exon, dubbed 41b, which is hominid-specific and introduces a potential phosphorylation site in the protein. The discovery of this hominid-specific isoform may shed light on human-specific pathogenic mechanisms of HTT, which could not be investigated with current mouse models of the disease. PMID:26010866

  17. Loss of Huntingtin stimulates capture of retrograde dense-core vesicles to increase synaptic neuropeptide stores.

    Science.gov (United States)

    Bulgari, Dinara; Deitcher, David L; Levitan, Edwin S

    2017-08-01

    The Huntington's disease protein Huntingtin (Htt) regulates axonal transport of dense-core vesicles (DCVs) containing neurotrophins and neuropeptides. DCVs travel down axons to reach nerve terminals where they are either captured in synaptic boutons to support later release or reverse direction to reenter the axon as part of vesicle circulation. Currently, the impact of Htt on DCV dynamics in the terminal is unknown. Here we report that knockout of Drosophila Htt selectively reduces retrograde DCV flux at proximal boutons of motoneuron terminals. However, initiation of retrograde transport at the most distal bouton and transport velocity are unaffected suggesting that synaptic capture rate of these retrograde DCVs could be altered. In fact, tracking DCVs shows that retrograde synaptic capture efficiency is significantly elevated by Htt knockout or knockdown. Furthermore, synaptic boutons contain more neuropeptide in Htt knockout larvae even though bouton size, single DCV fluorescence intensity, neuropeptide release in response to electrical stimulation and subsequent activity-dependent capture are unaffected. Thus, loss of Htt increases synaptic capture as DCVs travel by retrograde transport through boutons resulting in reduced transport toward the axon and increased neuropeptide in the terminal. These results therefore identify native Htt as a regulator of synaptic capture and neuropeptide storage. Copyright © 2017 Elsevier GmbH. All rights reserved.

  18. Huntingtin coordinates the dynein-mediated dynamic positioning of endosomes and lysosomes

    Science.gov (United States)

    Caviston, Juliane P.; Zajac, Allison L.; Tokito, Mariko; Holzbaur, Erika L.F.

    2011-01-01

    Huntingtin (Htt) is a membrane-associated scaffolding protein that interacts with microtubule motors as well as actin-associated adaptor molecules. We examined a role for Htt in the dynein-mediated intracellular trafficking of endosomes and lysosomes. In HeLa cells depleted of either Htt or dynein, early, recycling, and late endosomes (LE)/lysosomes all become dispersed. Despite altered organelle localization, kinetic assays indicate only minor defects in intracellular trafficking. Expression of full-length Htt is required to restore organelle localization in Htt-depleted cells, supporting a role for Htt as a scaffold that promotes functional interactions along its length. In dynein-depleted cells, LE/lysosomes accumulate in tight patches near the cortex, apparently enmeshed by cortactin-positive actin filaments; Latrunculin B-treatment disperses these patches. Peripheral LE/lysosomes in dynein-depleted cells no longer colocalize with microtubules. Htt may be required for this off-loading, as the loss of microtubule association is not seen in Htt-depleted cells or in cells depleted of both dynein and Htt. Inhibition of kinesin-1 relocalizes peripheral LE/lysosomes induced by Htt depletion but not by dynein depletion, consistent with their detachment from microtubules upon dynein knockdown. Together, these data support a model of Htt as a facilitator of dynein-mediated trafficking that may regulate the cytoskeletal association of dynamic organelles. PMID:21169558

  19. Impaired heat shock response in cells expressing full-length polyglutamine-expanded huntingtin.

    Directory of Open Access Journals (Sweden)

    Sidhartha M Chafekar

    Full Text Available The molecular mechanisms by which polyglutamine (polyQ-expanded huntingtin (Htt causes neurodegeneration in Huntington's disease (HD remain unclear. The malfunction of cellular proteostasis has been suggested as central in HD pathogenesis and also as a target of therapeutic interventions for the treatment of HD. We present results that offer a previously unexplored perspective regarding impaired proteostasis in HD. We find that, under non-stress conditions, the proteostatic capacity of cells expressing full length polyQ-expanded Htt is adequate. Yet, under stress conditions, the presence of polyQ-expanded Htt impairs the heat shock response, a key component of cellular proteostasis. This impaired heat shock response results in a reduced capacity to withstand the damage caused by cellular stress. We demonstrate that in cells expressing polyQ-expanded Htt the levels of heat shock transcription factor 1 (HSF1 are reduced, and, as a consequence, these cells have an impaired a heat shock response. Also, we found reduced HSF1 and HSP70 levels in the striata of HD knock-in mice when compared to wild-type mice. Our results suggests that full length, non-aggregated polyQ-expanded Htt blocks the effective induction of the heat shock response under stress conditions and may thus trigger the accumulation of cellular damage during the course of HD pathogenesis.

  20. A new Caenorhabditis elegans model of human huntingtin 513 aggregation and toxicity in body wall muscles.

    Directory of Open Access Journals (Sweden)

    Amy L Lee

    Full Text Available Expanded polyglutamine repeats in different proteins are the known determinants of at least nine progressive neurodegenerative disorders whose symptoms include cognitive and motor impairment that worsen as patients age. One such disorder is Huntington's Disease (HD that is caused by a polyglutamine expansion in the human huntingtin protein (htt. The polyglutamine expansion destabilizes htt leading to protein misfolding, which in turn triggers neurodegeneration and the disruption of energy metabolism in muscle cells. However, the molecular mechanisms that underlie htt proteotoxicity have been somewhat elusive, and the muscle phenotypes have not been well studied. To generate tools to elucidate the basis for muscle dysfunction, we engineered Caenorhabditis elegans to express a disease-associated 513 amino acid fragment of human htt in body wall muscle cells. We show that this htt fragment aggregates in C. elegans in a polyglutamine length-dependent manner and is toxic. Toxicity manifests as motor impairment and a shortened lifespan. Compared to previous models, the data suggest that the protein context in which a polyglutamine tract is embedded alters aggregation propensity and toxicity, likely by affecting interactions with the muscle cell environment.

  1. Binding, internalization and fate of Huntingtin Exon1 fibrillar assemblies in mitotic and nonmitotic neuroblastoma cells.

    Science.gov (United States)

    Ruiz-Arlandis, G; Pieri, L; Bousset, L; Melki, R

    2016-02-01

    The aggregation of Huntingtin (HTT) protein and of its moiety encoded by its Exon1 (HTTExon1) into fibrillar structures inside neurons is the molecular hallmark of Huntington's disease. Prion-like transmission of these aggregates between cells has been demonstrated. The cell-to-cell transmission mechanisms of these protein aggregates and the susceptibility of different kinds of neuronal cells to these toxic assemblies still need assessment. Here, we documented the binding to and internalization by differentiated and undifferentiated neuroblastoma cells of exogenous fibrillar HTTExon1 and polyglutamine (polyQ) polypeptides containing the same number of glutamines. We assessed the contribution of endocytosis to fibrillar HTTExon1 uptake, their intracellular localization and fate. We observed that undifferentiated neuroblastoma cells were more susceptible to fibrillar HTTExon1 and polyQ than their differentiated counterparts. Furthermore, we demonstrated that exogenous HTTExon1 aggregates are mainly taken up by endocytosis and directed to lysosomal compartments in both mitotic and quiescent cells. These data suggest that the rates of endocytic processes that differ in mitotic and quiescent cells strongly impact the uptake of exogenous HTTExon1 and polyQ fibrils. This may be either the consequence of distinct metabolisms or distributions of specific protein partners for amyloid-like assemblies at the surface of highly dividing versus quiescent cells. Our results highlight the importance of endocytic processes in the internalization of exogenous HTTExon1 fibrils and suggest that a proportion of those assemblies reach the cytosol where they can amplify by recruiting the endogenous protein after escaping, by yet an unknown process, from the endo-lysosomal compartments. © 2015 British Neuropathological Society.

  2. Huntingtin-Interacting Protein 1-Related Protein Plays a Critical Role in Dendritic Development and Excitatory Synapse Formation in Hippocampal Neurons

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    Lin Peng

    2017-06-01

    Full Text Available Huntingtin-interacting protein 1-related (HIP1R protein is considered to be an endocytic adaptor protein like the other two members of the Sla2 family, Sla2p and HIP1. They all contain homology domains responsible for the binding of clathrin, inositol lipids and F-actin. Previous studies have revealed that HIP1R is highly expressed in different regions of the mouse brain and localizes at synaptic structures. However, the function of HIP1R in the nervous system remains unknown. In this study, we investigated HIP1R function in cultured rat hippocampal neurons using an shRNA knockdown approach. We found that, after HIP1R knockdown, the dynamics and density of dendritic filopodia, and dendritic branching and complexity were significantly reduced in developing neurons, as well as the densities of dendritic spines and PSD95 clusters in mature neurons. Moreover, HIP1R deficiency led to significantly reduced expression of the ionotropic glutamate receptor GluA1, GluN2A and GluN2B subunits, but not the GABAA receptor α1 subunit. Similarly, HIP1R knockdown reduced the amplitude and frequency of the miniature excitatory postsynaptic current, but not of the miniature inhibitory postsynaptic current. In addition, the C-terminal proline-rich region of HIP1R responsible for cortactin binding was found to confer a dominant-negative effect on dendritic branching in cultured developing neurons, implying a critical role of cortactin binding in HIP1R function. Taken together, the results of our study suggest that HIP1R plays important roles in dendritic development and excitatory synapse formation and function.

  3. Reproductive parameters and mitochondrial function in spermatozoa of F1 and F2 minipig boars transgenic for n-terminal part of the human mutated huntingtin

    Czech Academy of Sciences Publication Activity Database

    Mačáková, Monika; Hansíková, H.; Pavlok, Antonín; Hajková, Z.; Sádková, J.; Juhás, Štefan; Juhásová, Jana; Baxa, Monika; Zeman, J.; Motlík, Jan

    2012-01-01

    Roč. 83, Suppl 1 (2012), A16-A16 ISSN 0022-3050. [European Huntington´s disease network 2012 plenary meeting. 14.09.2012-16.09.2012, Stockholm] R&D Projects: GA TA ČR TA01011466 Institutional support: RVO:67985904 Keywords : huntingtin Subject RIV: EB - Genetics ; Molecular Biology

  4. The role of polyglutamine expansion and protein context in disease-related huntingtin/lipid interactions

    Science.gov (United States)

    Burke, Kathleen Anne

    Huntington's Disease (HD) is a neurodegenerative disorder that is defined by the accumulation of nanoscale aggregates comprised of the huntingtin (htt) protein. Aggregation is directly caused by an expanded polyglutamine (polyQ) domain in htt, leading to a diverse population of aggregate species, such as oligomers, fibrils, and annular aggregates. Furthermore, the length of this polyQ domain is directly related to onset and severity of disease. The first 17 amino acids on the N-terminus (N17) and the polyproline domain on the C-terminal side of the polyQ domain have been shown to further modulate the aggregation process. Additionally, N17 appears to have lipid binding properties as htt interacts with a variety of membrane-containing structures present in cells, such as organelles, and interactions with these membrane surfaces may further modulate htt aggregation. To investigate the interaction between htt exon1 and lipid bilayers, in situ atomic force microscopy (AFM) was used to directly monitor the aggregation of htt exon1 constructs with varying Q-length (35Q, 46Q, 51Q, and myc- 53Q) or synthetic peptides with different polyQ domain flanking sequences (KK-Q35-KK, KK-Q 35-P10-KK, N17-Q35-KK, and N 17-Q35-P10-KK) on supported lipid membranes comprised of total brain lipid extract. The exon1 fragments accumulated on the lipid membranes, causing disruption of the membrane, in a polyQ dependent manner. By adding N-terminal tags to the htt exon1 fragments, the interaction with the lipid bilayer was impeded. The KK-Q35-KK and KK-Q 35-P10-KK peptides had no appreciable interaction with lipid bilayers. Interestingly, polyQ peptides with the N17 flanking sequence interacted with the bilayer. N17-Q35-KK formed discrete aggregates on the bilayer, but there was minimal membrane disruption. The N17-Q35-P10-KK peptide interacted more aggressively with the lipid bilayer in a manner reminiscent of the htt exon1 proteins.

  5. Folding Landscape of Mutant Huntingtin Exon1: Diffusible Multimers, Oligomers and Fibrils, and No Detectable Monomer.

    Directory of Open Access Journals (Sweden)

    Bankanidhi Sahoo

    Full Text Available Expansion of the polyglutamine (polyQ track of the Huntingtin (HTT protein above 36 is associated with a sharply enhanced risk of Huntington's disease (HD. Although there is general agreement that HTT toxicity resides primarily in N-terminal fragments such as the HTT exon1 protein, there is no consensus on the nature of the physical states of HTT exon1 that are induced by polyQ expansion, nor on which of these states might be responsible for toxicity. One hypothesis is that polyQ expansion induces an alternative, toxic conformation in the HTT exon1 monomer. Alternative hypotheses posit that the toxic species is one of several possible aggregated states. Defining the nature of the toxic species is particularly challenging because of facile interconversion between physical states as well as challenges to identifying these states, especially in vivo. Here we describe the use of fluorescence correlation spectroscopy (FCS to characterize the detailed time and repeat length dependent self-association of HTT exon1-like fragments both with chemically synthesized peptides in vitro and with cell-produced proteins in extracts and in living cells. We find that, in vitro, mutant HTT exon1 peptides engage in polyQ repeat length dependent dimer and tetramer formation, followed by time dependent formation of diffusible spherical and fibrillar oligomers and finally by larger, sedimentable amyloid fibrils. For expanded polyQ HTT exon1 expressed in PC12 cells, monomers are absent, with tetramers being the smallest molecular form detected, followed in the incubation time course by small, diffusible aggregates at 6-9 hours and larger, sedimentable aggregates that begin to build up at 12 hrs. In these cell cultures, significant nuclear DNA damage appears by 6 hours, followed at later times by caspase 3 induction, mitochondrial dysfunction, and cell death. Our data thus defines limits on the sizes and concentrations of different physical states of HTT exon1 along the

  6. A novel humanized mouse model of Huntington disease for preclinical development of therapeutics targeting mutant huntingtin alleles

    DEFF Research Database (Denmark)

    Southwell, Amber L; Skotte, Niels H; Villanueva, Erika B

    2017-01-01

    transgenes in Hu128/21 mice match the human HTT exon 1 reference sequence. Conversely, the BACHD transgene carries a floxed, synthetic exon 1 sequence. Hu128/21 mice will be useful for investigations of human HTT that cannot be addressed in Hu97/18 mice, for developing therapies targeted to exon 1......Huntington disease (HD) is a neurodegenerative disease caused by a mutation in the huntingtin (HTT) gene. HTT is a large protein, interacts with many partners and is involved in many cellular pathways, which are perturbed in HD. Therapies targeting HTT directly are likely to provide the most global......-length, genomic human HTT transgenes heterozygous for the HD mutation and polymorphisms associated with HD in populations of East Asian descent and in a minority of patients from other ethnic groups. Hu128/21 mice display a wide variety of HD-like phenotypes that are similar to YAC128 mice. Additionally, both...

  7. Huntingtin-interacting protein 14 is a type 1 diabetes candidate protein regulating insulin secretion and β-cell apoptosis

    DEFF Research Database (Denmark)

    Berchtold, Lukas Adrian; Størling, Zenia Marian; Ortis, Fernanda

    2011-01-01

    Type 1 diabetes (T1D) is a complex disease characterized by the loss of insulin-secreting β-cells. Although the disease has a strong genetic component, and several loci are known to increase T1D susceptibility risk, only few causal genes have currently been identified. To identify disease...... genes in T1D, including the INS gene. An unexpected top-scoring candidate gene was huntingtin-interacting protein (HIP)-14/ZDHHC17. Immunohistochemical analysis of pancreatic sections demonstrated that HIP14 is almost exclusively expressed in insulin-positive cells in islets of Langerhans. RNAi...... knockdown experiments established that HIP14 is an antiapoptotic protein required for β-cell survival and glucose-stimulated insulin secretion. Proinflammatory cytokines (IL-1β and IFN-γ) that mediate β-cell dysfunction in T1D down-regulated HIP14 expression in insulin-secreting INS-1 cells and in isolated...

  8. Huntingtin-associated protein-1 (HAP1) regulates endocytosis and interacts with multiple trafficking-related proteins.

    Science.gov (United States)

    Mackenzie, Kimberly D; Lim, Yoon; Duffield, Michael D; Chataway, Timothy; Zhou, Xin-Fu; Keating, Damien J

    2017-07-01

    Huntingtin-associated protein 1 (HAP1) was initially identified as a binding partner of huntingtin, mutations in which underlie Huntington's disease. Subcellular localization and protein interaction data indicate that HAP1 may be important in vesicle trafficking, cell signalling and receptor internalization. In this study, a proteomics approach was used for the identification of novel HAP1-interacting partners to attempt to shed light on the physiological function of HAP1. Using affinity chromatography with HAP1-GST protein fragments bound to Sepharose columns, this study identified a number of trafficking-related proteins that bind to HAP1. Interestingly, many of the proteins that were identified by mass spectrometry have trafficking-related functions and include the clathrin light chain B and Sec23A, an ER to Golgi trafficking vesicle coat component. Using co-immunoprecipitation and GST-binding assays the association between HAP1 and clathrin light chain B has been validated in vitro. This study also finds that HAP1 co-localizes with clathrin light chain B. In line with a physiological function of the HAP1-clathrin interaction this study detected a dramatic reduction in vesicle retrieval and endocytosis in adrenal chromaffin cells. Furthermore, through examination of transferrin endocytosis in HAP1 -/- cortical neurons, this study has determined that HAP1 regulates neuronal endocytosis. In this study, the interaction between HAP1 and Sec23A was also validated through endogenous co-immunoprecipitation in rat brain homogenate. Through the identification of novel HAP1 binding partners, many of which have putative trafficking roles, this study provides us with new insights into the mechanisms underlying the important physiological function of HAP1 as an intracellular trafficking protein through its protein-protein interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Cells exposed to a huntingtin fragment containing an expanded polyglutamine tract show no sign of ion channel formation: results arguing against the ion channel hypothesis

    DEFF Research Database (Denmark)

    Nørremølle, Anne; Grunnet, Morten; Hasholt, Lis

    2003-01-01

    Ion channels formed by expanded polyglutamine tracts have been proposed to play an important role in the pathological processes leading to neurodegeneration in Huntington's disease and other CAG repeat diseases. We tested the capacity of a huntingtin fragment containing an expanded polyglutamine...... in the currents recorded in any of the two expression systems, indicating no changes in ion channel activity. The results therefore argue against the proposed hypothesis of expanded polyglutamines forming ion channels....

  10. Mass spektrometry-based SRM assay for quantification of human mutant huntingtin protein in a transgenic minipig model of Huntington´s disease

    Czech Academy of Sciences Publication Activity Database

    Kotrčová, Eva; Suchá, Rita; Tylečková, Jiřina; Dresler, J.; Kovářová, Hana

    2015-01-01

    Roč. 78, Suppl 2 (2015), s. 17-17 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA TA ČR(CZ) TA01011466; GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) 7F14308 Institutional support: RVO:67985904 Keywords : huntingtin gene Subject RIV: FH - Neurology

  11. The mTOR kinase inhibitor Everolimus decreases S6 kinase phosphorylation but fails to reduce mutant huntingtin levels in brain and is not neuroprotective in the R6/2 mouse model of Huntington's disease

    Directory of Open Access Journals (Sweden)

    Frentzel Stefan

    2010-06-01

    Full Text Available Abstract Background Huntington's disease (HD is a progressive neurodegenerative disorder caused by a CAG repeat expansion within the huntingtin gene. Mutant huntingtin protein misfolds and accumulates within neurons where it mediates its toxic effects. Promoting mutant huntingtin clearance by activating macroautophagy is one approach for treating Huntington's disease (HD. In this study, we evaluated the mTOR kinase inhibitor and macroautophagy promoting drug everolimus in the R6/2 mouse model of HD. Results Everolimus decreased phosphorylation of the mTOR target protein S6 kinase indicating brain penetration. However, everolimus did not activate brain macroautophagy as measured by LC3B Western blot analysis. Everolimus protected against early declines in motor performance; however, we found no evidence for neuroprotection as determined by brain pathology. In muscle but not brain, everolimus significantly decreased soluble mutant huntingtin levels. Conclusions Our data suggests that beneficial behavioral effects of everolimus in R6/2 mice result primarily from effects on muscle. Even though everolimus significantly modulated its target brain S6 kinase, this did not decrease mutant huntingtin levels or provide neuroprotection.

  12. The amino-terminal domain of human signal transducers and ...

    Indian Academy of Sciences (India)

    Unknown

    transferase (GST) moiety was cloned into the expression vector pGEX-2T ... containing 100 µg/ml of ampicillin to mid log phase as indicated by the .... equipped with pulsed field gradients. ... ferent algorithms like hidden Markov model (HMM).

  13. Msh2 acts in medium-spiny striatal neurons as an enhancer of CAG instability and mutant huntingtin phenotypes in Huntington's disease knock-in mice.

    Directory of Open Access Journals (Sweden)

    Marina Kovalenko

    Full Text Available The CAG trinucleotide repeat mutation in the Huntington's disease gene (HTT exhibits age-dependent tissue-specific expansion that correlates with disease onset in patients, implicating somatic expansion as a disease modifier and potential therapeutic target. Somatic HTT CAG expansion is critically dependent on proteins in the mismatch repair (MMR pathway. To gain further insight into mechanisms of somatic expansion and the relationship of somatic expansion to the disease process in selectively vulnerable MSNs we have crossed HTT CAG knock-in mice (HdhQ111 with mice carrying a conditional (floxed Msh2 allele and D9-Cre transgenic mice, in which Cre recombinase is expressed specifically in MSNs within the striatum. Deletion of Msh2 in MSNs eliminated Msh2 protein in those neurons. We demonstrate that MSN-specific deletion of Msh2 was sufficient to eliminate the vast majority of striatal HTT CAG expansions in HdhQ111 mice. Furthermore, MSN-specific deletion of Msh2 modified two mutant huntingtin phenotypes: the early nuclear localization of diffusely immunostaining mutant huntingtin was slowed; and the later development of intranuclear huntingtin inclusions was dramatically inhibited. Therefore, Msh2 acts within MSNs as a genetic enhancer both of somatic HTT CAG expansions and of HTT CAG-dependent phenotypes in mice. These data suggest that the selective vulnerability of MSNs may be at least in part contributed by the propensity for somatic expansion in these neurons, and imply that intervening in the expansion process is likely to have therapeutic benefit.

  14. Systematic analysis of fly models with multiple drivers reveals different effects of ataxin-1 and huntingtin in neuron subtype-specific expression.

    Directory of Open Access Journals (Sweden)

    Risa Shiraishi

    Full Text Available The fruit fly, Drosophila melanogaster, is a commonly used model organism for neurodegenerative diseases. Its major advantages include a short lifespan and its susceptibility to manipulation using sophisticated genetic techniques. Here, we report the systematic comparison of fly models of two polyglutamine (polyQ diseases. We induced expression of the normal and mutant forms of full-length Ataxin-1 and Huntingtin exon 1 in cholinergic, dopaminergic, and motor neurons, and glial cells using cell type-specific drivers. We systematically analyzed their effects based on multiple phenotypes: eclosion rate, lifespan, motor performance, and circadian rhythms of spontaneous activity. This systematic assay system enabled us to quantitatively evaluate and compare the functional disabilities of different genotypes. The results suggest different effects of Ataxin-1 and Huntingtin on specific types of neural cells during development and in adulthood. In addition, we confirmed the therapeutic effects of LiCl and butyrate using representative models. These results support the usefulness of this assay system for screening candidate chemical compounds that modify the pathologies of polyQ diseases.

  15. Ser46 phosphorylation and prolyl-isomerase Pin1-mediated isomerization of p53 are key events in p53-dependent apoptosis induced by mutant huntingtin.

    Science.gov (United States)

    Grison, Alice; Mantovani, Fiamma; Comel, Anna; Agostoni, Elena; Gustincich, Stefano; Persichetti, Francesca; Del Sal, Giannino

    2011-11-01

    Huntington disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the gene coding for huntingtin protein. Several mechanisms have been proposed by which mutant huntingtin (mHtt) may trigger striatal neurodegeneration, including mitochondrial dysfunction, oxidative stress, and apoptosis. Furthermore, mHtt induces DNA damage and activates a stress response. In this context, p53 plays a crucial role in mediating mHtt toxic effects. Here we have dissected the pathway of p53 activation by mHtt in human neuronal cells and in HD mice, with the aim of highlighting critical nodes that may be pharmacologically manipulated for therapeutic intervention. We demonstrate that expression of mHtt causes increased phosphorylation of p53 on Ser46, leading to its interaction with phosphorylation-dependent prolyl isomerase Pin1 and consequent dissociation from the apoptosis inhibitor iASPP, thereby inducing the expression of apoptotic target genes. Inhibition of Ser46 phosphorylation by targeting homeodomain-interacting protein kinase 2 (HIPK2), PKCδ, or ataxia telangiectasia mutated kinase, as well as inhibition of the prolyl isomerase Pin1, prevents mHtt-dependent apoptosis of neuronal cells. These results provide a rationale for the use of small-molecule inhibitors of stress-responsive protein kinases and Pin1 as a potential therapeutic strategy for HD treatment.

  16. Onjisaponin B derived from Radix Polygalae enhances autophagy and accelerates the degradation of mutant α-synuclein and huntingtin in PC-12 cells.

    Science.gov (United States)

    Wu, An-Guo; Wong, Vincent Kam-Wai; Xu, Su-Wei; Chan, Wai-Kit; Ng, Choi-In; Liu, Liang; Law, Betty Yuen-Kwan

    2013-11-15

    Emerging evidence indicates important protective roles being played by autophagy in neurodegenerative disorders through clearance of aggregate-prone or mutant proteins. In the current study, we aimed to identify autophagy inducers from Chinese medicinal herbs as a potential neuroprotective agent that enhances the clearance of mutant huntingtin and α-synuclein in PC-12 cells. Through intensive screening using the green fluorescent protein-light chain 3 (GFP-LC3) autophagy detection platform, we found that the ethanol extracts of Radix Polygalae (Yuan Zhi) were capable of inducing autophagy. Further investigation showed that among three single components derived from Radix Polygalae--i.e., polygalacic acid, senegenin and onjisaponin B--onjisaponin B was able to induce autophagy and accelerate both the removal of mutant huntingtin and A53T α-synuclein, which are highly associated with Huntington disease and Parkinson disease, respectively. Our study further demonstrated that onjisaponin B induces autophagy via the AMPK-mTOR signaling pathway. Therefore, findings in the current study provide detailed insights into the protective mechanism of a novel autophagy inducer, which is valuable for further investigation as a new candidate agent for modulating neurodegenerative disorders through the reduction of toxicity and clearance of mutant proteins in the cellular level.

  17. BACHD rats expressing full-length mutant huntingtin exhibit differences in social behavior compared to wild-type littermates.

    Science.gov (United States)

    Manfré, Giuseppe; Novati, Arianna; Faccini, Ilaria; Rossetti, Andrea C; Bosch, Kari; Molteni, Raffaella; Riva, Marco A; Van der Harst, Johanneke E; Nguyen, Huu Phuc; Homberg, Judith R

    2018-01-01

    Huntington disease (HD) is a devastating inherited neurodegenerative disorder characterized by progressive motor, cognitive, and psychiatric symptoms without any cure to slow down or stop the progress of the disease. The BACHD rat model for HD carrying the human full-length mutant huntingtin protein (mHTT) with 97 polyQ repeats has been recently established as a promising model which reproduces several HD-like features. While motor and cognitive functions have been characterized in BACHD rats, little is known about their social phenotype. This study focuses especially on social behavior since evidence for social disturbances exists in human patients. Our objective was to compare social behavior in BACHD and wild-type (WT) rats at different ages, using two different measures of sociability. Animals were tested longitudinally at the age of 2, 4 and 8 months in the social interaction test to examine different parameters of sociability. A separate cohort of 7 month old rats was tested in the three chamber social test to measure both sociability and social novelty. Gene expression analyses in 8 months old animals were performed by real time qRT-PCR to evaluate a potential involvement of D1 and D2 dopaminergic receptors and the contribution of Brain-derived neurotrophic factor (BDNF) to the observed behavioral alterations. In the social interaction test, BACHD rats showed age-dependent changes in behaviour when they were-re introduced to their cagemate after a 24 hours-period of individual housing. The time spent on nape attacks increased with aging. Furthermore, a significant higher level of pinning at 2 months of age was shown in the BACHD rats compared to wild-types, followed by a reduction at 4 and 8 months. On the other hand, BACHD rats exhibited a decreased active social behaviour compared to wild-types, reflected by genotype-effects on approaching, following and social nose contact. In the three chamber social test, BACHD rats seemed to show a mild deficit in

  18. BACHD rats expressing full-length mutant huntingtin exhibit differences in social behavior compared to wild-type littermates.

    Directory of Open Access Journals (Sweden)

    Giuseppe Manfré

    Full Text Available Huntington disease (HD is a devastating inherited neurodegenerative disorder characterized by progressive motor, cognitive, and psychiatric symptoms without any cure to slow down or stop the progress of the disease. The BACHD rat model for HD carrying the human full-length mutant huntingtin protein (mHTT with 97 polyQ repeats has been recently established as a promising model which reproduces several HD-like features. While motor and cognitive functions have been characterized in BACHD rats, little is known about their social phenotype.This study focuses especially on social behavior since evidence for social disturbances exists in human patients. Our objective was to compare social behavior in BACHD and wild-type (WT rats at different ages, using two different measures of sociability.Animals were tested longitudinally at the age of 2, 4 and 8 months in the social interaction test to examine different parameters of sociability. A separate cohort of 7 month old rats was tested in the three chamber social test to measure both sociability and social novelty. Gene expression analyses in 8 months old animals were performed by real time qRT-PCR to evaluate a potential involvement of D1 and D2 dopaminergic receptors and the contribution of Brain-derived neurotrophic factor (BDNF to the observed behavioral alterations.In the social interaction test, BACHD rats showed age-dependent changes in behaviour when they were-re introduced to their cagemate after a 24 hours-period of individual housing. The time spent on nape attacks increased with aging. Furthermore, a significant higher level of pinning at 2 months of age was shown in the BACHD rats compared to wild-types, followed by a reduction at 4 and 8 months. On the other hand, BACHD rats exhibited a decreased active social behaviour compared to wild-types, reflected by genotype-effects on approaching, following and social nose contact. In the three chamber social test, BACHD rats seemed to show a mild

  19. BACHD rats expressing full-length mutant huntingtin exhibit differences in social behavior compared to wild-type littermates

    Science.gov (United States)

    Manfré, Giuseppe; Novati, Arianna; Faccini, Ilaria; Rossetti, Andrea C.; Bosch, Kari; Molteni, Raffaella; Riva, Marco A.; Van der Harst, Johanneke E.; Homberg, Judith R.

    2018-01-01

    Background Huntington disease (HD) is a devastating inherited neurodegenerative disorder characterized by progressive motor, cognitive, and psychiatric symptoms without any cure to slow down or stop the progress of the disease. The BACHD rat model for HD carrying the human full-length mutant huntingtin protein (mHTT) with 97 polyQ repeats has been recently established as a promising model which reproduces several HD-like features. While motor and cognitive functions have been characterized in BACHD rats, little is known about their social phenotype. Objective This study focuses especially on social behavior since evidence for social disturbances exists in human patients. Our objective was to compare social behavior in BACHD and wild-type (WT) rats at different ages, using two different measures of sociability. Methods Animals were tested longitudinally at the age of 2, 4 and 8 months in the social interaction test to examine different parameters of sociability. A separate cohort of 7 month old rats was tested in the three chamber social test to measure both sociability and social novelty. Gene expression analyses in 8 months old animals were performed by real time qRT-PCR to evaluate a potential involvement of D1 and D2 dopaminergic receptors and the contribution of Brain-derived neurotrophic factor (BDNF) to the observed behavioral alterations. Results In the social interaction test, BACHD rats showed age-dependent changes in behaviour when they were-re introduced to their cagemate after a 24 hours-period of individual housing. The time spent on nape attacks increased with aging. Furthermore, a significant higher level of pinning at 2 months of age was shown in the BACHD rats compared to wild-types, followed by a reduction at 4 and 8 months. On the other hand, BACHD rats exhibited a decreased active social behaviour compared to wild-types, reflected by genotype-effects on approaching, following and social nose contact. In the three chamber social test, BACHD rats

  20. Analysis of proteolytic processes and enzymatic activities in the generation of huntingtin n-terminal fragments in an HEK293 cell model.

    Directory of Open Access Journals (Sweden)

    Andrew T N Tebbenkamp

    Full Text Available N-terminal fragments of mutant huntingtin (htt that terminate between residues 90-115, termed cleavage product A or 1 (cp-A/1, form intracellular and intranuclear inclusion bodies in the brains of patients with Huntington's disease (HD. These fragments appear to be proteolytic products of the full-length protein. Here, we use an HEK293 cell culture model to investigate huntingtin proteolytic processing; previous studies of these cells have demonstrated cleavage of htt to cp-A/1 like htt fragments.Recombinant N-terminal htt fragments, terminating at residue 171 (also referred to as cp-B/2 like, were efficiently cleaved to produce cp-A/1 whereas fragments representing endogenous caspase, calpain, and metalloproteinase cleavage products, terminating between residues 400-600, were inefficiently cleaved. Using cysteine-labeling techniques and antibody binding mapping, we localized the C-terminus of the cp-A/1 fragments produced by HEK293 cells to sequences minimally limited by cysteine 105 and an antibody epitope composed of residues 115-124. A combination of genetic and pharmacologic approaches to inhibit potential proteases, including γ-secretase and calpain, proved ineffective in preventing production of cp-A/1.Our findings indicate that HEK293 cells express a protease that is capable of efficiently cleaving cp-B/2 like fragments of htt with normal or expanded glutamine repeats. For reasons that remain unclear, this protease cleaves longer htt fragments, with normal or expanded glutamine expansions, much less efficiently. The protease in HEK293 cells that is capable of generating a cp-A/1 like htt fragment may be a novel protease with a high preference for a cp-B/2-like htt fragment as substrate.

  1. Cloning and analysis of the promoter region of the human fibronectin gene

    International Nuclear Information System (INIS)

    Dean, D.C.; Bowlus, C.L.; Bourgeois, S.

    1987-01-01

    Human fibronectin (FN) genomic clones were isolated by screening a human genomic library with a 75-base oligonucleotide. The sequence of the oligonucleotide corresponds to a region near the 5' end of the human FN cDNA clone pFH6 that contains the amino-terminal coding sequences but does not extend to the 5' end of the mRNA. The 5' end of the FN gene is found on a 3.7-kilobase-pair EcoRI fragment that contains about 2.7 kilobase pairs of flanking sequence. The first exon is 414 base pairs long, with a 5' untranslated region of 267 base pairs. As deduced on the basis of the position of the initiation codon, FN is synthesized with a 31-residue amino acid extension on the amion terminus that is not present in the mature polypeptide. This amino-terminal extension appears to contain both a signal peptide and a propeptide. The first 200 base pairs of 5'-flanking sequence is very G+C rich. Upstream of this the sequence becomes relatively A+T rich. The sequence ATATAA is found at -25 and the sequence CAAT is present at -150. The sequence GGGGCGGGGC at -102 exhibits homology to the binding site for the transcription factor SP1, and the sequence TGACGTCA at -173 exhibits homology to 5'-flanking sequences important for induction by cAMP

  2. Generation of induced pluripotent stem cells from transgenic minipigs expressing the N-terminal part of the human mutant huntingtin - a new way to study pathogenesis of Huntington´s disease

    Czech Academy of Sciences Publication Activity Database

    Lišková, Irena; Vodička, P.; Juhás, Štefan; Klempíř, J.; Motlík, Jan

    2015-01-01

    Roč. 78, Suppl 2 (2015), s. 18-19 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) 7F14308 Institutional support: RVO:67985904 Keywords : Huntington ´s disease * huntingtin * induced pluripotent stem cells Subject RIV: FH - Neurology

  3. Exon organization of the mouse entactin gene corresponds to the structural domains of the polypeptide and has regional homology to the low-density lipoprotein receptor gene

    DEFF Research Database (Denmark)

    Durkin, M E; Wewer, U M; Chung, A E

    1995-01-01

    of the mouse entactin gene closely corresponds to the organization of the polypeptide into distinct structural and functional domains. The two amino-terminal globular domains are encoded by three exons each. Single exons encode the two protease-sensitive, O-glycosylated linking regions. The six EGF......Entactin is a widespread basement membrane protein of 150 kDa that binds to type IV collagen and laminin. The complete exon-intron structure of the mouse entactin gene has been determined from lambda genomic DNA clones. The gene spans at least 65 kb and contains 20 exons. The exon organization...

  4. Alteration of lysine 178 in the hinge region of the Escherichia coli ada protein interferes with activation of ada, but not alkA, transcription.

    OpenAIRE

    Saget, B M; Shevell, D E; Walker, G C

    1995-01-01

    The ada gene of Escherichia coli K-12 encodes the 39-kDa Ada protein, which consists of two domains joined by a hinge region that is sensitive to proteolytic cleavage in vitro. The amino-terminal domain has a DNA methyltransferase activity that repairs the S-diastereoisomer of methylphosphotriesters while the carboxyl-terminal domain has a DNA methyltransferase activity that repairs O6-methylguanine and O4-methylthymine lesions. Transfer of a methyl group to Cys-69 by repair of a methylphosph...

  5. Xyloketal-derived small molecules show protective effect by decreasing mutant Huntingtin protein aggregates in Caenorhabditis elegans model of Huntington’s disease

    Directory of Open Access Journals (Sweden)

    Zeng YX

    2016-04-01

    Full Text Available Yixuan Zeng,1,2,* Wenyuan Guo,1,* Guangqing Xu,3 Qinmei Wang,4 Luyang Feng,1,2 Simei Long,1 Fengyin Liang,1 Yi Huang,1 Xilin Lu,1 Shichang Li,5 Jiebin Zhou,5 Jean-Marc Burgunder,6 Jiyan Pang,5 Zhong Pei1,2 1Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Disease, The First Affiliated Hospital, Sun Yat-sen University, 2Guangzhou Center, Chinese Huntington’s Disease Network, 3Department of Rehabilitation, The First Affiliated Hospital, 4Key laboratory on Assisted Circulation, Ministry of Health, Department of Cardiovascular Medicine of the First Affiliated Hospital, 5School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 6Swiss Huntington’s Disease Center, Department of Neurology, University of Bern, Bern, Switzerland *These authors contributed equally to this work Abstract: Huntington’s disease is an autosomal-dominant neurodegenerative disorder, with chorea as the most prominent manifestation. The disease is caused by abnormal expansion of CAG codon repeats in the IT15 gene, which leads to the expression of a glutamine-rich protein named mutant Huntingtin (Htt. Because of its devastating disease burden and lack of valid treatment, development of more effective therapeutics for Huntington’s disease is urgently required. Xyloketal B, a natural product from mangrove fungus, has shown protective effects against toxicity in other neurodegenerative disease models such as Parkinson’s and Alzheimer’s diseases. To identify potential neuroprotective molecules for Huntington’s disease, six derivatives of xyloketal B were screened in a Caenorhabditis elegans Huntington’s disease model; all six compounds showed a protective effect. Molecular docking studies indicated that compound 1 could bind to residues GLN369 and GLN393 of the mutant Htt protein, forming a

  6. The Wnt receptor Ryk reduces neuronal and cell survival capacity by repressing FOXO activity during the early phases of mutant huntingtin pathogenicity.

