WorldWideScience

Sample records for central dogma sequence-specific

  1. Central Dogma Goes Digital.

    Science.gov (United States)

    Lin, Yihan; Elowitz, Michael B

    2016-03-17

    In this issue of Molecular Cell, Tay and colleagues (Albayrak et al., 2016) describe a new technique to digitally quantify the numbers of protein and mRNA in the same mammalian cell, providing a new way to look at the central dogma of molecular biology. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Channeling the Central Dogma.

    Science.gov (United States)

    Calabrese, Ronald L

    2014-05-21

    How do neurons and networks achieve their characteristic electrical activity, regulate this activity homeostatically, and yet show population variability in expression? In this issue of Neuron, O'Leary et al. (2014) address some of these thorny questions in this theoretical analysis that starts with the Central Dogma. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. The rise and fall of central dogmas.

    Science.gov (United States)

    Klein, George; Klein, Eva

    2016-01-01

    Stimulated by Francis Cricks "central dogma of molecular biology" open to criticism and rebuttal, five statements are formulated on current notions of tumor biology, inviting the criticism of the reader.

  4. Francis Crick, DNA, and the Central Dogma

    Science.gov (United States)

    Olby, Robert

    1970-01-01

    This essay describes how Francis Crick, ex-physicist, entered the field of biology and discovered the structure of DNA. Emphasis is upon the double helix, the sequence hypothesis, the central dogma, and the genetic code. (VW)

  5. The Central Dogma of Molecular Biology

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 14; Issue 3. The Central Dogma of Molecular Biology - A Retrospective after Fifty Years. Michel Morange. General Article Volume 14 Issue 3 March 2009 pp 236-247. Fulltext. Click here to view fulltext PDF. Permanent link:

  6. Does the central dogma still stand?

    Science.gov (United States)

    Koonin, Eugene V

    2012-08-23

    Prions are agents of analog, protein conformation-based inheritance that can confer beneficial phenotypes to cells, especially under stress. Combined with genetic variation, prion-mediated inheritance can be channeled into prion-independent genomic inheritance. Latest screening shows that prions are common, at least in fungi. Thus, there is non-negligible flow of information from proteins to the genome in modern cells, in a direct violation of the Central Dogma of molecular biology. The prion-mediated heredity that violates the Central Dogma appears to be a specific, most radical manifestation of the widespread assimilation of protein (epigenetic) variation into genetic variation. The epigenetic variation precedes and facilitates genetic adaptation through a general 'look-ahead effect' of phenotypic mutations. This direction of the information flow is likely to be one of the important routes of environment-genome interaction and could substantially contribute to the evolution of complex adaptive traits.

  7. Nucleotide Manipulatives to Illustrate the Central Dogma

    OpenAIRE

    Sonja B. Yung; Todd P. Primm

    2015-01-01

    The central dogma is a core concept that is critical for introductory biology and microbiology students to master. However, students often struggle to conceptualize the processes involved, and fail to move beyond simply memorizing the basic facts. To encourage critical thinking, we have designed a set of magnetic nucleotide manipulatives that allow students to model DNA structure, along with the processes of replication, transcription, and translation.

  8. Nucleotide Manipulatives to Illustrate the Central Dogma

    Directory of Open Access Journals (Sweden)

    Sonja B. Yung

    2015-08-01

    Full Text Available The central dogma is a core concept that is critical for introductory biology and microbiology students to master. However, students often struggle to conceptualize the processes involved, and fail to move beyond simply memorizing the basic facts. To encourage critical thinking, we have designed a set of magnetic nucleotide manipulatives that allow students to model DNA structure, along with the processes of replication, transcription, and translation.

  9. Does the central dogma still stand?

    OpenAIRE

    Koonin, Eugene V

    2012-01-01

    Abstract Prions are agents of analog, protein conformation-based inheritance that can confer beneficial phenotypes to cells, especially under stress. Combined with genetic variation, prion-mediated inheritance can be channeled into prion-independent genomic inheritance. Latest screening shows that prions are common, at least in fungi. Thus, there is non-negligible flow of information from proteins to the genome in modern cells, in a direct violation of the Central Dogma of molecular biology. ...

  10. Does the central dogma still stand?

    Directory of Open Access Journals (Sweden)

    Koonin Eugene V

    2012-08-01

    Full Text Available Abstract Prions are agents of analog, protein conformation-based inheritance that can confer beneficial phenotypes to cells, especially under stress. Combined with genetic variation, prion-mediated inheritance can be channeled into prion-independent genomic inheritance. Latest screening shows that prions are common, at least in fungi. Thus, there is non-negligible flow of information from proteins to the genome in modern cells, in a direct violation of the Central Dogma of molecular biology. The prion-mediated heredity that violates the Central Dogma appears to be a specific, most radical manifestation of the widespread assimilation of protein (epigenetic variation into genetic variation. The epigenetic variation precedes and facilitates genetic adaptation through a general ‘look-ahead effect’ of phenotypic mutations. This direction of the information flow is likely to be one of the important routes of environment-genome interaction and could substantially contribute to the evolution of complex adaptive traits. Reviewers This article was reviewed by Jerzy Jurka, Pierre Pontarotti and Juergen Brosius. For the complete reviews, see the Reviewers’ Reports section.

  11. Genomes, Proteomes and the Central Dogma

    Science.gov (United States)

    Franklin, Sarah; Vondriska, Thomas M.