    Directory of Open Access Journals (Sweden)

    Cendrine Tourette

    2014-06-01

    Full Text Available The Wnt receptor Ryk is an evolutionary-conserved protein important during neuronal differentiation through several mechanisms, including γ-secretase cleavage and nuclear translocation of its intracellular domain (Ryk-ICD. Although the Wnt pathway may be neuroprotective, the role of Ryk in neurodegenerative disease remains unknown. We found that Ryk is up-regulated in neurons expressing mutant huntingtin (HTT in several models of Huntington's disease (HD. Further investigation in Caenorhabditis elegans and mouse striatal cell models of HD provided a model in which the early-stage increase of Ryk promotes neuronal dysfunction by repressing the neuroprotective activity of the longevity-promoting factor FOXO through a noncanonical mechanism that implicates the Ryk-ICD fragment and its binding to the FOXO co-factor β-catenin. The Ryk-ICD fragment suppressed neuroprotection by lin-18/Ryk loss-of-function in expanded-polyQ nematodes, repressed FOXO transcriptional activity, and abolished β-catenin protection of mutant htt striatal cells against cell death vulnerability. Additionally, Ryk-ICD was increased in the nucleus of mutant htt cells, and reducing γ-secretase PS1 levels compensated for the cytotoxicity of full-length Ryk in these cells. These findings reveal that the Ryk-ICD pathway may impair FOXO protective activity in mutant polyglutamine neurons, suggesting that neurons are unable to efficiently maintain function and resist disease from the earliest phases of the pathogenic process in HD.

  7. The Evidence for the Spread and Seeding Capacities of the Mutant Huntingtin Protein in in Vitro Systems and Their Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Maria Masnata

    2017-11-01

    Full Text Available Neurodegenerative disorders are not only characterized by specific patterns of cell loss but the presence and accumulation of various pathological proteins—both of which correlate with disease evolution. There is now mounting evidence to suggest that these pathological proteins present with toxic, at times prion-like, properties and can therefore seed pathology in neighboring as well remotely connected healthy neurons as they spread across the brain. What is less clear, at this stage, is how much this actually contributes to, and drives, the core pathogenic events. In this review, we present a comprehensive, up-to-date summary of the reported in vitro studies that support the spreading and seeding capacities of pathological proteins, with an emphasis on mutant huntingtin protein in the context of Huntington's disease, although in vivo work remains to be performed to validate this theory in this particular disease. We have further reviewed these findings in light of their potential implications for the development of novel therapeutic approaches.

  8. Chaperone protein HYPK interacts with the first 17 amino acid region of Huntingtin and modulates mutant HTT-mediated aggregation and cytotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Choudhury, Kamalika Roy [Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064 (India); Centre for Neuroscience, Indian Institute of Science, Bangalore 560012 (India); Bhattacharyya, Nitai P., E-mail: nitai_sinp@yahoo.com [Biomedical Genomics Centre, PG Polyclinic Building, 5, Suburbun Hospital Road, Kolkata 700020 (India)

    2015-01-02

    Highlights: • HYPK reduces mutant HTT-mediated aggregate formation and cytotoxicity. • Interaction of HYPK with HTT requires N-terminal 17 amino acid of HTT (HTT-N17). • Deletion of HTT-N17 leads to SDS-soluble, smaller, nuclear aggregates. • These smaller aggregates do not associate with HYPK and are more cytotoxic. • Maybe, interaction of HYPK with amphipathic HTT-N17 block HTT aggregate formation. - Abstract: Huntington’s disease is a polyglutamine expansion disorder, characterized by mutant HTT-mediated aggregate formation and cytotoxicity. Many reports suggests roles of N-terminal 17 amino acid domain of HTT (HTT-N17) towards subcellular localization, aggregate formation and subsequent pathogenicity induced by N-terminal HTT harboring polyQ stretch in pathogenic range. HYPK is a HTT-interacting chaperone which can reduce N-terminal mutant HTT-mediated aggregate formation and cytotoxicity in neuronal cell lines. However, how HYPK interacts with N-terminal fragment of HTT remained unknown. Here we report that specific interaction of HYPK with HTT-N17 is crucial for the chaperone activity of HYPK. Deletion of HTT-N17 leads to formation of tinier, SDS-soluble nuclear aggregates formed by N-terminal mutant HTT. The increased cytotoxicity imparted by these tiny aggregates might be contributed due to loss of interaction with HYPK.

  9. Dysregulation of gene expression in the striatum of BACHD rats expressing full-length mutant huntingtin and associated abnormalities on molecular and protein levels.

    Science.gov (United States)

    Yu-Taeger, Libo; Bonin, Michael; Stricker-Shaver, Janice; Riess, Olaf; Nguyen, Hoa Huu Phuc

    2017-05-01

    Huntington disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the gene coding for the huntingtin protein (HTT). Mutant HTT (mHTT) has been proposed to cause neuronal dysfunction and neuronal loss through multiple mechanisms. Transcriptional changes may be a core pathogenic feature of HD. Utilizing the Affymetrix platform we performed a genome-wide RNA expression analysis in two BACHD transgenic rat lines (TG5 and TG9) at 12 months of age, both of which carry full-length human mHTT but with different expression levels. By defining the threshold of significance at p < 0.01, we found 1608 genes and 871 genes differentially expressed in both TG5 and TG9 rats when compared to the wild type littermates, respectively. We only chose the highly up-/down-regulated genes for further analysis by setting an additional threshold of 1.5 fold change. Comparing gene expression profiles of human HD brains and BACHD rats revealed a high concordance in both functional and IPA (Ingenuity Pathway Analysis) canonical pathways relevant to HD. In addition, we investigated the causes leading to gene expression changes at molecular and protein levels in BACHD rats including the involvement of polyQ-containing transcription factors TATA box-binding protein (TBP), Sp1 and CBP as well as the chromatin structure. We demonstrate that the BACHD rat model recapitulates the gene expression changes of the human disease supporting its role as a preclinical research animal model. We also show for the first time that TFIID complex formation is reduced, while soluble TBP is increased in an HD model. This finding suggests that mHTT is a competitor instead of a recruiter of polyQ-containing transcription factors in the transcription process in HD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression

    DEFF Research Database (Denmark)

    Pouladi, Mahmoud A; Xie, Yuanyun; Skotte, Niels Henning

    2010-01-01

    of the IGF-1 pathway in mediating the effect of htt on body weight. IGF-1 expression was examined in transgenic mouse lines expressing different levels of FL wild-type (WT) htt (YAC18 mice), FL mutant htt (YAC128 and BACHD mice) and truncated mutant htt (shortstop mice). We demonstrate that htt influences...... body weight by modulating the IGF-1 pathway. Plasma IGF-1 levels correlate with body weight and htt levels in the transgenic YAC mice expressing human htt. The effect of htt on IGF-1 expression is independent of CAG size. No effect on body weight is observed in transgenic YAC mice expressing...... and decreases the body weight of YAC128 animals to WT levels. Furthermore, given the ubiquitous expression of IGF-1 within the central nervous system, we also examined the impact of FL htt levels on IGF-1 expression in different regions of the brain, including the striatum, cerebellum of YAC18, YAC128...

  11. A series of N-terminal epitope tagged Hdh knock-in alleles expressing normal and mutant huntingtin: their application to understanding the effect of increasing the length of normal huntingtin’s polyglutamine stretch on CAG140 mouse model pathogenesis

    Directory of Open Access Journals (Sweden)

    Zheng Shuqiu

    2012-08-01

    Full Text Available Abstract Background Huntington’s disease (HD is an autosomal dominant neurodegenerative disease that is caused by the expansion of a polyglutamine (polyQ stretch within Huntingtin (htt, the protein product of the HD gene. Although studies in vitro have suggested that the mutant htt can act in a potentially dominant negative fashion by sequestering wild-type htt into insoluble protein aggregates, the role of the length of the normal htt polyQ stretch, and the adjacent proline-rich region (PRR in modulating HD mouse model pathogenesis is currently unknown. Results We describe the generation and characterization of a series of knock-in HD mouse models that express versions of the mouse HD gene (Hdh encoding N-terminal hemaglutinin (HA or 3xFlag epitope tagged full-length htt with different polyQ lengths (HA7Q-, 3xFlag7Q-, 3xFlag20Q-, and 3xFlag140Q-htt and substitution of the adjacent mouse PRR with the human PRR (3xFlag20Q- and 3xFlag140Q-htt. Using co-immunoprecipitation and immunohistochemistry analyses, we detect no significant interaction between soluble full-length normal 7Q- htt and mutant (140Q htt, but we do observe N-terminal fragments of epitope-tagged normal htt in mutant htt aggregates. When the sequences encoding normal mouse htt’s polyQ stretch and PRR are replaced with non-pathogenic human sequence in mice also expressing 140Q-htt, aggregation foci within the striatum, and the mean size of htt inclusions are increased, along with an increase in striatal lipofuscin and gliosis. Conclusion In mice, soluble full-length normal and mutant htt are predominantly monomeric. In heterozygous knock-in HD mouse models, substituting the normal mouse polyQ and PRR with normal human sequence can exacerbate some neuropathological phenotypes.

  12. Molecular characterization of the haptoglobin.hemoglobin receptor CD163. Ligand binding properties of the scavenger receptor cysteine-rich domain region

    DEFF Research Database (Denmark)

    Madsen, Mette; Møller, Holger J; Nielsen, Marianne Jensby

    2004-01-01

    CD163 is the macrophage receptor for endocytosis of haptoglobin.hemoglobin complexes. The extracellular region consisting of nine scavenger receptor cysteine rich (SRCR) domains also circulates in plasma as a soluble protein. By ligand binding analysis of a broad spectrum of soluble CD163...... truncation variants, the amino-terminal third of the SRCR region was shown to be crucial for the binding of haptoglobin.hemoglobin complexes. By Western blotting of the CD163 variants, a panel of ten monoclonal antibodies was mapped to SRCR domains 1, 3, 4, 6, 7, and 9, respectively. Only the two antibodies...... to CD163 demonstrated that optimal ligand binding requires physiological plasma calcium concentrations, and an immediate ligand release occurs at the low calcium concentrations measured in acidifying endosomes. In conclusion, SRCR domain 3 of CD163 is an exposed domain and a critical determinant...

  13. Embryonic chicken cornea and cartilage synthesize type IX collagen molecules with different amino-terminal domains.

    OpenAIRE

    Svoboda, K K; Nishimura, I; Sugrue, S P; Ninomiya, Y; Olsen, B R

    1988-01-01

    We have analyzed embryonic chicken cornea for the presence of type IX collagen mRNA and protein. Using RNA transfer blot analysis, we demonstrate that alpha 1(IX) and alpha 2(IX) mRNAs are expressed by corneal epithelial cells at the time that the primary stromal components are synthesized. The levels of the mRNAs decrease with increasing developmental age and are barely detectable at day 11 of development. In contrast, type IX collagen protein is detectable by immunofluorescence at days 5 an...

  14. Amino-Terminal Microdeletion within the CNTNAP2 Gene Associated with Variable Expressivity of Speech Delay

    Directory of Open Access Journals (Sweden)

    Amel Al-Murrani

    2012-01-01

    Full Text Available The contactin-associated protein-like 2 (CNTNAP2 gene is highly expressed in the frontal lobe circuits in the developing human brain. Mutations in this gene have been associated with several neurodevelopmental disorders such as autism and specific language impairment. Here we describe a 450 kb deletion within the CNTNAP2 gene that is maternally inherited in two male siblings, but with a variable clinical phenotype. This variability is described in the context of a limited number of other cases reported in the literature. The in-frame intragenic deletion removes a critical domain of the CNTNAP2 protein, and this case also highlights the challenges of correlating genotype and phenotype.

  15. Amino-Terminal Microdeletion within the CNTNAP2 Gene Associated with Variable Expressivity of Speech Delay

    Science.gov (United States)

    Al-Murrani, Amel; Ashton, Fern; Aftimos, Salim; George, Alice M.; Love, Donald R.

    2012-01-01

    The contactin-associated protein-like 2 (CNTNAP2) gene is highly expressed in the frontal lobe circuits in the developing human brain. Mutations in this gene have been associated with several neurodevelopmental disorders such as autism and specific language impairment. Here we describe a 450 kb deletion within the CNTNAP2 gene that is maternally inherited in two male siblings, but with a variable clinical phenotype. This variability is described in the context of a limited number of other cases reported in the literature. The in-frame intragenic deletion removes a critical domain of the CNTNAP2 protein, and this case also highlights the challenges of correlating genotype and phenotype. PMID:23074684

  16. Value of amino-terminal pro B-natriuretic peptide in diagnosing Kawasaki disease.

    Science.gov (United States)

    McNeal-Davidson, Ariane; Fournier, Anne; Spigelblatt, Linda; Saint-Cyr, Claire; Mir, Thomas S; Nir, Amiram; Dallaire, Frédéric; Cousineau, Jocelyne; Delvin, Edgard; Dahdah, Nagib

    2012-10-01

    The aim of the present study was to investigate the diagnostic value of the N-terminal B-type natriuretic peptide (NT-proBNP) in acute Kawasaki disease (KD) given that the clinical criteria and the current basic laboratory tests lack the necessary specificity for accurate diagnosis. Basic biological tests and serum NT-proBNP levels obtained from acute KD patients were compared to that of febrile controls. NT-proBNP was considered abnormal based on the following definitions: above a cut-off determined on receiver operator characteristic (ROC) analysis, above the upper limit for age, or above 2 SD calculated from healthy children. Analyses were also performed for KD cases with complete or incomplete criteria combined and separately. There were 81 patients and 49 controls aged 3.60 ± 2.77 versus 4.25 ± 3.88 years (P= 0.69). ROC analysis yielded significant area under the curve for NT-proBNP. The sensitivity, specificity, positive and negative predictive values were 70.4-88.9%, 69.4-91.8%, 82.8-93.4%, and 65.2-79.1%. The odds ratios based on NT-proBNP definitions varied between 18.13 (95% confidence interval [CI]: 7.21-45.57), 20.82 (95%CI: 8.18-53.0), and 26.71 (95%CI: 8.64-82.57; P < 0.001). Results were reproducible for cases with complete or incomplete criteria separately. NT-proBNP is a reliable marker for the diagnosis of KD. Prospective clinical studies with emphasis on NT-proBNP in a diagnostic algorithm are needed. © 2012 The Authors. Pediatrics International © 2012 Japan Pediatric Society.

  17. Amino-terminal pro-brain natriuretic peptide in children with latent rheumatic heart disease

    Directory of Open Access Journals (Sweden)

    Justin P Zachariah

    2016-01-01

    Conclusion: Serum NT-proBNP did not distinguish between latent RHD cases and the controls. Sex and within-family exposures may confound this result. More investigation into biomarker-based RHD detection is warranted.

  18. Amino-terminal sequence of glycoprotein D of herpes simplex virus types 1 and 2

    International Nuclear Information System (INIS)

    Eisenberg, R.J.; Long, D.; Hogue-Angeletti, R.; Cohen, G.H.

    1984-01-01

    Glycoprotein D (gD) of herpes simplex virus is a structural component of the virion envelope which stimulates production of high titers of herpes simplex virus type-common neutralizing antibody. The authors caried out automated N-terminal amino acid sequencing studies on radiolabeled preparations of gD-1 (gD of herpes simplex virus type 1) and gD-2 (gD of herpes simplex virus type 2). Although some differences were noted, particularly in the methionine and alanine profiles for gD-1 and gD-2, the amino acid sequence of a number of the first 30 residues of the amino terminus of gD-1 and gD-2 appears to be quite similar. For both proteins, the first residue is a lysine. When we compared out sequence data for gD-1 with those predicted by nucleic acid sequencing, the two sequences could be aligned (with one exception) starting at residue 26 (lysine) of the predicted sequence. Thus, the first 25 amino acids of the predicted sequence are absent from the polypeptides isolated from infected cells

  19. Regionalism, Regionalization and Regional Development

    Directory of Open Access Journals (Sweden)

    Liviu C. Andrei

    2016-03-01

    Full Text Available Sustained development is a concept associating other concepts, in its turn, in the EU practice, e.g. regionalism, regionalizing and afferent policies, here including structural policies. This below text, dedicated to integration concepts, will limit on the other hand to regionalizing, otherwise an aspect typical to Europe and to the EU. On the other hand, two aspects come up to strengthen this field of ideas, i.e. the region (al-regionalism-(regional development triplet has either its own history or precise individual outline of terms.

  20. Amino-terminal residues of ΔNp63, mutated in ectodermal dysplasia, are required for its transcriptional activity.

    Science.gov (United States)

    Lena, Anna Maria; Duca, Sara; Novelli, Flavia; Melino, Sonia; Annicchiarico-Petruzzelli, Margherita; Melino, Gerry; Candi, Eleonora

    2015-11-13

    p63, a member of the p53 family, is a crucial transcription factor for epithelial development and skin homeostasis. Heterozygous mutations in TP63 gene have been associated with human ectodermal dysplasia disorders. Most of these TP63 mutations are missense mutations causing amino acidic substitutions at p63 DNA binding or SAM domains that reduce or abolish the transcriptional activity of mutants p63. A significant number of mutants, however, resides in part of the p63 protein that apparently do not affect DNA binding and/or transcriptional activity, such as the N-terminal domain. Here, we characterize five p63 mutations at the 5' end of TP63 gene aiming to understand the pathogenesis of the diseases and to uncover the role of ΔNp63α N-terminus residues in determining its transactivation potential. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Structure-activity studies with carboxy- and amino-terminal fragments of neurotensin on hypothalamic neurons in vitro.

    Science.gov (United States)

    Baldino, F; Davis, L G; Wolfson, B

    1985-09-09

    The purpose of this study was to determine the structural requirements for the activity of neurotensin (NT1-13) on preoptic/anterior hypothalamic (POAH) neurons in vitro. Standard explant culture electrophysiological techniques were employed. NT was administered to POAH cultures through the superfusion fluid, or, to the vicinity of individual neurons by pressure ejection (0.5-10 psi) from micropipettes. Computer-generated, peri-event histograms were used to quantitate neuronal responses. Pressure ejection of NT1-13 (50 pM to 1 microM) consistently produced an excitatory effect on 30 of 42 neurons. The remaining cells were either inhibited or unaffected. Application of the C-terminal hexapeptide, NT8-13, but not the N-terminal octapeptide, NT1-8 (less than or equal to 1 mM), produced an excitatory response in 21 of 30 neurons, but was less potent than NT1-13. Application of an N-acetylated NT8-13 fragment (NTAC8-13) produced a response that was similar to that produced by NT8-13. The excitatory effects of NT1-13 and NT8-13 were maintained in medium which effectively blocked synaptic transmission (0 mM Ca2+/12 mM Mg2+ 1 mM EGTA). These data indicate that the C-terminal hexapeptide, but not the N-terminal octapeptide, produces a dose-related, excitatory effect on single neurons in the POAH in vitro. The persistence of these effects in Ca2+-free medium supports a postsynaptic site of action for these peptides.

  2. The amino terminal end determines the stability and assembling capacity of eukaryotic ribosomal stalk proteins P1 and P2.

    Science.gov (United States)

    Camargo, Hendricka; Nusspaumer, Gretel; Abia, David; Briceño, Verónica; Remacha, Miguel; Ballesta, Juan P G

    2011-05-01

    The eukaryotic ribosomal proteins P1 and P2 bind to protein P0 through their N-terminal domain to form the essential ribosomal stalk. A mutational analysis points to amino acids at positions 2 and 3 as determinants for the drastic difference of Saccharomyces cerevisiae P1 and P2 half-life, and suggest different degradation mechanisms for each protein type. Moreover, the capacity to form P1/P2 heterodimers is drastically affected by mutations in the P2β four initial amino acids, while these mutations have no effect on P1β. Binding of P2β and, to a lesser extent, P1β to the ribosome is also seriously affected showing the high relevance of the amino acids in the first turn of the NTD α-helix 1 for the stalk assembly. The negative effect of some mutations on ribosome binding can be reversed by the presence of the second P1/P2 couple in the ribosome, indicating a stabilizing structural influence between the two heterodimers. Unexpectedly, some mutations totally abolish heterodimer formation but allow significant ribosome binding and, therefore, a previous P1 and P2 association seems not to be an absolute requirement for stalk assembly. Homology modeling of the protein complexes suggests that the mutated residues can affect the overall protein conformation. © The Author(s) 2011. Published by Oxford University Press.

  3. Amino-terminal pro-B-type natriuretic peptide testing in patients with diabetes mellitus and with systemic hypertension

    DEFF Research Database (Denmark)

    Hildebrandt, P.; Richards, A.M.

    2008-01-01

    with diabetes mellitus, hypertension, or known coronary artery disease) appears logical and is supported by data. NT-proBNP has strong prognostic value in such at-risk patients. However, the exact implications for clinical management after detection of an elevated NT-proBNP value should be driven by clinical...

  4. The agonist-binding domain of the calcium-sensing receptor is located at the amino-terminal domain

    DEFF Research Database (Denmark)

    Bräuner-Osborne, H; Jensen, Anders A.; Sheppard, P O

    1999-01-01

    inositol phosphate production when exposed to the cationic agonists Ca2+, Mg2+, and Ba2+ in transiently transfected tsA cells (a transformed HEK 293 cell line). The pharmacological profile of Ca/1a (EC50 values of 3.3, 2.6, and 3.9 mM for these cations, respectively) was very similar to that of the wild...

  5. Amino-terminal extension present in the methionine aminopeptidase type 1c of Mycobacterium tuberculosis is indispensible for its activity

    Directory of Open Access Journals (Sweden)

    Kumaran Sangaralingam

    2011-07-01

    Full Text Available Abstract Background Methionine aminopeptidase (MetAP is a ubiquitous enzyme in both prokaryotes and eukaryotes, which catalyzes co-translational removal of N-terminal methionine from elongating polypeptide chains during protein synthesis. It specifically removes the terminal methionine in all organisms, if the penultimate residue is non-bulky and uncharged. The MetAP action for exclusion of N-terminal methionine is mandatory in 50-70% of nascent proteins. Such an activity is required for proper sub cellular localization, additional processing and eventually for the degradation of proteins. Results We cloned genes encoding two such metalloproteases (MtMetAP1a and MtMetAP1c present in Mycobacterium tuberculosis and expressed them as histidine-tagged proteins in Escherichia coli. Although they have different substrate preferences, for Met-Ala-Ser, we found, MtMetAP1c had significantly high enzyme turnover rate as opposed to MtMetAP1a. Circular dichroism spectroscopic studies as well as monitoring of enzyme activity indicated high temperature stability (up to 50°C of MtMetAP1a compared to that of the MtMetAP1c. Modelling of MtMetAP1a based on MtMetAP1c crystal structure revealed the distinct spatial arrangements of identical active site amino acid residues and their mutations affected the enzymatic activities of both the proteins. Strikingly, we observed that 40 amino acid long N-terminal extension of MtMetAP1c, compared to its other family members, contributes towards the activity and stability of this enzyme, which has never been reported for any methionine aminopeptidase. Furthermore, mutational analysis revealed that Val-18 and Pro-19 of MtMetAP1c are crucial for its enzymatic activity. Consistent with this observation, molecular dynamic simulation studies of wild-type and these variants strongly suggest their involvement in maintaining active site conformation of MtMetAP1c. Conclusion Our findings unequivocally emphasized that N-terminal extension of MtMetAP1c contributes towards the functionality of the enzyme presumably by regulating active site residues through "action-at-a-distance" mechanism and we for the first time are reporting this unique function of the enzyme.

  6. Separation of polyethylene glycols and amino-terminated polyethylene glycols by high-performance liquid chromatography under near critical conditions.

    Science.gov (United States)

    Wei, Y-Z; Zhuo, R-X; Jiang, X-L

    2016-05-20

    The separation and characterization of polyethylene glycols (PEGs) and amino-substituted derivatives on common silica-based reversed-phase packing columns using isocratic elution is described. This separation is achieved by liquid chromatography under the near critical conditions (LCCC), based on the number of amino functional end groups without obvious effect of molar mass for PEGs. The mobile phase is acetonitrile in water with an optimal ammonium acetate buffer. The separation mechanism of PEG and amino-substituted PEG under the near LCCC on silica-based packing columns is confirmed to be ion-exchange interaction. Under the LCCC of PEG backbone, with fine tune of buffer concentration, the retention factor ratios for benzylamine and phenol in buffered mobile phases, α(benzylamine/phenol)-values, were used to assess the ion-exchange capacity on silica-based reversed-phase packing columns. To the best of our knowledge, this is the first report on separation of amino-functional PEGs independent of the molar mass by isocratic elution using common C18 or phenyl reversed-phase packing columns. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Role of teh Rad52 Amino-terminal DNA Binding Activity in DNA Strand Capture in Homologous Recombination

    DEFF Research Database (Denmark)

    Shi, Idina; Hallwyl, Swee Chuang Lim; Seong, Changhyun

    2009-01-01

    Saccharomyces cerevisiae Rad52 protein promotes homologous recombination by nucleating the Rad51 recombinase onto replication protein A-coated single-stranded DNA strands and also by directly annealing such strands. We show that the purified rad52-R70A mutant protein, with a compromised amino-ter...

  8. The amino-terminal structure of human fragile X mental retardation protein obtained using precipitant-immobilized imprinted polymers

    Science.gov (United States)

    Hu, Yufeng; Chen, Zhenhang; Fu, Yanjun; He, Qingzhong; Jiang, Lun; Zheng, Jiangge; Gao, Yina; Mei, Pinchao; Chen, Zhongzhou; Ren, Xueqin

    2015-03-01

    Flexibility is an intrinsic property of proteins and essential for their biological functions. However, because of structural flexibility, obtaining high-quality crystals of proteins with heterogeneous conformations remain challenging. Here, we show a novel approach to immobilize traditional precipitants onto molecularly imprinted polymers (MIPs) to facilitate protein crystallization, especially for flexible proteins. By applying this method, high-quality crystals of the flexible N-terminus of human fragile X mental retardation protein are obtained, whose absence causes the most common inherited mental retardation. A novel KH domain and an intermolecular disulfide bond are discovered, and several types of dimers are found in solution, thus providing insights into the function of this protein. Furthermore, the precipitant-immobilized MIPs (piMIPs) successfully facilitate flexible protein crystal formation for five model proteins with increased diffraction resolution. This highlights the potential of piMIPs for the crystallization of flexible proteins.

  9. Definition of IgG- and albumin-binding regions of streptococcal protein G.

    Science.gov (United States)

    Akerström, B; Nielsen, E; Björck, L

    1987-10-05

    Protein G, the immunoglobin G-binding surface protein of group C and G streptococci, also binds serum albumin. The albumin-binding site on protein G is distinct from the immunoglobulin G-binding site. By mild acid hydrolysis of the papain-liberated protein G fragment (35 kDa), a 28-kDa fragment was produced which retained full immunoglobulin G-binding activity (determined by Scatchard plotting) but had lost all albumin-binding capacity. A protein G (65 kDa), isolated after cloning and expression of the protein G gene in Escherichia coli, had comparable affinity to immunoglobulin G (5-10 X 10(10)M-1), but much higher affinity to albumin than the 35- and 28-kDa protein G fragments (31, 2.6, and 0 X 10(9)M-1, respectively). The amino-terminal amino acid sequences of the 65-, 35-, and 28-kDa fragments allowed us to exactly locate the three fragments in an overall sequence map of protein G, based on the partial gene sequences published by Guss et al. (Guss, B., Eliasson, M., Olsson, A., Uhlen, M., Frej, A.-K., Jörnvall, H., Flock, J.-I., and Lindberg, M. (1986) EMBO J. 5, 1567-1575) and Fahnestock et al. (Fahnestock, S. R., Alexander, P., Nagle, J., and Filpula, D. (1986) J. Bacteriol. 167, 870-880). In this map could then be deduced the location of three homologous albumin-binding regions and three homologous immunoglobulin G-binding regions.

  10. Direct ATP photolabeling of Escherichia coli recA proteins: identification of regions required for ATP binding

    International Nuclear Information System (INIS)

    Banks, G.R.; Sedgwick, S.G.

    1986-01-01

    When the Escherichia coli RecA protein is UV irradiated in the presence of [alpha- 32 P]ATP, a labeled protein--ATP adduct is formed. All the experimental evidence indicates that, in forming such an adduct, the ATP becomes specifically immobilized in the catalytically relevant ATP binding site. The adduct can also be identified after irradiation of E. coli cell lysates in a similar manner. This direct ATP photolabeling of RecA proteins has been used to identify regions of the polypeptide chain involved in the binding of ATP. The photolabeling of a RecA protein that lacks wild-type carboxy-terminal amino acids is not detectable. A RecA protein in which the amino-terminal sequence NH2-Ala-Ile-Asp-Glu-Asn- is replaced by NH2-Thr-Met-Ile-Thr-Asn-Ser-Ser-Ser- is only about 5% as efficiently photolabeled as the wild-type protein. Both of these RecA protein constructions, however, contain all the elements previously implicated, directly or indirectly, in the binding of ATP. ATP-photolabeled RecA protein has also been chemically cleaved at specific amino acids in order to identify regions of the polypeptide chain to which the nucleotide becomes covalently photolinked. The evidence is consistent with a region comprising amino acids 116-170. Thus, this work and that of others suggest that several disparate regions of the unfolded polypeptide chain may combine to form the ATP binding site upon protein folding or may influence binding through long-range effects

  11. Cloning of cDNAs coding for the heavy chain region and connecting region of human factor V, a blood coagulation factor with four types of internal repeats

    International Nuclear Information System (INIS)

    Kane, W.H.; Ichinose, A.; Hagen, F.S.; Davie, E.W.

    1987-01-01

    Human factor V is a high molecular weight plasma glycoprotein that participates as a cofactor in the conversion of prothrombin to thrombin by factor X/sub a/. Prior to its participation in the coagulation cascade, factor V is converted to factor V/sub a/ by thrombin generating a heavy chain and a light chain, and these two chains are held together by calcium ions. A connecting region originally located between the heavy and light chains is liberated during the activation reaction. In a previous study, a cDNA of 2970 nucleotides that codes for the carboxyl-terminal 938 amino acids of factor V was isolated and characterized from a Hep G2 cDNA library. This cDNA has been used to obtain additional clones from Hep G2 and human liver cDNA libraries. Furthermore, a Hep G2 cDNA library prepared with an oligonucleotide from the 5' end of these cDNAs was screened to obtain overlapping cDNA clones that code for the amino-terminal region of the molecule. The composite sequence of these clones spans 6911 nucleotides and is consistent with the size of the factor V message present in Hep G2 cells (approximately 7 kilobases). The cDNA codes for a leader sequence of 28 amino acids and a mature protein of 2196 amino acids. The amino acid sequence predicted from the cDNA was in complete agreement with 139 amino acid residues that were identified by Edman degradation of cyanogen bromide peptides isolated from the heavy chain region and connecting region of plasma factor V. The domain structure of human factor V is similar to that previously reported for human coagulation factor VIII. Two types of tandem repeats (17 and 9 amino acids) have also been identified in the connecting region of factor V. The present data indicate that the amino acid sequence in the heavy and light chain regions of factor V is ∼ 40% identical with the corresponding regions of factor VIII

  12. Regions Matter

    DEFF Research Database (Denmark)

    Laursen, Keld; Masciarelli, Francesca; Prencipe, Andrea

    2012-01-01

    capital at the regional level, with a large-scale data set of the innovative activities of a representative sample of 2,413 Italian manufacturing firms from 21 regions, and controlling for a large set of firm and regional characteristics, we find that being located in a region characterized by a high...

  13. Regional development and regional policy

    OpenAIRE

    Šabić, Dejan; Vujadinović, Snežana

    2017-01-01

    Economic polarization is a process that is present at global, national and regional level. Economic activity is extremely spatially concentrated. Cities and developed regions use the agglomeration effect to attract labor and capital, thus achieving more favorable economic conditions than the agrarian region. Scientific research and European experiences over the past decades have contributed to the discrepancy among theorists about the causes and consequences of regional inequalities. Regional...

  14. Structural region

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Structural region. The two groups had 4 substitutions similar to Yawat strain. The Yawat strain had 5 unique mutations. 3 in the E2 region and 2 in the E1 region. The mutation, I702V (E2), though different from all the recent Indian and Reunion sequences was similar ...

  15. Regional Externalities

    NARCIS (Netherlands)

    Heijman, W.J.M.

    2007-01-01

    The book offers practical and theoretical insights in regional externalities. Regional externalities are a specific subset of externalities that can be defined as externalities where space plays a dominant role. This class of externalities can be divided into three categories: (1) externalities

  16. Refinement of glucagon-like peptide 1 docking to its intact receptor using mid-region photolabile probes and molecular modeling.

    Science.gov (United States)

    Miller, Laurence J; Chen, Quan; Lam, Polo C-H; Pinon, Delia I; Sexton, Patrick M; Abagyan, Ruben; Dong, Maoqing

    2011-05-06

    The glucagon-like peptide 1 (GLP1) receptor is an important drug target within the B family of G protein-coupled receptors. Its natural agonist ligand, GLP1, has incretin-like actions and the receptor is a recognized target for management of type 2 diabetes mellitus. Despite recent solution of the structure of the amino terminus of the GLP1 receptor and several close family members, the molecular basis for GLP1 binding to and activation of the intact receptor remains unclear. We previously demonstrated molecular approximations between amino- and carboxyl-terminal residues of GLP1 and its receptor. In this work, we study spatial approximations with the mid-region of this peptide to gain insights into the orientation of the intact receptor and the ligand-receptor complex. We have prepared two new photolabile probes incorporating a p-benzoyl-l-phenylalanine into positions 16 and 20 of GLP1(7-36). Both probes bound to the GLP1 receptor specifically and with high affinity. These were each fully efficacious agonists, stimulating cAMP accumulation in receptor-bearing CHO cells in a concentration-dependent manner. Each probe specifically labeled a single receptor site. Protease cleavage and radiochemical sequencing identified receptor residue Leu(141) above transmembrane segment one as its site of labeling for the position 16 probe, whereas the position 20 probe labeled receptor residue Trp(297) within the second extracellular loop. Establishing ligand residue approximation with this loop region is unique among family members and may help to orient the receptor amino-terminal domain relative to its helical bundle region.

  17. AMHARA REGION

    African Journals Online (AJOL)

    This study investigates the contribution of school curriculum committee in facilitating and coordinating ... schools of Amhara Region' ln undertaking the study the descriptive survey method was used. .... pupil and the teacher are available. ... prepared for each level and grade has ..... the principals have the opinion that the.

  18. Atlantic Region

    NARCIS (Netherlands)

    Elands, B.H.M.; Bell, S.; Blok, J.

    2010-01-01

    Chapter 2 explores recreation and tourism practices in forest areas in the Atlantic region, which refers to the geographical area close to the North Sea and the Atlantic Ocean. The Atlantic countries described in this section are Belgium (Flanders and Wallonia), Denmark, Iceland, Ireland, the

  19. Interaction region

    International Nuclear Information System (INIS)

    Anon.

    1982-01-01

    The Interaction Region Group addressed the basic questions of how to collide the SLC beams, how to maximize and monitor the luminosity, and how to minimize the detector backgrounds at the interaction region. In practice, five subgroups evolved to study these questions. The final focus group provided three alternative designs to acheive the 1 to 2 micron beam spot size required by the SLC, as well as studying other problems including: eta, eta' matching from the collider arcs, the implementation of soft bends near the interaction region, beam emittance growth, and magnet tolerances in the final focus. The beam position monitor group proposed two devices, a strip line monitor, and a beamstrahlung monitor, to bring the beams into collision. The luminosity monitor group reviewed the possible QED processes that would be insensitive to weak interaction (Z 0 ) effects. The beam dumping group proposed locations for kicker and septum magnets in the final focus that would achieve a high dumping efficiency and would meet the desired beam tolerances at the Moller scattering target in the beam dump line. Working with the Polarization Group, the Moller experiment was designed into the beam dump beam line. A beam dump was proposed that would maintain radiation backgrounds (penetrating muons) at acceptible levels. The detector backgrounds group proposed soft-bend and masking configurations to shield the detector from synchrotron radiation from the hard/soft bends and from the final focus quadrupoles and evaluated the effectiveness of these designs for the three final focus optics designs. Backgrounds were also estimated from: large angle synchrotron radiation, local and distant beam-gas interactions, 2-photon interactions, and from neutrons and backscattered photons from the beamstrahlung dump

  20. Transition region

    International Nuclear Information System (INIS)

    Jordan, C.

    1977-01-01

    The Glossary is designed to be a technical dictionary that will provide solar workers of various specialties, students, other astronomers and theoreticians with concise information on the nature and the properties of phenomena of solar and solar-terrestrial physics. Each term, or group of related terms, is given a concise phenomenological and quantitative description, including the relationship to other phenomena and an interpretation in terms of physical processes. The references are intended to lead the non-specialist reader into the literature. This section deals with: transition region; di-electronic recombination; intersystem or intercombination lines; satellite lines; grazing-incidence optics; and crystal spectrometers. (B.R.H.)

  1. The Processed Amino-Terminal Fragment of Human TLR7 Acts as a Chaperone To Direct Human TLR7 into Endosomes

    Science.gov (United States)

    Shepherd, Dawn; Booth, Sarah; Waithe, Dominic; Reis e Sousa, Caetano

    2015-01-01

    TLR7 mediates innate immune responses to viral RNA in endocytic compartments. Mouse and human (h)TLR7 undergo proteolytic cleavage, resulting in the generation of a C-terminal fragment that accumulates in endosomes and associates with the signaling adaptor MyD88 upon receptor triggering by TLR7 agonists. Although mouse TLR7 is cleaved in endosomes by acidic proteases, hTLR7 processing can occur at neutral pH throughout the secretory pathway through the activity of furin-like proprotein convertases. However, the mechanisms by which cleaved hTLR7 reaches the endosomal compartment remain unclear. In this study, we demonstrate that, after hTLR7 proteolytic processing, the liberated amino (N)-terminal fragment remains bound to the C terminus through disulfide bonds and provides key trafficking information that ensures correct delivery of the complex to endosomal compartments. In the absence of the N-terminal fragment, the C-terminal fragment is redirected to the cell surface, where it is functionally inactive. Our data reveal a novel role for the N terminus of hTLR7 as a molecular chaperone that provides processed hTLR7 with the correct targeting instructions to reach the endosomal compartment, hence ensuring its biological activity and preventing inadvertent cell surface responses to self-RNA. PMID:25917086

  2. Proteome-wide analysis of the amino terminal status of Escherichia coli proteins at the steady-state and upon deformylation inhibition.