    2011-01-01

    Systems biology, with its associated technologies of proteomics, genomics and metabolomics, is driving the evolution of our understanding of cardiovascular physiology. Rather than studying individual molecules or even single reactions, a systems approach allows integration of orthogonal datasets from distinct tiers of biological data, including gene, RNA, protein, metabolite and other component networks. Together these networks give rise to emergent properties of cellular function and it is their reprogramming that causes disease. We present five observations regarding how systems biology is guiding a revisiting of the central dogma: (i) de-emphasizing the unidirectional flow of information from genes to proteins; (ii) revealing the role of modules of molecules as opposed to individual proteins acting in isolation; (iii) enabling discovery of novel emergent properties; (iv) demonstrating the importance of networks in biology; and (v) adding new dimensionality to the study of biological systems. PMID:22010165

  12. Genomes, proteomes, and the central dogma.

    Science.gov (United States)

    Franklin, Sarah; Vondriska, Thomas M

    2011-10-01

    Systems biology, with its associated technologies of proteomics, genomics, and metabolomics, is driving the evolution of our understanding of cardiovascular physiology. Rather than studying individual molecules or even single reactions, a systems approach allows integration of orthogonal data sets from distinct tiers of biological data, including gene, RNA, protein, metabolite, and other component networks. Together these networks give rise to emergent properties of cellular function, and it is their reprogramming that causes disease. We present 5 observations regarding how systems biology is guiding a revisiting of the central dogma: (1) It deemphasizes the unidirectional flow of information from genes to proteins; (2) it reveals the role of modules of molecules as opposed to individual proteins acting in isolation; (3) it enables discovery of novel emergent properties; (4) it demonstrates the importance of networks in biology; and (5) it adds new dimensionality to the study of biological systems.

  13. The central dogma of cell biology.

    Science.gov (United States)

    Cooper, S

    1981-06-01

    The Continuum Model proposes that preparations for DNA synthesis occur continuously during all phases of the division cycle. Various stimuli activate cell proliferation by changing the rate of initiator (protein) synthesis. Cell division does not initiate any process regulating cell proliferation. Cell division is the end of a process and the beginning of nothing. The alternative model which has cell proliferation regulated in the G1 phase of the division cycle is reexamined and the two types of evidence for this model, G1-variability and G1-arrest are shown to be compatible with the Continuum Model. Here, the Continuum Model is generalized to produce a new look at the logic of the division cycle in prokaryotes and eukaryotes. This new view, the Central Dogma of Cell Biology, is presented and two predictions are made. I propose that (i) cell division does not have any regulatory function, and (ii) that DNA synthesis may, indeed, have some affect on the synthesis of initiator.

  14. Small molecules: the missing link in the central dogma.

    Science.gov (United States)

    Schreiber, Stuart L

    2005-07-01

    Small molecules have critical roles at all levels of biological complexity and yet remain orphans of the central dogma. Chemical biologists, working with small molecules, expand our understanding of these central elements of life.

  15. The central dogma, "GMO" and defective epistemology.

    Science.gov (United States)

    Tagliabue, Giovanni

    2017-10-02

    The expression "Genetically Modified Organisms" was coined to indicate a group of agricultural products (mostly crops and vegetables), modified through direct DNA recombination in order to obtain useful phenotypic traits or to inhibit undesirable characteristics. But the border between rDNA ("GMO") and other biotech methods is blurred. Moreover, the ill-assorted group is frequently charged with having peculiar, negative characteristics: many activists, part of the public and a few social science scholars think that "GMOs" are all dubious, even inherently dangerous. However, theoretical justifications of this alleged problematic nature which is supposed to be necessarily linked to the "splicing" of DNA, only when applied to agricultural products, are missing: the only text which tries to go in depth on the subject, an article by biologist Barry Commoner, takes aim at the wrong target, misunderstanding the Central Dogma. "GMO" is a term that has no clear reference, let alone in a detrimental sense. The only attempt to give it epistemological dignity fails.

  16. Development of the Central Dogma Concept Inventory (CDCI) Assessment Tool

    OpenAIRE

    Newman, Dina L.; Snyder, Christopher W.; Fisk, J. Nick; Wright, L. Kate

    2016-01-01

    Scientific teaching requires scientifically constructed, field-tested instruments to accurately evaluate student thinking and gauge teacher effectiveness. We have developed a 23-question, multiple select?format assessment of student understanding of the essential concepts of the central dogma of molecular biology that is appropriate for all levels of undergraduate biology. Questions for the Central Dogma Concept Inventory (CDCI) tool were developed and iteratively revised based on student lan...

  17. Is central dogma a global property of cellular information flow?

    Science.gov (United States)

    Piras, Vincent; Tomita, Masaru; Selvarajoo, Kumar

    2012-01-01

    The central dogma of molecular biology has come under scrutiny in recent years. Here, we reviewed high-throughput mRNA and protein expression data of Escherichia coli, Saccharomyces cerevisiae, and several mammalian cells. At both single cell and population scales, the statistical comparisons between the entire transcriptomes and proteomes show clear correlation structures. In contrast, the pair-wise correlations of single transcripts to proteins show nullity. These data suggest that the organizing structure guiding cellular processes is observed at omics-wide scale, and not at single molecule level. The central dogma, thus, globally emerges as an average integrated flow of cellular information.

  18. Is central dogma a global property of cellular information flow?

    Directory of Open Access Journals (Sweden)

    Vincent ePiras

    2012-11-01

    Full Text Available The central dogma of molecular biology has come under scrutiny in recent years. Here, we reviewed high-throughput mRNA and protein expression data of Escherichia coli, Saccharomyces cerevisiae, and several mammalian cells. At both single cell and population scales, the statistical comparisons between the entire transcriptomes and proteomes show clear correlation structures. In contrast, the pair-wise correlations of single transcript to protein show nullity. These data suggest that the organizing structure guiding cellular processes is observed at omics-wide scale and not at single molecule level. The central dogma, thus, globally emerges as an average integrated flow of cellular information.

  19. Development of the Central Dogma Concept Inventory (CDCI) Assessment Tool

    Science.gov (United States)

    Newman, Dina L.; Snyder, Christopher W.; Fisk, J. Nick; Wright, L. Kate

    2016-01-01

    Scientific teaching requires scientifically constructed, field-tested instruments to accurately evaluate student thinking and gauge teacher effectiveness. We have developed a 23-question, multiple select--format assessment of student understanding of the essential concepts of the central dogma of molecular biology that is appropriate for all…

  20. Revisiting the central dogma in the 21st century.

    Science.gov (United States)

    Shapiro, James A

    2009-10-01

    Since the elaboration of the central dogma of molecular biology, our understanding of cell function and genome action has benefited from many radical discoveries. The discoveries relate to interactive multimolecular execution of cell processes, the modular organization of macromolecules and genomes, the hierarchical operation of cellular control regimes, and the realization that genetic change fundamentally results from DNA biochemistry. These discoveries contradict atomistic pre-DNA ideas of genome organization and violate the central dogma at multiple points. In place of the earlier mechanistic understanding of genomics, molecular biology has led us to an informatic perspective on the role of the genome. The informatic viewpoint points towards the development of novel concepts about cellular cognition, molecular representations of physiological states, genome system architecture, and the algorithmic nature of genome expression and genome restructuring in evolution.

  1. Is central dogma a global property of cellular information flow?

    OpenAIRE

    Piras, Vincent; Tomita, Masaru; Selvarajoo, Kumar

    2012-01-01

    The central dogma of molecular biology has come under scrutiny in recent years. Here, we reviewed high-throughput mRNA and protein expression data of Escherichia coli, Saccharomyces cerevisiae, and several mammalian cells. At both single cell and population scales, the statistical comparisons between the entire transcriptomes and proteomes show clear correlation structures. In contrast, the pair-wise correlations of single transcripts to proteins show nullity. These data suggest that the orga...

  2. Protein-protein interactions and cancer: targeting the central dogma.

    Science.gov (United States)

    Garner, Amanda L; Janda, Kim D

    2011-01-01

    Between 40,000 and 200,000 protein-protein interactions have been predicted to exist within the human interactome. As these interactions are of a critical nature in many important cellular functions and their dysregulation is causal of disease, the modulation of these binding events has emerged as a leading, yet difficult therapeutic arena. In particular, the targeting of protein-protein interactions relevant to cancer is of fundamental importance as the tumor-promoting function of several aberrantly expressed proteins in the cancerous state is directly resultant of its ability to interact with a protein-binding partner. Of significance, these protein complexes play a crucial role in each of the steps of the central dogma of molecular biology, the fundamental processes of genetic transmission. With the many important discoveries being made regarding the mechanisms of these genetic process, the identification of new chemical probes are needed to better understand and validate the druggability of protein-protein interactions related to the central dogma. In this review, we provide an overview of current small molecule-based protein-protein interaction inhibitors for each stage of the central dogma: transcription, mRNA splicing and translation. Importantly, through our analysis we have uncovered a lack of necessary probes targeting mRNA splicing and translation, thus, opening up the possibility for expansion of these fields.

  3. The protein side of the central dogma: permanence and change.

    Science.gov (United States)

    Morange, Michel

    2006-01-01

    There are two facets to the central dogma proposed by Francis Crick in 1957. One concerns the relation between the sequence of nucleotides and the sequence of amino acids, the second is devoted to the relation between the sequence of amino acids and the native three-dimensional structure of proteins. 'Folding is simply a function of the order of the amino acids,' i.e. no information is required for the proper folding of a protein other than the information contained in its sequence. This protein side of the central dogma was elaborated in a scientific context in which the characteristics and functions of proteins, and the mechanisms of protein folding, were seen very differently. This context, which made the folding problem a simple one, supported the bold proposition of Francis Crick. The protein side of the central dogma was not challenged by the discovery of prions if one adopts the definition of information given by Francis Crick. It might have been challenged by the discovery that regulatory enzymes exist in different conformations, and the evidence for the existence of chaperones assisting protein folding. But it was not, and folding remains what it was for Francis Crick, 'simply a function of the order of amino acids'. But the meaning of 'function' has dramatically changed. It is no longer the result of simple physicochemical laws, but that of a long evolutionary process which has optimized protein folding. Molecular mechanistic explanations have to be allied with evolutionary explanations, in a way characteristic of present biology.

  4. Revisiting the Central Dogma One Molecule at a Time

    Science.gov (United States)

    Bustamante, Carlos; Cheng, Wei; Meija, Yara

    2011-01-01

    The faithful relay and timely expression of genetic information depend on specialized molecular machines, many of which function as nucleic acid translocases. The emergence over the last decade of single-molecule fluorescence detection and manipulation techniques with nm and Å resolution, and their application to the study of nucleic acid translocases are painting an increasingly sharp picture of the inner workings of these machines, the dynamics and coordination of their moving parts, their thermodynamic efficiency, and the nature of their transient intermediates. Here we present an overview of the main results arrived at by the application of single-molecule methods to the study of the main machines of the central dogma. PMID:21335233

  5. Genome semantics, in silico multicellular systems and the Central Dogma.

    Science.gov (United States)

    Werner, Eric

    2005-03-21

    Genomes with their complexity and size present what appears to be an impossible challenge. Scientists speak in terms of decades or even centuries before we will understand how genomes and their hosts the cell and the city of cells that make up the multicellular context function. We believe that there will be surprisingly quick progress made in our understanding of genomes. The key is to stop taking the Central Dogma as the only direction in which genome research can scale the semantics of genomes. Instead a top-down approach coupled with a bottom-up approach may snare the unwieldy beast and make sense of genomes. The method we propose is to take in silico biology seriously. By developing in silico models of genomes cells and multicellular systems, we position ourselves to develop a theory of meaning for artificial genomes. Then using that develop a natural semantics of genomes.