    Science.gov (United States)

    Bienvenut, Willy V; Giglione, Carmela; Meinnel, Thierry

    2015-07-01

    A proteome wide analysis was performed in Escherichia coli to identify the impact on protein N-termini of actinonin, an antibiotic specifically inhibiting peptide deformylase (PDF). A strategy and tool suite (SILProNaQ) was employed to provide large-scale quantitation of N-terminal modifications. In control conditions, more than 1000 unique N-termini were identified with 56% showing initiator methionine removal. Additional modifications corresponded to partial or complete Nα-acetylation (10%) and N-formyl retention (5%). Among the proteins undergoing these N-terminal modifications, 140 unique N-termini from translocated membrane proteins were highlighted. The very early time-course impact of actinonin was followed after addition of bacteriostatic concentrations of the drug. Under these conditions, 26% of all proteins did not undergo deformylation any longer after 10 min, a value reaching more than 60% of all characterized proteins after 40 min of treatment. The N-formylation ratio measured on individual proteins increased with the same trend. Upon early PDF inhibition, two major categories of proteins retained their N-formyl group: a large number of inner membrane proteins and many proteins involved in protein synthesis including factors assisting the nascent chains in early cotranslational events. All MS data have been deposited in the ProteomeXchange with identifiers PXD001979, PXD002012 and PXD001983 (http://proteomecentral.proteomexchange.org/dataset/PXD001979, http://proteomecentral.proteomexchange.org/dataset/PXD002012 and http://proteomecentral.proteomexchange.org/dataset/PXD001983). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. ELECTROCATALYTIC ACTIVITY FOR O2 REDUCTION OF UNSUBSTITUTED AND PERCHLORINATED IRON PHTHALOCYANINES ADSORBED ON AMINO-TERMINATED MULTIWALLED CARBON NANOTUBES DEPOSITED ON GLASSY CARBON ELECTRODES

    OpenAIRE

    CAÑETE, PAULINA; SILVA, J. FRANCISCO; ZAGAL, JOSÉ H

    2014-01-01

    Amino-functionalized multiwalled carbon nanotubes (MWCNT-NH2) were modified with Fe phthalocyanine (FePc) and perchlorinated Fe phthalocyanine (16(Cl)FePc) and deposited on glassy carbon electrodes (GCE). The electrocatalytic activity of these hybrid electrodes was examined for the reduction of molecular oxygen in alkaline media (0.2 M NaOH) using stationary and rotating disk electrodes. Electrodes containing 16(Cl)FePc are more active than those containing FePc. Electrodes containing CNTs ar...

  4. Effect of body mass index on diagnostic and prognostic usefulness of amino-terminal pro-brain natriuretic peptide in patients with acute dyspnea

    NARCIS (Netherlands)

    Bayes-Genis, Antoni; Lloyd-Jones, Donald M.; van Kimmenade, Roland R. J.; Lainchbury, John G.; Richards, A. Mark; Ordoñez-Llanos, Jordi; Santaló, Miquel; Pinto, Yigal M.; Januzzi, James L.

    2007-01-01

    BACKGROUND: Amino (N)-terminal pro-brain natriuretic peptide (NT-proBNP) testing is useful for diagnostic and prognostic evaluation in patients with dyspnea. An inverse relationship between body mass index (BMI); (calculated as weight in kilograms divided by height in meters squared) and NT-proBNP

  5. Inhibition of Cartilage Acidic Protein 1 Reduces Ultraviolet B Irradiation Induced-Apoptosis through P38 Mitogen-Activated Protein Kinase and Jun Amino-Terminal Kinase Pathways

    OpenAIRE

    Yinghong Ji; Xianfang Rong; Dan Li; Lei Cai; Jun Rao; Yi Lu

    2016-01-01

    Background/Aims: Ultraviolet B (UVB) irradiation can easily induce apoptosis in human lens epithelial cells (HLECs) and further lead to various eye diseases including cataract. Here for the first time, we investigated the role of cartilage acidic protein 1 (CRTAC1) gene in UVB irradiation induced-apoptosis in HLECs. Methods: Three groups of HLECs were employed including model group, empty vector group, and CRTAC1 interference group. Results: After UVB irradiation, the percentage of primary ap...

  6. Dramatic elevation in urinary amino terminal titin fragment excretion quantified by immunoassay in Duchenne muscular dystrophy patients and in dystrophin deficient rodents.

    Science.gov (United States)

    Robertson, Alan S; Majchrzak, Mark J; Smith, Courtney M; Gagnon, Robert C; Devidze, Nino; Banks, Glen B; Little, Sean C; Nabbie, Fizal; Bounous, Denise I; DiPiero, Janet; Jacobsen, Leslie K; Bristow, Linda J; Ahlijanian, Michael K; Stimpson, Stephen A

    2017-07-01

    Enzyme-linked and electrochemiluminescence immunoassays were developed for quantification of amino (N-) terminal fragments of the skeletal muscle protein titin (N-ter titin) and qualified for use in detection of urinary N-ter titin excretion. Urine from normal subjects contained a small but measurable level of N-ter titin (1.0 ± 0.4 ng/ml). A 365-fold increase (365.4 ± 65.0, P = 0.0001) in urinary N-ter titin excretion was seen in Duchene muscular dystrophy (DMD) patients. Urinary N-ter titin was also evaluated in dystrophin deficient rodent models. Mdx mice exhibited low urinary N-ter titin levels at 2 weeks of age followed by a robust and sustained elevation starting at 3 weeks of age, coincident with the development of systemic skeletal muscle damage in this model; fold elevation could not be determined because urinary N-ter titin was not detected in age-matched wild type mice. Levels of serum creatine kinase and serum skeletal muscle troponin I (TnI) were also low at 2 weeks, elevated at later time points and were significantly correlated with urinary N-ter titin excretion in mdx mice. Corticosteroid treatment of mdx mice resulted in improved exercise performance and lowering of both urinary N-ter titin and serum skeletal muscle TnI concentrations. Low urinary N-ter titin levels were detected in wild type rats (3.0 ± 0.6 ng/ml), while Dmd mdx rats exhibited a 556-fold increase (1652.5 ± 405.7 ng/ml, P = 0.002) (both at 5 months of age). These results suggest that urinary N-ter titin is present at low basal concentrations in normal urine and increases dramatically coincident with muscle damage produced by dystrophin deficiency. Urinary N-ter titin has potential as a facile, non-invasive and translational biomarker for DMD. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Utility of amino-terminal pro-brain natriuretic peptide, galectin-3, and apelin for the evaluation of patients with acute heart failure

    NARCIS (Netherlands)

    van Kimmenade, Roland R.; Januzzi, James L.; Ellinor, Patrick T.; Sharma, Umesh C.; Bakker, Jaap A.; Low, Adrian F.; Martinez, Abelardo; Crijns, Harry J.; MacRae, Calum A.; Menheere, Paul P.; Pinto, Yigal M.

    2006-01-01

    OBJECTIVES: This study sought to explore the role of new biomarkers in heart failure (HF). BACKGROUND: We investigated the utility of novel serum markers alone or together with natriuretic peptide testing for diagnosis and short-term prognosis estimation in subjects with acute HF. METHODS: Plasma

  8. Sequence and expression pattern of a novel human orphan G-protein-coupled receptor, GPRC5B, a family C receptor with a short amino-terminal domain

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Krogsgaard-Larsen, P

    2000-01-01

    Query of GenBank with the amino acid sequence of human metabotropic glutamate receptor subtype 2 (mGluR2) identified a predicted gene product of unknown function on BAC clone CIT987SK-A-69G12 (located on chromosome band 16p12) as a homologous protein. The transcript, entitled GPRC5B, was cloned f...... from an expressed sequence tag clone that contained the entire open reading frame of the transcript encoding a protein of 395 amino acids. Analysis of the protein sequence reveal that GPRC5B contains a signal peptide and seven transmembrane alpha-helices, which is a hallmark of G...

  9. Inhibition of the Androgen Receptor Amino-Terminal Domain by a Small Molecule as Treatment for Castrate-Resistant Prostate Cancer

    Science.gov (United States)

    2013-10-01

    abiraterone or Tok -001. Although a negative finding this is an important finding since it shows no off target effects on tumor suppression by EPI...1500 Control MDV-3100 Weeks Post Enrollment Tu m or V ol um e (m m 3 ) LuCaP 49--TOK001 0 1 2 3 4 5 6 0 500 1000 1500 Control TOK -001 only 2 animals

  10. Carboxy terminal region of the Fanconi anemia protein, FANCG/XRCC9, is required for functional activity.

    Science.gov (United States)

    Kuang, Y; Garcia-Higuera, I; Moran, A; Mondoux, M; Digweed, M; D'Andrea, A D

    2000-09-01

    Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome with eight complementation groups. Four of the FA genes have been cloned, and at least three of the encoded proteins, FANCA, FANCC, and FANCG/XRCC9, interact in a nuclear complex, required for the maintenance of normal chromosome stability. In the current study, mutant forms of the FANCA and FANCG proteins have been generated and analyzed with respect to protein complex formation, nuclear translocation, and functional activity. The results demonstrate that the amino terminal two-thirds of FANCG (FANCG amino acids 1-428) binds to the amino terminal nuclear localization signal (NLS) of the FANCA protein. On the basis of 2-hybrid analysis, the FANCA/FANCG binding is a direct protein-protein interaction. Interestingly, a truncated mutant form of the FANCG protein, lacking the carboxy terminus, binds in a complex with FANCA and translocates to the nucleus; however, this mutant protein fails to bind to FANCC and fails to correct the mitomycin C sensitivity of an FA-G cell line. Taken together, these results demonstrate that binding of FANCG to the amino terminal FANCA NLS sequence is necessary but not sufficient for the functional activity of FANCG. Additional amino acid sequences at the carboxy terminus of FANCG are required for the binding of FANCC in the complex. (Blood. 2000;96:1625-1632)

  11. Huntingtin gene repeat size variations affect risk of lifetime depression.

    Science.gov (United States)

    Gardiner, Sarah L; van Belzen, Martine J; Boogaard, Merel W; van Roon-Mom, Willeke M C; Rozing, Maarten P; van Hemert, Albert M; Smit, Johannes H; Beekman, Aartjan T F; van Grootheest, Gerard; Schoevers, Robert A; Oude Voshaar, Richard C; Roos, Raymund A C; Comijs, Hannie C; Penninx, Brenda W J H; van der Mast, Roos C; Aziz, N Ahmad

    2017-12-11

    Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is frequently complicated by depression, it is still unknown to what extent common HTT CAG repeat size variations in the normal range could affect depression risk in the general population. Using binary logistic regression, we assessed the association between HTT CAG repeat size and depression risk in two well-characterized Dutch cohorts─the Netherlands Study of Depression and Anxiety and the Netherlands Study of Depression in Older Persons─including 2165 depressed and 1058 non-depressed persons. In both cohorts, separately as well as combined, there was a significant non-linear association between the risk of lifetime depression and HTT CAG repeat size in which both relatively short and relatively large alleles were associated with an increased risk of depression (β = -0.292 and β = 0.006 for the linear and the quadratic term, respectively; both P < 0.01 after adjustment for the effects of sex, age, and education level). The odds of lifetime depression were lowest in persons with a HTT CAG repeat size of 21 (odds ratio: 0.71, 95% confidence interval: 0.52 to 0.98) compared to the average odds in the total cohort. In conclusion, lifetime depression risk was higher with both relatively short and relatively large HTT CAG repeat sizes in the normal range. Our study provides important proof-of-principle that repeat polymorphisms can act as hitherto unappreciated but complex genetic modifiers of depression.

  12. Huntingtin gene repeat size variations affect risk of lifetime depression

    DEFF Research Database (Denmark)

    Gardiner, Sarah L.; van Belzen, Martine J.; Boogaard, Merel W.

    2017-01-01

    Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is frequently complicated by depression, it is still unknown to what extent common HTT CAG repeat size variations in the normal range could affect...

  13. Returning "Region" to World Regional Geography

    Science.gov (United States)

    Rees, Peter W.; Legates, Margaret

    2013-01-01

    World regional geography textbooks rarely focus on the process of region formation, despite frequent calls to reincorporate a regional approach to teaching global geography. An instructional strategy using problem-based learning in a small honors section of a large world regional geography course is described. Using a hypothetical scenario…

  14. Regional alternative transportation evaluation report - Region 4

    Science.gov (United States)

    2013-08-15

    The U.S. Fish and Wildlife Service (FWS) and the U.S. Department of Transportation (DOT) Volpe Center (Volpe Center) conducted a regional alternative transportation evaluation (RATE) in Region 4, which is comprised of Alabama, Arkansas, Florida, Geor...

  15. Regional alternative transportation evaluation report - region 2

    Science.gov (United States)

    2012-03-01

    The U.S. Fish and Wildlife Service (FWS) and the U.S. Department of Transportation (DOT) Volpe : Center (Volpe Center) conducted a regional alternative transportation evaluation (RATE) in Region 2, : which is comprised of Arizona, Oklahoma, New Mexic...

  16. Regional alternative transportation evaluation report - region 5

    Science.gov (United States)

    2011-11-14

    The U.S. Fish and Wildlife Service (FWS) and the U.S. Department of Transportation (DOT) Volpe Center (Volpe Center) conducted a regional alternative transportation evaluation (RATE) in Region 3, which is comprised of Illinois, Indiana, Iowa, Michiga...

  17. Molecular cloning of Ly-1, a membrane glycoprotein of mouse T lymphocytes and a subset of B cells: molecular homology to its human counterpart Leu-1/T1 (CD5)

    International Nuclear Information System (INIS)

    Huang, H.J.S.; Jones, N.H.; Strominger, J.L.; Herzenberg, L.A.

    1987-01-01

    The authors report the isolation of cDNA clones of the mouse lymphocyte differentiation antigen Ly-1. One of these cDNA clones was confirmed to be full-length by DNA sequencing and by expression of Ly-1 by L cells transfected with this clone. Analysis of the predicted amino acid sequence indicated that the Ly-1 polypeptide is synthesized with a 23 amino acid leader and that the mature protein consists of an amino-terminal region of 347 amino acids, a transmembrane sequence of 30 residues, and a carboxyl-terminal region of 94 amino acids. The amino-terminal region appears to be divided into two subregions by a threonine- and proline-rich sequence of 23 amino acids that is highly conserved between Ly-1 and its human homologue Leu-1 (CD5) in position and amino acid composition. The first amino-terminal subregion of 111 amino acids is predicted to be arranged in a β-pleated sheet structure of six strands. The entire amino-terminal region is rich in cysteine, with all of its 22 cysteine residues conserved between Ly-1 and Leu-1. The carboxyl-terminal region has no cysteins. Ly-1 and Leu-1 are 63% identical, with a gradient of identical residues from 43% for the first amino-terminal to 58% for the second amino-terminal subregion and 90% for the carboxyl-terminal region. The predicted secondary structure of the first amino-terminal subregion and identities of certain conserved residues among most members of the immunoglobulin gene superfamily suggest that Ly-1 and Leu-1 are distant members of this family

  18. Central Region Regionally Ecological Significant Areas

    Data.gov (United States)

    Minnesota Department of Natural Resources — This is an analysis of regionally significant Terrestrial and Wetland Ecological Areas in the seven county metropolitan area. Individual forest, grassland and...

  19. Regional alternative transportation evaluation report - region 1

    Science.gov (United States)

    2011-01-21

    The U.S. Fish and Wildlife Service (FWS) and the U.S. Department of Transportation (DOT) Volpe Center (Volpe Center) conducted a regional alternative transportation evaluation (RATE) in Region 1, which is comprised of Oregon, Idaho, Washington, and H...

  20. Regionalization: A Story Map Lesson on Regions

    Science.gov (United States)

    Edmondson, Deborah

    2018-01-01

    This lesson introduces the concept of regionalization and types of regions. After a brief introductory activity, students explore a story map to learn the material. The teacher can project the story map on a screen for all students to follow or students may work individually on computers. Working individually will allow students to set their own…

  1. HD CAG-correlated gene expression changes support a simple dominant gain of function

    Science.gov (United States)

    Jacobsen, Jessie C.; Gregory, Gillian C.; Woda, Juliana M.; Thompson, Morgan N.; Coser, Kathryn R.; Murthy, Vidya; Kohane, Isaac S.; Gusella, James F.; Seong, Ihn Sik; MacDonald, Marcy E.; Shioda, Toshi; Lee, Jong-Min

    2011-01-01

    Huntington's disease is initiated by the expression of a CAG repeat-encoded polyglutamine region in full-length huntingtin, with dominant effects that vary continuously with CAG size. The mechanism could involve a simple gain of function or a more complex gain of function coupled to a loss of function (e.g. dominant negative-graded loss of function). To distinguish these alternatives, we compared genome-wide gene expression changes correlated with CAG size across an allelic series of heterozygous CAG knock-in mouse embryonic stem (ES) cell lines (HdhQ20/7, HdhQ50/7, HdhQ91/7, HdhQ111/7), to genes differentially expressed between Hdhex4/5/ex4/5 huntingtin null and wild-type (HdhQ7/7) parental ES cells. The set of 73 genes whose expression varied continuously with CAG length had minimal overlap with the 754-member huntingtin-null gene set but the two were not completely unconnected. Rather, the 172 CAG length-correlated pathways and 238 huntingtin-null significant pathways clustered into 13 shared categories at the network level. A closer examination of the energy metabolism and the lipid/sterol/lipoprotein metabolism categories revealed that CAG length-correlated genes and huntingtin-null-altered genes either were different members of the same pathways or were in unique, but interconnected pathways. Thus, varying the polyglutamine size in full-length huntingtin produced gene expression changes that were distinct from, but related to, the effects of lack of huntingtin. These findings support a simple gain-of-function mechanism acting through a property of the full-length huntingtin protein and point to CAG-correlative approaches to discover its effects. Moreover, for therapeutic strategies based on huntingtin suppression, our data highlight processes that may be more sensitive to the disease trigger than to decreased huntingtin levels. PMID:21536587

  2. Regional Alternative Transportation Evaluation: Region 8

    Science.gov (United States)

    2016-02-28

    The U.S. Fish and Wildlife Service (FWS), Federal Lands Highway (FLH), and the U.S. Department of Transportation (DOT) Volpe Center (Volpe Center) have conducted regional alternative transportation evaluations (RATEs) in almost each of FWSs eight ...

  3. Local, Regional or Global?

    DEFF Research Database (Denmark)

    Geisler Asmussen, Christian

    to be consistent with models of internationalization that incorporate different assumptions about strategic choice and global competition. Preliminary results show that large multinationals follow home region oriented internationalization paths, although much of the regional effect reported by previous studies...

  4. COMPETITIVENESS IN REGIONAL DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    ELENA MĂDĂLINA OPRIȚESCU

    2012-12-01

    Full Text Available The development and diversification of the economic activities, the stimulation of investments both in the public sector, but mainly in the private one, the reduction of unemployment, the improvement of living standards are just some of the concepts aimed at by the regional development. The main method which can lead to a balanced development of the regions is financing them differentially so that the underdeveloped regions would obtain proportionally more funds that the developed ones. At a region level, the main objective is represented by the more accelerated growth of the less developed regions, in an effort to diminish the inter-regional and intra-regional development disparities. A key role is played by the sustainable economic growth concept, while also analyzing the competitiveness at a regional level, as well as the main development factors.

  5. REGIONAL DEVELOPMENT IN ROMANIA

    Directory of Open Access Journals (Sweden)

    Remus Gherman

    2015-10-01

    Full Text Available Regional development policy is a policy of investment for economic development by supporting competitiveness, increasing the standards of living, improving the quality of life, creating new jobs. Regions and regional development policy occupies in recent decades an increasingly important position in the list of the economic and social factors being found on the agendas of governments, both central and local authorities, of political groups and civil society. Regional development and regional development policy in Romania are present both in the economic reform and in social one. Development Regions from Romania are set up in 1998 by Law number 151 and supported by their own institutional framework. The applicability of regional development in Romania must take into account the fundamental elements of the possibilities of Regional Development, meaning the major indicators of reference for measuring the level of disparities, GDP per capita and unemployment.

  6. Drycleaner Database - Region 7

    Data.gov (United States)

    U.S. Environmental Protection Agency — THIS DATA ASSET NO LONGER ACTIVE: This is metadata documentation for the Region 7 Drycleaner Database (R7DryClnDB) which tracks all Region7 drycleaners who notify...

  7. Regional Seismic Threshold Monitoring

    National Research Council Canada - National Science Library

    Kvaerna, Tormod

    2006-01-01

    ... model to be used for predicting the travel times of regional phases. We have applied these attenuation relations to develop and assess a regional threshold monitoring scheme for selected subregions of the European Arctic...

  8. Regional inequalities in mortality.

    OpenAIRE

    Illsley, R; Le Grand, J

    1993-01-01

    STUDY OBJECTIVE--To examine the hypothesis of sustained and persistent inequalities in health between British regions and to ask how far they are a consequence of using standardised mortality ratios as the tool of measurement. DESIGN, SETTING AND PARTICIPANTS--Data are regional, age specific death rates at seven points in time from 1931 to 1987-89 for the British regions, reconstructed to make them comparable with the 1981 regional definitions. Log variance is used to measure inequality; regi...

  9. Regional manpower planning

    OpenAIRE

    G. Erens; P. Salamink; C.A. Van der Merwe CA

    2003-01-01

    Particular problems come to the fore when planning development at the regional level. These range from the complexities of the multifarious interactions between the sect oral and local components of the region to the necessity of achieving extensive participation of regional stakeholders in the planning process. In this paper a methodology for regional manpower planning is proposed. The methodology is designed to accommodate the full range of problems by applying a systems approach which is b...

  10. HRM: HII Region Models

    Science.gov (United States)

    Wenger, Trey V.; Kepley, Amanda K.; Balser, Dana S.

    2017-07-01

    HII Region Models fits HII region models to observed radio recombination line and radio continuum data. The algorithm includes the calculations of departure coefficients to correct for non-LTE effects. HII Region Models has been used to model star formation in the nucleus of IC 342.

  11. Constructing Regional advantage

    DEFF Research Database (Denmark)

    Asheim, Bjørn T.; Boschma, Ron; Cooke, Phil

    2011-01-01

    This paper presents a regional innovation policy model based on the idea of constructing regional advantage. This policy model brings together concepts like related variety, knowledge bases and policy platforms. Related variety attaches importance to knowledge spillovers across complementary...... economic development within and between regions in action lines appropriate to incorporate the basic principles behind related variety and differentiated knowledge bases....

  12. Regional Economic Development

    Science.gov (United States)

    ; Sponsored Work Regional Economic Development Technology Opportunities User Facilities About Us Metrics In the News Publications Policies Feynman Center » Deploying Innovation » Regional Economic Development Regional Economic Development Supporting companies in every stage of development through access to

  13. The zitterbewegung region

    Science.gov (United States)

    Sidharth, B. G.; Das, Abhishek

    2017-07-01

    This paper deals with a precise description of the region of zitterbewegung below the Compton scale and the stochastic nature associated with it. We endeavor to delineate this particular region by means of Ito’s calculus and instigate certain features that are in sharp contrast with conventional physics. Interestingly, our work substantiates that the zitterbewegung region represents a pre-space-time region and from therein emerges the notion of our conventional space-time. Interestingly, this unique region engenders the relativistic and quantum mechanical aspects of space-time.

  14. Entrepreneurship and regional development

    DEFF Research Database (Denmark)

    Müller, Sabine

    This literature review examines how entrepreneurship and regional development has been previously addressed theoretically and empirically. Regional Science and Entrepreneurship are two fields with their own distinct literature's. The question is therefore, how do these two fields talk about...... the respective other? What are the commonalities and differences? The purpose of this article is to create an analytical synthesis by combining the insights of the two literature's in order to gain a fuller understanding of the relation between entrepreneurship and regional development....

  15. Regional Innovation Clusters

    Data.gov (United States)

    Small Business Administration — The Regional Innovation Clusters serve a diverse group of sectors and geographies. Three of the initial pilot clusters, termed Advanced Defense Technology clusters,...

  16. Border region studies

    DEFF Research Database (Denmark)

    Makkonen, Teemu; Williams, Allan

    2016-01-01

    The contemporary conditions of academic capitalism exert pressures on researchers to avoid ‘peripheral’ journals and ‘unfashionable’ topics. Here an attempt is made to shed light onto the structure of one such ‘offbeat’ field, namely ‘border region studies’, by discussing its geographical...... distribution, key themes, significance and impact. The review suggests that border region studies can be considered a significant and important ‘branch’ of regional studies, which accounts for a small but increasing proportion of regional studies research particularly in Europe and North America. Four main...

  17. Regional Redistribution and Migration

    DEFF Research Database (Denmark)

    Manasse, Paolo; Schultz, Christian

    We study a model with free migration between a rich and a poor region. Since there is congestion, the rich region has an incentive to give the poor region a transfer in order to reduce immigration. Faced with free migration, the rich region voluntarily chooses a transfer, which turns out...... to be equal to that a social planner would choose. Provided migration occurs in equilibrium, this conclusion holds even in the presence of moderate mobility costs. However, large migration costs will lead to suboptimal transfers in the market solution...

  18. Approaching Regional Coherence

    DEFF Research Database (Denmark)

    Vestenskov, David; Shah, Ali; Kazmi, Atia

    The report contains ideas on enhanced cooperation on both security and economy. It is a particular relevant read for regional political decision makers, institutions, private companies, and researchers that wish to gain insight into the present and future political and economic developments...... of Afghan-Pakistani relations and to the region in general. Military institutions, officers and officials facing deployment in the region as well as universities and scholars with ongoing research and programmes in the region will also benefit from output of the stabilization project that this report...

  19. Styringskapaciteten i regional arbejdsmarkedspolitik

    DEFF Research Database (Denmark)

    Hansen, Charlotte

    This book discovers the potential in regional labour market policy. It raises the question whether the regional labour market councils seek for and follows deliberative proces norms when they formulate the regional policy, and the more theoretical question about whether corporatism is compatible...... with deliberative proces norms at all. The conclusion is that if certain circumstances are fullfilled such as 1) competence to decide the policy, 2) trust from the central level and 3) an orientation towards a regional identity then there actually exists an institutional basis for deliberation....

  20. Tourism of Khmelnytskyi region

    Directory of Open Access Journals (Sweden)

    Інна Шоробура

    2017-09-01

    Full Text Available The peculiarities of tourism in Khmelnytskyi region, its priority areas, types, including cultural-educational, environmental, sportrecreative and others have been revealed in the article. The basic tasks of tourism development in the region, aimed at the formation and protection of the tourism-recreational sector, market of competitive services, attraction of maximum number of tourists to the region, etc. have been cleared out. The attention is focused on the main tourist potential of Khmelnytskyi region, including National Nature Park «Podilski Tovtry», National historical-cultural nature reserve «Kamianets», «Samchyky», Medzhybizh regional historical-ethnographic museum-fortress, sanatorium-resort facilities based on mineral waters and others. The attention is paid to the increase in income from tourism. Traditional hospitality of the population of the region, especially in rural areas, provides the possibility to combine tourists’ accommodation with the study of rural customs and traditions directly in the villages. Tourism in Khmelnytskyi region will be attractive to all tourists who want to eat healthy food, to stay outdoors and enjoy the beauty of the region. Also the article tells us about the development of other directions and familiarizes tourists with other enticements of Khmelnytskyi region using the positive brand of Kamianets-Podilskyi. All three potential areas of tourism development (historical tourism in Kamianets-Podilskyi, recreational tourism on rivers, lakes and in the forests, as well as rural tourism can be combined within the global promotion of nature and traditions of the region. It is indicated that Khmelnytskyi is a promising tourist region of Ukraine. The main problems of the region are inadequate tourism infrastructure, accommodation facilities, food and roads. The experience of the tourism cluster «Oberih» (Protective Charm proves the perspectives of agritourism. Developing these two areas together, we

  1. On Austrian regional economics

    NARCIS (Netherlands)

    Heijman, W.J.M.; Leen, A.R.

    2004-01-01

    The aim of this research note is two-fold, firstly, to clarify the growing interaction between regional science and Austrian economics and their awareness of each other. We elucidate the Austrian methodology, called praxeology, which is especially misunderstood in regional science. Secondly, we

  2. The Wealth of Regions

    DEFF Research Database (Denmark)

    Nistotskaya, Marina; Charron, Nicholas; Lapuente, Victor

    2015-01-01

    . Using original survey data on QoG from 172 regions in eighteen European Union countries, we find that regions where governments are perceived by their citizens as impartial and free from corruption have on average significantly more SMEs. We also find that in less corrupt countries the spatial...... distribution of SMEs is more even than in more corrupt countries...

  3. Forest regions of Montana

    Science.gov (United States)

    Stephen F. Arno

    1979-01-01

    In this paper, Montana is divided into eight geographic subdivisions called "forest regions," based on distributions of tree and undergrowth species and the relationship of these patterns to climate and topography. The regions serve as a geographic reference for describing patterns of forest vegetation across the State. Data on the distributions of plant...

  4. Regionalism, Devolution and Education

    Science.gov (United States)

    Bogdanor, Vernon

    1977-01-01

    Described are effects of political decentralization in the United Kingdom on political and social institutions, particularly education. The author concludes that regionalism could yield advantages of power decentralization, diversity of decision making, and educational systems which are more closely connected to regional and local traditions.…

  5. Ad Hoc Rural Regionalism

    Science.gov (United States)

    Hamin, Elisabeth M.; Marcucci, Daniel J.

    2008-01-01

    A new regionalism has been much documented and researched for metropolitan areas; this article documents that there is a new rural regionalism as well. In the United States, these groups appear most likely to emerge in areas that are challenged by outcomes characterizing globalization's effects on the rural condition: namely, exurban or…

  6. Politics, Planning and Regionalism.

    Science.gov (United States)

    Zukosky, Jerome

    The concept of regionalism identifies the issues in public affairs pertaining to a region and develops structures through which citizens can participate in the decisionmaking process. This speech describes educational decisions in the State of New York as affected by local decentralization and by concentration of power at the State level. Relevant…

  7. The Scandinavian regional model

    DEFF Research Database (Denmark)

    Torfing, Jacob; Lidström, Anders; Røiseland, Asbjørn

    2015-01-01

    This article maps how the sub-national regional levels of governance in Denmark, Norway and Sweden have changed from a high degree of institutional convergence to a pattern of institutional divergence. It analyses the similarities and differences in the changes in regional governance and discusses...

  8. Regional final energy consumptions

    International Nuclear Information System (INIS)

    2011-01-01

    This report comments the differences observed between the French regions and also between these regions and national data in terms of final energy consumption per inhabitant, per GDP unit, and per sector (housing and office building, transport, industry, agriculture). It also comments the evolutions during the last decades, identifies the most recent trends

  9. Measuring regional authority

    NARCIS (Netherlands)

    Marks, G.W.; Hooghe, E.A.E.B.; Schakel, A.H.

    2008-01-01

    This article sets out a conceptual basis for measuring regional authority and engages basic measurement issues. Regional authority is disaggregated into two domains (self-rule and shared rule) and these are operationalised in eight dimensions. The article concludes by examining the robustness of

  10. Emergence of regional clusters

    DEFF Research Database (Denmark)

    Dahl, Michael S.; Østergaard, Christian Richter; Dalum, Bent

    2010-01-01

    The literature on regional clusters has increased considerably during the last decade. The emergence and growth patterns are usually explained by such factors as unique local culture, regional capabilities, tacit knowledge or the existence of location-specific externalities (knowledge spillovers...

  11. Arkadien. Region og identitet

    DEFF Research Database (Denmark)

    Nielsen, Thomas Heine

    Oldtidens Grækenland bestod af et mylder af bystater, grupperet i regioner, og grækerne mente, at de forskellige regioners beboere havde hver deres karakteristika. Bogen undersøger dette emne nærmere i forhold til Arkadien på Peloponnes: Hvad ville det sige at være arkader? Var det et geografisk...

  12. Connecting to Regional Markets?

    DEFF Research Database (Denmark)

    Coulibaly, Souleymane; Thomsen, Lotte

    2016-01-01

    Central Asian food processors face a number of constraints when they attempt to export to the region and beyond. The Central Asian economies in focus here are landlocked, and thus lack easy access to sea transport. In addition, the region's transport network was built to reinforce the interdepend......Central Asian food processors face a number of constraints when they attempt to export to the region and beyond. The Central Asian economies in focus here are landlocked, and thus lack easy access to sea transport. In addition, the region's transport network was built to reinforce...... the interdependence of the then Soviet republics, while conflicting economic interests make cross-border cooperation difficult. Based on extensive fieldwork on infrastructure systems and firm export strategies, this paper identifies contemporary infrastructure and transportation issues within the Central Asian region...

  13. Crisis and Regional Integration

    DEFF Research Database (Denmark)

    Dosenrode, Søren

    , Tunisia, Egypt …. ), where the crisis referred to could be humanitarian, environmental, economic, political … Europe, too, has also according to mass media, been a victim of a crisis, the financial one. Could ‘crisis’ be a beginning of enhanced regional integration? This paper will try to look...... at the processes of regional integration in relation to ‘crisis’ in Africa and Europe. First, this paper will look at the concept of ‘crisis’, before it moves on to discuss ‘regional integration’ and the correlation between the two, emphasizing the approaches of neo-functionalism and federal theory....... This is the basis for two short case studies of African and European regional integration. The paper tentative answers to the question: will the crisis in Africa and Europe respectively further or block regional integration? With a ‘that depends’. But the use of Federalism theory and neo-functionalism is seen...

  14. The Regional Dimension

    DEFF Research Database (Denmark)

    Eskjær, Mikkel Fugl

    2013-01-01

    is largely dependent on regional media systems, yet the role this regional dimension plays has been largely overlooked. This article presents a comparative study of climate-change coverage in three geo-cultural regions, The Middle East, Scandinavia, and North America, and explores the link between global......Global perspectives and national approaches have dominated studies of climate-change communication, reflecting the global nature of climate change as well as the traditional research focus on national media systems. In the absence of a global public sphere, however, transnational issue attention...... climate-change communication and regional media systems. It finds that regional variations in climate-change communication carry important communicative implications concerning perceptions of climate change's relevance and urgency...

  15. Bridging regional innovation

    DEFF Research Database (Denmark)

    Hansen, Teis

    2013-01-01

    to assess the progress of integration in the regions, as well as the effect of cross-border innovation policies. Consequently, important questions are left unanswered, including the central research question of this paper: does the sudden removal of significant physical barriers directly impacts......The topics of regional innovation systems (RIS) and cross-border regions attract increasing attention, but few studies combine the themes. Further, the existing empirical studies of cross-border innovation and knowledge creation analyse one case at one point in time, thus, making it difficult...... collaboration activity in cross-border innovation systems? This paper examines regional integration in the Oresund Region over time. It deals with a specific part of the RIS, as it analyses research collaboration between actors from the Danish and Swedish sides, with a specific emphasis on the biotech industry...

  16. Die Region braucht die Kultur - die Kultur braucht die Region

    OpenAIRE

    Klemm, Ulrich

    1995-01-01

    Die Region braucht die Kultur - die Kultur braucht die Region. - In: Region in Aktion - oder: Region im Abseits? - Boxberg-Wölchingen : Eigenständige Regionalentwicklung Baden-Württemberg, 1995. - S. 25 f.

  17. Evolved H II regions

    International Nuclear Information System (INIS)

    Churchwell, E.

    1975-01-01

    A probable evolutionary sequence of H II regions based on six distinct types of observed objects is suggested. Two examples which may deviate from this idealized sequence, are discussed. Even though a size-mean density relation of H II regions can be used as a rough indication of whether a nebula is very young or evolved, it is argued that such a relation is not likely to be useful for the quantitative assignment of ages to H II regions. Evolved H II regions appear to fit into one of four structural types: rings, core-halos, smooth structures, and irregular or filamentary structures. Examples of each type are given with their derived physical parameters. The energy balance in these nebulae is considered. The mass of ionized gas in evolved H II regions is in general too large to trace the nebula back to single compact H II regions. Finally, the morphological type of the Galaxy is considered from its H II region content. 2 tables, 2 figs., 29 refs

  18. Building Regional Competencies

    DEFF Research Database (Denmark)

    Norus, Jesper

    2004-01-01

    This paper analyzes the foundations of regional knowledge and its long-term impact onthe region's companies' and how a particular knowledge has developed an ability tostay competitive within a specific technological field. The case illustrates how theCopenhagen region has been able to develop...... a dominating position in the global marketfor industrial enzymes from 1870-2004. The case of industrial enzymes shows how aregion has been able to build sustainable competitive advantages from its distinctivecompetencies. This is done through a mixture of outsourcing and in sourcing ofcompetencies, knowledge...

  19. Regional Stability & Peacebuilding

    DEFF Research Database (Denmark)

    It seems that regional decision makers during the last two decades has been unable to produce a sustainable peacebuilding plan for the region and it is questionable whether any remarkable change will occur in the near future. Some would argue that the political differences are simply too far apart...... to the process of peacebuilding, this could prove as a useful tool, and for this reason politicians, officials, and persons in general with an interest in this region will benefit from the perspectives presented here....

  20. Regional Ocean Data Assimilation

    KAUST Repository

    Edwards, Christopher A.

    2015-01-03

    This article reviews the past 15 years of developments in regional ocean data assimilation. A variety of scientific, management, and safety-related objectives motivate marine scientists to characterize many ocean environments, including coastal regions. As in weather prediction, the accurate representation of physical, chemical, and/or biological properties in the ocean is challenging. Models and observations alone provide imperfect representations of the ocean state, but together they can offer improved estimates. Variational and sequential methods are among the most widely used in regional ocean systems, and there have been exciting recent advances in ensemble and four-dimensional variational approaches. These techniques are increasingly being tested and adapted for biogeochemical applications.

  1. Regional Air Quality Data

    Data.gov (United States)

    U.S. Environmental Protection Agency — This asset provides data on regional air quality, including trace level SO2, nitric acid, ozone, carbon monoxide, and NOy; and particulate sulfate, nitrate, and...

  2. Regional Education Partners

    Science.gov (United States)

    & Development (LDRD) National Security Education Center (NSEC) Office of Science Programs Richard P Databases National Security Education Center (NSEC) Center for Nonlinear Studies Engineering Institute Scholarships STEM Education Programs Teachers (K-12) Students (K-12) Higher Education Regional Education

  3. Regional Snowfall Index (RSI)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Climatic Data Center is now producing the Regional Snowfall Index (RSI) for significant snowstorms that impact the eastern two thirds of the U.S. The...

  4. Aeromagnetic Regional Grid Data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Several regions are represented in this unique collection of earth surface measurements of magnetic field parameters and their related anomalies. The DNAG Magnetics...

  5. Region 9 Tribal Lands

    Data.gov (United States)

    U.S. Environmental Protection Agency — Dataset of all Indian Reservations in US EPA Region 9 (California, Arizona and Nevada) with some reservation border areas of adjacent states included (adjacent areas...

  6. Paediatric regional anaesthesia:

    African Journals Online (AJOL)

    induced respiratory depression. The purpose ... regional blocks are usually performed under anaesthesia or .... brachial plexus, as well as the axillary, musculo-cutaneous, ulnar, ... of their use for continuous postoperative pain management or.

  7. Regional Ocean Data Assimilation

    KAUST Repository

    Edwards, Christopher A.; Moore, Andrew M.; Hoteit, Ibrahim; Cornuelle, Bruce D.

    2015-01-01

    This article reviews the past 15 years of developments in regional ocean data assimilation. A variety of scientific, management, and safety-related objectives motivate marine scientists to characterize many ocean environments, including coastal

  8. Second region of stability

    International Nuclear Information System (INIS)

    Greene, J.M.; Chance, M.S.

    1980-10-01

    A new type of axisymmetric magnetohydrodynamic equilibrium is presented. It is characterized by a region of pressure and safety factor variation with a short scale length imposed as a perturbation. The equilibrium consistent with these profile variations can be calculated by means of an asymptotic expansion. The flexibility obtained by generating such equilibria allows for a close examination of the mechanisms that are relevant to ballooning instabilities - ideal MHD modes with large toroidal mode number. The so-called first and second regions of stability against these modes are seen well within the limits of validity of the asymptotic expansion. It appears that the modes must be localized in regions with small values of the local shear of the magnetic field. The second region of stability occurs where the local shear is large throughout the range where the magnetic field line curvature is destabilizing

  9. Regional utvikling og partnerskap

    DEFF Research Database (Denmark)

    Halkier, H.; Gjertsen, A.

    2004-01-01

    Since the beginning of the 1990s, Danish regional policy has changed dramatically. As of January 1991, all central government incentive schemes were terminated, and since then the main components of spatial economic policy have been a host of subnational initiatives and the European Structural...... in European matters as envisaged in the ?Europe of the Regions? slogan. The aim of this chapter is to examine the transformation of regional policy in Denmark from the perspective of political decentralization and Europeanization in order to establish to what extent recent changes have increased the capacity...... of Danish regions to pursue their own agendas with regard to economic development, and explore the organizational strategies pursued by varies tiers of government in this process of rapid and profound policy change. The text is divided into three parts. The following section provides a brief outline...

  10. Promoting regional mobility

    DEFF Research Database (Denmark)

    Jensen, Anne

    Pricing of transport has been part of EU's common transport policy since this gained momentum in the early 1990s. Since then, it has been closely connected to the trans-European transport network (TEN-T) and to rising demands of efficient mobility systems at a local, regional and Community scale....... Development of pricing policies is contested at Community level and has taken place in a clash between different policy rationalities. Significantly though, the effects of the pricing policies are closely related to regional mobility systems, e.g. through financing large trans-border infrastructure projects...... and establishing common technical charging systems thus changing the conditions for regional mobility. This paper explores how policies of infrastructure pricing shape new ways of governing mobility which influences trans-border, regional policy-making. The key findings are that there is a tendency to include...

  11. Southeast DIVER Regional Metadata

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — DIVER environmental data holdings are primarily comprised of datasets gathered from regional studies, site specific studies from non-NOAA entities, and NOAA...

  12. Northeast DIVER Regional Metadata

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — DIVER environmental data holdings are primarily comprised of datasets gathered from regional studies, site specific studies from non-NOAA entities, and NOAA...

  13. Regional Hearing Clerk

    Science.gov (United States)

    The Regional Hearing Clerk receives filings for proceedings under the Consolidated Rules of Practice Governing the Administrative Assessment of Civil Penalties and the Revocation/Termination or Suspension of Permits, 40 Code of Federal Regulations Part 22

  14. Regional National Cooperative Observer

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA publication dedicated to issues, news and recognition of observers in the National Weather Service Cooperative Observer program. Issues published regionally...

  15. Active regions, ch. 7

    International Nuclear Information System (INIS)

    Martres, M.J.; Bruzek, A.

    1977-01-01

    The solar Active Region is an extremely complex phenomenon comprising a large variety of features (active,region phenomena) in the photosphere, chromosphere and corona. The occurrence of the various active phenomena depends on the phase and state of evolution of the AR; their appearance depends on the radiation used for the observation. The various phenomena are described and illustrated with photographs. Several paragraphs are dedicated to magnetic classification of AR, Mt. Wilson Spot Classification, solar activity indices, and solar activity data publications

  16. RCA's regional industrial project

    International Nuclear Information System (INIS)

    Ali, A.T.

    1988-01-01

    The Regional Cooperation Agreement (RCA) for Research Development and Training Related to Nuclear Science and Technology, formulated under the auspices of the International Atomic Energy Agency (IAEA), came into force in June 1972. The overall objective of RCA is to promote technical cooperation among the developing and developed countries in the Asia Pacific region in the peaceful uses of nuclear energy and related technology. Currently, the biggest project under RCA is the Regional Project on the Industrial Applications of Isotopes and Radiation Technology for Asia and the Pacific. The project was established in 1982 for a period of five years and was completed in December 1986. The first phase of the project has generated a high degree of awareness on the industrial potential of isotopes and radiation technology throughout the region; produced a cadre of trained manpower in all areas covered by the project; identified the expertise available in the region; and developed in the region, a unique network of people and institutions involved with the utilization of isotope and radiation technology. A Phase II of the project, which cover all but one of the sub-projects under Phase I, was approved in early 1987 for another five years until 1991. (Nogami, K.)

  17. Regional boundaries study

    International Nuclear Information System (INIS)

    Zavatsky, S.; Phaneuf, P.; Topaz, D.; Ward, D.

    1978-02-01

    The NRC Office of Inspection and Enforcement (IE) has elected to evaluate the effectiveness and efficiency of its existing regional boundary alignment because of the anticipated future growth of nuclear power generating facilities and corresponding inspection requirements. This report documents a management study designed to identify, analyze, and evaluate alternative regional boundary configurations for the NRC/IE regions. Eight boundary configurations were chosen for evaluation. These configurations offered alternatives ranging from two to ten regions, and some included the concepts of subregional or satellite offices. Each alternative configuration was evaluated according to three major criteria: project workload, cost, and office location. Each major criterion included elements such as management control, program uniformity, disruption, costs, and coordination with other agencies. The conclusion reached was that regional configurations with regions of equal and relatively large workloads, combined with the concepts of subregional or satellite offices, may offer a significant benefit to the Office of Inspection and Enforcement and the Commission and are worthy of further study. A phased implementation plan, which is suitable to some configurations, may help mitigate the disruption created by realignment

  18. Nuclear power regional analysis

    International Nuclear Information System (INIS)

    Parera, María Delia

    2011-01-01

    In this study, a regional analysis of the Argentine electricity market was carried out considering the effects of regional cooperation, national and international interconnections; additionally, the possibilities of insertion of new nuclear power plants in different regions were evaluated, indicating the most suitable areas for these facilities to increase the penetration of nuclear energy in national energy matrix. The interconnection of electricity markets and natural gas due to the linkage between both energy forms was also studied. With this purpose, MESSAGE program was used (Model for Energy Supply Strategy Alternatives and their General Environmental Impacts), promoted by the International Atomic Energy Agency (IAEA). This model performs a country-level economic optimization, resulting in the minimum cost for the modelling system. Regionalization executed by the Wholesale Electricity Market Management Company (CAMMESA, by its Spanish acronym) that divides the country into eight regions. The characteristics and the needs of each region, their respective demands and supplies of electricity and natural gas, as well as existing and planned interconnections, consisting of power lines and pipelines were taken into account. According to the results obtained through the model, nuclear is a competitive option. (author) [es

  19. North American Regional Report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-11-15

    North America is an energy community fortunate to be endowed with a rich and varied resource base. It consumes about a third of the world's energy and produces about one quarter of world energy supply. North America depends on a mix of complementary energy sources that should remain competitive but not in conflict. The current supply mix varies between Canada, the United States and Mexico, but fossil fuels are dominant across the region, leaving the three member countries vulnerable to a myriad of risks associated with traditional supply sources. Energy trade between all three countries is also a major contributor to the region's economy. Thus, the impetus for collaboration across the region has grown out of the common goals of energy security and economic prosperity. The goal of the WEC regional group was to discuss avenues for advancing North American cooperation and coordination on a range of energy issues. An additional objective was to develop policy recommendations that will facilitate effective development and use of the region's energy resources. Results and recommendtaions are summarized from three forums that focused on the pertinent issues of energy trade, energy efficiency and energy diversification. The inaugural forum (Energy Trade) was held in Washington, D.C. in the fall of 2005. The following summer, the second forum (Energy Efficiency) took place in Mexico City. The third forum (Energy Diversification) was hosted in Halifax, Nova Scotia.

  20. North American Regional Report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-11-15

    North America is an energy community fortunate to be endowed with a rich and varied resource base. It consumes about a third of the world's energy and produces about one quarter of world energy supply. North America depends on a mix of complementary energy sources that should remain competitive but not in conflict. The current supply mix varies between Canada, the United States and Mexico, but fossil fuels are dominant across the region, leaving the three member countries vulnerable to a myriad of risks associated with traditional supply sources. Energy trade between all three countries is also a major contributor to the region's economy. Thus, the impetus for collaboration across the region has grown out of the common goals of energy security and economic prosperity. The goal of the WEC regional group was to discuss avenues for advancing North American cooperation and coordination on a range of energy issues. An additional objective was to develop policy recommendations that will facilitate effective development and use of the region's energy resources. Results and recommendtaions are summarized from three forums that focused on the pertinent issues of energy trade, energy efficiency and energy diversification. The inaugural forum (Energy Trade) was held in Washington, D.C. in the fall of 2005. The following summer, the second forum (Energy Efficiency) took place in Mexico City. The third forum (Energy Diversification) was hosted in Halifax, Nova Scotia.

  1. Transient regional osteoporosis

    Directory of Open Access Journals (Sweden)

    F. Trotta

    2011-09-01

    Full Text Available Transient osteoporosis of the hip and regional migratory osteoporosis are uncommon and probably underdiagnosed bone diseases characterized by pain and functional limitation mainly affecting weight-bearing joints of the lower limbs. These conditions are usually self-limiting and symptoms tend to abate within a few months without sequelae. Routine laboratory investigations are unremarkable. Middle aged men and women during the last months of pregnancy or in the immediate post-partum period are principally affected. Osteopenia with preservation of articular space and transitory edema of the bone marrow provided by magnetic resonance imaging are common to these two conditions, so they are also known by the term regional transitory osteoporosis. The appearance of bone marrow edema is not specific to regional transitory osteoporosis but can be observed in several diseases, i.e. trauma, reflex sympathetic dystrophy, avascular osteonecrosis, infections, tumors from which it must be differentiated. The etiology of this condition is unknown. Pathogenesis is still debated in particular the relationship with reflex sympathetic dystrophy, with which regional transitory osteoporosis is often identified. The purpose of the present review is to remark on the relationship between transient osteoporosis of the hip and regional migratory osteoporosis with particular attention to the bone marrow edema pattern and relative differential diagnosis.

  2. Migration and regional inequality

    DEFF Research Database (Denmark)

    Peng, Lianqing; Swider, Sarah

    2017-01-01

    Scholars studying economic inequality in China have maintained that regional inequality and economic divergence across provinces have steadily increased over the past 30 years. New studies have shown that this trend is a statistical aberration; calculations show that instead of quickly and sharply...... rising, regional inequality has actually decreased, and most recently, remained stable. Our study suggests that China’s unique migratory regime is crucial to understanding these findings. We conduct a counterfactual simulation to demonstrate how migration and remittances have mitigated income inequality...... across provinces in order to show that without these processes, we would have seen more of a rise in interprovincial income inequality. We conclude by arguing that inequality in China is still increasing, but it is changing and becoming less place-based. As regional inequality decreases, there are signs...

  3. Entrepreneurship and Regional Development:

    DEFF Research Database (Denmark)

    Müller, Sabine

    influenced by such interactions? In approaching these questions, this dissertation focuses on why entrepreneurs act (the causes of entrepreneurship, anchored in the context), how they act (the entrepreneurial practices, action, and activities), and what happens when they act (the outcomes and impact...... of entrepreneurship). This study sets out to obtain an in-depth understanding of the micro-, community-, and regional-level localized entrepreneurial processes as well as the way in which these processes are intertwined with the spatial context. The contribution of this dissertation lies in the illustration of how......, culture, history, and natural resources. The insights of this thesis are believed to be vital for understanding why certain types of local entrepreneurship prevail in certain regions. This can further our knowledge of how to foster and enable entrepreneurship in lagging regions. In addition, this study...

  4. GRTgaz and the regions

    International Nuclear Information System (INIS)

    2017-01-01

    GRTgaz is a European leader in natural gas transmission, a world expert in gas transmission networks and systems, and an operator firmly committed to the energy transition. It owns and operates the gas transmission network throughout most of France and it manages the transmission network in Germany, thereby helping to ensure correct operation of the French and European gas market. It contributes to the energy security of regional supply systems and performs a public service mission to ensure the continuity of consumer supply. This document presents the regional activities of GRTgaz in France in the form of 12 regional fact sheets summarizing the key data by the end of 2016: network structure, financial indicators (investments, orders), public and industrial gas consumptions, 2017 projects, institutional and environmental partnerships

  5. Northeast Regional Biomass Program

    Energy Technology Data Exchange (ETDEWEB)

    O' Connell, R.A.

    1991-11-01

    The management structure and program objectives for the Northeast Regional Biomass Program (NRBP) remain unchanged from previous years. Additional funding was provided by the Bonneville Power Administration Regional Biomass Program to continue the publication of articles in the Biologue. The Western Area Power Administration and the Council of Great Lakes Governors funded the project Characterization of Emissions from Burning Woodwaste''. A grant for the ninth year was received from DOE. The Northeast Regional Biomass Steering Committee selected the following four projects for funding for the next fiscal year. (1) Wood Waste Utilization Conference, (2) Performance Evaluation of Wood Systems in Commercial Facilities, (3) Wood Energy Market Utilization Training, (4) Update of the Facility Directory.

  6. Northeast Regional Biomass Program

    International Nuclear Information System (INIS)

    O'Connell, R.A.

    1991-11-01

    The management structure and program objectives for the Northeast Regional Biomass Program (NRBP) remain unchanged from previous years. Additional funding was provided by the Bonneville Power Administration Regional Biomass Program to continue the publication of articles in the Biologue. The Western Area Power Administration and the Council of Great Lakes Governors funded the project ''Characterization of Emissions from Burning Woodwaste''. A grant for the ninth year was received from DOE. The Northeast Regional Biomass Steering Committee selected the following four projects for funding for the next fiscal year. (1) Wood Waste Utilization Conference, (2) Performance Evaluation of Wood Systems in Commercial Facilities, (3) Wood Energy Market Utilization Training, (4) Update of the Facility Directory

  7. ASEAN : Extra-Regional Cooperation Triggers Regional Integration

    NARCIS (Netherlands)

    Krapohl, S.; Krapohl, S.

    2017-01-01

    This chapter contains two case studies of regional cooperation within Southeast Asia. The network analysis of ASEAN demonstrates that the region is dependent on extra-regional trade with the EU and the USA, but also with China and Japan. However, the region is not dominated by a single regional

  8. Regional Resource Planning Study

    International Nuclear Information System (INIS)

    2001-01-01

    Natural gas and electricity commodities are among the most volatile commodities in the world. Spurred on by the recent significant increases in the price of natural gas, the BC Utilities Commission initiated an investigation into factors impacting on natural gas prices, and the validity of the Sumas index (a market trading point, or interchange where multiple pipelines interconnect, allowing the purchase and sale of gas among market participants) as a price setting mechanism. The Commission also sought the opinions and perspectives of the the province's natural gas industry regarding the high volatility of the Sumas gas prices, and as to what could be done to alleviate the wild fluctuations. Following review of the responses from stakeholders, the Commission issued a directive to BC Gas to undertake discussions on regional resource planning with full representation from all stakeholders. This study is the result of the Commission's directive, and is intended to address the issues contained in the directives. Accordingly, the study examined gas demand in the region, demand growth, including power generation, natural gas resource balance in the region, the California impacts on demand and on supply to the region, supply shortfalls on a peak day, and on a seasonal and annual basis, near term remedies, possible resource additions in the longer term, the economic justification for adding major resources and proposed actions to develop needed resource additions. The study confirmed the existence of a growing capacity deficit, which limits the supply of natural gas to the region. Near term options to alleviate the regional capacity deficit were found to be limited to discouraging power generation from serving export markets, demand side management efforts, and expansion of the WEI's systems by 105 mmcf/d. Longer term solutions would involve larger scale expansion of WEI's T-South capacity, the BC Gas' Inland Pacific Connector Project and the Washington Lateral proposed by

  9. From corridor to region

    DEFF Research Database (Denmark)

    Jensen, Anne; Jespersen, Per Homann

    2006-01-01

    The corridor between Oslo and Berlin is by the politicians of the regional authorities in the Scandinavian part of the corridor seen a region with unique qualities and a large innovation and growth potential. In order to explore and develop this potential an In-terreg project has been launched...... this task by applying principles of participative planning and with action research methodology are involving stakeholders in the process of defining, developing and disseminating the idea of the Corridor of Innovation and Cooperation - COINCO....

  10. Cold regions isotope applications

    International Nuclear Information System (INIS)

    Perrigo, L.D.; Divine, T.E.

    1976-04-01

    Pacific Northwest Laboratories (PNL) started the Cold Regions Isotope Applications Program in FY-1975 to identify special conditions in the Arctic and similar geographic areas (Cold Regions) where radioisotope power, heater, or sterilization systems would be desirable and economically viable. Significant progress was made in the first year of this program and all objectives for this initial 12-month period were achieved. The major conclusions and recommendations resulting for this effort are described below. The areas of interest covered include: radiosterilization of sewage; heating of septic tanks; and radioisotope thermoelectric generators as power sources for meteorological instruments and navigational aids

  11. Regional Governance Matters

    DEFF Research Database (Denmark)

    Charron, Nicholas; Dijkstra, Lewis; Lapuente, Victor

    2014-01-01

    study presents novel data (European QoG Index – EQI) on the ‘quality of government’ (QoG) – understood as low corruption, impartial public services and rule of law – for national and sub-national levels in twenty-seven European Union countries. The EQI shows notable within-country variations: while...... high-performing regions in Italy and Spain (for example, Bolzano, País Vasco) rank amongst the best European Union regions, others perform well below the European Union average. The index is highly correlated with sub-national levels of socio-economic development and levels of social trust, yet...

  12. REGIONAL DEVELOPMENT STRATEGY

    Directory of Open Access Journals (Sweden)

    Vaduva Maria

    2011-01-01

    Full Text Available Regional development policies in the EU Member States have included tools whoseimportance varied from one country to another. Can be identified by negative incentives forregional development policy towards location in crowded areas or control over the location,the reallocation of economic activities in national territory, creation of adequateinfrastructure, measures to enhance development, financial incentives granted toenterprises. Sustainable business development, rehabilitation of social infrastructure,including social housing and improved social services. Improved regional and localtransportation are key areas of intervention rehabilitation and upgrading of county roads,city streets, including road construction and rehabilitation of belt.

  13. Eastern Baltic Sea Region

    DEFF Research Database (Denmark)

    Jakobsen, Johnny Grandjean Gøgsig

    2016-01-01

    Kort over den østlige Østersøregion i middelalderen med angivelse af lokaliteter omtalt i antologien, placeret på s.8 i bogen "Church and Belief in the Middle Ages", red. Kirsi Salonen & Sari Katajala-Peltomaa (Amsterdam, 2016).......Kort over den østlige Østersøregion i middelalderen med angivelse af lokaliteter omtalt i antologien, placeret på s.8 i bogen "Church and Belief in the Middle Ages", red. Kirsi Salonen & Sari Katajala-Peltomaa (Amsterdam, 2016)....

  14. Voksenuddannelse og regional udvikling

    DEFF Research Database (Denmark)

    Rasmussen, Palle

    2008-01-01

    Med udgangspunkt i regionale og lokale forskelle uddannelsesforskelle behandler artiklen uddannelsers rolle i regional udvikling. Der lægges særlig vægt på forskellige former for voksenuddannelse. Hvad betyder udviklingen mod vidensamfundet for udviklingen i erhverv, beskæftigelse og sociale...... forhold? Hvilken rolle spiller uddannelse i centerområder og udkantsområder? Hvordan kan uddannelse og læring bidrage til regional udvikling? Hvilke roller kan voksenuddannelse have i denne sammenhæng?...

  15. AFRA: Supporting regional cooperation

    International Nuclear Information System (INIS)

    2016-01-01

    The African Regional Cooperative Agreement for Research, Development and Training Related to Nuclear Science and Technology (AFRA) provides a framework for African Member States to intensify their collaboration through programmes and projects focused on the specific shared needs of its members. It is a formal intergovernmental agreement which entered into force in 1990. In the context of AFRA, Regional Designated Centres for training and education in radiation protection (RDCs) are established African institutions able to provide services, such as training of highly qualified specialists or instructors needed at the national level and also to facilitate exchange of experience and information through networks of services operating in the field

  16. Regional Geography is Dead. Long Live Regional Geography!

    Czech Academy of Sciences Publication Activity Database

    Vaishar, Antonín; Werner, M.

    2006-01-01

    Roč. 14, č. 3 (2006), s. 2-8 ISSN 1210-8812 Institutional research plan: CEZ:AV0Z30860518 Keywords : regional geography * regions * geography * methodology * Ostrava region Subject RIV: DE - Earth Magnetism, Geodesy, Geography

  17. Regionalism in Scottish Universities

    Science.gov (United States)

    Hutchison, Dougal

    1976-01-01

    It is well-known that Scottish universities are highly local institutions and that over two-fifth of Scottish university students live at home. Attempts to ascertain if this regionalism has relaxed over the past twenty years with student grant regulations, improvement in communications and the increasing affluence of today's society. (Author/RK)

  18. Regionalism. Clip and Save.

    Science.gov (United States)

    Hubbard, Guy

    2002-01-01

    Focuses on the art movement, called Regionalism, discussing the painters involved and describing the characteristics of the art movement. Provides a set of learning activities and background information on John Steuart Curry. Includes a discussion of Curry's painting, "Tornado Over Kansas," and a reproduction of the painting. (CMK)

  19. Complex Regional Pain Syndrome

    Science.gov (United States)

    Complex regional pain syndrome (CRPS) is a chronic pain condition. It causes intense pain, usually in the arms, hands, legs, or feet. It may happen ... move the affected body part The cause of CRPS is unknown. There is no specific diagnostic test. ...

  20. Global, Local, or Regional?

    DEFF Research Database (Denmark)

    Verbeke, Alain; Geisler Asmussen, Christian

    2016-01-01

    of analysis, in addition to the country-level and the global level. Regional strategy analysis requires a fundamental rethink of mainstream theories in the international strategy sphere. This rethink involves, inter alia, internalization theory, with its resource-based view and transaction cost economics...

  1. H2 region detection

    International Nuclear Information System (INIS)

    Comte, G.

    1978-01-01

    The now classical technique of detection of HII regions is by means of photography and/or interferometry through narrow-band interference filters, with a large aperture ratio of the imaging optics. It enables the detailed study of the spiral structure and the repartition of ionized gas in our Galaxy as well as in the external galaxies [fr

  2. REGIONAL CUSTOMS DIRECTORATES MANAGEMENT

    Directory of Open Access Journals (Sweden)

    CABA STEFAN

    2009-05-01

    Full Text Available The management of a regional customs directorate is analyzed. A new approach of the managerial system, in the European integration context, is presented. The customs system is one of the first “doors” to a new economic, social and cultural community. For

  3. Modern regional innovation policy

    NARCIS (Netherlands)

    McCann, Philip; Ortega-Argiles, Raquel

    This paper analyses the evolution of regional innovation policy into the mainstream of public policy. The paper examines the empirical and theoretical developments which have shifted much of the focus on innovation-related issues to matters of economic geography. As well as academic material we also

  4. Regionalizing global climate models

    NARCIS (Netherlands)

    Pitman, A.J.; Arneth, A.; Ganzeveld, L.N.

    2012-01-01

    Global climate models simulate the Earth's climate impressively at scales of continents and greater. At these scales, large-scale dynamics and physics largely define the climate. At spatial scales relevant to policy makers, and to impacts and adaptation, many other processes may affect regional and

  5. Aid for regional development

    Directory of Open Access Journals (Sweden)

    Ion POPESCU

    2011-06-01

    Full Text Available The issue of regional development has captured the attention of researchers long UMA, but some trends in contemporary economy and international division of labor, cooperation, integration and globalization bring it back to the forefront of current theoretical and methodological concerns. Especially the process of European integration requires comprehensive and pragmatic approach, realistic subject (2, 3, 4.

  6. Regional anaesthesia in obstetrics.

    Science.gov (United States)

    Pedersen, H; Finster, M

    1984-01-01

    This review includes a brief discussion of the indications and pitfalls of regional anaesthetic techniques commonly used during parturition. Emphasis is given to the physiological changes of pregnancy and the potential effects on the fetus. The criteria for the choice of local anaesthetic are also presented.

  7. Venus - Phoebe Region

    Science.gov (United States)

    1990-01-01

    This Magellan radar image is of part of the Phoebe region of Venus. It is a mosaic of parts of revolutions 146 and 147 acquired in the first radar test on Aug. 16, 1990. The area in the image is located at 291 degrees east longitude, 19 degrees south latitude. The image shows an area 30 kilometers (19.6 miles) wide and 76 km (47 miles) long. On the basis of Pioneer Venus and Arecibo data, it is known that two major rift zones occur in southern Phoebe Regio and that they terminate at about 20 to 25 degrees south latitude, about 2,000 km (1,240 miles) apart. This image is of an area just north of the southern end of the western rift zone. The region is characterized by a complex geologic history involving both volcanism and faulting. Several of the geologic units show distinctive overlapping or cross cutting relationships that permit identification and separation of geologic events and construction of the geologic history of the region. The oldest rocks in this image form the complexly deformed and faulted, radar bright, hilly terrain in the northern half. Faults of a variety of orientations are observed. A narrow fault trough (about one-half to one km (three tenths to six tenths of a mile) wide is seen crossing the bright hills near the lower part in the middle of the image. This is one of the youngest faults in the faulted, hilly unit as it is seen to cut across many other structures. The fault trough in turn appears to be embayed and flooded by the darker plains that appear in the south half of the image. These plains are interpreted to be of volcanic origin. The dark plains may be formed of a complex of overlapping volcanic flows. For example, the somewhat darker region of plains in the lower left (southwest) corner of the image may be a different age series of plains forming volcanic lava flows. Finally, the narrow bright line crossing the image in its lower part is interpreted to be a fault which cross cuts both plains units and is thus the youngest event in

  8. Regional planning without means - search for regional leadership

    DEFF Research Database (Denmark)

    Groth, Niels Boje; Fertner, Christian

    and stakeholders, not least due to its polycentric urban structure with several medium-sized towns. Besides the regional authority and the regions 22 municipalities, sub-regional collaboration is gaining momentum. Furthermore, different fora, councils and associations are engaging in regional issues. However......, collaboration is often focused on specific sectors or sub-regions, while the joint development of the region is left behind. The regional authority has changed its focus from planning to the provision of knowledge, suitable to kick-off joint action with regional stakeholders, while municipalities keep focus...... on their own territories, eventually in the context of one of the new sub-regional collaborations. Based on an empirical analysis of the regional interplay in Southern Denmark and results from the ESPON ReSSI project, we go through these new settings of regional collaboration in the search for new forms...

  9. Immunization with Tc52 or its amino terminal domain adjuvanted with c-di-AMP induces Th17+Th1 specific immune responses and confers protection against Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Marina N Matos

    2017-02-01

    Full Text Available The development of new adjuvants enables fine modulation of the elicited immune responses. Ideally, the use of one or more adjuvants should result in the induction of a protective immune response against the specific pathogen. We have evaluated the immune response and protection against Trypanosoma cruzi infection in mice vaccinated with recombinant Tc52 or its N- and C-terminal domains (NTc52 and CTc52 adjuvanted either with the STING (Stimulator of Interferon Genes agonist cyclic di-AMP (c-di-AMP, a pegylated derivative of α-galactosylceramide (αGC-PEG, or oligodeoxynucleotides containing unmethylated CpG motifs (ODN-CpG. All groups immunized with the recombinant proteins plus adjuvant: Tc52+c-di-AMP, NTc52+c-di-AMP, CTc52+c-di-AMP, NTc52+c-di-AMP+αGC-PEG, NTc52+CpG, developed significantly higher anti-Tc52 IgG titers than controls. Groups immunized with c-di-AMP and Tc52, NTc52 or CTc52 showed the highest Tc52-specific IgA titers in nasal lavages. All groups immunized with the recombinant proteins plus adjuvant developed a strong specific cellular immune response in splenocytes and lymph node cells with significant differences for groups immunized with c-di-AMP and Tc52, NTc52 or CTc52. These groups also showed high levels of Tc52-specific IL-17 and IFN-γ producing cells, while NTc52+CpG group only showed significant difference with control in IFN-γ producing cells. Groups immunized with c-di-AMP and Tc52, NTc52 or CTc52 developed predominantly a Th17 and Th1immune response, whereas for NTc52+CpG it was a dominant Th1 response. It was previously described that αGC-PEG inhibits Th17 differentiation by activating NKT cells. Thus, in this work we have also included a group immunized with both adjuvants (NTc52+c-di-AMP+αGC-PEG with the aim to modulate the Th17 response induced by c-di-AMP. This group showed a significant reduction in the number of Tc52-specific IL-17 producing splenocytes, as compared to the group NTc52+c-di-AMP, which has in turn correlated with a reduction in protection against infection. These results suggest that the Th17 immune response developed after immunizing with NTc52+c-di-AMP could have a protective role against T. cruzi infection. Groups NTc52+c-di-AMP, Tc52+c-di-AMP and NTc52PB, were the ones that showed better protection against infection with lower parasitemia and weight loss, and higher survival.

  10. Comparison of copeptin, B-type natriuretic peptide, and amino-terminal pro-B-type natriuretic peptide in patients with chronic heart failure: prediction of death at different stages of the disease.

    Science.gov (United States)

    Neuhold, Stephanie; Huelsmann, Martin; Strunk, Guido; Stoiser, Brigitte; Struck, Joachim; Morgenthaler, Nils G; Bergmann, Andreas; Moertl, Deddo; Berger, Rudolf; Pacher, Richard

    2008-07-22

    This study sought to evaluate the predictive value of copeptin over the entire spectrum of heart failure (HF) and compare it to the current benchmark markers, B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Vasopressin has been shown to increase with the severity of chronic HF. Copeptin is a fragment of pre-pro-vasopressin that is synthesized and secreted in equimolar amounts to vasopressin. Both hormones have a short lifetime in vivo, similar to BNPs, but in contrast to vasopressin, copeptin is very stable in vitro. The predictive value of copeptin has been shown in advanced HF, where it was superior to BNP for predicting 24-month mortality. This was a long-term observational study in 786 HF patients from the whole spectrum of heart failure (New York Heart Association [NYHA] functional class I to IV, BNP 688 +/- 948 pg/ml [range 3 to 8,536 pg/ml], left ventricular ejection fraction 25 +/- 10% [range 5% to 65%]). The NYHA functional class was the most potent single predictor of 24-month outcome in a stepwise Cox regression model. The BNP, copeptin, and glomerular filtration rate were related to NYHA functional class (p linked to excess mortality, and this link is maintained irrespective of the clinical signs of severity of the disease. Copeptin was superior to BNP or NT-proBNP in this study, but the markers seem to be closely related.

  11. Human adenovirus serotype 12 virion precursors pMu and pVI are cleaved at amino-terminal and carboxy-terminal sites that conform to the adenovirus 2 endoproteinase cleavage consensus sequence.

    Science.gov (United States)

    Freimuth, P; Anderson, C W

    1993-03-01

    The sequence of a 1158-base pair fragment of the human adenovirus serotype 12 (Ad12) genome was determined. This segment encodes the precursors for virion components Mu and VI. Both Ad12 precursors contain two sequences that conform to a consensus sequence motif for cleavage by the endoproteinase of adenovirus 2 (Ad2). Analysis of the amino terminus of VI and of the peptide fragments found in Ad12 virions demonstrated that these sites are cleaved during Ad12 maturation. This observation suggests that the recognition motif for adenovirus endoproteinases is highly conserved among human serotypes. The adenovirus 2 endoproteinase polypeptide requires additional co-factors for activity (C. W. Anderson, Protein Expression Purif., 1993, 4, 8-15). Synthetic Ad12 or Ad2 pVI carboxy-terminal peptides each permitted efficient cleavage of an artificial endoproteinase substrate by recombinant Ad2 endoproteinase polypeptide.

  12. Retrospective study on prognostic importance of serum procalcitonin and amino - terminal pro - brain natriuretic peptide levels as compared to Acute Physiology and Chronic Health Evaluation IV Score on Intensive Care Unit admission, in a mixed Intensive Care Unit population

    Directory of Open Access Journals (Sweden)

    Chitra Mehta

    2016-01-01

    Full Text Available Background: Timely decision making in Intensive Care Unit (ICU is very essential to improve the outcome of critically sick patients. Conventional scores like Acute Physiology and Chronic Health Evaluation (APACHE IV are quite cumbersome with calculations and take minimum 24 hours. Procalcitonin has shown to have prognostic value in ICU/Emergency department (ED in disease states like pneumonia, sepsis etc. NTproBNP has demonstrated excellent diagnostic and prognostic importance in cardiac diseases. It has also been found elevated in non-cardiac diseases. We chose to study the prognostic utility of these markers on ICU admission. Settings and Design: Retrospective observational study. Materials and Methods: A Retrospective analysis of 100 eligible patients was done who had undergone PCT and NTproBNP measurements on ICU admission. Their correlations with all cause mortality, length of hospital stay, need for ventilator support, need for vasopressors were performed. Results: Among 100 randomly selected ICU patients, 28 were non-survivors. NTproBNP values on admission significantly correlated with all cause mortality (P = 0.036, AUC = 0.643 and morbidity (P = 0.000, AUC = 0.763, comparable to that of APACHE-IV score. PCT values on admission did not show significant association with mortality, but correlated well with morbidity and prolonged hospital length of stay (AUC = 0.616, P = 0.045. Conclusion: The current study demonstrated a good predictive value of NTproBNP, in terms of mortality and morbidity comparable to that of APACHE-IV score. Procalcitonin, however, was found to have doubtful prognostic importance. These findings need to be confirmed in a prospective larger study.

  13. Value of Combining Left Atrial Diameter and Amino-terminal Pro-brain Natriuretic Peptide to the CHA2DS2-VASc Score for Predicting Stroke and Death in Patients with Sick Sinus Syndrome after Pacemaker Implantation

    Directory of Open Access Journals (Sweden)

    Bin-Feng Mo

    2017-01-01

    Conclusions: CHA2DS2-VASc score is valuable for predicting stroke and death risk in patients with SSS after pacemaker implantation. The addition of LAD and NT-proBNP to the CHA2DS2-VASc score improved its predictive power for stroke and death, respectively, in this patient cohort. Future prospective studies are warranted to validate the benefit of adding LAD and NT-proBNP to the CHA2DS2-VASc score for predicting stroke and death risk in non-AF populations.

  14. Midwest regional management plan

    International Nuclear Information System (INIS)

    Paton, R.F.

    1986-01-01

    In response to the Low-Level Radioactive Waste Policy Act of 1980, the States of Indiana, Iowa, Michigan, Minnesota, Missouri, Ohio and Wisconsin formed the Midwest Interstate Low-Level Radioactive Waste Compact. One of the top priorities of the Compact Commission is the development of a comprehensive regional waste management plan. The plan consists of five major elements: (1) waste inventory; (2) waste stream projections; (3) analysis of waste management and disposal options; (4) development of a regional waste management system; and (5) selection of a host state(s) for future low-level waste facilities. When completed, the Midwest Management Plan will serve as the framework for future low-level radioactive waste management and disposal decisions

  15. A region in turbulence

    International Nuclear Information System (INIS)

    Proulx, M.U.; Nicolet, R.; Dufour, J.

    1998-01-01

    On July 19 and 20 of 1996, torrential rains provoked catastrophic floods in the Saguenay Region of Quebec. The overflowing waters of the region's rivers damaged 3000 residential buildings, completely destroyed another 426, and seriously affected the activities of 850 business establishments. In this comprehensive report, the physical causes and the social, economic, psychological, cultural, political and administrative consequences of this natural catastrophe are discussed by several experts. The report is divided into three parts. The first part describes the actual flooding conditions and the immediate response of local emergency services such as the Red Cross and the Saint-Vincent-de-Paul agencies. Reactions of the various public agencies and governments to the disaster are described in Part Two. Part Three of the document focuses on lessons to be drawn from this natural disaster, in particular the need to improve emergency relief strategies. The legal implications and consequences of the disaster are also discussed. refs., tabs., figs

  16. Banks, regions and development

    Directory of Open Access Journals (Sweden)

    Pietro Alessandrini

    2003-03-01

    Full Text Available From the 1980s onwards the banking sectors in all the industrialised countries have been experiencing intense restructuring, aggregation and consolidation, radically changing their ownership structures and geography. Whatever the reasons behind such restructuring processes, the globalisation of the credit markets, the consolidation of banking structures, the removal of barriers to the free location of banks and their penetration of peripheral markets pose two main questions. Will integration of the banking systems lead to a narrowing or a widening of the development gap between regions? What relations will there be between financial centres and the periphery, and how will financial labour be divided between national (international banks and local (regional banks? The aim of this paper is to address such questions in the light of recent developments in the theoretical and empirical literature on financial integration.

  17. Entropy region and convolution

    Czech Academy of Sciences Publication Activity Database

    Matúš, František; Csirmaz, L.

    2016-01-01

    Roč. 62, č. 11 (2016), s. 6007-6018 ISSN 0018-9448 R&D Projects: GA ČR GA13-20012S Institutional support: RVO:67985556 Keywords : entropy region * information-theoretic inequality * polymatroid Subject RIV: BD - Theory of Information Impact factor: 2.679, year: 2016 http://library.utia.cas.cz/separaty/2016/MTR/matus-0465564.pdf

  18. Disarmament through regional dialogue

    International Nuclear Information System (INIS)

    Kono, Yuhei

    1994-01-01

    The role played by the United Nations in the pursuit of peace and disarmament and in support of the construction of a stable order in the region is very great. The attitude of Japan as a 'peace loving state' shown by its support to Non-proliferation is expressed by its high appreciation of the fact that this Second United Nations Conference in Hiroshima has been convened, as such exchanges of views constitute an important aspect of the process of disarmament

  19. Regional Renewable Energy Cooperatives

    Science.gov (United States)

    Hazendonk, P.; Brown, M. B.; Byrne, J. M.; Harrison, T.; Mueller, R.; Peacock, K.; Usher, J.; Yalamova, R.; Kroebel, R.; Larsen, J.; McNaughton, R.

    2014-12-01

    We are building a multidisciplinary research program linking researchers in agriculture, business, earth science, engineering, humanities and social science. Our goal is to match renewable energy supply and reformed energy demands. The program will be focused on (i) understanding and modifying energy demand, (ii) design and implementation of diverse renewable energy networks. Geomatics technology will be used to map existing energy and waste flows on a neighbourhood, municipal, and regional level. Optimal sites and combinations of sites for solar and wind electrical generation (ridges, rooftops, valley walls) will be identified. Geomatics based site and grid analyses will identify best locations for energy production based on efficient production and connectivity to regional grids and transportation. Design of networks for utilization of waste streams of heat, water, animal and human waste for energy production will be investigated. Agriculture, cities and industry produce many waste streams that are not well utilized. Therefore, establishing a renewable energy resource mapping and planning program for electrical generation, waste heat and energy recovery, biomass collection, and biochar, biodiesel and syngas production is critical to regional energy optimization. Electrical storage and demand management are two priorities that will be investigated. Regional scale cooperatives may use electric vehicle batteries and innovations such as pump storage and concentrated solar molten salt heat storage for steam turbine electrical generation. Energy demand management is poorly explored in Canada and elsewhere - our homes and businesses operate on an unrestricted demand. Simple monitoring and energy demand-ranking software can easily reduce peaks demands and move lower ranked uses to non-peak periods, thereby reducing the grid size needed to meet peak demands. Peak demand strains the current energy grid capacity and often requires demand balancing projects and

  20. Cleantech Region Stedendriehoek

    NARCIS (Netherlands)

    Heidema, A. (Andries)

    2016-01-01

      http://dx.doi.org/10.14261/postit/B1917A51-5AA6-4723-9EDF87AB64EC267B Keynote speech. In 2015 and 2016, Saxion University of Applied Sciences organized the 2nd and 3rd edition of the Regional Innovation and Entrepreneurship Conference (RIEC).  It just so happens that innovation and

  1. Regionalization Lessons from Denmark

    DEFF Research Database (Denmark)

    Vrangbæk, Karsten

    2016-01-01

    and coordination. Regions and municipalities in Denmark are governed by directly elected democratic councils. The Danish case is thus an example of democratic decentralization, but within a framework of national coordination and fiscal control. In spite of the difference in size and historical traditions...... there are also many similarities between Canada and Denmark, particularly in terms of health and social policy goals and aspirations, and in terms of the commitment to a comprehensive, universal healthcare system. These similarities provide interesting opportunities for comparison....