  6. Using Analogy Role-Play Activity in an Undergraduate Biology Classroom to Show Central Dogma Revision

    Science.gov (United States)

    Takemura, Masaharu; Kurabayashi, Mario

    2014-01-01

    For the study of biology in an undergraduate classroom, a classroom exercise was developed: an analogy role-play to learn mechanisms of gene transcription and protein translation (central dogma). To develop the central dogma role-play exercise, we made DNA and mRNA using paper sheets, tRNA using a wire dress hanger, and amino acids using Lego®…

  7. Tracking the Resolution of Student Misconceptions about the Central Dogma of Molecular Biology.

    Science.gov (United States)

    Briggs, Amy G; Morgan, Stephanie K; Sanderson, Seth K; Schulting, Molly C; Wieseman, Laramie J

    2016-12-01

    The goal of our study was to track changes in student understanding of the central dogma of molecular biology before and after taking a genetics course. Concept maps require the ability to synthesize new information into existing knowledge frameworks, and so the hypothesis guiding this study was that student performance on concept maps reveals specific central dogma misconceptions gained, lost, and retained by students. Students in a genetics course completed pre- and posttest concept mapping tasks using terms related to the central dogma. Student maps increased in complexity and validity, indicating learning gains in both content and complexity of understanding. Changes in each of the 351 possible connections in the mapping task were tracked for each student. Our students did not retain much about the central dogma from their introductory biology courses, but they did move to more advanced levels of understanding by the end of the genetics course. The information they retained from their introductory courses focused on structural components (e.g., protein is made of amino acids) and not on overall mechanistic components (e.g., DNA comes before RNA, the ribosome makes protein). Students made the greatest gains in connections related to transcription, and they resolved the most prior misconceptions about translation. These concept-mapping tasks revealed that students are able to correct prior misconceptions about the central dogma during an intermediate-level genetics course. From these results, educators can design new classroom interventions to target those aspects of this foundational principle with which students have the most trouble.

  8. Why the Central Dogma: on the nature of the great biological exclusion principle.

    Science.gov (United States)

    Koonin, Eugene V

    2015-09-16

    The Central Dogma of molecular biology posits that transfer of information from proteins back to nucleic acids does not occur in biological systems. I argue that the impossibility of reverse translation is indeed a major, physical exclusion principle that emerges due to the transition from the digital information carriers, nucleic acids, to analog information carriers, proteins, which involves irreversible suppression of the digital information.

  9. What history tells us XIII. Fifty years of the Central Dogma

    Indian Academy of Sciences (India)

    2008-05-14

    May 14, 2008 ... Home; Journals; Journal of Biosciences; Volume 33; Issue 2. What history tells us XIII. Fifty years of the Central Dogma. Michel Morange. Series Volume 33 Issue 2 June 2008 pp 171-175. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/jbsc/033/02/0171-0175 ...

  10. Hands on Group Work Paper Model for Teaching DNA Structure, Central Dogma and Recombinant DNA

    Science.gov (United States)

    Altiparmak, Melek; Nakiboglu Tezer, Mahmure

    2009-01-01

    Understanding life on a molecular level is greatly enhanced when students are given the opportunity to visualize the molecules. Especially understanding DNA structure and function is essential for understanding key concepts of molecular biology such as DNA, central dogma and the manipulation of DNA. Researches have shown that undergraduate…

  11. Exploration of the Central Dogma at the Interface of Chemistry and Biology

    OpenAIRE

    Zhou, Alice Qinhua

    2010-01-01

    Ever since the term ?central dogma? was coined in 1958, researchers have sought to control information flow from nucleic acids to proteins. Talks delivered by Drs. Anna Pyle and Hiroaki Suga at this year?s Chemical Biology Symposium at Yale in May 2010 applauded recent advances in this area, at the interface between chemistry and biology.

  12. Tracking the Resolution of Student Misconceptions about the Central Dogma of Molecular Biology†

    Science.gov (United States)

    Briggs, Amy G.; Morgan, Stephanie K.; Sanderson, Seth K.; Schulting, Molly C.; Wieseman, Laramie J.

    2016-01-01

    The goal of our study was to track changes in student understanding of the central dogma of molecular biology before and after taking a genetics course. Concept maps require the ability to synthesize new information into existing knowledge frameworks, and so the hypothesis guiding this study was that student performance on concept maps reveals specific central dogma misconceptions gained, lost, and retained by students. Students in a genetics course completed pre- and posttest concept mapping tasks using terms related to the central dogma. Student maps increased in complexity and validity, indicating learning gains in both content and complexity of understanding. Changes in each of the 351 possible connections in the mapping task were tracked for each student. Our students did not retain much about the central dogma from their introductory biology courses, but they did move to more advanced levels of understanding by the end of the genetics course. The information they retained from their introductory courses focused on structural components (e.g., protein is made of amino acids) and not on overall mechanistic components (e.g., DNA comes before RNA, the ribosome makes protein). Students made the greatest gains in connections related to transcription, and they resolved the most prior misconceptions about translation. These concept-mapping tasks revealed that students are able to correct prior misconceptions about the central dogma during an intermediate-level genetics course. From these results, educators can design new classroom interventions to target those aspects of this foundational principle with which students have the most trouble. PMID:28101260

  13. Tracking the Resolution of Student Misconceptions about the Central Dogma of Molecular Biology

    Directory of Open Access Journals (Sweden)

    Amy G. Briggs

    2016-12-01

    Full Text Available The goal of our study was to track changes in student understanding of the central dogma of molecular biology before and after taking a genetics course. Concept maps require the ability to synthesize new information into existing knowledge frameworks, and so the hypothesis guiding this study was that student performance on concept maps reveals specific central dogma misconceptions gained, lost, and retained by students. Students in a genetics course completed pre- and posttest concept mapping tasks using terms related to the central dogma. Student maps increased in complexity and validity, indicating learning gains in both content and complexity of understanding. Changes in each of the 351 possible connections in the mapping task were tracked for each student. Our students did not retain much about the central dogma from their introductory biology courses, but they did move to more advanced levels of understanding by the end of the genetics course. The information they retained from their introductory courses focused on structural components (e.g., protein is made of amino acids and not on overall mechanistic components (e.g., DNA comes before RNA, the ribosome makes protein. Students made the greatest gains in connections related to transcription, and they resolved the most prior misconceptions about translation. These concept-mapping tasks revealed that students are able to correct prior misconceptions about the central dogma during an intermediate-level genetics course. From these results, educators can design new classroom interventions to target those aspects of this foundational principle with which students have the most trouble.