  2. Region 9 Tribal Lands

    Science.gov (United States)

    Dataset of all Indian Reservations in US EPA Region 9 (California, Arizona and Nevada) with some reservation border areas of adjacent states included (adjacent areas of Colorado, New Mexico and Utah). Reservation boundaries are compiled from multiple sources and are derived from several different source scales. Information such as reservation type, primary tribe name are included with the feature dataset. Public Domain Allotments are not included in this data set.

  3. Regional greenhouse climate effects

    International Nuclear Information System (INIS)

    Hansen, J.; Rind, D.; Delgenio, A.; Lacis, A.; Lebedeff, S.; Prather, M.; Ruedy, R.; Karl, T.

    1990-01-01

    The authors discuss the impact of an increasing greenhouse effect on three aspects of regional climate: droughts, storms and temperature. A continuous of current growth rates of greenhouse gases causes an increase in the frequency and severity of droughts in their climate model simulations, with the greatest impacts in broad regions of the subtropics and middle latitudes. But the greenhouse effect enhances both ends of the hydrologic cycle in the model, that is, there is an increased frequency of extreme wet situations, as well as increased drought. Model results are shown to imply that increased greenhouse warming will lead to more intense thunderstorms, that is, deeper thunderstorms with greater rainfall. Emanual has shown that the model results also imply that the greenhouse warming leads to more destructive tropical cyclones. The authors present updated records of observed temperatures and show that the observations and model results, averaged over the globe and over the US, are generally consistent. The impacts of simulated climate changes on droughts, storms and temperature provide no evidence that there will be regional winners if greenhouse gases continue to increase rapidly

  4. SERVICES AND REGIONAL DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Sven ILLERIS

    2009-12-01

    Full Text Available The purpose of this contribution is to discuss what roles the different economic sectors, and in particular services activities (the tertiary sector play in regional development, understood as growth in production, incomes and employment in weakly developedregions. This question is approached in two ways. The contribution first contains a – primarily theoretical – re-examination of the so-called economic base model, which states that services play a passive role in regional development. The discussion leads to substantial modifications of the model. The second approach is more empirical. It will take as its point of departure the proposition – often heard, but rarely examined – that since service activities are more concentrated in big cities than other activities and in recent decades have shown higher growth rates than other economic activities, it follows that the economic development is now pulled towards big city regions. Examined by way of a statistical analysisin Denmark and France, this proposition could not be verified.

  5. Alligator Rivers Region

    International Nuclear Information System (INIS)

    1992-01-01

    An introduction to the Alligator Rivers Region is presented. It contains general information regarding the physiography, climate, hydrology and mining of the region. The Alligator Rivers Region is within an ancient basin, the Pine Creek Geosyncline, which has an area of approximately 66000 km 2 . The Geosyncline has a history of mineral exploitation dating back to 1865, during which time 16 metals have been extracted (silver, arsenic, gold, bismuth, cadmium, cobalt, copper, iron, manganese, molybdenum, lead, tin, tantalum, uranium, tungsten, zinc). Uranium exploration in the Pine Creek Geosyncline was stimulated by the discovery in 1949 of secondary uranium mineralisation near Rum June, 70 km south-east of Darwin. This was followed by a decade of intense exploration activity resulting in the discoveries of economic uranium ore bodies at Rum Jungle and in the upper reaches of the South Alligator River Valley. All the known major uranium deposits of the East Alligator River uranium field have been discovered since 1969. The present known resources of the Geosyncline are approximately 360 000 tonnes of contained U 3 O 8 . 2 refs., 2 figs., 1 tab

  6. Andean region study

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-10-01

    New opportunities for climate change mitigation arising from a higher energy integration among Andean Pact nations were analysed within the framework of the UNEP/GEF Project. Apart from the search for regional mitigation actions, the study was mainly aimed at detecting methodological problems which arise when passing from a strictly national view to the co-ordination of regional actions to deal with climate change. In accordance with the available resources and data, and in view of the mainly methodological nature of the project, it was decided to analyse the opportunities to delve into the energy integration of the Region as regards electricity and natural gas industries and their eventual impact on the emission of greenhouse gases. Although possibilities of setting up electricity and natural gas markets are real, their impacts on GHG emission from the energy system would not prove substantially higher than those which the nations could achieve through the use of their own energy resources, in view that the Andean systems are competitive rather than complementary. More in-depth studies and detail information will be required - unavailable for the present study - to be able to properly evaluate all benefits associated with higher energy integration. Nevertheless, the supply of natural gas to Ecuador seems to be the alternative with the highest impact on GHG emission. If we were to analyse the supply and final consumption of energy jointly, we would most certainly detect additional mitigation options resulting from higher co-operation and co-ordination in the energy field. (EHS)

  7. Regional Shelter Analysis Methodology

    Energy Technology Data Exchange (ETDEWEB)

    Dillon, Michael B. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Dennison, Deborah [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Kane, Jave [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Walker, Hoyt [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Miller, Paul [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-08-01

    The fallout from a nuclear explosion has the potential to injure or kill 100,000 or more people through exposure to external gamma (fallout) radiation. Existing buildings can reduce radiation exposure by placing material between fallout particles and exposed people. Lawrence Livermore National Laboratory was tasked with developing an operationally feasible methodology that could improve fallout casualty estimates. The methodology, called a Regional Shelter Analysis, combines the fallout protection that existing buildings provide civilian populations with the distribution of people in various locations. The Regional Shelter Analysis method allows the consideration of (a) multiple building types and locations within buildings, (b) country specific estimates, (c) population posture (e.g., unwarned vs. minimally warned), and (d) the time of day (e.g., night vs. day). The protection estimates can be combined with fallout predictions (or measurements) to (a) provide a more accurate assessment of exposure and injury and (b) evaluate the effectiveness of various casualty mitigation strategies. This report describes the Regional Shelter Analysis methodology, highlights key operational aspects (including demonstrating that the methodology is compatible with current tools), illustrates how to implement the methodology, and provides suggestions for future work.

  8. A subspecies of region crossing change, region freeze crossing change

    OpenAIRE

    Inoue, Ayumu; Shimizu, Ryo

    2016-01-01

    We introduce a local move on a link diagram named a region freeze crossing change which is close to a region crossing change, but not the same. We study similarity and difference between region crossing change and region freeze crossing change.

  9. Hunting for huntingtin associated factors: Identification and characterization of huntingtin expanded polyglutamine aggregate associated factors and their impact on Huntington disease model cellular toxicity

    Science.gov (United States)

    2016-05-20

    for her assistance with the statistical analysis. Drs. Aviva Symes, Dennis McDaniel, Jeff Stinson, and Rachel Cox provided invaluable assistance...with fluorescence and confocal microscopy. The Snow lab – Dr. Andy Snow, Sasha Larsen, Dr. Gil Katz, and Dr. Jeff Stinson – provided vital support...and human genetics 11:25-44 20. Castello A, Fischer B, Eichelbaum K, Horos R, Beckmann BM, et al. 2012. Insights into RNA biology from an atlas of

  10. Hawaii Regional Sediment Management (RSM): Regional Sediment Budget for the West Maui Region

    Science.gov (United States)

    2016-06-01

    ER D C/ CH L TR -1 6- 5 Regional Sediment Management (RSM) Program Hawaii Regional Sediment Management (RSM): Regional Sediment Budget...acwc.sdp.sirsi.net/client/default. Regional Sediment Management (RSM) Program ERDC/CHL TR-16-5 June 2016 Hawaii Regional Sediment Management...distribution is unlimited. Prepared for U.S. Army Corps of Engineers Washington, DC 20314-1000 Under Project 454632, “ Hawaii Regional Sediment Management

  11. Regional Studies Program

    International Nuclear Information System (INIS)

    Parzyck, D.C.

    1978-01-01

    Progress is reported on methodology studies with regard to hydrologic analysis; atmospheric transport; forest growth models; distribution of sensitive species; agricultural analysis; and environmental objectives in energy facility siting. National coal utilization assessment studies are reported with regard to technology characterization; air quality impacts; water resources; regional characterization; forest impacts; coal extraction impacts on sensitive animal species; and health impacts. The following special projects were carried out: water resource aspects of inexhaustible technology deployment; ecological constraints on the rapidly expanded use of coal; and U.S. coal and the global carbon problem

  12. Region & Gateway Mapping

    OpenAIRE

    Schröter, Derik

    2007-01-01

    State-of-the-art robot mapping approaches are capable of acquiring impressively accurate 2D and 3D models of their environments. To the best of our knowledge, few of them represent structure or acquire models of task-relevant objects. In this work, a new approach to mapping of indoor environments is presented, in which the environment structure in terms of regions and gateways is automatically extracted, while the robot explores. Objects, both in 2D and 3D, are modeled explicitly in those map...

  13. Regional Legal Assistance

    Directory of Open Access Journals (Sweden)

    Abdul Fatah

    2015-06-01

    Full Text Available Legal aid policy in the area carried out on several considerations including: Implementation of the authority given to the legal aid act, granting the guarantee and protection of access to justice and equality before the law in the area, equitable distribution of justice and increase public awareness and understanding of the law, and legal implications that accompanied the emergence of the right to legal counsel without pay and the right to choose the legal settlement. How To Cite Fatah, A. (2015. Regional Legal Assistance. Rechtsidee, 2(1, 1-10. doi:http://dx.doi.org/10.21070/jihr.v2i1.7

  14. OECD Reviews of Regional Innovation

    DEFF Research Database (Denmark)

    Maguire, Karen; Marsan, Giulia Ajmone; Nauwelaers, Claire

    This book examines regional innovation in central and southern Denmark, looking at its role in the economy, its governance and policy context and regional strategies for innovation driven growth.......This book examines regional innovation in central and southern Denmark, looking at its role in the economy, its governance and policy context and regional strategies for innovation driven growth....

  15. Region segmentation along image sequence

    International Nuclear Information System (INIS)

    Monchal, L.; Aubry, P.

    1995-01-01

    A method to extract regions in sequence of images is proposed. Regions are not matched from one image to the following one. The result of a region segmentation is used as an initialization to segment the following and image to track the region along the sequence. The image sequence is exploited as a spatio-temporal event. (authors). 12 refs., 8 figs

  16. First peptide vaccine providing protection against viral infection in the target animal: studies of canine parvovirus in dogs.

    NARCIS (Netherlands)

    J.P.M. Langeveld; J.I. Casal; A.D.M.E. Osterhaus (Albert); E. Cortes; R.L. de Swart (Rik); C. Vela (Carmen); K. Dalsgaard (Kristian); W.C. Puijk (Wouter); W.M.M. Schaaper (Wim); R.H. Meloen

    1994-01-01

    textabstractA synthetic peptide vaccine which protects dogs against challenge with virulent canine parvovirus is described. The amino acid sequence used was discovered in previous studies on the immunogenic properties of previously mapped antigenic sites and represents the amino-terminal region of

  17. Active region structures in the transition region and corona

    International Nuclear Information System (INIS)

    Webb, D.F.

    1981-01-01

    Observational aspects of the transition region and coronal structures of the solar active region are reviewed with an emphasis on imaging of the plasma loops which act as tracers of the magnetic flux loops. The study of the basic structure of an active region is discussed in terms of the morphological and thermal classifications of active region loops, including umbral structures, and observational knowledge of the thermal structure of loops is considered in relation to scaling laws, emission measures and the structures of individual loops. The temporal evolution of active region loop structures is reviewed with emphasis on ephemeral regions and the emergence of active regions. Planned future spaceborne observations of active region loop structures in the EUV and soft X-ray regions are also indicated

  18. Regional climate change scenarios

    International Nuclear Information System (INIS)

    Somot, S.

    2005-01-01

    Because studies of the regional impact of climate change need higher spatial resolution than that obtained in standard global climate change scenarios, developing regional scenarios from models is a crucial goal for the climate modelling community. The zoom capacity of ARPEGE-Climat, the Meteo-France climate model, allows use of scenarios with a horizontal resolution of about 50 km over France and the Mediterranean basin. An IPCC-A2 scenario for the end of the 21. century in France shows higher temperatures in each season and more winter and less summer precipitation than now. Tuning the modelled statistical distributions to observed temperature and precipitation allows us to study changes in the frequency of extreme events between today's climate and that at the end of century. The frequency of very hot days in summer will increase. In particular, the frequency of days with a maximum temperature above 35 deg C will be multiplied by a factor of 10, on average. In our scenario, the Toulouse area and Provence might see one quarter of their summer days with a maximum temperature above 35 deg C. (author)

  19. Transient regional osteoporosis.

    Science.gov (United States)

    Cano-Marquina, Antonio; Tarín, Juan J; García-Pérez, Miguel-Ángel; Cano, Antonio

    2014-04-01

    Transient regional osteoporosis (TRO) is a disease that predisposes to fragility fracture in weight bearing joints of mid-life women and men. Pregnant women may also suffer the process, usually at the hip. The prevalence of TRO is lower than the systemic form, associated with postmenopause and advanced age, but may be falsely diminished by under-diagnosis. The disease may be uni- or bilateral, and may migrate to distinct joints. One main feature of TRO is spontaneous recovery. Pain and progressive limitation in the functionality of the affected joint(s) are key symptoms. In the case of the form associated with pregnancy, difficulties in diagnosis derive from the relatively young age at presentation and from the clinical overlapping with the frequent aches during gestation. Densitometric osteoporosis in the affected region is not always present, but bone marrow edema, with or without joint effusion, is detected by magnetic resonance. There are not treatment guidelines, but the association of antiresorptives to symptomatic treatment seems to be beneficial. Surgery or other orthopedic interventions can be required for specific indications, like hip fracture, intra-medullary decompression, or other. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Regional Population Projections for China

    OpenAIRE

    Toth, F.L.; Cao, G.-Y.; Hizsnyik, E.

    2003-01-01

    Considering the size and the regional diversity of China, a prudent analysis of many economic and policy issues needs to consider the regional differences in climate, soil, water, and other natural resource endowments, population density, and social and economic development. Future-oriented multi-regional assessments require regionally detailed scenarios. A key component of such scenarios is the evolution of the population in different regions. For studies of land-use change and agriculture, ...

  1. Regional Healthcare Effectiveness

    Directory of Open Access Journals (Sweden)

    Olga Vladimirovna Kudelina

    2016-03-01

    Full Text Available An evaluation of healthcare systems effectiveness of the regions of the Russian Federation (federal districts was conducted using the Minmax method based on the data available at the United Interdepartmental Statistical Information System. Four groups of components (i.e. availability of resources; use of resources; access to resources and medical effectiveness decomposed into 17 items were analyzed. The resource availability was measured by four indicators, including the provision of doctors, nurses, hospital beds; agencies providing health care to the population. Use of resources was measured by seven indicators: the average hospital stay, days; the average bed occupancy, days; the number of operations per 1 physician surgical; the cost per unit volume of medical care: in outpatient clinics, day hospitals, inpatient and emergency care. Access to the resources was measured by three indicators: the satisfaction of the population by medical care; the capacity of outpatient clinics; the average number of visits to health facility. The medical effectiveness was also measured by three indicators: incidence with the "first-ever diagnosis of malignancy"; life expectancy at birth, years; the number of days of temporary disability. The study of the dynamics of the components and indexes for 2008–2012 allows to indicate a multidirectional influence on the regional healthcare system. In some federal districts (e.g. North Caucasian, the effectiveness decreases due to resource availability, in others (South, North Caucasian — due to the use of resources, in others (Far Eastern, Ural — due to access to resources. It is found that the effectiveness of the healthcare systems of the federal districts differs significantly. In addition, the built matrix proves the variability the of effectiveness (comparison of expenditures and results of healthcare systems of the federal districts of the Russian Federation: the high results can be obtained at high costs

  2. Strengthening regional safeguards

    International Nuclear Information System (INIS)

    Palhares, L.; Almeida, G.; Mafra, O.

    1996-01-01

    Nuclear cooperation between Argentina and Brazil has been growing since the early 1980's and as it grew, so did cooperation with the US Department of Energy (DOE). The Brazilian-Argentine Agency for Accounting and Control of Nuclear Materials (ABACC) was formed in December 1991 to operate the Common System of Accounting and Control of Nuclear Materials (SCCC). In April 1994, ABACC and the DOE signed an Agreement of Cooperation in nuclear material safeguards. This cooperation has included training safeguards inspectors, exchanging nuclear material measurement and containment and surveillance technology, characterizing reference materials, and studying enrichment plant safeguards. The goal of the collaboration is to exchange technology, evaluate new technology in Latin American nuclear facilities, and strengthen regional safeguards. This paper describes the history of the cooperation, its recent activities, and future projects. The cooperation is strongly supported by all three governments: the Republics of Argentina and Brazil and the United States

  3. Regional Course: Progress Report

    International Nuclear Information System (INIS)

    Cordero Calderon, C.F.

    1995-01-01

    They chose the Arenal's Dam and its damming, which has a control established from 1978. Currently, this technique is not applied in any other work of the 'Instituto Costarricense de Electricidad'. Their interest is to apply it in similar works. Among the projects that has been accomplished, they have the sampling of different sites water, the most representative to see the quality of water, the most representative waters Ions analysis of the damming, in underground waters of the region, in the available wells and for all of the river banks about the dam. With this technique they hope to obtain some parameters to define the water sources, the underground flow dynamics, the water turbulent stream, the mixings, the movement time and the relation to the damming. (author)

  4. Regional transmission subsystem planning

    Energy Technology Data Exchange (ETDEWEB)

    Costa Bortoni, Edson da [Quadrante Softwares Especializados Ltda., Itajuba, MG (Brazil); Bajay, Sergio Valdir; Barros Correia, Paulo de [Universidade Estadual de Campinas, SP (Brazil). Faculdade de Engenharia Mecanica; Santos, Afonso Henriques Moreira; Haddad, Jamil [Escola Federal de Engenharia de Itajuba, MG (Brazil)

    1994-12-31

    This work presents an approach for the planning of transmission systems by employing mixed--integer linear programming to obtain a cost and operating characteristics optimized system. The voltage loop equations are written in a modified form, so that, at the end of the analysis, the model behaves as a DC power flow, with the help of the two Kirchhoff`s laws, exempting the need of interaction with an external power flow program for analysis of the line loading. The model considers the occurrence of contingencies, so that the final result is a network robust to the most severe contingencies. This whole technique is adapted to the regional electric power transmission subsystems. (author) 9 refs., 4 figs.

  5. Regional Sociological Research Experience

    Directory of Open Access Journals (Sweden)

    Mikhail Vladimirovich Morev

    2015-11-01

    Full Text Available The article presents the experience of the Institute of Socio-Economic Development of Territories of RAS in conducting sociological research on the territory of the Vologda Oblast and the Northwestern Federal District. It describes the historical aspects of formation of the system for public opinion monitoring and examines its theoretical and methodological foundations. The author of the article analyzes the structure of monitoring indicators and provides a brief interpretation of research findings that reflect social wellbeing and social perception trends. In addition, the paper analyzes people’s attitude toward the activities of federal and regional authorities, trends in social well-being, consumer sentiment and also the complex indicator – the index of public sentiment in the region – developed by ISEDT RAS researchers. The results of sociological studies carried out at ISEDT RAS correlate with the dynamics of the all-Russian public opinion polls conducted by the Institute of Sociology of the Russian Academy of Sciences, the Russian Public Opinion Research Center (VCIOM, Levada-Center, etc. They indicate that Russian society gradually adapts to new conditions of life after the collapse of the USSR. Besides, opinion polls show the most important features of the post-Soviet Russian history at its present stage; they are associated with the intensification of international political relations, the consequences of the “Crimean spring” and the new challenges Russia’s economy is facing now. The article concludes that as global community, of which Russian society is part, is evolving, sociological knowledge begins to play an increasingly important role in administration and national security; this is associated with the greater importance attached to intangible development factors. Therefore, a necessary prerequisite for administration effectiveness in all its stages is to implement the results of sociological research on social

  6. Landslides of Palestinian Region

    Science.gov (United States)

    Alwahsh, H.

    2013-12-01

    Natural disasters are extreme sudden events caused by environmental and natural actors that take away the lives of many thousands of people each year and damage large amount of properties. They strike anywhere on earth, often without any warning. A risk maps of natural disaster are very useful to identify the places that might be adversely affected in the event of natural disaster. The earthquakes are one of natural disaster that have the greatest hazards and will cause loss of life and properties due to damaging the structures of building, dams, bridges. In addition, it will affect local geology and soil conditions. The site effects play an important role in earthquake risk because of its amplification or damping simulation. Another parameter in developing risk map is landslide, which is also one of the most important topics in site effect hazards. Palestine region has been suffering landslide hazards because of the topographical and geological conditions of this region. Most Palestine consists of mountainous area, which has great steep slopes and the type of soil is mainly grayish to yellowish silty clay (Marl Soil). Due to the above mentioned factors many landslides have been occurred from Negev south to the northern borders of Palestine. An example of huge and destruction landslide in a Palestine authority is the landslide in the White Mountain area in the city of Nablus, which occurred in 1997. The geotechnical and geophysical investigation as well as slope stability analysis should be considered in making landslide maps that are necessary to develop risk levels of the natural disaster. Landslides occurred in slopes that are created naturally or by human beings. Failure of soil mass occurs, and hence landslide of soil mass happen due to sliding of soil mass along a plane or curved surface. In general, the slopes become unstable when the shear stresses (driving force) generated in the soil mass exceed the available shearing resistance on the rupture surface

  7. MOVES regional level sensitivity analysis

    Science.gov (United States)

    2012-01-01

    The MOVES Regional Level Sensitivity Analysis was conducted to increase understanding of the operations of the MOVES Model in regional emissions analysis and to highlight the following: : the relative sensitivity of selected MOVES Model input paramet...

  8. American Red Cross Chapter Regions

    Data.gov (United States)

    Department of Homeland Security — The Regions are part of the national field level structure to support chapters. The Regions role is admistrative as well as provides oversight and program technical...

  9. CLIMATE IMPACTS ON REGIONAL WATER

    Science.gov (United States)

    The New England region (including the 6 New Englandstates plus upstate New York) offers a very diverse geography,matched by an equally diverse economy and humanpopulation. Livelihoods throughout the region are basedon service industries that depend heavily on comm...

  10. Region Sønderjylland-Schleswig

    DEFF Research Database (Denmark)

    Klatt, Martin

    2011-01-01

    3 bidrag til leksikon over Sønderjylland: Dansk Generalsekretariat, dansk foreningsliv, Region Sønderjylland-Schleswig......3 bidrag til leksikon over Sønderjylland: Dansk Generalsekretariat, dansk foreningsliv, Region Sønderjylland-Schleswig...

  11. Regional employment growth, shocks and regional industrial resilience

    DEFF Research Database (Denmark)

    Holm, Jacob Rubæk; Østergaard, Christian Richter

    2013-01-01

    The resilience of regional industries to economic shocks has gained a lot of attention in evolutionary economic geography recently. This paper uses a novel quantitative approach to investigate the regional industrial resilience of the Danish ICT sector to the shock following the burst of the dot......-com bubble. It is shown that regions characterised by small and young ICT service companies were more adaptable and grew more than others, while diversity and urbanisation increased the sensitivity to the business cycle after the shock. Different types of resilient regions are found: adaptively resilient......, rigidly resilient, entrepreneurially resilient and non-resilient regions....

  12. Regional Employment Growth, Shocks and Regional Industrial Resilience

    DEFF Research Database (Denmark)

    Holm, J.R.; Østergaard, Christian Richter

    2015-01-01

    The resilience of regional industries to economic shocks has gained a lot of attention in evolutionary economic geography recently. This paper uses a novel quantitative approach to investigate the regional industrial resilience of the Danish information and communication technology (ICT) sector...... to the shock following the burst of the dot.com bubble. It is shown that regions characterized by small and young ICT service companies were more adaptable and grew more than others, while diversity and urbanization increased the sensitivity to the business cycle after the shock. Different types of resilient...... regions are found: adaptively resilient, rigidly resilient, entrepreneurially resilient and non-resilient regions....

  13. Regional odontodysplasia: case report

    Directory of Open Access Journals (Sweden)

    Ana Carolina Magalhães

    2007-12-01

    Full Text Available Regional odontodysplasia (RO is a rare developmental anomaly involving both mesodermal and ectodermal dental components in a group of contiguous teeth. It affects the primary and permanent dentitions in the maxilla and mandible or both jaws. Generally it is localized in only one arch. The etiology of this dental anomaly is uncertain. Clinically, affected teeth have an abnormal morphology, are soft on probing and typically discolored, yellow or yellowish-brown. Radiographically, the affected teeth show a "ghostlike" appearance. This paper reports the case of a 5-year-old girl presenting this rare anomaly on the left side of the maxillary arch, which crossed the midline. The primary maxillary left teeth (except for the canine and the primary maxillary right central incisor were missing due to previous extractions. The permanent teeth had a "ghostlike" appearance radiographically. The treatment performed was rehabilitation with temporary partial acrylic denture and periodic controls. In the future, the extraction of affected permanent teeth and rehabilitation with dental implants will be evaluated. The presentation of this case adds valuable information to pediatric dentists to review special clinical and radiographic features of RO, which will facilitate the diagnosis and treatment of patients with this condition.

  14. regional economic development

    Directory of Open Access Journals (Sweden)

    Robert J. Stimson

    2005-01-01

    Full Text Available Este artículo propone que un círculo virtuoso para el desarrollo sostenible de una ciudad o región se logra a través de un proceso por el que el liderazgo proactivo y fuerte y las instituciones efectivas refuerzan la capacidad y aptitud de un lugar para hacer un mejor uso de sus dotaciones de recursos y lograr un mercado mejorado que consiga ser competitivo y emprendedor. Se propone que el funcionamiento de una ciudad o región en un punto en el tiempo y la trayectoria de su desarrollo económico a lo largo del tiempo puede representarse por su posición en un Cubo de resultados de Competitividad Regional. El artículo propone una nueva estructura de modelo donde el desarrollo económico y funcionamiento de una ciudad o región sea un resultado dependiente de cómo sus dotaciones de recursos y mercado ajustadas como variables cuasi-independientes son mediadas por la interacción entre el liderazgo, instituciones y espíritu empresarial como variables intervinientes. Las experiencias de un cierto número de casos de estudio de ciudades dentro de una variedad de lugares en EE.UU., Europa, Asia y Australia se exploran dentro de esa estructura.

  15. Brazil: anchoring the region

    International Nuclear Information System (INIS)

    Costamilan, L.C.L.

    1997-01-01

    The role of Brazil's state-run petroleum company, Petrobras, in providing a national supply of oil and natural gas and their products to Brazil was discussed. Petrobras is the sole state-run enterprise which carries out research, exploration, production, refining, imports, exports and the transportation of oil and gas in Brazil. Petrobras has built a complete and modern infrastructure made up of refineries, distribution bases, terminals and oil and gas pipelines. Recently (1995) the Brazilian National Assembly approved legislation that while confirming the state monopoly, also provides private contractors and other state-owned companies ways to participate in the petroleum sector. There exists a great potential for oil and gas in many of Brazil's 29 sedimentary basins. The regulatory legislation also created two new organs to deal with the partial deregulation of the petroleum sector, the National Board for Energy Policy and the National Petroleum Agency. The first of these will deal with policy issues, measures and guidelines regarding regional energy supply and demand and specific programs such as those affecting natural gas, fuel alcohol, coal and nuclear energy. The National Petroleum Agency will manage the hydrocarbon sector on behalf of the government. Its functions will include regulation and monitoring of the sector, managing the bidding process for concessions for exploration and production, and other related activities. The new legislation opens up new horizons for the Brazilian oil sector, providing opportunities for private investment, both domestic and foreign, as well as for new technological capabilities associated with these investments. 1 tab., 6 figs

  16. Regional identity and family

    Directory of Open Access Journals (Sweden)

    Tripković Gordana D.

    2003-01-01

    Full Text Available This paper is a continuation of a study on regionalisation and family, within the project named Sociological Aspects of Multiculturality and Regionalisation and their influence on the development of AP Vojvodina and the Republic of Serbia. The author focuses her attention to operationalisation of the theoretical and methodological premises that were developed in the previous paper (Tripković, 2002: 111-127, which means that it represents the results of the second phase of the research plan. This phase includes adjusting of theoretical concepts to the fieldwork displaying the results of the research and the analysis of the findings that put a family in the context of confronting different identities, above all national and regional. As possible "identity difference" was emphasized in the research, theoretical and methodological apparatus was adjusted to this goal. That is why in this paper the replies of interviewees that can suggest or reject the assumption that their national identity can influence significantly the evaluation of identity specificities are presented and analyzed, concerning more or less visible aspects of family life, like welfare status, relations between spouses, respect to the elder, family harmony, number of children, connections with relatives, etc.

  17. Planning for regional centers

    International Nuclear Information System (INIS)

    O'Donnell, A.J.

    1981-01-01

    In conclusion, the successful development and implementation of a multinational nuclear fuel cycle project will require that it be economically viable and satisfy the overlying interests and concerns of the participants. To assure success, it is absolutely essential that the initial planning, development of project criteria, and implementation be based on an authoritative understanding of the real needs of and benefits to all potential participants. The organizational structure for such a project must contain appropriate checks and balances that are sufficient to protect investors, owners, and consumers. Because of its special nature, these checks and balances must also provide for satisfying other important interests, such as an operating organization that addresses nonproliferation concerns and nuclear safeguards. The next logical step in the evolution of regional nuclear complexes is to determine whether such an approach is, indeed, economically viable, financially attractive, and operationally practical. Those who have succeeded in structuring nonnuclear, energy-related complexes currently operating throughout the world today should be looked to for developing the feasibility study of this concept in the nuclear field

  18. Regional differences in family poverty

    OpenAIRE

    Robert K. Triest

    1997-01-01

    Poverty rates vary considerably over regions, as do the demographic characteristics of the poor, but why the extent of poverty varies as much as it does across different regions of the country is not fully understood. This is an unfortunate gap in our knowledge, since it is difficult to analyze how recent changes in federal anti-poverty policy will affect the regional distribution of poverty without a better understanding of current regional differences in the poverty rate.> The main goal of ...

  19. Networking in gendered regional development

    OpenAIRE

    Mona Hedfeldt; Gun Hedlund

    2011-01-01

    The present Swedish regionalization process creates a lack of institutionalisation called the "regional mess" (Stegmann McCallion 2008:587). According to a state investigation, Sweden has a "fragmented growth- and development policy as well as a weak and unclear regional organisation of society" (SOU 2007:10:18). Old and new structures are intertwined and the question emerges if this situation may create a space for women regarding regional development (Hedfeldt & Hedlund 2009). A multi-level...

  20. Physics of fully ionized regions

    International Nuclear Information System (INIS)

    Flower, D.

    1975-01-01

    In this paper the term fully ionised regions is taken to embrace both planetary nebulae and the so-called 'H II' regions referred to as H + regions. Whilst these two types of gaseous nebulae are very different from an evolutionary standpoint, they are physically very similar, being characterised by photoionisation of a low-density plasma by a hot star. (Auth.)

  1. Regional futures: British Columbia

    International Nuclear Information System (INIS)

    Rees, W.

    1993-01-01

    Two paradigms that are the source of present-day economic development policies are described. The dominant paradigm is the expansionist world view that assumes economic growth is essentially unlimited, subject to certain constraints, and that the best way to monitor the human economy is through money flows. The steady-state or ecological world view assumes there are real constraints on material throughput and growth, and puts a significant emphasis on natural capital as a form of wealth which is distinct from economic or manufactured capital. Over the long term, each generation must receive from the previous generation at least an adequate stock of natural capital assets to ensure long-term sustainability. For every major category of consumption, such as food and energy, an ecological footprint can be assigned which represents the land needed to sustain a given pattern of consumption. For the lower mainland of British Columbia, this footprint would be about 22 times the actual land area; for the Netherlands, it would be about 15 times larger than the country itself. On a global basis, only about 1.7 hectares per capita of ecologically productive land is actually available, showing that Canadian material standards would not be sustainable on a global level. The steady-state approach to economic development would involve a local and regional approach from the bottom up, preferring small-scale labor-intensive enterprise. Trade would be limited to trading in real ecological surpluses, and value-added products would be made locally instead of shipping raw materials for processing elsewhere. 5 figs

  2. Regional and economic development

    International Nuclear Information System (INIS)

    Fortin, P.

    2004-01-01

    A leading economics expert was asked to list the economic advantages and disadvantages associated with electricity exports. This paper presents his expert opinion and presents a regional and economic analysis of the hydroelectric reserves that Hydro-Quebec should maintain in order to ensure long-term reliability of energy supplies while maintaining its potential for profitable exports. Electricity exports from Hydro-Quebec are extremely profitable for the province. From 1999 to 2003, net cumulative exports of 63 TWh brought in 4.2 billion dollars to the province of Quebec. This income was redistributed to Quebecers in the form of low energy prices. From 1994 to 2003, the average annual electricity export from Hydro-Quebec was 18 TWh which represents 11 per cent of all electricity delivered by the producer. Most of this export was sold to short-term markets. This ensures that electricity remains available to Quebec should the need arise. Long term sales agreement have never dominated the utility, and today account for only 1.5 per cent of electricity production. In order to ensure a secure electricity supply, Hydro-Quebec has kept a safety margin of 10 TWh through its large hydro-reservoirs. However, the year 2003 proved to be a difficult year for the producer due to low precipitation. The safety margin was completely consumed and the utility had to import electricity. A theoretical analysis of the market suggests that Hydro-Quebec's safety margin should be increased from 10 to 20 TWh to better meet energy demands during years of low precipitation. 1 tab., 2 figs

  3. Thinking regionally: narrative, the medical humanities and region.

    Science.gov (United States)

    Waddington, Keir

    2015-06-01

    Drawing on multiple literatures from history, geography, anthropology, sociology and literature, this essay asks questions about what we mean by region and why narratives of region should matter to the medical humanities. The essay surveys how region can be used as a lens of analysis, exploring the various academic approaches to region and their limitations. It argues that regions are dynamic but also unstable as a category of analysis and are often used uncritically by scholars. In encouraging scholars working in the medical humanities to be aware that regions are not simple objective or analytical boxes, the essay shows how an awareness of region helps challenge metropolitan whiggism and ideas of core and periphery to give a more prominent place to hinterlands, market towns and rural environments. Furthermore, the essay considers how incorporating region into our understanding of illness can offer new insights. It demonstrates the need for scholars to be attuned to the narratives constructed around regions, suggesting that regions can be viewed as discursive formations that provide a frame for understanding both collective and personal ideas of, and responses to, health and illness, disease and healing, to create what Megan Davies calls a more nuanced 'intellectual cartography'. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  4. Food Independence of the Region

    Directory of Open Access Journals (Sweden)

    Vasiliy Vladimirovich Tyutyunik

    2016-06-01

    Full Text Available The article deals with such basic definitions as food security, food independence and food self- sufficiency of the region. The author shows the ambiguity problem of interpretations of these terms in the Russian legislation, which is especially evident in the transition from the national to the regional level. Using the example of legislative acts of some of the Russian Federation’s subjects the study demonstrates the incorrect use of mentioned terms. In author’s opinion, regional authorities in the Russian Federation must introduce amendments to the legislative documents concerning food security. To be more concrete, the regional authorities should either deny the goal of food independence for a particular region, or specify that the goal of reaching food independence for the region does not mean food self-sufficiency, but just import substitution on the regional level

  5. Regional Trends in Electromobility - Regional Study North America

    OpenAIRE

    Turrentine, Tom; Garas, Dhalia

    2015-01-01

    The subproject “Regional Trends in Electro mobility” aims at identifying and analyzing major trends in the field of electro mobility. The trend analysis will monitor research effort and upcoming technologies, policies, products and market developments in different focus regions around the world continuously to enable a systematic analysis of global trends. The regional trend analysis for electro mobility is a major keystone for the project success and therefore cooperation with...

  6. Regional geochemical prospecting of uranium in the Amazon region

    International Nuclear Information System (INIS)

    Zenker, A.O.; Hohn, H.

    1982-01-01

    A regional geochemical prospecting program for uranium in the Serra dos Carajas area, south of Para, was performed by NUCLEBRAS using stream sediment samples obtained from other companies acting in this area. The results of the survey are presented compared to regional geology and an aerial total count map. The different data showed a good correlation, particularly in areas mapped regionally as granitic rocks. (Author) [pt

  7. Regional Stability & Lessons Learned in Regional Peace Building

    DEFF Research Database (Denmark)

    Vestenskov, David; Johnsen, Anton Asklund

    , as none of the countries is able to deal with the intrastate and interstate conflicts on its own. The conference Regional Stability & Lessons Learned in Regional Peace Building was the result of comprehensive cooperation between Pakistan’s National Defence University and the Royal Danish Defence College......The NATO-led intervention in Afghanistan is coming to an end, and the necessity of regional peace building solutions for the region’s security issues seems more exigent than ever before. Regional states have to come to terms with each other in some ways if violent extremists are to be countered...

  8. A Declining Region: Provincial Renaissance Revisited (Case of Volgograd Region

    Directory of Open Access Journals (Sweden)

    Drozdova Yuliya

    2014-12-01

    Full Text Available The paper analyzes findings yielded by the empirical study performed in the framework of an RGNF grant entitled “Image of a region as a communicative strategy for the authorities and mass media”. The methods of study included expert survey and formal survey (N=1000, July-September 2013, studying the opinion of respondents who were either internal experts residing in the Volgograd region (N=20; May-September 2013 or external experts who reside outside the region but maintain stable ties with the representatives of state and municipal authorities, regional mass media and business. The findings indicate that the Volgograd region has fallen behind other modernized Russian regions, that young people tend to leave it, that a negative image of the region as a declining territory persists. Answers to the open question “What is unacceptable for you in the existing image of the Volgograd region?” revealed major problems determining the local context of a declining region, and those were issues associated with inefficient regional/municipal administration: “the condition of the roads”, “constant replacement of people in the administration”, “politics as a whole”, “a destitute region without a good manager”, “unemployment”, “countryside is dying off”, “indifference of the authorities”, “roads, housing and public utilities and the administration”, “the authorities are not responsible for the people”, “the authorities do not solve the problems of the city or its people”, “thieving”, “dishonest authorities”, “the region goes to rack and ruin, no kindergartens or jobs”, “one cannot even walk in the streets”, “corruption”, “a stagnant region with low pay”, “no perspectives in the future”, “the region is stagnating due to corruption among officials”. According to the local Census Bureau, the Volgograd region can be classified as a declining territory where the population decline

  9. Regional governance: strategies and disputes in health region management

    Directory of Open Access Journals (Sweden)

    Adriano Maia dos Santos

    2014-08-01

    Full Text Available OBJECTIVE To analyze the regional governance of the health systemin relation to management strategies and disputes. METHODOLOGICAL PROCEDURES A qualitative study with health managers from 19 municipalities in the health region of Bahia, Northeastern Brazil. Data were drawn from 17 semi-structured interviews of state, regional, and municipal health policymakers and managers; a focus group; observations of the regional interagency committee; and documents in 2012. The political-institutional and the organizational components were analyzed in the light of dialectical hermeneutics. RESULTS The regional interagency committee is the chief regional governance strategy/component and functions as a strategic tool for strengthening governance. It brings together a diversity of members responsible for decision making in the healthcare territories, who need to negotiate the allocation of funding and the distribution of facilities for common use in the region. The high turnover of health secretaries, their lack of autonomy from the local executive decisions, inadequate technical training to exercise their function, and the influence of party politics on decision making stand as obstacles to the regional interagency committee’s permeability to social demands. Funding is insufficient to enable the fulfillment of the officially integrated agreed-upon program or to boost public supply by the system, requiring that public managers procure services from the private market at values higher than the national health service price schedule (Brazilian Unified Health System Table. The study determined that “facilitators” under contract to health departments accelerated access to specialized (diagnostic, therapeutic and/or surgical services in other municipalities by direct payment to physicians for procedure costs already covered by the Brazilian Unified Health System. CONCLUSIONS The characteristics identified a regionalized system with a conflictive pattern of

  10. Cooperation in regional nuclear training

    International Nuclear Information System (INIS)

    Newstead, C.M.; Lee, D.S.; Spitalnik, J.