  14. Making metabolism accessible and meaningful: is the definition of a central metabolic dogma within reach?

    Science.gov (United States)

    LaRossa, Robert A

    2015-04-01

    Intermediary metabolism, a dominant research area before the emergence of molecular biology, is attracting renewed interest for fundamental and applied reasons as documented here. Nonetheless, the field may appear to be a thicket precluding entry to all but the most determined. Here we present a metabolic overview that makes this important and fascinating area accessible to a broad range of the molecular biological and biotechnological communities that are being attracted to biological problems crying out for metabolic solutions. This is accomplished by identifying seven key concepts, a so-called metabolic central dogma, that provide a core understanding analogous to the "Central Dogma of Molecular Biology" which focused upon maintenance and flow of genetic information.

  15. Why the Central Dogma: on the nature of the great biological exclusion principle

    OpenAIRE

    Koonin, Eugene V.

    2015-01-01

    Abstract The Central Dogma of molecular biology posits that transfer of information from proteins back to nucleic acids does not occur in biological systems. I argue that the impossibility of reverse translation is indeed a major, physical exclusion principle that emerges due to the transition from the digital information carriers, nucleic acids, to analog information carriers, proteins, which involves irreversible suppression of the digital information. Reviewers This article was reviewed by...

  16. Central dogma at the single-molecule level in living cells.

    Science.gov (United States)

    Li, Gene-Wei; Xie, X Sunney

    2011-07-20

    Gene expression originates from individual DNA molecules within living cells. Like many single-molecule processes, gene expression and regulation are stochastic, that is, sporadic in time. This leads to heterogeneity in the messenger-RNA and protein copy numbers in a population of cells with identical genomes. With advanced single-cell fluorescence microscopy, it is now possible to quantify transcriptomes and proteomes with single-molecule sensitivity. Dynamic processes such as transcription-factor binding, transcription and translation can be monitored in real time, providing quantitative descriptions of the central dogma of molecular biology and the demonstration that a stochastic single-molecule event can determine the phenotype of a cell.

  17. Of arrows and flows. Causality, determination, and specificity in the Central Dogma of molecular biology.

    Science.gov (United States)

    Fantini, Bernardino

    2006-01-01

    From its first proposal, the Central Dogma had a graphical form, complete with arrows of different types, and this form quickly became its standard presentation. In different scientific contexts, arrows have different meanings and in this particular case the arrows indicated the flow of information among different macromolecules. A deeper analysis illustrates that the arrows also imply a causal statement, directly connected to the causal role of genetic information. The author suggests a distinction between two different kinds of causal links, defined as 'physical causality' and 'biological determination', both implied in the production of biological specificity.

  18. Using Student Writing and Lexical Analysis to Reveal Student Thinking about the Role of Stop Codons in the Central Dogma

    Science.gov (United States)

    Prevost, Luanna B.; Smith, Michelle K.; Knight, Jennifer K.

    2016-01-01

    Previous work has shown that students have persistent difficulties in understanding how central dogma processes can be affected by a stop codon mutation. To explore these difficulties, we modified two multiple-choice questions from the Genetics Concept Assessment into three open-ended questions that asked students to write about how a stop codon…

  19. Exploration of the central dogma at the interface of chemistry and biology: 2010 Yale Chemical Biology Symposium.

    Science.gov (United States)

    Zhou, Alice Qinhua

    2010-09-01

    Ever since the term "central dogma" was coined in 1958, researchers have sought to control information flow from nucleic acids to proteins. Talks delivered by Drs. Anna Pyle and Hiroaki Suga at this year's Chemical Biology Symposium at Yale in May 2010 applauded recent advances in this area, at the interface between chemistry and biology.

  20. Systems theoretic analysis of the central dogma of molecular biology: some recent results.

    Science.gov (United States)

    Gao, Rui; Yu, Juanyi; Zhang, Mingjun; Tarn, Tzyh-Jong; Li, Jr-Shin

    2010-03-01

    This paper extends our early study on a mathematical formulation of the central dogma of molecular biology, and focuses discussions on recent insights obtained by employing advanced systems theoretic analysis. The goal of this paper is to mathematically represent and interpret the genetic information flow at the molecular level, and explore the fundamental principle of molecular biology at the system level. Specifically, group theory was employed to interpret concepts and properties of gene mutation, and predict backbone torsion angle along the peptide chain. Finite state machine theory was extensively applied to interpret key concepts and analyze the processes related to DNA hybridization. Using the proposed model, we have transferred the character-based model in molecular biology to a sophisticated mathematical model for calculation and interpretation.

  1. Normally occurring environmental and behavioral influences on gene activity: from central dogma to probabilistic epigenesis.

    Science.gov (United States)

    Gottlieb, G

    1998-10-01

    The central dogma of molecular biology holds that "information" flows from the genes to the structure of the proteins that the genes bring about through the formula DNA-->RNA-->Protein. In this view, a set of master genes activates the DNA necessary to produce the appropriate proteins that the organism needs during development. In contrast to this view, probabilistic epigenesis holds that necessarily there are signals from the internal and external environment that activate DNA to produce the appropriate proteins. To support this view, a substantial body of evidence is reviewed showing that external environmental influences on gene activation are normally occurring events in a large variety of organisms, including humans. This demonstrates how genes and environments work together to produce functional organisms, thus extending the author's model of probabilistic epigenesis.

  2. Gene expression regulation in photomorphogenesis from the perspective of the central dogma.

    Science.gov (United States)

    Wu, Shu-Hsing

    2014-01-01

    Depending on the environment a young seedling encounters, the developmental program following seed germination could be skotomorphogenesis in the dark or photomorphogenesis in the light. Light signals are interpreted by a repertoire of photoreceptors followed by sophisticated gene expression networks, eventually resulting in developmental changes. The expression and functions of photoreceptors and key signaling molecules are highly coordinated and regulated at multiple levels of the central dogma in molecular biology. Light activates gene expression through the actions of positive transcriptional regulators and the relaxation of chromatin by histone acetylation. Small regulatory RNAs help attenuate the expression of light-responsive genes. Alternative splicing, protein phosphorylation/dephosphorylation, the formation of diverse transcriptional complexes, and selective protein degradation all contribute to proteome diversity and change the functions of individual proteins.