    1985-01-01

    This paper presents an overview of the nuclear training currently being undertaken in the countries of the co-authors, and considers the degree to which training problems are amenable to common solutions such as cooperative regional training programs. Different types of cooperation are discussed including the development of regional and international training centers, cooperative bilateral and multilateral training, and the proposed US International Nuclear Safety Training Academy. The paper provides suggestions of ways for enhancing regional cooperation

  11. Vietnam and the regional crisis

    DEFF Research Database (Denmark)

    Masina, Pietro Paolo

    2002-01-01

    inflows, should be understood in the broader frame of regional contingencies, and not be simplistically explained as investors' discontent (i.e., in order to pressure Vietnamese authorities into implementing a more orthodox neo-liberal agenda). And in a post-crisis regional economic reorganisation...... that Vietnam can successfully exploit market niches opened up by postcrisis regional economic reorganisation, thus offering some optimism for the country's immediate economic future....

  12. Fiscal competition and regional differentiation

    OpenAIRE

    Justman, Moshe; Thisse, Jacques-François; Van Ypersele, Tanguy

    2001-01-01

    Regions can benefit by offering infrastructure services that are differentiated. Competition between regions over potential investors is then less direct, allowing them to realize greater benefits from external investors. The two polar cases of full and incomplete information about investors' needs are studied. In both cases, there is regional differentiation. However, fiscal competition is efficient in the former case but not in the latter. Finally, it is shown that free entry in the loc...

  13. Regional energy facility siting analysis

    International Nuclear Information System (INIS)

    Eberhart, R.C.; Eagles, T.W.

    1976-01-01

    Results of the energy facility siting analysis portion of a regional pilot study performed for the anticipated National Energy Siting and Facility Report are presented. The question of cell analysis versus site-specific analysis is explored, including an evaluation of the difference in depth between the two approaches. A discussion of the possible accomplishments of regional analysis is presented. It is concluded that regional sitting analysis could be of use in a national siting study, if its inherent limits are recognized

  14. Regional radiation standards for population of Chelyabinsk region

    International Nuclear Information System (INIS)

    Kravtsova, Eh.M.; Zajtseva, Yh.A.; Panteleev, V.V.; Gavrilov, A.P.; Kolotygina, N.V.; Pudovkina, L.V.; Kravtsova, O.S.

    1996-01-01

    Regional radiation regulations for population exposures in Chelyabinsk region are developed which are to play the role of standard limits. The priority goal of setting standard level is to consolidate the achieved radioecological balance on the contaminated territories and to establish a mechanism of control over the activities of the facility and over the use of lands in restriction zone by the population

  15. Cloaks with multiple invisible regions

    International Nuclear Information System (INIS)

    Luo, Yang; Zhu, Shouzheng; He, Lianxing; Wang, Yu

    2011-01-01

    This paper proposes a general method of extending the effective invisible regions for both the shell-like interior cloak and the complementary media exterior cloak, without affecting their original cloaking regions. The proposed method is based on layered spatial mapping instead of the intact mapping. Certain interior or exterior invisible regions can be obtained by properly using a compressed or folded transformation in each space layer. Therefore, the proposal enables the as-designed cloaks to provide multiple invisible regions of different types simultaneously. Thus objects can be hidden in the interior cavity and/or in the exterior space, or even be embedded between the cloaking shells

  16. Productive Regions: Criteria and Classification

    Directory of Open Access Journals (Sweden)

    Vlasyuk L. I.

    2012-03-01

    Full Text Available An official statistical dataset for 80 territorial subjects of the Russian Federation for 2000, 2007 and 2009 has proved the hypothesis that, under the neoclassical concept, the resources move to regions with the highest marginal productivity of the factors of production, which leads to the accumulation of investment resources, while providing financial and social efficiency. Based on cluster analysis by three performance criteria, productive regions are identified, which are dominated by regions productive in the extraction of minerals. It is shown that the stability of the factors’ distribution in space determines the current and future specialization of regional economies

  17. THE REGIONAL STRUCTURE OF SERBIA

    Directory of Open Access Journals (Sweden)

    Marina TODOROVIC

    2009-12-01

    Full Text Available This paper approaches some of the characteristics of the regional development of Serbia, from the perspective of two models of territorial organization: one is governmental (administrative and statistical, and the other is functional. The imbalances in the levels of development of various territorial units of Serbia (regional disproportions are the consequence of many structural disharmonies, material limitations, and problems with populationstructure, during many years, all worsened by political and economic events at the end of the twentieth century. Also, in this paper we point out the main characteristics of undeveloped regions, the criteria with which we can define them, and a typology of the municipalities inside each such region.

  18. Regions and the Territorial Cohesion

    Directory of Open Access Journals (Sweden)

    Ioan Ianos

    2013-08-01

    Full Text Available Territorial cohesion is an important target of European Union, constantly promoted by its institutions and their representatives. In the context of the Europe 2020 strategy, one of the most important support documents, the region represents a very important issue, being considered to be the key to its successfulness. The region is seen as a support for the smart growth and all the operational policy concepts try to make use of the spatial potential, by taking better account of the territorial specificities. Two main questions play attention: the need to transform the present-day developmental regions into administrative ones is a priority? What kind of regionalization it must to be promoted? Correlating these issues with already defined territorial cohesion, the administrative region is a real tool for the future territorial development. The experience of the last 14 years asks urgently the building of a new territorial administrative reform, giving competences to regions. For instant, each development region is a construction resulted from a free association of the counties. Their role in the regional development is much reduced one, because their regional councils are not elected; decisions taken at this level are consultative for the social, economical, cultural or political actors.

  19. VT Regional Development Corporation (RDC)

    Data.gov (United States)

    Vermont Center for Geographic Information — The Department of Economic Development partners with the twelve Regional Development Corporations around the state to provide technical assistance. They can assist...

  20. Regional cooperation in transportation planning.

    Science.gov (United States)

    2012-02-01

    As Floridas urbanized areas grow and merge, : neighboring jurisdictions experience interrelated : problems and opportunities, and regional : cooperation becomes an imperative. In the : transportation sector, Floridas metropolitan : planning org...

  1. Latin America Region: Between Dependence and Autonomy in Regional Processes

    Directory of Open Access Journals (Sweden)

    Wendy Vaca Hernández

    2017-01-01

    Full Text Available The space called Latin America has a particular history marked by centuries of colonialism and coloniality. The latter concept implies that the basic structure of the colonial system has not changed even though formal independence has been achieved. For this reason, the subcontinent has fluctuated between dependence and the quest for autonomy. These successive cycles have manifested themselves both in the internal configurations and in the regional schemes that have been undertaken. This paper analyzes the construction and evolution of the idea of a region: Latin America and the Caribbean. To that end it examines the concepts of region, regionalism, what Latin America and the Caribbean implies, and what are the transformations in these ideas that have emerged from the regional configurations of the Union of South American Nations (UNASUR and the Community of Latin American and Caribbean States (CELAC as plural organisms with broad objectives.

  2. The effect of melatonin on proliferation of primary porcine cells expressing mutated huntingtin

    Czech Academy of Sciences Publication Activity Database

    Rausová, Petra; Valášek, Jan; Ellederová, Zdeňka; Motlík, Jan

    2015-01-01

    Roč. 78, Suppl 2 (2015), s. 27-27 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) 7F14308 Institutional support: RVO:67985904 Keywords : Huntington ´s disease * melatonin * time lapse microscopy Subject RIV: FH - Neurology

  3. The Effect of Melatonin on Proliferation of Primary Porcine Cells Expressing Mutated Huntingtin

    Czech Academy of Sciences Publication Activity Database

    Rausová, Petra; Valášek, Jan; Ellederová, Zdeňka; Motlík, Jan

    2015-01-01

    Roč. 78, Suppl. 2 (2015), s. 43-48 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. Liblice, 08.11.2015-10.11.2015] R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) 7F14308 Institutional support: RVO:67985904 Keywords : Huntington´s disease * melatonin * time lapse microscopy Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.209, year: 2015

  4. Huntingtin Protein is Essential for Mitochondrial Metabolism, Bioenergetics and Structure in Murine Embryonic Stem Cells

    Science.gov (United States)

    Ismailoglu, Ismail; Chen, Qiuying; Popowski, Melissa; Yang, Lili; Gross, Steven S.; Brivanlou, Ali H.

    2014-01-01

    Mutations in the Huntington locus (htt) have devastating consequences. Gain-of-poly-Q repeats in Htt protein causes Huntington's disease (HD), while htt-/- mutants display early embryonic lethality. Despite its importance, the function of Htt remains elusive. To address this, we compared more than 3,700 compounds in three syngeneic mouse embryonic stem cell (mESC) lines: htt-/-, extended poly-Q (Htt-Q140/7), and wildtype mESCs (Htt-Q7/7) using untargeted metabolite profiling. While Htt-Q140/7 cells, did not show major differences in cellular bioenergetics, we find extensive metabolic aberrations in htt-/- mESCs, including: (i) complete failure of ATP production despite preservation of the mitochondrial membrane potential; (ii) near-maximal glycolysis, with little or no glycolytic reserve; (iii) marked ketogenesis; (iv) depletion of intracellular NTPs; (v) accelerated purine biosynthesis and salvage; and (vi) loss of mitochondrial structural integrity. Together, our findings reveal that Htt is necessary for mitochondrial structure and function from the earliest stages of embryogenesis, providing a molecular explanation for htt-/- early embryonic lethality. PMID:24780625

  5. CTG repeat-targeting oligonucleotides for down-regulating Huntingtin expression

    DEFF Research Database (Denmark)

    Zaghloul, Eman M; Gissberg, Olof; Moreno, Pedro M D

    2017-01-01

    Huntington's disease (HD) is a fatal, neurodegenerative disorder in which patients suffer from mobility, psychological and cognitive impairments. Existing therapeutics are only symptomatic and do not significantly alter the disease progression or increase life expectancy. HD is caused by expansion....... Thus, reduction of both muHTT mRNA and protein levels would ideally be the most useful therapeutic option. We herein present a novel strategy for HD treatment using oligonucleotides (ONs) directly targeting the HTT trinucleotide repeat DNA. A partial, but significant and potentially long-term, HTT...

  6. β-catenin expression in minipigs transgenic for human mutated huntingtin

    Czech Academy of Sciences Publication Activity Database

    Žižková, Martina; Hrabáková, Rita; Juhásová, Jana; Juhás, Štefan; Halada, Petr; Kovářová, Hana; Motlík, Jan

    2012-01-01

    Roč. 83, Suppl 1 (2012), A15-A16 ISSN 0022-3050. [EHDN Plenary Meeting /7./. 14.02.2012-16.02.2012, Stockholm] R&D Projects: GA TA ČR TA01011466 Institutional support: RVO:67985904 ; RVO:61388971 Keywords : beta-catenin * Huntington disease Subject RIV: CE - Biochemistry

  7. Unusual structures are present in DNA fragments containing super-long Huntingtin CAG repeats.

    Directory of Open Access Journals (Sweden)

    Daniel Duzdevich

    2011-02-01

    Full Text Available In the R6/2 mouse model of Huntington's disease (HD, expansion of the CAG trinucleotide repeat length beyond about 300 repeats induces a novel phenotype associated with a reduction in transcription of the transgene.We analysed the structure of polymerase chain reaction (PCR-generated DNA containing up to 585 CAG repeats using atomic force microscopy (AFM. As the number of CAG repeats increased, an increasing proportion of the DNA molecules exhibited unusual structural features, including convolutions and multiple protrusions. At least some of these features are hairpin loops, as judged by cross-sectional analysis and sensitivity to cleavage by mung bean nuclease. Single-molecule force measurements showed that the convoluted DNA was very resistant to untangling. In vitro replication by PCR was markedly reduced, and TseI restriction enzyme digestion was also hindered by the abnormal DNA structures. However, significantly, the DNA gained sensitivity to cleavage by the Type III restriction-modification enzyme, EcoP15I."Super-long" CAG repeats are found in a number of neurological diseases and may also appear through CAG repeat instability. We suggest that unusual DNA structures associated with super-long CAG repeats decrease transcriptional efficiency in vitro. We also raise the possibility that if these structures occur in vivo, they may play a role in the aetiology of CAG repeat diseases such as HD.

  8. NOAA Miami Regional Library > Home

    Science.gov (United States)

    Library Collections Open Access Resources Research Tools E-resources NOAA S. and NOAA N.E. Library Institutional Repository DIVE INTO About the Library | Collections | Research Tools | Library Services & NOAA Miami Regional Library @ AOML & NHC NOAA Miami Regional Library at National Hurricane

  9. Regional Inflation and Financial Dollarization

    NARCIS (Netherlands)

    Brown, M.; de Haas, R.; Sokolov, V.

    2013-01-01

    Abstract: We exploit variation in consumer price inflation across 71 Russian regions to examine the relationship between the perceived stability of the local currency and financial dollarization. Our results show that regions with higher inflation experience an increase in the dollarization of

  10. Robustness Regions for Dichotomous Decisions.

    Science.gov (United States)

    Vijn, Pieter; Molenaar, Ivo W.

    1981-01-01

    In the case of dichotomous decisions, the total set of all assumptions/specifications for which the decision would have been the same is the robustness region. Inspection of this (data-dependent) region is a form of sensitivity analysis which may lead to improved decision making. (Author/BW)

  11. Metropolitan region of Copenhagen, Denmark

    DEFF Research Database (Denmark)

    Fertner, Christian

    the boundaries of the city further out. With the opening of the suburban train lines in 1934, the until today known finger structure was consolidated. A regional strategy, the “Fingerplan”, incorporating this structure was elaborated in 1947, but individual motorisation eroded some of the principles. Still...... in Sweden, forming a cross-border region with around 3.5 mio. inhabitants....

  12. Archives: Town and Regional Planning

    African Journals Online (AJOL)

    Items 1 - 12 of 12 ... Archives: Town and Regional Planning. Journal Home > Archives: Town and Regional Planning. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register · Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives. 1 - 12 of 12 ...

  13. Risk assessment: A regional approach

    Energy Technology Data Exchange (ETDEWEB)

    Palecek, M [Occupational Safety Research Institute, Prague (Czech Republic)

    1992-07-01

    An assessment of the region of North Bohemia which suffered from forty years socialist economy and heavy emissions from German and Polish factories and power stations is presented. The case strongly underlines the need for regional and international cooperation both in the assessment of hazards and finding solution to public health and environmental problems.

  14. Risk assessment: A regional approach

    International Nuclear Information System (INIS)

    Palecek, M.

    1992-01-01

    An assessment of the region of North Bohemia which suffered from forty years socialist economy and heavy emissions from German and Polish factories and power stations is presented. The case strongly underlines the need for regional and international cooperation both in the assessment of hazards and finding solution to public health and environmental problems

  15. Analysis of regional climate strategies in the Barents region

    Energy Technology Data Exchange (ETDEWEB)

    Himanen, S.; Inkeroeinen, J.; Latola, K.; Vaisanen, T.; Alasaarela, E.

    2012-11-15

    Climate change is a global phenomenon with especially harsh effects on the Arctic and northern regions. The Arctic's average temperature has risen at almost twice the rate as elsewhere in the past few decades. Since 1966, the Arctic land area covered by snow in early summer has shrunk by almost a fifth. The Barents Region consists of the northern parts of Norway, Sweden, Finland and Russia (i.e. the European part of Russia). Climate change will cause serious impacts in the Barents Region because of its higher density of population living under harsh climatic conditions, thus setting it apart from other Arctic areas. In many cases, economic activities, like tourism, rely on certain weather conditions. For this reason, climate change and adaptation to it is of special urgency for the region. Regional climate change strategies are important tools for addressing mitigation and adaptation to climate change as they can be used to consolidate the efforts of different stakeholders of the public and private sectors. Regional strategies can be important factors in achieving the national and international goals. The study evaluated how the national climate change goals were implemented in the regional and local strategies and programmes in northern Finland. The specific goal was to describe the processes by which the regional strategies were prepared and implemented, and how the work was expanded to include the whole of northern Finland. Finally, the Finnish preparatory processes were compared to case examples of processes for preparing climate change strategies elsewhere in the Barents Region. This analysis provides examples of good practices in preparing a climate change strategy and implementing it. (orig.)

  16. COMBINATION OF GOALS STRATEGY REGION

    Directory of Open Access Journals (Sweden)

    Denys Yu. Lapigin

    2015-01-01

    Full Text Available Currently the tools to identify strategicallyimportant objectives of regional development is not enough to build a developmentperspective, relying on something special,what distinguishes each region from therest. The article discusses approaches to the formation of the regional developmentstrategy, which is based on goals set by the results of the analysis of the main factors inthe development of the region. The study is based on the methodology of systems theoryand methods of strategic management. The most important results should include tools tobuild the tree of strategic objectives resultingfrom the implementation of the algorithm forconstructing planes of analysis and development of the region. The results can be used to develop a strategy for the developmentof socio-economic systems of various typesand forms.

  17. Croatia in a Regional Context

    Directory of Open Access Journals (Sweden)

    Branko Caratan

    2007-01-01

    Full Text Available In this paper, the author examines the regional context of Croatian politics, highlighting the main reasons for its significance: involvement of the region in war in recent history, the rootedness, aside from that, of extremely strong economic, political and cultural bonds between the countries in the region, and the importance of cooperation in the region for EU accession and further economic development. On these grounds, the author seeks to examine the possibility for stabilisation of the region, and to establish what interests the neighbouring countries such as Italy, Austria, Hungary and others have in strenghtening the bonds with the new democracies in Central and Southeast Europe. All of this eventually provides the answer to the question what is the interest of the EU in this region’s stability and in its admission to the European Union

  18. Dust in H II regions

    International Nuclear Information System (INIS)

    Isobe, S.

    1977-01-01

    Several pieces of evidence indicate that H II regions may contain dust: 1) the continuum light scattered by dust grains (O'Dell and Hubbard, 1965), 2) thermal radiation from dust grains at infrared wavelengths (Ney and Allen, 1969), 3) the abnormal helium abundance in some H II regions (Peimbert and Costero, 1969), etc. Although observations of the scattered continuum suggest that the H II region cores may be dust-free, dust grains and gas must be well mixed in view of the infrared observations. This difficulty may be solved by introducing globules with sizes approximately 0.001 pc. These globules and the molecular clouds adjacent to H II regions are the main sources supplying dust to H II regions. (Auth.)

  19. Initiatives for regional dialogue consideration of regional disarmament guidelines

    International Nuclear Information System (INIS)

    Marschik, R.

    1994-01-01

    The General Assembly of the United Nations adopted guidelines and recommendations for regional approaches to disarmament within the context of global security. The guidelines contain 52 principles on: relationship between regional disarmament, arm limitation and global security; general guidelines and recommendations for regional disarmament efforts; possible ways and means to assist and implement these efforts; possible role of the United Nations in aiding these efforts. Experiences gained in Europe and Near East are analysed in the framework of the situation in Northeast, South and Southeast Asia

  20. The Region is Dead, Long Live the Region

    DEFF Research Database (Denmark)

    Metzger, Jonathan; Olesen, Kristian

    2017-01-01

    If it today is commonly accepted that regions are ‘constructs’ – then who or what construct them, for what reasons, and by which means? How are they made manifest and durable as both mental geographies and mundane everyday realities (cf. Metzger, 2013)? Paasi (2010, p.2298) suggests that regions...... practices that have led to the formation and more recently encroaching dissipation of a well-known EUropean region: Öresund. In this endeavour we will make an effort to be sensitive to how Öresund as a spatial entity interrelates with, depends upon or partially challenges/is challenged by other geographical...

  1. Regional Development of Eastern Slovakia

    Directory of Open Access Journals (Sweden)

    Monika Hergezelová

    2017-08-01

    Full Text Available Purpose and Originality: The aim of the work is to provide an overview of regional development in Eastern Slovakia, where are Košice and Prešov Region. The originality of the work lies in the work of enriching the SWOT analysis from the author Eve Rajčáková, which is given in the book deals with the issue of Regional development and regional policy of the European Union and Slovakia. Research question: The conditions of life of people in eastern Slovakia. Method: For writing this contribution will be used method of analysis and statistics. Knowledge on this subject have been looking on the internet and in books and sources of information publicly available. Using the data collected, we dealt with the issue of regional development in the Košice and Prešov regions. Results: The topic was the beginning focused on the overall characteristics of eastern Slovakia. Furthermore, we are at work we dealt with social and economic phenomena in both regions of eastern Slovakia. We focused on GDP, unemployment and tourism, which is in the region is widespread. Society: It is well known that there are obviously different living conditions in eastern Slovakia as in other parts of Slovakia. People are forced to, mainly because of employment, leave their region to move or commute to work to the west. The paper point out the right of this negative phenomenon that is quite visible - high unemployment. Limitations: The limits of work are limited by problems of regional development in eastern Slovakia, mainly focusing on economic and social phenomena in the society.

  2. Sources of Regional Banks Capitalization

    Directory of Open Access Journals (Sweden)

    Olga Sergeevna Miroshnichenko

    2018-03-01

    Full Text Available Searching of sources to increase the capitalization of Russian banks is an important economic problem for both the national and regional economy. Moreover, a strong capital base allows to credit institutions to meet the demands of economic agents for banking service. The research focuses on the choice of sources of regulatory capital for the banks of Tyumen region in the context of changing supervisory requirements in the period of 2005–2016, in different phases of the business cycle. We apply econometric methods of statistical information using IBM SPSS Statistics software. We have calculated the individual correlations of regional banks’ capital with gross domestic product (GDP (excluding gross regional product (GRP and GRP (with the exception of the effect of GDP. These calculations have shown that the capital of regional banks is related only to GDP. The increase in the capital of regional banks is accompanied by a change in its structure: the share of authorized capital has halved, and the share of subordinated debt has grown. All sources of capital, other than the reserve fund, are related to GDP. Authorized capital is associated with the profit of profitable lending institutions; retained earnings in the capital of regional banks — with the aggregated amount of risks of the banking system of the Russian Federation. Subordinated debt, like capital as a whole, is negatively affected by the profitability of the banking sector. The change in the capital of regional banks is determined by the change in retained earnings, subordinated debt and reserve fund. Modelling of these relations has allowed to obtain a system of equations. This system synthesizes linear regression models of changing the capital of regional banks in the context of their sourcing. The results of this study are significant for theoretical justification and practical development of a balanced financial policy of regional banks. Our research will contribute to

  3. Tribal Land Polygons, Region 9, 2006, US EPA Region 9

    Data.gov (United States)

    U.S. Environmental Protection Agency — Dataset of all Indian Reservations in US EPA Region 9 (California, Arizona and Nevada) with some reservation border areas of adjacent states included (adjacent areas...

  4. regional. Un análisis para las regiones europeas

    Directory of Open Access Journals (Sweden)

    José A. Camacho

    2005-01-01

    Full Text Available Pese a encontrarnos inmersos en una economía globalizada, la innovación es en muchos aspectos un fenómeno esencialmente regional, donde los servicios (ignorados hasta ahora, y en particular aquellos denominados como servicios intensivos conocimiento (SIC, adquieren un papel central, gracias a su capacidad para transmitir conocimiento, en especial de tipo tácito. El objetivo de este trabajo es realizar una primera aproximación empírica a los efectos asociados a la localización de SIC, tomando 107 regiones europeas. Los resultados obtenidos apoyan la hipótesis de que los SIC ejercen un impacto positivo sobre el desempeño innovador regional, impacto que podría desbordarse hacia las regiones vecinas.

  5. Tribal Boundary Polygons, Region 9, 2007, US EPA Region 9

    Data.gov (United States)

    U.S. Environmental Protection Agency — Dataset of all Indian Reservations in US EPA Region 9 (California, Arizona and Nevada) with some reservation border areas of adjacent states included (adjacent areas...

  6. Minimum deterrence and regional security. Section 2. Other regions

    International Nuclear Information System (INIS)

    Azikiwe, A.E.

    1993-01-01

    Compared to European political and security circumstance, minimum deterrence is less an illusion in other regions where weapon free zones already exist. It will continue to be relevant to the security of other regions. Strategic arms limitation should be pursued vigorously in a constructive and pragmatic manner, bearing in mind the need to readjust to new global challenges. The Comprehensive Test Ban Treaty is the linchpin on which the Non-proliferation Treaty rests

  7. Malaysia in international regional relationships

    International Nuclear Information System (INIS)

    Kamarulnizam Abdullah

    2010-01-01

    The changes in the international system saw the structure and survival issues that grip the country will also change. The main challenge to the nation is how to adapt these changes that running quite rapidly and outside the country's ability to cope alone. Issues and global structural changes also affect the international system of East Asia region that contains two important sub-Southeast Asia and Northeast Asia. Changes inherent in both these sub certainly affect the foreign policy and diplomacy, security and bilateral relations between Malaysia and other countries. Malaysia is not a global power capable of changing the international system. However, Malaysia is an important country in East Asia that has contributed to the prosperity of this region. The big question is how to adapt these changes into the Malaysia international regional policy and bilateral relations? What extent international issues affecting the regional survival of the country? What is the contribution to regional stability of Malaysia? This book explores the impact of selective regional issues to Malaysia, while also discussing the role and response to changes in regional Malaysia since the country gained independence. (author)

  8. Regional Courts as Judicial Brakes?

    Directory of Open Access Journals (Sweden)

    Metcalf Katrin Nyman

    2017-12-01

    Full Text Available The article examines how regional integration courts can act as judicial brakes, at a time when “constitutional coups” – leaders staying in power past constitutional time limits or other forms of actions against the spirit if not always the letter of the constitution – are alarmingly common. The article discusses how regional courts can be used to modify or protect national rule of law and the constitutional order from the outside (i.e. from the regional integration aspect and the extent to which this can be valid particularly to promote a uniform interpretation and application of human rights. Although this trend is visible in Europe, it is more striking, because less expected, on other continents, in particular Africa and the Americas, where the developments take place in less than perfect democratic environments. The article contains evidence from cases dealt with in the various regional courts, supporting that a system of political and judicial oversight, especially in regions with weak or fragile democratic systems, can be a useful addition to national judicial or other mechanisms of protection of rule of law and control of the executive. Action by regional courts helps defeat perceptions of majoritarian politics, which in many countries allow for the winner to take all. Under a system of regional oversight, states become aware of the limits they themselves have set and citizens become aware of their possibilities to challenge political power.

  9. Regional Branding: Building Brand Value

    Directory of Open Access Journals (Sweden)

    Klára Margarisová

    2016-01-01

    Full Text Available Regional branding is one of several ways to promote rural regions and support development of socially, culturally and environmentally oriented economies in areas that are interesting due to their natural and cultural heritage. The article attempts to review the conceptual and theoretical underpinnings of branding as conveyed by leading authors in the marketing field. The aim of this paper is to define brand as a broad complex of variables, which are used in building of its identity as a basis for creating value proposition and the position of a brand. Article briefly describes the most comprehensive labeling system for regional products at the micro-regional level is the one guaranteed by Association of Regional Brands (ARB. The main contribution of this article is a theoretical model of strategic management of a regional brand, which captures the interdependence of the individual steps of brand building as well as stakeholders. The starting point for building of brand value is a strategic analysis of the brand, including analysis of customer and competitors. The analysis of external factors is followed by analysis of the brand itself. The resulting relationship between the brand and the customer is based on value proposition representing benefits (functional, emotional, self‑expression. The concept of total product is connected with the concept of total brand and it is offered to the customer as a regional product. Finally it suggests possibilities for further research.

  10. Regional climate change mitigation analysis

    Energy Technology Data Exchange (ETDEWEB)

    Rowlands, Ian H [UNEP Collaborating Centre on Energy and Environment, and Univ. of Waterloo (Canada)

    1998-10-01

    The purpose of this paper is to explore some of the key methodological issues that arise from an analysis of regional climate change mitigation options. The rationale for any analysis of regional mitigation activities, emphasising both the theoretical attractiveness and the existing political encouragement and the methodology that has been developed are reviewed. The differences arising from the fact that mitigation analyses have been taken from the level of the national - where the majority of the work has been completed to date - to the level of the international - that is, the `regional` - will be especially highlighted. (EG)

  11. LLNL's Regional Seismic Discrimination Research

    International Nuclear Information System (INIS)

    Hanley, W; Mayeda, K; Myers, S; Pasyanos, M; Rodgers, A; Sicherman, A; Walter, W

    1999-01-01

    As part of the Department of Energy's research and development effort to improve the monitoring capability of the planned Comprehensive Nuclear-Test-Ban Treaty international monitoring system, Lawrence Livermore Laboratory (LLNL) is testing and calibrating regional seismic discrimination algorithms in the Middle East, North Africa and Western Former Soviet Union. The calibration process consists of a number of steps: (1) populating the database with independently identified regional events; (2) developing regional boundaries and pre-identifying severe regional phase blockage zones; (3) measuring and calibrating coda based magnitude scales; (4a) measuring regional amplitudes and making magnitude and distance amplitude corrections (MDAC); (4b) applying the DOE modified kriging methodology to MDAC results using the regionalized background model; (5) determining the thresholds of detectability of regional phases as a function of phase type and frequency; (6) evaluating regional phase discriminant performance both singly and in combination; (7) combining steps 1-6 to create a calibrated discrimination surface for each stations; (8) assessing progress and iterating. We have now developed this calibration procedure to the point where it is fairly straightforward to apply earthquake-explosion discrimination in regions with ample empirical data. Several of the steps outlined above are discussed in greater detail in other DOE papers in this volume or in recent publications. Here we emphasize the results of the above process: station correction surfaces and their improvement to discrimination results compared with simpler calibration methods. Some of the outstanding discrimination research issues involve cases in which there is little or no empirical data. For example in many cases there is no regional nuclear explosion data at IMS stations or nearby surrogates. We have taken two approaches to this problem, first finding and using mining explosion data when available, and

  12. Regional climate change mitigation analysis

    International Nuclear Information System (INIS)

    Rowlands, Ian H.

    1998-01-01

    The purpose of this paper is to explore some of the key methodological issues that arise from an analysis of regional climate change mitigation options. The rationale for any analysis of regional mitigation activities, emphasising both the theoretical attractiveness and the existing political encouragement and the methodology that has been developed are reviewed. The differences arising from the fact that mitigation analyses have been taken from the level of the national - where the majority of the work has been completed to date - to the level of the international - that is, the 'regional' - will be especially highlighted. (EG)

  13. BUDGETARY REGIONAL POLICY: THEORETICAL CONCEPTUALIZATION

    Directory of Open Access Journals (Sweden)

    Shyshpanova Nataliia

    2018-01-01

    Full Text Available Introduction. Formation and implementation of the budget policy of the regions in Ukraine is directly related to the processes of decentralization of power, increase of budget powers and strengthening of financial capacity of the territories. Formation of balanced local budgets and support of an effective system of managing budget resources is a key to strengthening the economic potential of the regions and increasing the well-being of citizens. The purpose of this article is to assess the current concepts of the fiscal policy of the region in Ukraine and to determine the impact of fiscal policy on the socio-economic development of the regions. Results. In this article the essence and content of budget policy are considered, the interpretation of different scientists is presented. An author’s approach to the definition of the essence of the budget policy of the region as a set of economic and administrative measures in the budget sphere, determined by the interrelated goals and objectives of the state and local self-government, aimed at the socio-economic development of the territory. The conceptual model of the fiscal policy of the region is presented and it is determined that the strategic goal of fiscal policy at the local level should be to ensure sustainable socio-economic development of the territories. The main principles that need to be observed during the implementation of the budget policy of the region are described; functions to be performed by local level fiscal policy; and the main tools by which local authorities carry out their functions. Conclusions. It is noted that the content of the budget policy of the region should be to determine the course, tasks and directions of the state and local self-government activities in the field of the formation and use of budget funds. The budget policy of the region should respond to a combination of the following systemic challenges: 1. the restoration of economic growth, as soon as

  14. Regional transport sector mitigation options

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Peter [EECG Consultants, Gaborone (Botswana)

    1998-10-01

    The rationale for conducting climate change mitigation studies in the transport sector is on the premise that: The transport sector is the second largest consumer of fossil fuels in the region; The regional transport sector is an area with high opportunity for infrastructural development under UNFCCC financial mechanism; The regional transport sector is crucial in the SADC region for trade and coupled with the Trade Protocol will play a major role in development hence the need to make it efficient in terms of energy demand and provision of services; The sector offers many mitigation options but with a challenge to evaluate their energy saving and GHG saving potential and yet there is need to quantify possible emission reduction for possible future emission trading. This is also a sector with potential to qualify for financing through Clean Development Mechanism (CDM) recently stipulated in the Kyoto Protocol. (au)

  15. Region 7 Title V facilities

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web map shows the Region 7 Title V facilities (Clean Air Act major sources), any Class I areas within 300 km of R7 States, and any Tribal areas within 50 miles...

  16. Penguins of the Magellan region

    Directory of Open Access Journals (Sweden)

    M. Bingham

    1999-12-01

    Full Text Available The Magellan region, including the Falkland Islands, is one of the world´s most important areas for seabirds, and especially penguins. World-wide there are 17 species of penguin; 7 of these regularly breed around the coastal waters of South America, and 5 within the Magellan region. These are the King Penguin (Aptenodytes patagonicus, Gentoo Penguin (Pygoscelis papua, Rockhopper Penguin (Eudyptes c. chrysocome, Macaroni Penguin (Eudyptes chrysolophus and Magellanic Penguin (Spheniscus magellanicus. During the last five years, a review of the breeding populations of penguins within the Magellan region was conducted. This work included population censuses of all the surface breeding species throughout the Falkland Islands and southern South America. The results of this work are presented, along with other cited information, to provide a summary of the current knowledge of penguin populations within the Magellan region.

  17. Regional Assessment of South America

    National Research Council Canada - National Science Library

    Jarrett, Kenneth; McMillen, Gary K

    1997-01-01

    .... Economically, the countries of the region have emerged from the debt crisis of the 1980s with a zealous belief in the advantages of export-oriented policies, privatization, and the elimination...

  18. Acoustic holograms of active regions

    International Nuclear Information System (INIS)

    Chou, Dean-Yi

    2008-01-01

    We propose a method to study solar magnetic regions in the solar interior with the principle of optical holography. A magnetic region in the solar interior scatters the solar background acoustic waves. The scattered waves and background waves could form an interference pattern on the solar surface. We investigate the feasibility of detecting this interference pattern on the solar surface, and using it to construct the three-dimensional scattered wave from the magnetic region with the principle of optical holography. In solar acoustic holography, the background acoustic waves play the role of reference wave; the magnetic region plays the role of the target object; the interference pattern, acoustic power map, on the solar surface plays the role of the hologram.

  19. Acoustic holograms of active regions

    Energy Technology Data Exchange (ETDEWEB)

    Chou, Dean-Yi [Physics Department, National Tsing Hua University, Hsinchu, 30013, Taiwan (China)], E-mail: chou@phys.nthu.edu.tw

    2008-10-15

    We propose a method to study solar magnetic regions in the solar interior with the principle of optical holography. A magnetic region in the solar interior scatters the solar background acoustic waves. The scattered waves and background waves could form an interference pattern on the solar surface. We investigate the feasibility of detecting this interference pattern on the solar surface, and using it to construct the three-dimensional scattered wave from the magnetic region with the principle of optical holography. In solar acoustic holography, the background acoustic waves play the role of reference wave; the magnetic region plays the role of the target object; the interference pattern, acoustic power map, on the solar surface plays the role of the hologram.

  20. Regions compete for French synchrotron

    CERN Multimedia

    2000-01-01

    Ten regions in France have placed bids to host the planned national synchrotron Soleil. Leading contenders include a joint bid from Ile-de-France and Essonne for Orsay, offering FF 1 billion towards the construction costs (2 paragraphs).

  1. Pacific Northwest DIVER Regional Metadata

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — DIVER environmental data holdings are primarily comprised of datasets gathered from regional studies, site specific studies from non-NOAA entities, and NOAA...

  2. Groundwater Vulnerability Regions of Iowa

    Data.gov (United States)

    Iowa State University GIS Support and Research Facility — The regions onThis map represent areas with similar hydrogeologic characteristics thought to represent similar potentials for contamination of groundwater and/or...

  3. Conformity Adequacy Review: Region 5

    Science.gov (United States)

    Resources are for air quality and transportation government and community leaders. Information on the conformity SIP adequacy/inadequacy of state implementation plans (SIPs) in EPA Region 5 (IL, IN, MI, OH, WI) is provided here.

  4. Conformity Adequacy Review: Region 7

    Science.gov (United States)

    Resources are for air quality and transportation government and community leaders. Information on the adequacy/inadequacy of state implementation plans (SIPs) in EPA Region 7 (IA, KS, MO, NE) is provided here.

  5. Conformity Adequacy Review: Region 9

    Science.gov (United States)

    Resources are for air quality and transportation government and community leaders. Information on the adequacy/inadequacy of state implementation plans (SIPs) in EPA Region 9 (AZ, CA, HI, NV, AS, GU) is provided here.

  6. Conformity Adequacy Review: Region 2

    Science.gov (United States)

    Resources are for air quality and transportation government and community leaders. Information on the adequacy/inadequacy of state implementation plans (SIPs) in EPA Region 2 (NJ, NY, PR, VI) is provided here.

  7. Conformity Adequacy Review: Region 1

    Science.gov (United States)

    Resources are for air quality and transportation government and community leaders. Information on the adequacy/inadequacy of state implementation plans (SIPs) in EPA Region 1 (CT, ME, MA, NH, RI, VT) is provided here.

  8. Conformity Adequacy Review: Region 10

    Science.gov (United States)

    Resources are for air quality and transportation government and community leaders. Information on the adequacy/inadequacy of state implementation plans (SIPs) in EPA Region 10 (AK, ID, OR, WA) is provided here.

  9. Conformity Adequacy Review: Region 4

    Science.gov (United States)

    Resources are for air quality and transportation government and community leaders. Information on the adequacy/inadequacy of state implementation plans (SIPs) in EPA Region 4 (AL, FL, GA, KY, MS, NC, SC, TN) is provided here.

  10. Conformity Adequacy Review: Region 6

    Science.gov (United States)

    Resources are for air quality and transportation government and community leaders. Information on the adequacy/inadequacy of state implementation plans (SIPs) in EPA Region 6 (AR, LA, NM, OK, TX) is provided here.

  11. Conformity Adequacy Review: Region 3

    Science.gov (United States)

    Resources are for air quality and transportation government and community leaders. Information on the adequacy/inadequacy of state implementation plans (SIPs) in EPA Region 3 (DE, DC, MD, PA, VA, WV) is provided here.

  12. Conformity Adequacy Review: Region 8

    Science.gov (United States)

    Resources are for air quality and transportation government and community leaders. Information on the adequacy/inadequacy of state implementation plans (SIPs) in EPA Region 3 (CO, MT, ND, SD, UT, WY) is provided here.

  13. National Marine Fisheries Service Regions

    Data.gov (United States)

    Department of Homeland Security — The NOAA Coastal Services Center's Legislative Atlas is a regional geographic information system (GIS) that provides spatial data for state and federal coastal and...

  14. The Landform Regions of Iowa

    Data.gov (United States)

    Iowa State University GIS Support and Research Facility — A landscape is a collection of land shapes or land forms. Landform regions are a grouping of individual landscape features that have a common geomophology. In Iowa,...

  15. Regional transport sector mitigation options

    International Nuclear Information System (INIS)

    Zhou, Peter

    1998-01-01

    The rationale for conducting climate change mitigation studies in the transport sector is on the premise that: The transport sector is the second largest consumer of fossil fuels in the region; The regional transport sector is an area with high opportunity for infrastructural development under UNFCCC financial mechanism; The regional transport sector is crucial in the SADC region for trade and coupled with the Trade Protocol will play a major role in development hence the need to make it efficient in terms of energy demand and provision of services; The sector offers many mitigation options but with a challenge to evaluate their energy saving and GHG saving potential and yet there is need to quantify possible emission reduction for possible future emission trading. This is also a sector with potential to qualify for financing through Clean Development Mechanism (CDM) recently stipulated in the Kyoto Protocol. (au)

  16. Regional differences of consumer preferences when shopping for regional products

    Directory of Open Access Journals (Sweden)

    Jitka Kalábová

    2013-01-01

    Full Text Available This paper presents partial results of a research on consumer preferences when shopping for groceries. It is focused on regional products and consumer preferences in relation to the country of origin of food products. The main objective of this paper is to find the existence of spatial relationships between spatial deployment of regional products and consumer preferences for regional products. It will be necessary to create a data model for monitoring the deployment of regional products and also a data model for tracking important indicators of consumer behavior in all regions of the Czech Republic. The results are based on questionnaire survey that was conducted within the period from October 2010 to January 2011 on a sample of 3767 respondents from the Czech Republic, via both online questionnaires and their printed version. For the data collection the questionnaire system ReLa, developed by the Department of Marketing and Trade at Faculty of Business and Economics at Mendel University in Brno, was used. Data was processed with statistical software STATISTICA (ver. 10. Spatial visualisation was processed with GIS software ArcGIS (ver. 10.1. Preferences for food of Czech origin were analysed in relation to identification criteria. The research results show that the origin of food has an important role in consumer purchase decision-making. There is no significant difference in importance of this factor based on gender of consumers, however, we could prove moderate dependence on respondent’s occupation, education and age. We could also experience regional differences in levels of preferences of local products or products of Czech origin in regard of 14 regions of the Czech Republic. χ2 (N = 3767 = 245.25; p < 0.001. Value of Pearson’s coefficient of contingency is 0.334.

  17. Regional energy-environmental planning

    International Nuclear Information System (INIS)

    Colavecchio, Antonio

    2007-01-01

    In consideration of the relationship existing between energy and environment, it's clear that tools are needed to reach a pre-emptive convergence of different interests coming from the management of these sectors. The main tool to realize the above-mentioned convergence of interests in the Regional Energy and Environment Plan (PEAR). The plan allows italian Regions to schedule and to address energy measures in their own area and to regulate Local entities functions [it

  18. Managing regional innovation strategy projects

    OpenAIRE

    Wolf, Patricia; Hanisch, Christoph

    2014-01-01

    This paper presents a qualitative interview study with 28 RIS project managers that aimed at understanding whether or not this is true in the context of regional innovation and what the specifics of managing regional innovation projects are. In taking up a recent claim for policy intervention studies which allow to “derive precise suggestions for their design and management”.  The study investigated the interrelation between the agility of the management approach and the achievements of RIS p...

  19. Competition for biomass. Regional imbalances

    International Nuclear Information System (INIS)

    Wiklund, S.E.; Bohlin, B.; Remes, M.; Aakesson, H.; Warnqvist, B.; Norrstroem, H.; Jonsson, Tomas

    1997-04-01

    The main aim of this study has been to investigate if a substantial increase in biofuel utilization may lead to pronounced regional differences in supply and demand, and what effects such imbalances could lead to. In the study the country has been split up into ten regions, from north to south, and it is confirmed that there would be an imbalance effect. confirmed that there would be an imbalance effect

  20. Regional and Global Monetary Cooperation

    OpenAIRE

    Mario Lamberte; Peter J. Morgan

    2012-01-01

    The increasing occurrence of national, regional, and global financial crises, together with their rising costs and complexity, have increased calls for greater regional and global monetary cooperation. This is particularly necessary in light of volatile capital flow movements that can quickly transmit crisis developments in individual countries to other countries around the world. Global financial safety nets (GFSNs) are one important area for monetary cooperation. This paper reviews the c...

  1. ASEAN: Regional Integration and Reforms

    OpenAIRE

    Mari PANGESTU; Lili Yan ING

    2015-01-01

    Over recent decades, the Association of Southeast Asian Nations (ASEAN) has advanced a policy of regional integration, starting with the ASEAN Free Trade Area, followed by the ASEAN+1 free trade agreements with its six main trading partners, and now with ASEAN+6. For ASEAN to further advance regional integration in the East Asian context, it should continue to focus on trade in goods, investment, and services, to smooth out the process of trade creation and investment realisation. East Asian ...

  2. Why are Trade Agreements Regional?

    OpenAIRE

    Zissimos, Ben

    2007-01-01

    This paper shows how distance may be used to coordinate on a unique equilibrium in which trade agreements are regional. Trade agreement formation is modeled as coalition formation. In a standard trade model with no distance between countries, a familiar problem of coordination failure arises giving rise to multiple equilibria; any one of many possible trade agreements can form. With distance between countries, and through strategic interaction in tariff setting, regional trade agreements gene...

  3. Social attitudes and regional inequalities

    Directory of Open Access Journals (Sweden)

    Vinko Muštra

    2014-03-01

    Full Text Available As the budgets of the European Union (EU become tighter, the questions about the effectiveness of EU’s expenditure, especially the most important parts such as Cohesion policy, are hotly debated. The aim of this paper is to examine whether the presence of social attitudes may influence the effectiveness of EU budget expenditure, measured by the level of regional inequalities. The analysis starts by focusing on individuals’ attitudes towards income from their own effort and income which is derived from other people’s effort, having in mind that individual actions depend on their attitudes. The next step establishes the link between the income from other people’s effort with the re-distributive dimension of the EU budget, considering that different attitudes among individuals in the EU could lead to significant differences in effectiveness of this redistributive policy among European regions and, consequently, diverse regional inequalities. Empirical research uses data for 27 EU countries observed over two waves of European Value Surveys: 1999-2000 (Wave 1 and 2008–2009 (Wave 2. The results indicate a significant role of social attitudes for regional inequalities, which raises the question of the appropriateness of simplification and uniform regional policy instruments in solving EU regional problems.

  4. Promotion and regional development. Implementation of regional productive development agencies. The case of Maule region, Chile

    Directory of Open Access Journals (Sweden)

    Enrique Yamil Alul González

    2010-12-01

    Full Text Available The Regional Productive Development Agencies implemented in Chile in 2006, were developed as a way to answer the longing desire to territorially decentralize, and that the own Regions be whom define their future. The Agencies have the responsibility to develop innovation and productive development Agendas in participative processes, which means with public, academic and private actors. Also, the Agencies have the mission to implement Competitive Improvement Plans-PMC (clusters in prioritized economic sectors by the own region. These PMC are leaded by private actors in each sector.

  5. REGIONAL ECONOMIC GROWTH THROUGH TOURISM. THE CASE OF REGION WEST

    Directory of Open Access Journals (Sweden)

    Dragoi Ionut

    2010-12-01

    Full Text Available The regional development should aim to correlate and integrate tourism among the other integrative parts of the regional and local development, taking into account the fact that a region’s prosperity as effect of tourism development may be shown clearly in several stages: on the spot (as a result of direct consumption of the tourist product, on short term (through continuous absorption of the work-force and encouraging the welcoming commerce and in the long run (concentrating capital for investment in the general infrastructure and the one of tourism, in structures of reception for tourism and in the development of urban services. The analysis of intra-regional disparities as part of the economic growth at the level of Region West starts off with the idea that each component county has a different landscape, which favored or inhibited their economic growth; in the same time, each component county has its own specific, which can be promoted through tourism, inducing in time a regional income, and respectively, a social-economic and cultural growth of less developed areas.

  6. THE ENVIRONMENT OF REGIONAL DEVELOPMENT FINANCIAL ANALYSIS

    OpenAIRE

    Bechis Liviu; MOSCVICIOV Andrei

    2012-01-01

    The paper presents the difference between the two concepts regionalism and regionalization. It also presents the three types of regionalism analysis depending on the dimension and the nature of the relations: regionalism at national level, transnational regionalism and international regionalism analysis.

  7. Regional Aspects of New Industrialization

    Directory of Open Access Journals (Sweden)

    Yakov Petrovich Silin

    2017-09-01

    Full Text Available In the article, the authors substantiate the need to consider the regional economic and other conditions when carrying out various essential transformations in the national economy of the country. We have argued the importance of new industrialization for overcoming the technological lag of the country and its regions and for supporting the large-scale structural transformations. We have proved that the complex set of the interconnected concepts and the theories of macro- and microlevels may be the theoretical platform for the paradigm of new industrialization. These are the theory of economic growth, the theory of the modernization of the economy, the theory of the change of technological ways during the industrial revolutions, theories of innovative development, developments in the field of the institutional theory. The authors have shown that the transition to new industrialization is the fundamental historical pattern for the majority of the countries of the world, including industrially developed ones. The purpose of the article is to identify the brightest tendencies and features of the development of the Ural macro-region in the years of market reforms as well as the definition of the strategic transformations in the context of the formation of new industrialization. The hypothesis of the research assumes that the revealed regional features of the Ural macroregion’s economic development are the prerequisites of its development as the centre of the modernization of the Russian economy. On the basis of the analysis of three groups of statistic data for the twenty-five year period of liberal and monetary reforms, the brightest tendencies and features of the development of the Ural macro-region are revealed. We have emphasized that the Ural macro-region has managed to keep its historically developed code — the industrial model of the economy, which have been developing for many decades. The authors have made a significant contribution of

  8. Users guide to REGIONAL-1: a regional assessment model

    International Nuclear Information System (INIS)

    Davis, W.E.; Eadie, W.J.; Powell, D.C.

    1979-09-01

    A guide was prepared to allow a user to run the PNL long-range transport model, REGIONAL 1. REGIONAL 1 is a computer model set up to run atmospheric assessments on a regional basis. The model has the capability of being run in three modes for a single time period. The three modes are: (1) no deposition, (2) dry deposition, (3) wet and dry deposition. The guide provides the physical and mathematical basis used in the model for calculating transport, diffusion, and deposition for all three modes. Also the guide includes a program listing with an explanation of the listings and an example in the form of a short-term assessment for 48 hours. The purpose of the example is to allow a person who has past experience with programming and meteorology to operate the assessment model and compare his results with the guide results. This comparison will assure the user that the program is operating in a proper fashion

  9. Regional Community and International Relations: the Volgograd Region Experience

    Directory of Open Access Journals (Sweden)

    Danakari Richard A.

    2016-06-01

    Full Text Available The article deals with the complex and controversial problems of the new regional communities’ formation and the impact of the interethnic relations sphere on them. The author notes that the processes of interaction between representatives of different cultures and civilizations, ethnic groups and religions have become increasingly controversial and tense in the context of continuous social dynamics. Similarly to the Russian society as a whole, regional communities are in a state of transitivity. They get transformed, they acquire new qualities such as multicasting and heterogeneity, multi-ethnicity and multi-confessionalism, fragmentarity and multiculturality. This fact increases the risks and uncertainties, problematizes future prospects. National non-governmental organizations are increasingly positioning themselves as civil society institutions at the present stage of social development at the regional level. They perform a difficult dual task: on the one hand, they ensure the preservation and development of history, native language, culture, ethnic traditions, and on the other hand, they work on the integration, on the common identity and the Russian nation formation. On the territory of the Volgograd region, largely due to the active cooperation of regional authorities and local authorities with national public associations, international and inter-confessional relations are stable. The basis of such activity is respect for history, native language, culture, tradition, religion, national dignity of all people in the region, regardless of their belonging to a certain ethnic group or religion. Over two decades of accumulated considerable experience of joint inter-ethnic dialogue and cooperation, provided tolerance and peace, harmony and mutual understanding between people of different ethnicities and religions in the country.

  10. Regional Transmission Projects: Finding Solutions

    Energy Technology Data Exchange (ETDEWEB)

    The Keystone Center

    2005-06-15

    The Keystone Center convened and facilitated a year-long Dialogue on "Regional Transmission Projects: Finding Solutions" to develop recommendations that will help address the difficult and contentious issues related to expansions of regional electric transmission systems that are needed for reliable and economic transmission of power within and across regions. This effort brought together a cross-section of affected stakeholders and thought leaders to address the problem with the collective wisdom of their experience and interests. Transmission owners sat at the table with consumer advocates and environmental organizations. Representatives from regional transmission organizations exchanged ideas with state and federal regulators. Generation developers explored common interests with public power suppliers. Together, the Dialogue participants developed consensus solutions about how to begin unraveling some of the more intractable issues surrounding identification of need, allocation of costs, and reaching consensus on siting issues that can frustrate the development of regional transmission infrastructure. The recommendations fall into three broad categories: 1. Recommendations on appropriate institutional arrangements and processes for achieving regional consensus on the need for new or expanded transmission infrastructure 2. Recommendations on the process for siting of transmission lines 3. Recommendations on the tools needed to support regional planning, cost allocation, and siting efforts. List of Dialogue participants: List of Dialogue Participants: American Electric Power American Transmission Company American Wind Energy Association California ISO Calpine Corporation Cinergy Edison Electric Institute Environmental Defense Federal Energy Regulatory Commission Great River Energy International Transmission Company ISO-New England Iowa Public Utility Board Kanner & Associates Midwest ISO National Association of Regulatory Utility Commissioners National Association

  11. Obesity and Regional Immigrant Density.

    Science.gov (United States)

    Emerson, Scott D; Carbert, Nicole S

    2017-11-24

    Canada has an increasingly large immigrant population. Areas of higher immigrant density, may relate to immigrants' health through reduced acculturation to Western foods, greater access to cultural foods, and/or promotion of salubrious values/practices. It is unclear, however, whether an association exists between Canada-wide regional immigrant density and obesity among immigrants. Thus, we examined whether regional immigrant density was related to obesity, among immigrants. Adult immigrant respondents (n = 15,595) to a national population-level health survey were merged with region-level immigrant density data. Multi-level logistic regression was used to model the odds of obesity associated with increased immigrant density. The prevalence of obesity among the analytic sample was 16%. Increasing regional immigrant density was associated with lower odds of obesity among minority immigrants and long-term white immigrants. Immigrant density at the region-level in Canada may be an important contextual factor to consider when examining obesity among immigrants.

  12. Vital coalitions, vital regions; cooperation in sustainable, regional development

    NARCIS (Netherlands)

    Horlings, L.G.

    2010-01-01

    Many rural regions in Europe are undergoing a dynamic transition, driven by forces of urbanisation and agricultural development, new patterns of production and consumption, and new societal demands. However, while the historical rural-urban divide is eroding, rural landscapes are becoming more

  13. Regional climate services: A regional partnership between NOAA and USDA

    Science.gov (United States)

    Climate services in the Midwest and Northern Plains regions have been enhanced by a recent addition of the USDA Climate Hubs to NOAA’s existing network of partners. This new partnership stems from the intrinsic variability of intra and inter-annual climatic conditions, which makes decision-making fo...

  14. 75 FR 28564 - Fisheries of the Northeast Region; Pacific Region

    Science.gov (United States)

    2010-05-21

    ... overfishing or an overfished condition. SUMMARY: This action serves as a notice that NMFS, on behalf of the... to overfishing and are in an overfished condition. Also, in the Northeast Region, Southern New England/Mid-Atlantic windowpane is subject to overfishing and Georges Bank winter flounder is in an...

  15. Regional welfare disparities and regional economic growth in Vietnam

    NARCIS (Netherlands)

    Nguyen Huy Hoang,

    2009-01-01

    This study had multiple objectives. First, it aimed at examining regional inequality
    in several welfare variables, such as health and education during the 1998-2004 period, and
    per capita income over time from 1990 to 2006. The first objective of the study was to gain
    a better

  16. Regional profile, energy-impacted communities: Region VIII

    Energy Technology Data Exchange (ETDEWEB)

    None

    1979-03-01

    This report has data on population, administration, finance, housing, health and safety, human services, education, and water and sewage for 325 energy-impacted communities. A review of current and potential energy developments in the region shows over 900 energy resource impacts listed for the 325 impacted communities. Coal development represents over one-third of the developments listed. Communities reporting coal development are distributed as follows: Colorado (36), Montana (42), North Dakota (61), South Dakota (13), Utah (73), and Wyoming (35). Energy-conversion initiatives represent another high incidence of energy-resource impact, with uranium development following closely with 83 communities reporting uranium development impact in the region. These projections indicate continued development of regional energy resources to serve national energy requirements. The 325 impacted communities as reported: Colorado (46), Montana (73), North Dakota (62), South Dakota (21), Utah (80), and Wyoming (43) follow a distribution pattern similar to that of future projects which illustrates that no area of the region will escape the impacts of energy development. (ERA citation 04:041706)

  17. Regional Solutions for Regional Problems: East Timor and Solomon Islands

    Science.gov (United States)

    2012-03-21

    perceived Australia in this light and were openly opposed to Australian leadership of the multi- national mission. Prime Minister Mahathir bin Mohamad of...such as Malaysia’s Prime Minister Mahathir , expressed concern over Australia’s forceful responses, regional leaders were broadly supportive and

  18. Regional cooperation prospects in Korea

    International Nuclear Information System (INIS)

    Yoon, Wan Ki

    2006-01-01

    The Republic of Korea follows a well-established nuclear nonproliferation policy and could consider regional cooperation as proposed by many nuclear experts over the years. Real problems exist in establishing cooperation, but as the nuclear industry continues to grow, the motivation increases. The US should be a partner in the regional cooperation also. This paper summarizes significant advances made by the NNCA in applying remote monitoring technologies to support international safeguards in the ROK, providing the technical foundation for the use of these technologies for transparency between partner countries. Concrete steps are proposed to form an institutional and then a governmental approach for transparency in the use of nuclear material and even, eventual establishment of a regional safeguards inspection regime. (author)

  19. Security assurances and regional stability

    International Nuclear Information System (INIS)

    Sanders, B.

    1995-01-01

    This paper discusses whether and how security assurances affect political stability in geographic regions. Before embarking on what is necessarily a limited analysis of a complex subject, I point out that the subject is by no means new. For centuries, vast areas of the world have been affected by forces used against them by more powerful States, which at one time or another incorporated large parts of them into overseas colonies or contiguous empires. The new factors are the emancipation of those areas into independent regions, made up of States that play their own parts in international affairs, and the possession by a handful of Powers, outside or on the edge of those regions, of a specific form of superior force: nuclear weapons. (author)

  20. Employment growth and regional development

    DEFF Research Database (Denmark)

    Eriksson, Rikard; Hansen, Høgni Kalsø; Winther, Lars

    2017-01-01

    This paper explores the potential drivers behind uneven regional development in the context of employment growth in Denmark and Sweden. In particular, we are interested in the roles of urbanization, industrial change and the rise of the new economy as manifested in the growth of the two economies...... in 2002–2007. The aim of this paper is, therefore, to analyse the impact of a number of key industrial sectors on regional employment growth in the two countries. The empirical analysis is based on longitudinal matched employer–employee data retrieved from official registers in each economy from 2002...... economies, we find that, although in general these economies react relatively similarly to changes, embarking on a narrower analysis of the individual sectors reveals marked national differences. This indicates that context matters in the analysis of regional economic dynamics in terms of structure, system...

  1. Regional indexes for France. Methodology

    International Nuclear Information System (INIS)

    2006-01-01

    According to the U.S. Department of Energy, an estimated 25% of the GNP is affected by weather-related events. The variations in temperature - even small ones - can also have long-lasting effects on the operational results of a company. Among other, the Energy supply sector is sensitive to weather risks: a milder or harsher than usual winter leads to a decrease or increase of energy consumption. The price of electricity on power trading facilities like Powernext is especially sensitive to odd changes in temperatures. Powernext and Meteo-France (the French meteorological agency) have joined expertise in order to promote the use of weather indices in term of decision making or underlying of hedging tools to energy actors, end users from any other sector of activity and specialists of the weather risk hedging. The Powernext Weather indices are made from information collected by Meteo-France's main observation network according to the norms of international meteorology, in areas carefully selected. The gross data are submitted to a thorough review allowing the correction of abnormalities and the reconstitution of missing data. Each index is fashioned to take into account the economic activity in the various regions of the country as represented by each region's population. This demographic information represents a fair approximation of the weight of the regional economic activity. This document presents the calculation methodology of regional weather indexes for France. Each regional index covers an homogenous area in terms of temperature represented by the biggest city. Five reference cities are used to represent the 22 economical regions of France (Paris Orly, Lyon, Marignane, Bordeaux and Strasbourg). (J.S.)

  2. Social Facilitation: the Kaliningrad Region and Russian Mainland Regions

    Directory of Open Access Journals (Sweden)

    Toropov Pavel

    2015-03-01

    Full Text Available The authors look at the concept of social facilitation as a possible component of Russian social consolidation in the course of social reforms. The article focuses on the results of an empirical study of the levels and characteristics of competence in social facilitation, which is here understood as the ability to apply certain knowledge and systems of skills and as a success rate of actions based on experience in improving the conditions of social development. The study was conducted in the Kaliningrad region in 2012—2013. The data was obtained through a survey of 400 respondents using the authors’ methodology encompassing eight basic elements of competence and a structured interview aimed at a better understanding of the subject of the study and attitudes towards it. The data is compared against the results of a similar study in two regions of central Russia with similar conditions. The results suggest a disharmonic and inconsistent structure of competence in social facilitation, low motivation for social activity in youth, and a narrow range of ideas about possible areas of personal activities in the current conditions. Gender differences are identified in the level and structure of competence. The authors believe that certain differences in competence components identified through mathematical methods are determined by the geographical characteristics of the Kaliningrad region — its exclave nature, a relatively small territory, and proximity to the EU countries. It is stressed that the regional conditions affecting motivation, forms and areas of activities, and structure of experience should be taken into account in selecting means and methods of organising youth activities. They can also serve as a basis for the regional youth policy.

  3. Regional cooperative agreement for the Asia and Pacific region

    International Nuclear Information System (INIS)

    Anon.

    1981-01-01

    Among the means available to the International Atomic Energy Agency to promote cooperative efforts in the nuclear field is the Regional Cooperative Agreement (RCA) for Research, Development, and Training related to Nuclear Science and Technology for the Asia and Pacific Region. Under the terms of this agreement, which came into force on June 12, 1972, participating countries aim to promote and coordinate research, development, and training projects in nuclear fields through collaborative efforts among relevant national institutions in the region. The Agency's role is to provide organizational, administrative, advisory, technical, and financial assistance when needed to secure successful execution of the projects undertaken within the framework of the RCA. Although this presentation deals primarily with the benefits of regional cooperation under the agreement, a review of the RCA would be somewhat imbalanced without a mention of its shortcomings. One of the principal impediments to more rapid progress, as is the case in many other areas, is financing. There is no stable source of funding outside the research contract program and, the likelihood of large-scale UNDP support notwithstanding, a greater willingness on the part of participating Member States to support the program along with the development of a greater sense of common purpose are called for. In this connection serious consideration is being given to the possibility of establishing an Asian Centre for Research and Training, an institute that would bring together scientists from the region to collaborate on problems common to the RCA countries. A study group has already been convened to investigate the feasibility of this proposal

  4. Regional Competitiveness and Its Implications for Development

    OpenAIRE

    Daryono Soebagyo; Triyono Triyono; Yuli Tri Cahyono

    2015-01-01

    This study was conducted to identify regional competitiveness in some areas of Central Java. Regional competitiveness became one of the issues in regional development policy since the enactment of local autonomy.Measurement of regional competitiveness has been mostly done through ranking as a benchmark the competitiveness of the region. Mapping regional competitiveness in Indonesia has been made to all counties and cities, which shows the competitiveness ranking of each region. Competitivenes...

  5. Geospatial Absorption and Regional Effects

    Directory of Open Access Journals (Sweden)

    IOAN MAC

    2009-01-01

    Full Text Available The geospatial absorptions are characterized by a specific complexity both in content and in their phenomenological and spatial manifestation fields. Such processes are differentiated according to their specificity to pre-absorption, absorption or post-absorption. The mechanisms that contribute to absorption are extremely numerous: aggregation, extension, diffusion, substitution, resistivity (resilience, stratification, borrowings, etc. Between these mechanisms frequent relations are established determining an amplification of the process and of its regional effects. The installation of the geographic osmosis phenomenon in a given territory (a place for example leads to a homogenization of the geospatial state and to the installation of the regional homogeneity.

  6. Deep mycoses in Amazon region.

    Science.gov (United States)

    Talhari, S; Cunha, M G; Schettini, A P; Talhari, A C

    1988-09-01

    Patients with deep mycoses diagnosed in dermatologic clinics of Manaus (state of Amazonas, Brazil) were studied from November 1973 to December 1983. They came from the Brazilian states of Amazonas, Pará, Acre, and Rondônia and the Federal Territory of Roraima. All of these regions, with the exception of Pará, are situated in the western part of the Amazon Basin. The climatic conditions in this region are almost the same: tropical forest, high rainfall, and mean annual temperature of 26C. The deep mycoses diagnosed, in order of frequency, were Jorge Lobo's disease, paracoccidioidomycosis, chromomycosis, sporotrichosis, mycetoma, cryptococcosis, zygomycosis, and histoplasmosis.

  7. Hydrodynamics of post CHF region

    International Nuclear Information System (INIS)

    Ishii, M.; De Jarlais, G.

    1984-04-01

    Among various two-phase flow regimes, the inverted flow in the post-dryout region is relatively less well understood due to its special heat transfer conditions. The review of existing data indicates further research is needed in the areas of basic hydrodynamics related to liquid core disintegration mechanisms, slug and droplet formations, entrainment, and droplet size distributions. In view of this, the inverted flow is studied in detail both analytically and experimentally. Criteria for initial flow regimes in the post-dryout region are given. Preliminary models for subsequent flow regime transition criteria are derived together with correlations for a mean droplet diameter based on the adiabatic simulation data

  8. Meteorological tracers in regional planning

    International Nuclear Information System (INIS)

    Mueller, K.H.

    1974-11-01

    Atmospheric tracers can be used as indicators to study both the ventilation of an urban region and its dispersion meteorology for air pollutants. A correlation analysis applied to the space-time dependent tracer concentrations is able to give transfer functions, the structure and characteristic parameters of which describe the meteorological and topographical situation of the urban region and its surroundings in an integral manner. To reduce the number of persons usually involved in a tracer experiment an automatic air sampling system had to be developed

  9. Regional cooperation on nuclear safety

    International Nuclear Information System (INIS)

    Kato, W.Y.; Chen, J.H.; Kim, D.H.; Simmons, R.B.V.; Surguri, S.

    1985-01-01

    A review has been conducted of a number of multi-national and bilateral arrangements between governments and between utility-sponsored organizations which provide the framework for international cooperation in the field of nuclear safety. These arrangements include the routine exchange operational data, experiences, technical reports and regulatory data, provision of special assistance when requested, collaboration in safety research, and the holding of international conferences and seminars. Areas which may be better suited for cooperation on a regional basis are identified. These areas include: exchange of operational data and experience, sharing of emergency planning information, and collaboration in safety research. Mechanisms to initiate regional cooperation in these areas are suggested

  10. Governance in regional development planning?

    DEFF Research Database (Denmark)

    Galland, Daniel

    2008-01-01

    The purpose of this paper is to lay part of the groundwork for a new project aimed at exploring governance aspects concerned with regional development planning (RDP) in Denmark. The fundamental objective is to help establish and clarify a number of research questions to delve into the conditions...... and opportunities for anchoring and implementing such RDP. The paper mainly adopts a descriptive approach to portray tentative pathways to explore and discuss regional governance structures, procedures and practices that are being developed in establishing new RDP processes, strategies and plans....

  11. Cophasal regions on the Sun

    Energy Technology Data Exchange (ETDEWEB)

    Kozhevnikov, N I [Moskovskij Gosudarstvennyj Univ. (USSR). Gosudarstvennyj Astronomicheskij Inst. ' ' GAISh' '

    1977-01-01

    The subsequent development of the phenomenological model of the solar convective zone is carried out. The cophasal region, in which unilateral movement of the matter is supposed, is considered. Quantitative relations for kinematic parameters of solar sport groups, agreeing well with the observations, are given. The cophasal regions distribution due to their linear dimensions is obtained. It is shown that the effective depth of the convective zone is found to change with the phase of the activity cycle: less in the minimum and more in the maximum of activity.

  12. Extinction of H II regions

    International Nuclear Information System (INIS)

    Israel, F.P.; Kennicutt, R.C.

    1980-01-01

    Visual extinction of H II regions in nine nearby galaxies as derived from the ratio of the radio continuum emission to H-alpha emission is systematically larger than visual extinction deduced from the Balmer lines alone, if one assumes a value Av/E(B-V) 3. An optically-limited sample of about 30 extragalactic H II regions has a mean extinction of 1.7 m in the visual while about 1.2 m is not seen in the reddening of the Balmer lines. Both reddening and extinction decreases with increasing galactic radius, at least for M33 and M101

  13. Unges uddannelsesvalg i Region Midtjylland

    DEFF Research Database (Denmark)

    Høyen, Marianne; Tjørnelund, Henning

    Rapporten belyser nogle af de faktorer, som har betydning, når unge i Region Midtjylland vælger eller fravælger at få en uddannelse. Godt 2.000 unge er blevet spurgt om deres geografiske, økonomiske og familiemæssige baggrund og deres overvejelser i forhold til uddannelse. Fælles for de unge er......, at de var 18 år i år 2002 og boede i Region Midtjylland. Det vil sige, at de nu er omkring 25 år og allerede har truffet flere valg, der har betydning for deres fremtidige uddannelsesniveau og tilknytning til arbejdsmarkedet...

  14. Renewable Energy in European Regions

    NARCIS (Netherlands)

    Krozer, Yoram

    2012-01-01

    The regional dynamics of energy innovation, in particular the shift from fossil fuels to renewable energy in the EU, is discussed within the framework of neo-Schumpeterian theory. The EU’s 4.2% average annual growth in renewable energy production in the last decade has been accompanied by diverging

  15. Higher Education and European Regionalism.

    Science.gov (United States)

    Paterson, Lindsay

    2001-01-01

    Speculates about the relationship between two fundamental social changes occurring in Europe: the development of a mass higher education system and the slow decay of the old states that were inherited from the 19th century, eroded from below by various movements for national and regional autonomy, and eroded from above by the growing power and…

  16. China from a regional perspective

    DEFF Research Database (Denmark)

    Schmidt, Johannes Dragsbæk

    The paper explains the political economic background for China's insertion to the world system. It furthermore expands on a critical perspective on China's soft power strategy. It goes on to discuss China's foreign policy strategy towards Southeast Asia and China's rivalry with the US in the region....

  17. Pacific Northwest regional assessment program

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    The Pacific Northwest (comprised of the states of Alaska, Idaho, Montana, Oregon, Washington and Wyoming) can by several measures be regarded as a national warehouse of fossil energy resources. This condition coupled with an evolving national policy stressing utilization of fossil fuels in the near term prior to development of more advanced technologies for energy supply, could result in the imposition of major changes in the region's environmental, socioeconomic and possibly health status. The objective of the Pacific Northwest Regional Assessment Program is to establish and exercise an integrated analytical assessment program for evaluation of these potential changes that may result from various energy development or conservation scenarios. After consideration of a variety of approaches to integrated assessment at a regional level, Pacific Northwest Laboratories (PNL) has concluded that dynamic simulation techniques provide the best available approach to evaluating the issues pertinent to the Northwest. As a result, the PNW Regional Assessment Program has been structured in a framework involving ten sectors. Each of these sectors involve their own submodels that receive information either from outside the model as exogenous inputs or from other sector submodels

  18. Biocapacity optimization in regional planning

    Science.gov (United States)

    Guo, Jianjun; Yue, Dongxia; Li, Kai; Hui, Cang

    2017-01-01

    Ecological overshoot has been accelerating across the globe. Optimizing biocapacity has become a key to resolve the overshoot of ecological demand in regional sustainable development. However, most literature has focused on reducing ecological footprint but ignores the potential of spatial optimization of biocapacity through regional planning of land use. Here we develop a spatial probability model and present four scenarios for optimizing biocapacity of a river basin in Northwest China. The potential of enhanced biocapacity and its effects on ecological overshoot and water consumption in the region were explored. Two scenarios with no restrictions on croplands and water use reduced the overshoot by 29 to 53%, and another two scenarios which do not allow croplands and water use to increase worsened the overshoot by 11 to 15%. More spatially flexible transition rules of land use led to higher magnitude of change after optimization. However, biocapacity optimization required a large amount of additional water resources, casting considerable pressure on the already water-scarce socio-ecological system. Our results highlight the potential for policy makers to manage/optimize regional land use which addresses ecological overshoot. Investigation on the feasibility of such spatial optimization complies with the forward-looking policies for sustainable development and deserves further attention.

  19. Snakes of the Guianan region

    NARCIS (Netherlands)

    Hoogmoed, M.S.

    1982-01-01

    The study of snaks from the Guianan region got an early start in 1705 when several species were pictured by Merian. As relatively large proportion of the snakes described by Linnaeus originated from Surinam. Interest for and knowledge of this group of animals steadily increased in the 18th and 19th

  20. GLOBALIZATION & REGIONALIZATION IN INTERNATIONAL TRADE

    Directory of Open Access Journals (Sweden)

    Ramona Frunză

    2009-12-01

    Full Text Available The concept of globalization refers to the growing interdependence of countries, resulting from the increasing integration of trade, finance, investments, labor markets and ideas in one globalmarketplace. The most important elements of this process are the international trade and the cross-border investment flows. Economic globalization has increased the specialization of workers, while the companies compete in global markets. Even globalization has recently become a common topic in academic discourse, many economists focused, from the 1980s and 1990s, in addition to globalization, on regionalization - the growth of networks of interdependence within multinational regions of the world. The recent decades arecharacterized by the fact that the world trade grew faster than world output, which implies that an increasing share of world GDP crosses international borders. The trend is explained, mostly, by thesubstantially declining of the trade barriers during the same period, as a result of successive trade negotiation rounds under the auspices of the GATT/WTO, unilateral trade liberalization and regional tradeagreements. Even there are global connections between all the countries, the strongest political and economic integration is being created within a few specific regions of the world: Europe, North America and East Asia.

  1. Regional Highlights of Climate Change

    Science.gov (United States)

    David L. Peterson; J.M. Wolken; Teresa Hollingsworth; Christian Giardina; J.S. Littell; Linda Joyce; Chris Swanston; Stephen Handler; Lindsey Rustad; Steve McNulty

    2014-01-01

    Climatic extremes, ecological disturbance, and their interactions are expected to have major effects on ecosystems and social systems in most regions of the United States in the coming decades. In Alaska, where the largest temperature increases have occurred, permafrost is melting, carbon is being released, and fire regimes are changing, leading to a...

  2. Hybrid technology for regional railcars

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Christoph [DVV Eurailpress, Hamburg (Germany)

    2012-05-15

    It is possible to reduce the fuel consumed by diesel railcars operating short-distance regional services by making use of newly developed hybrid technology. Voith Turbo is setting out to produce evidence of that through two completely different projects. (orig.)

  3. Education and Italian Regional Development

    Science.gov (United States)

    Di Liberto, Adriana

    2008-01-01

    In this paper, we study the connection between growth and human capital in a convergence regression for the panel of Italian regions. We include measures of average primary, secondary and tertiary education. We find that increased education seems to contribute to growth only in the South. Decomposing total schooling into its three constituent…

  4. Regionalization--Deja Vu Again?

    Science.gov (United States)

    Hallanan, Edwin J.

    The subject of regionalization or the consolidation of schools has been a major issue of discussion and educational research for the past 15 years. A fact that has come out of the research is that consolidation is expensive. Yet, some observers continue to recommend consolidating the remaining school districts. When schools are closed, children…

  5. Assessing Regional Attitudes about Entrepreneurship

    OpenAIRE

    Loveridge, Scott; Miller, Steven R.; Komarek, Timothy M.; Satimanon, Thasanee

    2012-01-01

    Much of the current discussion on factors that influence entrepreneurial activity focuses on availability of human, social, and financial capitals, regional economic conditions, and dynamics of population. We discuss social attitudes toward entrepreneurship and how attitudes may influence entrepreneurial activity. We analyze telephone survey questions designed to gauge attitudes towards community entrepreneurship. High school entrepreneurship career exploration and positive spin-offs from loc...

  6. Transport, logistics and the region

    NARCIS (Netherlands)

    Langen, de P.W.

    2010-01-01

    Cargo transport and logistics have a huge impact on sustainable (regional) economic development. Two broad (policy) challenges are center stage: enhancing co-location of logistics activities and improving efficiency in intermodal transport chains. Academic research can provide relevant insights for

  7. Regional labour market dynamics in the Netherlands

    NARCIS (Netherlands)

    Broersma, Lourens; van Dijk, J.

    This article analyzes the response of regional labor markets in the Netherlands to region-specific labor demand shocks. Previous studies show remarkable differences in response between regions in European countries and regions in the United States. The analysis shows that, in Dutch regions, the

  8. 32 CFR 1605.7 - Region Manager.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Region Manager. 1605.7 Section 1605.7 National... ORGANIZATION Region Administration § 1605.7 Region Manager. (a) Subject to the direction and control of the Director of Selective Service, the Region Manager of Selective Service for each region shall be in...

  9. Shaping Regional Strategies of Multinational Corporations

    DEFF Research Database (Denmark)

    Gilbert, Dirk Ulrich; Heinicke, Patrick; Rasche, Andreas

    This paper examines the factors that drive the success of multinational corporations (MNCs) in their pursuit of regional strategies. We develop a comprehensive regional success factor model to investigate the effects of regional management autonomy and regional product/service adaption...... management autonomy and regional product/service adaption are higly contingent upon contextual influences on MNCs....

  10. First regional CSM program planned.

    Science.gov (United States)

    1982-09-01

    6 countries in the English-speaking Caribbean (Antigua, Barbados, Dominica, St. Kitts/Nevis, St. Lucia, and St. Vincent) are scheduled to form the 1st regional contraceptive social marketing program. The program will be under the auspices of the Barbados Family Planning Association. By combining resources, contraceptive social marketing should be able to effectively augment family planning activities in smaller countries where individual programs wuld be too costly. The regional program will also determine whether program elements from 1 country in a region are relevant in other countries. The Caribbean region as a whole has experienced a general decline in both crude birth rates and fertility rates during the past 15 years; however, adolescent fertility rates remain high and an average of 46% of the populations of Caribbean countries are under 15 years of age. Although heavy emigration has traditionally curbed population increases, new restrictive immigration laws are expected. Further increases in the working age population will contribute to already high unemployment rates and hinder economic development. The 6 countries selected for the social marketing program are receptive to innovative family planning approaches and have the basic marketing infrastructure required. Community-based distribution programs already in operation in these countries distribute condoms, oral contraceptives, and barrier methods. The success of these programs has plateaued, and there is a need for delivery systems capable of reaching broader segments of the population. The social marketing program will be phased in to ensure local acceptance among national leaders and consumers. The regional program hopes to borrow elements from Jamaica's contraceptive social marketing program to avoid the costs involved in starting a program from scratch. A major innovation will be the use of mass media advertising for contraceptives.