  3. Central Dog-ma Disease Detectives: A Molecular Biology Inquiry Activity for Undergraduates

    Science.gov (United States)

    Quan, T. K.; Yuh, P.; Black, F.

    2010-12-01

    The Minority Access to Research Careers (MARC) and Minority Biomedical Research Support (MBRS) are programs at the University of California at Santa Cruz designed to support minority undergraduate students majoring in the sciences. Each summer MARC/MBRS sponsors a Summer Institute that involves week long "rotations" with different faculty mentors. In 2008, the Center for Adaptive Optics (CfAO) Professional Development Program (PDP) was responsible for overseeing one week of the Summer Institute, and designed it to be a Biomedical Short Course. As part of this short course, we designed a four-hour activity in which students collected their own data and explored relationships between the basic biomolecules DNA, RNA, and protein. The goal was to have the students use experimental data to support their explanation of the "Central Dogma" of molecular biology. Here we describe details of our activity and provide a post-teaching reflection on its success.

  4. From the selfish gene to selfish metabolism: revisiting the central dogma.

    Science.gov (United States)

    de Lorenzo, Víctor

    2014-03-01

    The standard representation of the Central Dogma (CD) of Molecular Biology conspicuously ignores metabolism. However, both the metabolites and the biochemical fluxes behind any biological phenomenon are encrypted in the DNA sequence. Metabolism constrains and even changes the information flow when the DNA-encoded instructions conflict with the homeostasis of the biochemical network. Inspection of adaptive virulence programs and emergence of xenobiotic-biodegradation pathways in environmental bacteria suggest that their main evolutionary drive is the expansion of their metabolic networks towards new chemical landscapes rather than perpetuation and spreading of their DNA sequences. Faulty enzymatic reactions on suboptimal substrates often produce reactive oxygen species (ROS), a process that fosters DNA diversification and ultimately couples catabolism of the new chemicals to growth. All this calls for a revision of the CD in which metabolism (rather than DNA) has the leading role. © 2014 WILEY Periodicals, Inc.

  5. Along the Central Dogma-Controlling Gene Expression with Small Molecules.

    Science.gov (United States)

    Schneider-Poetsch, Tilman; Yoshida, Minoru

    2018-05-04

    The central dogma of molecular biology, that DNA is transcribed into RNA and RNA translated into protein, was coined in the early days of modern biology. Back in the 1950s and 1960s, bacterial genetics first opened the way toward understanding life as the genetically encoded interaction of macromolecules. As molecular biology progressed and our knowledge of gene control deepened, it became increasingly clear that expression relied on many more levels of regulation. In the process of dissecting mechanisms of gene expression, specific small-molecule inhibitors played an important role and became valuable tools of investigation. Small molecules offer significant advantages over genetic tools, as they allow inhibiting a process at any desired time point, whereas mutating or altering the gene of an important regulator would likely result in a dead organism. With the advent of modern sequencing technology, it has become possible to monitor global cellular effects of small-molecule treatment and thereby overcome the limitations of classical biochemistry, which usually looks at a biological system in isolation. This review focuses on several molecules, especially natural products, that have played an important role in dissecting gene expression and have opened up new fields of investigation as well as clinical venues for disease treatment. Expected final online publication date for the Annual Review of Biochemistry Volume 87 is June 20, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  6. Unstable genes unstable mind: beyond the central dogma of molecular biology.

    Science.gov (United States)

    Hegde, Mahabaleshwar V; Saraph, Arundhati A

    2011-08-01

    Schizophrenia has a polygenic mode of inheritance and an estimated heritability of over 80%, but success in understanding its genetic underpinnings to date has been modest. Unlike in trinucleotide neurodegenerative disorders, the phenomenon of genetic anticipation observed in schizophrenia or bipolar disorder has not been explained. For the first time, we provide a plausible molecular explanation of genetic anticipation and pathophysiology of schizophrenia, at least in part, with supporting evidence. We postulate that abnormally increased numbers of CAG repeats in many genes being expressed in the brain, coding for glutamine, cumulatively press for higher demand of glutamine in the respective brain cells, resulting in a metabolic crisis and dysregulation of the glutamate-glutamine cycle. This can adversely affect the functioning of both glutamate and GABA receptors, which are known to be involved in psychosis, and may also affect glutathione levels, increasing oxidative stress. The resulting psychosis (gain in function), originating from unstable genes, is described as an effect "beyond the central dogma of molecular biology". The hypothesis explains genetic anticipation, as further expansions in subsequent generations may result in increased severity and earlier occurrence. Many other well described findings provide proof of concept. This is a testable hypothesis, does not deny any known facts and opens up new avenues of research. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. A logic-based dynamic modeling approach to explicate the evolution of the central dogma of molecular biology.

    Science.gov (United States)

    Jafari, Mohieddin; Ansari-Pour, Naser; Azimzadeh, Sadegh; Mirzaie, Mehdi

    It is nearly half a century past the age of the introduction of the Central Dogma (CD) of molecular biology. This biological axiom has been developed and currently appears to be all the more complex. In this study, we modified CD by adding further species to the CD information flow and mathematically expressed CD within a dynamic framework by using Boolean network based on its present-day and 1965 editions. We show that the enhancement of the Dogma not only now entails a higher level of complexity, but it also shows a higher level of robustness, thus far more consistent with the nature of biological systems. Using this mathematical modeling approach, we put forward a logic-based expression of our conceptual view of molecular biology. Finally, we show that such biological concepts can be converted into dynamic mathematical models using a logic-based approach and thus may be useful as a framework for improving static conceptual models in biology.

  8. Disease Transmission by Misfolded Prion-Protein Isoforms, Prion-Like Amyloids, Functional Amyloids and the Central Dogma.