  11. Sustainable development of Russian regions

    Directory of Open Access Journals (Sweden)

    V. D. Kuz’menkova

    2016-01-01

    Full Text Available Sustainable development of administrative-territorial units (ATU refers to the main directions of Russian Federation state policy to ensure the security of the national economy to meet the vital needs of people and the preservation of such a possibility for the future generations. The article describes and analyzes the factors that have the most significant impact on the level of ATE development. The dynamics of the gross output of agriculture in Russia and its critical evaluation are presents. It was revealed that the development of the region is the basis of the national economy security. At present, the concept of “sustainable development” in Russia is relevant and the role of regions in the sustainable development of the Russian Federation is constantly increasing. Stability of self-financing of the regional economy is achieved through conducting effective fiscal, financial, credit, tax and price policy, establishment of equal inter-budgetary relations with the federal center, the development of the securities market, increasing the volume of exports. Conducted research allowed: to identify the main factors influencing the sustainable development of Russia regions. The reasons for the backlog of economy of the Smolensk region of the nationwide growth rate and direction of their elimination are examined. Formation of the forecast of domestic agriculture development in the period up to 2020 should be based on the priority position of the industry in the agricultural sector, which is determined by its decisive role in meeting the population’s needs for basic food products. Prospective volumes of production of major agricultural products are based on the need to meet the challenges provided by the Russian Federation Government Decree.

  12. Building a competitive regional innovation environment : the regional development platform method as a tool for regional innovation policy

    OpenAIRE

    Harmaakorpi, Vesa

    2004-01-01

    The study focuses on building a regional innovation policy tool that takes into account the demands of the present techno-economic and socio-institutional paradigms. Regions are seen to be strongly dependent on their history. The competitiveness of a region is based on the regional resource configurations. In a turbulent world these resource configurations have to be renewed over time setting demands for regional dynamic capabilities. This study emphasises five regional dynamic capabilities: ...

  13. Regionalism vs. Multilateralism : An overview of the effects of Regionalism

    OpenAIRE

    Pöntinen, Martina

    2012-01-01

    The Purpose of this dissertation was to first find the motives behind and causes for regionalism and to explore the advantages and disadvantages of the phenomenon. Secondly, the intension was to determine the benefits of a possible bilateral FTA between Australia and China and whether a bilateral trade agreement would be more beneficial for the Australian economy than waiting for a multilateral WTO regulated framework. The research was conducted through an extensive literature review...

  14. Models of Regional Modernization of the Donbass Region

    Directory of Open Access Journals (Sweden)

    Konstantin Viktorovich Pavlov

    2016-03-01

    Full Text Available The article deals with the methodical approach to the assessment of a level of development of post-industrial and neoindustrial models of economic modernization in regional aspect on the basis of various indicators. The proposed approach is approved with use of the statistical materials characterizing the state of economy in the regions of Donbass. The strategy of development of Donbass areas and their industrial cities would have to be based (we mean the situation if there were no military operations on this territory on the basis of the model of neoindustrialization assuming development of the sphere of the hi-tech industry, automation and a computerization of productive forces, replacement of physical work by intellectual labor that is radically capable to change nature of work and structure of labor balance of this macro-region. Branches and sectors of a socio-economic complex of the Donbass region using achievements of fundamental and applied science, engineering and design thought for increase in a share of automation, a computerization and mechanization of workplaces, physical and brainwork prior to the beginning of a political conflict in Ukraine have the potential of development. The authors also pay attention to need of studying the agglomerative effect from interaction of the cities and areas of the Donbass euroregion. It is connected, first of all, with development of vertical and horizontal mechanisms of active use of potential of so-called “cities-kernels”, capable to make the catalyzing impact on production, social infrastructure, creation and development of new perspective branches in the cities-satellites.

  15. Regional Integration of Renewable Energies; Integracion Regional de energias Renovables

    Energy Technology Data Exchange (ETDEWEB)

    Amador Guerra, J; Dominguez Bravo, J [Ciemat.Madrid (Spain)

    2000-07-01

    The aim of this report is to show how Energetic Planning and Territorial Policy should be working together for a better integration of Renewable Energies into Region. This Integration should to contemplate social, economic and environmental aspects of the territory. The report has been classified into 7 items: planning, energetic scenarios, technology transfer for Renewable Energies dissemination, barriers for this dissemination, environmental aspects, European Union Policy and Decision Support Systems (and specially GIS). (Author) 54 refs.

  16. Desarrollo multinivel: Implicaciones macro-regional, local y micro- regional

    Directory of Open Access Journals (Sweden)

    José Guadalupe Vargas Hernández

    2006-11-01

    Full Text Available Este trabajo se propone analizar las implicaciones del desarrollo en los niveles macro-regional, local y micro- regional, a partir de la hipótesis central de la teoría del desarrollo que plantea que el desarrollo económico traerá consigo el desarrollo político y social. Después de hacer de un acercamiento conceptual al desarrollo, se repasan brevemente las teorías del desarrollo existentes como herramientas de análisis de la realidad. En la discusión se concluye que los procesos de desarrollo locales y regionales requieren de una transformación sustancial de las relaciones negociadas entre los agentes económicos y los actores políticos. Ante el paulatino retroceso que en las sociedades contemporáneas está teniendo el Estado de bienestar, uno de los principales retos es el empoderamiento de las organizaciones sociales y comunitarias para que desempeñen activamente su rol en los procesos de desarrollo local y regional.

  17. Regional innovation systems in the Lisbon strategy

    NARCIS (Netherlands)

    Bruijn, P.J.M. de; Lagendijk, A.

    2005-01-01

    This contribution explores the framing of the concept of Regional Innovation Systems (RISs) within European ecoruomic policies. Regional innovation systems are analytically and empirically assessed within the policy corltext of the Lisbon strategy, with special reference to regional dimensions in

  18. Allegheny County Kane Regional Center Census

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — Total number of residents in each Kane Regional Center facility by race and gender. The Kane Regional Centers are skilled nursing and rehabilitation centers run by...

  19. Regional Innovation Policies in MERCOSUR : Obstacles and ...

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

    ... review existing regional cooperation initiatives, identify sectors with strong potential for regional cooperation, review other experiences in regional cooperation for innovation (European Union - EU, North American Free Trade Agreement - NAFTA), and propose institutional arrangements for promoting innovation among ...

  20. Regional Competitive Intelligence: Benchmarking and Policymaking

    OpenAIRE

    Huggins , Robert

    2010-01-01

    Benchmarking exercises have become increasingly popular within the sphere of regional policymaking in recent years. The aim of this paper is to analyse the concept of regional benchmarking and its links with regional policymaking processes. It develops a typology of regional benchmarking exercises and regional benchmarkers, and critically reviews the literature, both academic and policy oriented. It is argued that critics who suggest regional benchmarking is a flawed concept and technique fai...

  1. Dust deposit in recirculation regions

    International Nuclear Information System (INIS)

    Griemert, R.

    1985-03-01

    The present report shows investigations, which have been carried out in a closed duct at forward and backward facing steps. Distribution of fluid velocity and fluid fluctuations in and normal to main flow direction as well as the distribution of Reynolds shear stress have been measured. The mass transfer downstream of a backward facing step has been investigated as well. By using graphite-, copper-, tin- and rubber dust, conditions of deposition have been defined experimentally. A serie of photos shows the filling of a recirculation region downstream of a backward facing step with graphite dust. The present investigations allow to avoid deposition of dust in recirculation regions by selecting the fluid numbers in an appropriate way. (orig.) [de

  2. Marine cloud brightening: regional applications.

    Science.gov (United States)

    Latham, John; Gadian, Alan; Fournier, Jim; Parkes, Ben; Wadhams, Peter; Chen, Jack

    2014-12-28

    The general principle behind the marine cloud brightening (MCB) climate engineering technique is that seeding marine stratocumulus clouds with substantial concentrations of roughly monodisperse sub-micrometre-sized seawater particles might significantly enhance cloud albedo and longevity, thereby producing a cooling effect. This paper is concerned with preliminary studies of the possible beneficial application of MCB to three regional issues: (1) recovery of polar ice loss, (2) weakening of developing hurricanes and (3) elimination or reduction of coral bleaching. The primary focus is on Item 1. We focus discussion herein on advantages associated with engaging in limited-area seeding, regional effects rather than global; and the levels of seeding that may be required to address changing current and near-term conditions in the Arctic. We also mention the possibility that MCB might be capable of producing a localized cooling to help stabilize the West Antarctic Ice Sheet.

  3. Regional Assessment of Supplementation Project

    International Nuclear Information System (INIS)

    1991-10-01

    The Fish and Wildlife Program of the Northwest Power Planning Council (NPPC) prescribes several approaches to achieve its goal of doubling the salmon and steelhead runs of the Columbia River. Among those approaches are habitat restoration, improvements in adult and juvenile passage at dams and artificial propagation. Supplementation will be a major part of the new hatchery programs. The purpose of the Regional Assessment of Supplementation Project (RASP) is to provide an overview of ongoing and planned supplementation activities, to construct a conceptual framework and model for evaluating the potential benefits and risks of supplementation and to develop a plan for better regional coordination of research and monitoring and evaluation of supplementation. RASP has completed its first year of work. Progress toward meeting the first year's objectives and recommendations for future tasks are contained in this report

  4. Regional Anaesthesia in Thyroid Surgery

    International Nuclear Information System (INIS)

    Akhtar, N.; Abbas, S.A.

    2013-01-01

    Thyroidectomy is usually performed under general anaesthesia with endotracheal intubation. Bilateral cervical plexus block has been occasionally used as sole anaesthesia technique for this operation in certain parts of world. Indications for regional anaesthesia elsewhere in the world are patient's preference and associated marked cardio-respiratory disease. This is the first report of thyroidectomy done solely under bilateral cervical plexus block in Pakistan. The patient had thyroid cancer and was medically compromised due to cardiac failure with ejection fraction of 25%. Bilateral cervical plexus block was performed to avoid the high risk with general anaesthesia. Total thyroidectomy was done while patient remained painfree during the procedure and top-up local anaesthetic infiltration was not required. Patient remained stable without any morbidity. Positive experience from this case indicates that regional anaesthesia with monitored anaesthesia care is safer than general anaesthesia in high risk patients and could be offered to selective thyroidectomy candidates. (author)

  5. Regional cooperation for emergency plan

    International Nuclear Information System (INIS)

    Chu, D.S.L.; Liu, P.C.

    1981-01-01

    It has become increasingly evident since the Three Mile Island (TMI) accident that a sound emergency plan is indispensable to the overall nuclear power generation program. In some developing countries in Eastern Aisa, the availability of manpower resources and facilities to handle a nuclear power plant accident are rather limited. Therefore, the establishment of a regional mutual emergency plan is deemed necessary. A preliminary idea concerning this establishment is presented for deliberation by this Conference

  6. Evolution of the European region

    International Nuclear Information System (INIS)

    Jeger, Eh.

    1984-01-01

    The problem on geochronological study of the European region is covered. The most ancient age values are determined by U-Pb methods by zircones from paragneisses. The model of evolution, being in agreement with the data obtained by U-Pb and Rb-Sr methods, is considered. The history of the Schwarzwald development is typical for the continent as a whole. The diagram of evolution of primary 87 Sr/ 86 Sr for orthogneisses and granites in France is given

  7. Regional power and local ecologies

    DEFF Research Database (Denmark)

    Lawrence, D.; Philip, G.; Wilkinson, K.

    2017-01-01

    Archaeological data tend to be gathered at the local level: human agency also operates at this scale. By combining data from multiple surveys conducted within a larger area, it is possible to use local datasets to obtain a perspective on regional trends in settlement, population, and human activity...... and climate are then examined side by side in order to assess long-term human interactions. Crown Copyright (C) 2015 Published by Elsevier Ltd. All rights reserved....

  8. Regional Management Plan: Summary report

    International Nuclear Information System (INIS)

    Drobny, N.L.

    1986-01-01

    This summary report describes the results of a 16-month project to develop a Regional Management Plan for low-level radioactive waste management in a seven-state area. The seven states are Indiana, Iowa, Michigan, Minnesota, Missouri, Ohio, and Wisconsin. These states have formed the Midwest Interstate Low-Level Radioactive Waste Commission in accord with Congressional requirements established in 1980. 14 refs., 13 figs., 9 tabs

  9. Regional ground-water system

    International Nuclear Information System (INIS)

    Long, J.

    1985-01-01

    The Containment and Isolation Working Group considered issues related to the postclosure behavior of repositories in crystalline rock. This working group was further divided into subgroups to consider the progress since the 1978 GAIN Symposium and identify research needs in the individual areas of regional ground-water flow, ground-water travel time, fractional release, and cumulative release. The analysis and findings of the Ground-Water Regime Subgroup are presented

  10. Il Lazio: una regione economica?

    OpenAIRE

    Toscano Pia

    2000-01-01

    Economic growth of Italy has proceeded in several directions through different ages from the unity of the nation on. Only in recent years, e.g., has Latium caught up with the most highly developed regions of northern Italy, aiming, like the north-east area, at a productive system made up of small and medium-sized industrial enterprises, and furthermore, concentrating on the tertiary sector which produces services for enterprises. Only in Rome and district has the economic development been con...

  11. FLOSSWorld Africa regional workshop agenda

    CSIR Research Space (South Africa)

    Tucker, KC

    2006-02-01

    Full Text Available their activities – does this differ from country to country, and does it differ from Europe? Comparisons with previous studies such as FLOSS, FLOSS-US, FLOSS-Japan. • How are local FLOSS activities in target countries related with other institutions (public... administration, companies, schools, universities, etc.)? • What is the present and possible future impact of FLOSS activities on the labour market, education, governance, and the economy of developing countries? FLOSSWorld Africa Regional Agenda 4 FLOSSWorld...

  12. Southeast Regional Carbon Sequestration Partnership

    Energy Technology Data Exchange (ETDEWEB)

    Kenneth J. Nemeth

    2006-08-30

    The Southeast Regional Carbon Sequestration Partnership's (SECARB) Phase I program focused on promoting the development of a framework and infrastructure necessary for the validation and commercial deployment of carbon sequestration technologies. The SECARB program, and its subsequent phases, directly support the Global Climate Change Initiative's goal of reducing greenhouse gas intensity by 18 percent by the year 2012. Work during the project's two-year period was conducted within a ''Task Responsibility Matrix''. The SECARB team was successful in accomplishing its tasks to define the geographic boundaries of the region; characterize the region; identify and address issues for technology deployment; develop public involvement and education mechanisms; identify the most promising capture, sequestration, and transport options; and prepare action plans for implementation and technology validation activity. Milestones accomplished during Phase I of the project are listed below: (1) Completed preliminary identification of geographic boundaries for the study (FY04, Quarter 1); (2) Completed initial inventory of major sources and sinks for the region (FY04, Quarter 2); (3) Completed initial development of plans for GIS (FY04, Quarter 3); (4) Completed preliminary action plan and assessment for overcoming public perception issues (FY04, Quarter 4); (5) Assessed safety, regulatory and permitting issues (FY05, Quarter 1); (6) Finalized inventory of major sources/sinks and refined GIS algorithms (FY05, Quarter 2); (7) Refined public involvement and education mechanisms in support of technology development options (FY05, Quarter 3); and (8) Identified the most promising capture, sequestration and transport options and prepared action plans (FY05, Quarter 4).

  13. Heartland Alliance for Regional Transmission

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, Nancy [Climate and Energy Project, Inc., Hutchinson, KS (United States)

    2017-03-15

    The Heartland Alliance for Regional Transmission (HART) will foster a candid, productive conversation among stakeholders that identifies challenges to and benefits from a massive build out of wind generation and transmission across the Southwest Power Pool. Based on the outcomes of those deliberations, HART will develop and deliver an ambitious, coordinated, peer-to-peer outreach effort that spans the SPP to improve market acceptance for wind.

  14. Nordic Regional Report; Selected Issues

    OpenAIRE

    International Monetary Fund

    2013-01-01

    This Selected Issues paper elaborates findings and discussions of 2013 Cluster Consultation Nordic Regional report. The countries have close economic and financial ties and face some common challenges and shared risks, such as large banking sectors and high household debt. The economic performance of the four continental Nordic economies (Denmark, Finland, Norway, and Sweden—Nordic-4) ranks among the advanced economic development circle. It is analyzed that the large Nordic banking systems su...

  15. Super magnets for interaction regions

    International Nuclear Information System (INIS)

    Biallas, G.; Fowler, W.; Diebold, R.

    1977-01-01

    The feasibility of using superconducting magnets in the beam interaction regions of particle accelerators is discussed. These higher field magnets can be shorter, leaving more room for detectors, but also must have a large aperture and magnetic shielding. The ''kissing geometry'' was investigated, and design and scaling considerations are given. A rough estimate of the cost of such superconducting magnets is given as an aid to the selection of interaction geometry

  16. Regional Integration of Renewable Energies

    International Nuclear Information System (INIS)

    Amador Guerra, J.; Dominguez Bravo, J.

    2000-01-01

    The aim of this report is to show how Energetic Planning and Territorial Policy should be working together for a better integration of Renewable Energies into Region. This Integration should to contemplate social, economic and environmental aspects of the territory. The report has been classified into 7 items: planning, energetic scenarios, technology transfer for Renewable Energies dissemination, barriers for this dissemination, environmental aspects, European Union Policy and Decision Support Systems (and specially GIS). (Author) 54 refs

  17. Corporate Corruption in Russian Regions

    OpenAIRE

    Ledeneva, A. V.

    2011-01-01

    To understand corporate corruption in Russia and to develop both effective anti-corruption policies at the macro level and anti-corruption strategies at the firm level one has to move beyond the predominant paradigm and to disaggregate its measurement. This article outlines the results of a pilot survey of CEOs of leading companies operating in the Russian regions with regard to their use of informal practices.

  18. Structure of the human vitreoretinal border region

    DEFF Research Database (Denmark)

    Heegaard, Steffen

    1994-01-01

    Øjenpatologi, vitreoretinal border region, inner limiting membrane, retina, topographical variation, human......Øjenpatologi, vitreoretinal border region, inner limiting membrane, retina, topographical variation, human...

  19. EPA Region 3 Quality Management Plans

    Science.gov (United States)

    Has links to resources that describe the Region's Quality Assurance Program, which is a collection of the Region's ongoing quality assurance (QA) policies, procedures, responsibilities and management systems.

  20. Selected Regional Judicial Officer Cases, 2005 - Present

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset contains selected cases involving EPA's Regional Judicial Officers (RJOs) from 2005 to present. EPA's Regional Judicial Officers (RJOs) perform...

  1. Quantifying China's regional economic complexity

    Science.gov (United States)

    Gao, Jian; Zhou, Tao

    2018-02-01

    China has experienced an outstanding economic expansion during the past decades, however, literature on non-monetary metrics that reveal the status of China's regional economic development are still lacking. In this paper, we fill this gap by quantifying the economic complexity of China's provinces through analyzing 25 years' firm data. First, we estimate the regional economic complexity index (ECI), and show that the overall time evolution of provinces' ECI is relatively stable and slow. Then, after linking ECI to the economic development and the income inequality, we find that the explanatory power of ECI is positive for the former but negative for the latter. Next, we compare different measures of economic diversity and explore their relationships with monetary macroeconomic indicators. Results show that the ECI index and the non-linear iteration based Fitness index are comparative, and they both have stronger explanatory power than other benchmark measures. Further multivariate regressions suggest the robustness of our results after controlling other socioeconomic factors. Our work moves forward a step towards better understanding China's regional economic development and non-monetary macroeconomic indicators.

  2. Wind power in Arctic regions

    International Nuclear Information System (INIS)

    Lundsager, P.; Ahm, P.; Madsen, B.; Krogsgaard, P.

    1993-07-01

    Arctic or semi-arctic regions are often endowed with wind resources adequate for a viable production of electricity from the wind. Only limited efforts have so far been spent to introduce and to demonstrate the obvious synergy of combining wind power technology with the problems and needs of electricity generation in Arctic regions. Several factors have created a gap preventing the wind power technology carrying its full role in this context, including a certain lack of familiarity with the technology on the part of the end-users, the local utilities and communities, and a lack of commonly agreed techniques to adapt the same technology for Arctic applications on the part of the manufacturers. This report is part of a project that intends to contribute to bridging this gap. The preliminary results of a survey conducted by the project are included in this report, which is a working document for an international seminar held on June 3-4, 1993, at Risoe National Laboratory, Denmark. Following the seminar a final report will be published. It is intended that the final report will serve as a basis for a sustained, international effort to develop the wind power potential of the Arctic and semi-arctic regions. The project is carried out by a project group formed by Risoe, PA Energy and BTM Consult. The project is sponsored by the Danish Energy Agency of the Danish Ministry of Energy through grant no. ENS-51171/93-0008. (au)

  3. How to teach regional anesthesia.

    Science.gov (United States)

    Bröking, Katrin; Waurick, René

    2006-10-01

    The demand for peripheral nerve blocks and neuroaxial blocks from both patients and surgeons has increased over the last few years. This change in attitude towards regional anesthesia is prompted by the insight that adequate perioperative pain management leads to earlier ambulation, shorter hospital stay, reduced cost and increased patient satisfaction. To avoid serious complications of these techniques structured residency programs need to be available. Until 2004, the Residency Review Committee for Anesthesiology in the United States required a minimum of 50 epidurals, 40 spinals and 40 peripheral nerve blocks during residency. Similarly, the German Society for Anesthesia and Intensive Care required 100 neuroaxial blocks and 50 peripheral nerve blocks. In 2004 the American Society of Regional Anesthesia and Pain Medicine endorsed standardized guidelines for regional anesthesia fellowships which regulate the administrative, equipment and educational demands. This review introduces the reader to the different teaching methods available, including cadaver workshops, three-dimensional videoclips, video filming, ultrasound guidance and acoustic assist devices as well as demonstrating their advantages and disadvantages. Moreover, an overview is given of future residency training programs, which integrate administrative, material and educative demands as well as the teaching means into the daily clinical routine.

  4. Insertion and crossing region design

    International Nuclear Information System (INIS)

    Wienands, U.; Beloshitsky, P.

    2001-01-01

    This article is the summary of the 5-afternoon tutorial on insertions for circular machines. Roughly half the course (Part 1) was spent discussing interaction regions, We start by recapitulating basic beam optics including building blocks. This provides the tools to analyze the basic structure of interaction regions and explore the parameter space. This simple example is then successively refined and made more realistic. Examples of realized interaction regions for both hadron and electron machines are shown and their salient features and differences explained. A brief discussion of solenoid-decoupling brings Part 1 to a close. In Part 2 we discussed various utility sections. Dispersion suppressors are presented in detail discussing the principles as well as the practical implementation of flexible suppressors using LEP as an example. Injection schemes, both single-turn and multi-turn stacking, are presented in depth. The matching of wiggler and undulator insertions and a discussion of the impact of these devices on beam parameters closes out Part 2

  5. Regional hyperthermia of the liver

    International Nuclear Information System (INIS)

    Petrovich, Z.; Langholz, B.; Astrahan, M.; Emami, B.; Oleson, J.R.

    1989-01-01

    From 1981 through 1986, 49 patients with metastatic liver tumors received deep regional hyperthermia in phase I protocols in six major medical centers in the United States. Adenocarcinoma was seen in 80% of patients with colon as the primary site in 26%. The remaining patients had the following histological diagnoses: Soft tissue sarcoma in seven, malignant melanoma in two and transitional cell carcinoma in one. Deep regional hyperthermia treatments with a BSD-1000 annular phased array were given once or twice a week with a total of 167 treatment sessions, mean 3.4 (range 1 to 8). In addition to deep regional hyperthermia, 17 patients received radiotherapy, and 14 received chemotherapy. The median survival for all patients was 25 weeks. Complete response was obtained in two patients and partial response in four patients. An additional ten patients had nominal response. There was no complete or partial response among the 14 hyperthermia alone treated patients. Of the 26 patients who presented with severe pain, five had complete pain relief, five had partial relief and the majority had a lesser degree of pain relief or no pain relief. Acute treatment toxicity consisted of pain in ten, systemic temperature increase to 39 0 C in four tachycardia in two, claustrophobia in one. The majority of patients did not experience acute toxicity. No late toxicity was recorded in this group of 49 patients. (orig./MG)

  6. Dvigateli regional'nogo stroitel'stva. Vlijanie regional'nyh politicheskih organizacij na sotrudnichestvo universitetov v regione Baltijskogo morja [Motors for regional development: impact on regional political organizations on the university cooperation in the Baltic Sea region

    Directory of Open Access Journals (Sweden)

    Ewert Stefan

    2010-01-01

    Full Text Available Educational co-operation is one of the main aspects of the regional political agenda in the Baltic Sea Region. The article analyzes the political impact of the organizations, as perceived by the universities in the region and political decision-makers on national and regional levels. Based on the success of the OECD in becoming an influential actor in educational policies, this article discusses different strategies for the regional political organizations to enhance their influence.

  7. Regional projection of climate impact indices over the Mediterranean region

    Science.gov (United States)

    Casanueva, Ana; Frías, M.; Dolores; Herrera, Sixto; Bedia, Joaquín; San Martín, Daniel; Gutiérrez, José Manuel; Zaninovic, Ksenija

    2014-05-01

    Climate Impact Indices (CIIs) are being increasingly used in different socioeconomic sectors to transfer information about climate change impacts and risks to stakeholders. CIIs are typically based on different weather variables such as temperature, wind speed, precipitation or humidity and comprise, in a single index, the relevant meteorological information for the particular impact sector (in this study wildfires and tourism). This dependence on several climate variables poses important limitations to the application of statistical downscaling techniques, since physical consistency among variables is required in most cases to obtain reliable local projections. The present study assesses the suitability of the "direct" downscaling approach, in which the downscaling method is directly applied to the CII. In particular, for illustrative purposes, we consider two popular indices used in the wildfire and tourism sectors, the Fire Weather Index (FWI) and the Physiological Equivalent Temperature (PET), respectively. As an example, two case studies are analysed over two representative Mediterranean regions of interest for the EU CLIM-RUN project: continental Spain for the FWI and Croatia for the PET. Results obtained with this "direct" downscaling approach are similar to those found from the application of the statistical downscaling to the individual meteorological drivers prior to the index calculation ("component" downscaling) thus, a wider range of statistical downscaling methods could be used. As an illustration, future changes in both indices are projected by applying two direct statistical downscaling methods, analogs and linear regression, to the ECHAM5 model. Larger differences were found between the two direct statistical downscaling approaches than between the direct and the component approaches with a single downscaling method. While these examples focus on particular indices and Mediterranean regions of interest for CLIM-RUN stakeholders, the same study

  8. Regional insertion: an emergent approach; Insercao regional: uma abordagem emergente

    Energy Technology Data Exchange (ETDEWEB)

    Serra, M T.F.; Nascimento Teixeira, P do [ELETROBRAS, Rio de Janeiro, RJ (Brazil). Dept. de Meio Ambiente

    1990-12-31

    The Brazilian Electrical Sector incorporates new variables that expressing the extensive spectrum of environmental impacts in the take of decisions, referring to the viability of realizing a electrical undertaking, attends the several restrictions that are important by the sector and by the society in the environment area and promotes the adequate generation of liquid benefits, consequential of the electrical undertaking. Due to these factors, the Electrical Sector is improving the concept of regional insertion, with the sectorial expansion in long-dated and the created demand in the environmental and social area, focalizing the solution for these questions. (C.G.C.). 1 fig, 2 tabs.

  9. Regional air pollution over Malaysia

    Science.gov (United States)

    Krysztofiak, G.; Catoire, V.; Dorf, M.; Grossmann, K.; Hamer, P. D.; Marécal, V.; Reiter, A.; Schlager, H.; Eckhardt, S.; Jurkat, T.; Oram, D.; Quack, B.; Atlas, E.; Pfeilsticker, K.

    2012-12-01

    During the SHIVA (Stratospheric Ozone: Halogen Impacts in a Varying Atmosphere) campaign in Nov. and Dec. 2011 a number of polluted air masses were observed in the marine and terrestrial boundary layer (0 - 2 km) and in the free troposphere (2 - 12 km) over Borneo/Malaysia. The measurements include isoprene, CO, CO2, CH4, N2O, NO2, SO2 as primary pollutants, O3 and HCHO as secondary pollutants, and meteorological parameters. This set of trace gases can be used to fingerprint different sources of local and regional air pollution (e.g., biomass burning and fossil fuel burning, gas flaring on oil rigs, emission of ships and from urban areas, volcanic emissions, and biogenic emissions). Individual sources and location can be identified when the measurements are combined with a nested-grid regional scale chemical and meteorological model and lagrangian particle dispersion model (e.g., CCATT-BRAMS and FLEXPART). In the case of the former, emission inventories of the primary pollutants provide the basis for the trace gas simulations. In this region, the anthropogenic influence on air pollution seems to dominate over natural causes. For example, CO2 and CH4 often show strong correlations with CO, suggesting biomass burning or urban fossil fuel combustion dominates the combustion sources. The study of the CO/CO2 and CH4/CO ratios can help separate anthropogenic combustion from biomass burning pollution sources. In addition, these ratios can be used as a measure of combustion efficiency to help place the type of biomass burning particular to this region within the wider context of fire types found globally. On several occasions, CH4 enhancements are observed near the ocean surface, which are not directly correlated with CO enhancements thus indicating a non-combustion-related CH4 source. Positive correlations between SO2 and CO show the anthropogenic influence of oil rigs located in the South China Sea. Furthermore, SO2 enhancements are observed without any increase in CO

  10. The politics of inter-regionalism: relations between international regional organizations

    NARCIS (Netherlands)

    Vleuten, J.M. van der; Ribeiro Hoffman, A.; Reinalda, B.

    2013-01-01

    As the development of relations between international regional organizations, inter-regionalism denotes a relatively recent phenomenon. Largely due to systemic bipolarity, inter-regional relations remained limited to 'dialogue partnerships' between the European Community (EC) and other regional

  11. Assessment of homogeneity of regions for regional flood frequency analysis

    Science.gov (United States)

    Lee, Jeong Eun; Kim, Nam Won

    2016-04-01

    This paper analyzed the effect of rainfall on hydrological similarity, which is an important step for regional flood frequency analysis (RFFA). For the RFFA, storage function method (SFM) using spatial extension technique was applied for the 22 sub-catchments that are partitioned from Chungju dam watershed in Republic of Korea. We used the SFM to generate the annual maximum floods for 22 sub-catchments using annual maximum storm events (1986~2010) as input data. Then the quantiles of rainfall and flood were estimated using the annual maximum series for the 22 sub-catchments. Finally, spatial variations in terms of two quantiles were analyzed. As a result, there were significant correlation between spatial variations of the two quantiles. This result demonstrates that spatial variation of rainfall is an important factor to explain the homogeneity of regions when applying RFFA. Acknowledgements: This research was supported by a grant (11-TI-C06) from Advanced Water Management Research Program funded by Ministry of Land, Infrastructure and Transport of Korean government.

  12. Regional energy system optimization - Potential for a regional heat market

    International Nuclear Information System (INIS)

    Karlsson, Magnus; Gebremedhin, Alemayehu; Klugman, Sofia; Henning, Dag; Moshfegh, Bahram

    2009-01-01

    Energy supply companies and industrial plants are likely to face new situations due to, for example, the introduction of new energy legislation, increased fuel prices and increased environmental awareness. These new prerequisites provide companies with new challenges but also new possibilities from which to benefit. Increased energy efficiency within companies and increased cooperation between different operators are two alternatives to meet the new conditions. A region characterized by a high density of energy-intensive processes is used in this study to find the economic potential of connecting three industrial plants and four energy companies, within three local district heating systems, to a regional heat market, in which different operators provide heat to a joint district heating grid. Also, different investment alternatives are studied. The results show that the economical potential for a heat market amounts to between 5 and 26 million EUR/year with payback times ranging from two to eleven years. However, the investment costs and the net benefit for the total system need to be allotted to the different operators, as they benefit economically to different extents from the introduction of a heat market. It is also shown that the emissions of CO 2 from the joint system would decrease compared to separate operation of the systems. However, the valuation of CO 2 emissions from electricity production is important as the difference of emitted CO 2 between the accounting methods exceeds 650 kton/year for some scenarios

  13. Regional energy integration in Africa

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-06-15

    This report is the first publication produced within the framework of the WEC's Africa Regional Action Plan as part of the 2005-2007 Work Programme. Presently, over 80% of the total energy consumption in Africa is based on traditional biomass used mostly for cooking. This lack of access to modern energy is holding back economic and social development for 1.6 billion people around the world. The situation is particularly grave in sub-Sahara Africa where over 80% of the population lives in rural areas and the average electrification rate is less than 5%. At least 50 million new connections are needed to provide electricity to supply the non-connected areas in Africa. The over 700 million potential customers represented by these new connections provide a major business opportunity. It is now widely recognised that development assistance, bilateral aid, multilateral financing institutions, a multitude of international aid agencies, NGOs and others have failed to make a significant difference. A new approach is required, otherwise the number of people without access to electricity will continue to grow, and none of the Millennium Development Goals set by the United Nations will be achieved. This regional report highlights key factors that affect cooperative energy projects. The geopolitical context, investment climate and appropriate regulation are just as important as the institutional and technical capacity required to execute many of these projects. The report identifies four key benefits of regional integration: improved security of supply and accessibility; increased economic efficiency; enhanced environmental quality and broader development of renewable resources.

  14. Regional energy integration in Africa

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-06-15

    This report is the first publication produced within the framework of the WEC's Africa Regional Action Plan as part of the 2005-2007 Work Programme. Presently, over 80% of the total energy consumption in Africa is based on traditional biomass used mostly for cooking. This lack of access to modern energy is holding back economic and social development for 1.6 billion people around the world. The situation is particularly grave in sub-Sahara Africa where over 80% of the population lives in rural areas and the average electrification rate is less than 5%. At least 50 million new connections are needed to provide electricity to supply the non-connected areas in Africa. The over 700 million potential customers represented by these new connections provide a major business opportunity. It is now widely recognised that development assistance, bilateral aid, multilateral financing institutions, a multitude of international aid agencies, NGOs and others have failed to make a significant difference. A new approach is required, otherwise the number of people without access to electricity will continue to grow, and none of the Millennium Development Goals set by the United Nations will be achieved. This regional report highlights key factors that affect cooperative energy projects. The geopolitical context, investment climate and appropriate regulation are just as important as the institutional and technical capacity required to execute many of these projects. The report identifies four key benefits of regional integration: improved security of supply and accessibility; increased economic efficiency; enhanced environmental quality and broader development of renewable resources.

  15. Solar active region display system

    Science.gov (United States)

    Golightly, M.; Raben, V.; Weyland, M.

    2003-04-01

    The Solar Active Region Display System (SARDS) is a client-server application that automatically collects a wide range of solar data and displays it in a format easy for users to assimilate and interpret. Users can rapidly identify active regions of interest or concern from color-coded indicators that visually summarize each region's size, magnetic configuration, recent growth history, and recent flare and CME production. The active region information can be overlaid onto solar maps, multiple solar images, and solar difference images in orthographic, Mercator or cylindrical equidistant projections. Near real-time graphs display the GOES soft and hard x-ray flux, flare events, and daily F10.7 value as a function of time; color-coded indicators show current trends in soft x-ray flux, flare temperature, daily F10.7 flux, and x-ray flare occurrence. Through a separate window up to 4 real-time or static graphs can simultaneously display values of KP, AP, daily F10.7 flux, GOES soft and hard x-ray flux, GOES >10 and >100 MeV proton flux, and Thule neutron monitor count rate. Climatologic displays use color-valued cells to show F10.7 and AP values as a function of Carrington/Bartel's rotation sequences - this format allows users to detect recurrent patterns in solar and geomagnetic activity as well as variations in activity levels over multiple solar cycles. Users can customize many of the display and graph features; all displays can be printed or copied to the system's clipboard for "pasting" into other applications. The system obtains and stores space weather data and images from sources such as the NOAA Space Environment Center, NOAA National Geophysical Data Center, the joint ESA/NASA SOHO spacecraft, and the Kitt Peak National Solar Observatory, and can be extended to include other data series and image sources. Data and images retrieved from the system's database are converted to XML and transported from a central server using HTTP and SOAP protocols, allowing

  16. 5. Regional focus: Central Europe

    International Nuclear Information System (INIS)

    Livernash, R.; Levy, B.S.; Hertzman, C.

    1992-01-01

    The industrial regions of Central Europe are so choked by pollution that the health of children is impaired and the lives of adults shortened. The paper discusses this situation under the following headings: industrial development and energy efficiency; dependence on coal; the extent of the damage (atmospheric pollution: low stacks, auto emissions; water pollution (agricultural sources); forest and soil damage; transboundary pollution); managing market forces (impact of higher prices, managing growth: the case of motor vehicles); looking for least-cost solutions (coping with coal, adjusting the fuel mix, energy conservation); developing effective laws and regulations

  17. REGIONAL JUSTICE AND NATIONAL UNITY

    Directory of Open Access Journals (Sweden)

    V. P. Loguinov

    2012-01-01

    Full Text Available In regions of Russia who lag behind the national average both in pay and in economic development, the problem of raising living standards should be solved through a nation-wide program which would be believed by peoples of Russia regardless of ethnicity. It should include creation of jobs, leveling of wages, abolition of fees for education and for a significant portion of health services, reducing utility tariffs and prices for public transportation, introduction of an income-based progressive taxation system, improving law enforcement activities, etc. Considerable attention is paid to the analysis of macroeconomic indicators of Russian economy in recent years.

  18. Radiotherapy in the maxillofacial region

    International Nuclear Information System (INIS)

    Niederdellmann, H.; Otten, J.E.; Lachard, J.

    1984-01-01

    Radiotherapeutic treatment of patients with tumours in the oral, perignathic, facial, and neck region can lead to considerable complications under irradiation and any time after irradiation if dental aspects are not considered. A dental treatment should therefore be planned in close cooperation with a dental-, oral-, and orthodontic centre before starting radiotherapy. In many cases, a preparing treatment is not possible for important reasons. Therefore, it is very important that patients who are being or have been treated with radiation are dealt with extremely carefully. (orig.) [de

  19. Regional insertion: an emergent approach

    International Nuclear Information System (INIS)

    Serra, M.T.F.; Nascimento Teixeira, P. do

    1989-01-01

    The Brazilian Electrical Sector incorporates new variables that expressing the extensive spectrum of environmental impacts in the take of decisions, referring to the viability of realizing a electrical undertaking, attends the several restrictions that are important by the sector and by the society in the environment area and promotes the adequate generation of liquid benefits, consequential of the electrical undertaking. Due to these factors, the Electrical Sector is improving the concept of regional insertion, with the sectorial expansion in long-dated and the created demand in the environmental and social area, focalizing the solution for these questions. (C.G.C.). 1 fig, 2 tabs

  20. Pacific Northwest regional AGU meeting

    Science.gov (United States)

    Hyndman, Roy

    The 27th Annual Pacific Northwest Regional American Geophysical Union Meeting, held September 25 and 26, 1980, was hosted by the Pacific Geoscience Centre at the Institute of Ocean Sciences, near Victoria, British Columbia. A total of 79 papers was presented to the 150 registrants in six general sessions: seismology; electromagnetic induction; general geophysics; volcanology; hydrology; and oceanography, and in three special symposia: ‘The Queen Charlotte-Fairweather fault system and other active faults of the Pacific Northwest’ ‘Coastal circulation in the northeast Pacific’ and ‘Studies of the eruption of Mount St. Helens.’