    Science.gov (United States)

    Daus, Martin L

    2016-01-04

    In 1982, the term "prions" (proteinaceous infectious particles) was coined to specify a new principle of infection. A misfolded isoform of a cellular protein has been described as the causative agent of a fatal neurodegenerative disease. At the beginning of prion research scientists assumed that the infectious agent causing transmissible spongiform encephalopathy (TSE) was a virus, but some unconventional properties of these pathogens were difficult to bring in line with the prevailing viral model. The discovery that prions (obviously devoid of any coding nucleic acid) can store and transmit information similarly to DNA was initially even denoted as being "heretical" but is nowadays mainly accepted by the scientific community. This review describes, from a historical point of view, how the "protein-only hypothesis" expands the Central Dogma. Definition of both, the prion principle and the Central Dogma, have been essential steps to understand information storage and transfer within and among cells and organisms. Furthermore, the current understanding of the infectivity of prion-proteins after misfolding is summarized succinctly. Finally, prion-like amyloids and functional amyloids, as found in yeast and bacteria, will be discussed.

  9. Using Student Writing and Lexical Analysis to Reveal Student Thinking about the Role of Stop Codons in the Central Dogma.

    Science.gov (United States)

    Prevost, Luanna B; Smith, Michelle K; Knight, Jennifer K

    2016-01-01

    Previous work has shown that students have persistent difficulties in understanding how central dogma processes can be affected by a stop codon mutation. To explore these difficulties, we modified two multiple-choice questions from the Genetics Concept Assessment into three open-ended questions that asked students to write about how a stop codon mutation potentially impacts replication, transcription, and translation. We then used computer-assisted lexical analysis combined with human scoring to categorize student responses. The lexical analysis models showed high agreement with human scoring, demonstrating that this approach can be successfully used to analyze large numbers of student written responses. The results of this analysis show that students' ideas about one process in the central dogma can affect their thinking about subsequent and previous processes, leading to mixed models of conceptual understanding. © 2016 L. B. Prevost et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  10. Disease Transmission by Misfolded Prion-Protein Isoforms, Prion-Like Amyloids, Functional Amyloids and the Central Dogma

    Directory of Open Access Journals (Sweden)

    Martin L. Daus

    2016-01-01

    Full Text Available In 1982, the term “prions” (proteinaceous infectious particles was coined to specify a new principle of infection. A misfolded isoform of a cellular protein has been described as the causative agent of a fatal neurodegenerative disease. At the beginning of prion research scientists assumed that the infectious agent causing transmissible spongiform encephalopathy (TSE was a virus, but some unconventional properties of these pathogens were difficult to bring in line with the prevailing viral model. The discovery that prions (obviously devoid of any coding nucleic acid can store and transmit information similarly to DNA was initially even denoted as being “heretical” but is nowadays mainly accepted by the scientific community. This review describes, from a historical point of view, how the “protein-only hypothesis” expands the Central Dogma. Definition of both, the prion principle and the Central Dogma, have been essential steps to understand information storage and transfer within and among cells and organisms. Furthermore, the current understanding of the infectivity of prion-proteins after misfolding is summarized succinctly. Finally, prion-like amyloids and functional amyloids, as found in yeast and bacteria, will be discussed.

  11. A logic-based dynamic modeling approach to explicate the evolution of the central dogma of molecular biology.

    Directory of Open Access Journals (Sweden)

    Mohieddin Jafari

    Full Text Available It is nearly half a century past the age of the introduction of the Central Dogma (CD of molecular biology. This biological axiom has been developed and currently appears to be all the more complex. In this study, we modified CD by adding further species to the CD information flow and mathematically expressed CD within a dynamic framework by using Boolean network based on its present-day and 1965 editions. We show that the enhancement of the Dogma not only now entails a higher level of complexity, but it also shows a higher level of robustness, thus far more consistent with the nature of biological systems. Using this mathematical modeling approach, we put forward a logic-based expression of our conceptual view of molecular biology. Finally, we show that such biological concepts can be converted into dynamic mathematical models using a logic-based approach and thus may be useful as a framework for improving static conceptual models in biology.

  12. The Simplest Flowchart Stating the Mechanisms for Organic Xenobiotics-induced Toxicity: Can it Possibly be Accepted as a "Central Dogma" for Toxic Mechanisms?

    Science.gov (United States)

    Park, Yeong-Chul; Lee, Sundong; Cho, Myung-Haing

    2014-09-01

    Xenobiotics causing a variety of toxicity in biological systems could be classified as two types, inorganic and organic chemicals. It is estimated that the organic xenobiotics are responsible for approximately 80~90% of chemical-induced toxicity in human population. In the class for toxicology, we have encountered some difficulties in explaining the mechanisms of toxicity caused especially by organic chemicals. Here, a simple flowchart was introduced for explaining the mechanism of toxicity caused by organic xenobiotics, as the central dogma of molecular biology. This flowchart, referred to as a central dogma, was described based on a view of various aspects as follows: direct-acting chemicals vs. indirect-acting chemicals, cytochrome P450-dependent vs. cytochrome P450-independent biotransformation, reactive intermediates, reactivation, toxicokinetics vs. toxicodynamics, and reversibility vs. irreversibility. Thus, the primary objective of this flowchart is to help better understanding of the organic xenobiotics-induced toxic mechanisms, providing a major pathway for toxicity occurring in biological systems.

  13. Exploration of the Central Dogma at the Interface of Chemistry and Biology

    Science.gov (United States)

    Zhou, Alice Qinhua

    2010-01-01

    Ever since the term “central dogma” was coined in 1958, researchers have sought to control information flow from nucleic acids to proteins. Talks delivered by Drs. Anna Pyle and Hiroaki Suga at this year’s Chemical Biology Symposium at Yale in May 2010 applauded recent advances in this area, at the interface between chemistry and biology. PMID:20885900

  14. The function of central bank's communication: From dogma to argumentation in the virtual times

    Directory of Open Access Journals (Sweden)

    Drvendžija Jelena

    2014-01-01

    Full Text Available Communication is one of the important instruments for conducting a central bank's policy. The recent financial crisis and the development of communication technology have made central banks face some new challenges: communication with the market versus communication with political stakeholders; transferring the message versus participating in the public discourse; and balancing between short-term and long-term focus. The significance of a consistent message has remained the same, but the context in which a message is sent and received has drastically changed, having resulted in non-homogenous target groups, versatile communication genres, and the public discourse media unused so far. Today, a central bank communicates beyond the narrow circle of economic experts, and against the constant attempts at simplification and exaggeration for the purpose of making things look spectacular. The fact that communication takes place in a multi-lingual context adds to the complexity of communication. The debate on essential issues has to be anticipated; arguments and key messages have to be conveyed in a clear, consistent and responsible manner, resorting to the new potential granted by modern means of communication.

  15. Evolution: Theory or Dogma?

    Science.gov (United States)

    Mayer, William V.

    In this paper the author examines the question of whether evolution is a theory or a dogma. He refutes the contention that there is a monolithic scientific conspiracy to present evolution as dogma and suggests that his own presentation might be more appropriately entitled "Creationism: Theory or Dogma." (PEB)

  16. Seven fundamental, unsolved questions in molecular biology. Cooperative storage and bi-directional transfer of biological information by nucleic acids and proteins: an alternative to "central dogma".

    Science.gov (United States)

    Biro, J C

    2004-01-01

    The Human Genome Mapping Project provided us a large amount of sequence data. However our understanding of these data did not grow proportionally, because old dogmas still set the limits of our thinking. The gene-centric, reductionistical side of molecular biology is reviewed and seven problems are formulated, each indicating the insufficiency of the "central dogma". The following is concluded and suggested: 1. Genes are located and expressed on both DNA strands; 2. Introns are the source of important biological regulation and diversity; 3. Repeats are the frame of the chromatin structure and participate in the chromatin regulation; 4. The molecular accessibility of the canonical dsDNA structure is poor; 5. The genetic code is co-evolved with the amino acids and there is a stereochemical matching between the codes andamino acids; 6. The flow of information between nucleic acids and proteins is bi-directional and reverse translation might exist; 7. Complex genetic information is always carried and stored by nucleic acids and proteins together.

  17. BioCichlid: central dogma-based 3D visualization system of time-course microarray data on a hierarchical biological network.

    Science.gov (United States)

    Ishiwata, Ryosuke R; Morioka, Masaki S; Ogishima, Soichi; Tanaka, Hiroshi

    2009-02-15

    BioCichlid is a 3D visualization system of time-course microarray data on molecular networks, aiming at interpretation of gene expression data by transcriptional relationships based on the central dogma with physical and genetic interactions. BioCichlid visualizes both physical (protein) and genetic (regulatory) network layers, and provides animation of time-course gene expression data on the genetic network layer. Transcriptional regulations are represented to bridge the physical network (transcription factors) and genetic network (regulated genes) layers, thus integrating promoter analysis into the pathway mapping. BioCichlid enhances the interpretation of microarray data and allows for revealing the underlying mechanisms causing differential gene expressions. BioCichlid is freely available and can be accessed at http://newton.tmd.ac.jp/. Source codes for both biocichlid server and client are also available.

  18. Subluxation: dogma or science?

    Science.gov (United States)

    Keating, Joseph C; Charlton, Keith H; Grod, Jaroslaw P; Perle, Stephen M; Sikorski, David; Winterstein, James F

    2005-01-01

    Subluxation syndrome is a legitimate, potentially testable, theoretical construct for which there is little experimental evidence. Acceptable as hypothesis, the widespread assertion of the clinical meaningfulness of this notion brings ridicule from the scientific and health care communities and confusion within the chiropractic profession. We believe that an evidence-orientation among chiropractors requires that we distinguish between subluxation dogma vs. subluxation as the potential focus of clinical research. We lament efforts to generate unity within the profession through consensus statements concerning subluxation dogma, and believe that cultural authority will continue to elude us so long as we assert dogma as though it were validated clinical theory. PMID:16092955

  19. The Equalitarian Dogma Revisited.

    Science.gov (United States)

    Rushton, J. Philippe

    1994-01-01

    The egalitarian dogma, the belief that blacks and whites are genetically equal in cognitive ability, has been perpetuated through intimidation and pious thinking. Data on racial differences and the corruption of scholarship that causes them to be ignored are discussed. (SLD)

  20. The Central Dogma in Action.

    Science.gov (United States)

    Pigage, Helen K.

    1991-01-01

    Activity in which students act out process of protein synthesis is described. An overview of the events and a demonstration of some simple errors that may occur in the process are included. The simulation has been designed so that each student in a class has at least 1 specific role to play and requires from 20 to 40 students. (KR)

  1. Two Dogmas of Biology

    Directory of Open Access Journals (Sweden)

    Leonore Fleming

    2017-01-01

    Full Text Available The problem with reductionism in biology is not the reduction, but the implicit attitude of determinism that usually accompanies it. Methodological reductionism is supported by deterministic beliefs, but making such a connection is problematic when it is based on an idea of determinism as fixed predictability. Conflating determinism with predictability gives rise to inaccurate models that overlook the dynamic complexity of our world, as well as ignore our epistemic limitations when we try to model it. Furthermore, the assumption of a strictly deterministic framework is unnecessarily hindering to biology. By removing the dogma of determinism, biological methods, including reductive methods, can be expanded to include stochastic models and probabilistic interpretations. Thus, the dogma of reductionism can be saved once its ties with determinism are severed. In this paper, I analyze two problems that have faced molecular biology for the last 50 years—protein folding and cancer. Both cases demonstrate the long influence of reductionism and determinism on molecular biology, as well as how abandoning determinism has opened the door to more probabilistic and unconstrained reductive methods in biology.

  2. Does dogma have a future?

    Directory of Open Access Journals (Sweden)

    C.J. Wethmar

    2002-08-01

    Full Text Available This article deals with the question whether the negative connotation that the term dogma has developed in its present-day usage poses a threat to the future validity and relevance of doctrine in the church. In an attempt to answer this question an analysis is made of the development of the notion of dogma since its initial appearance in Greek thinking up to its function in the contemporary ecclesiastical context. The conclusion drawn from this analysis is that the negative connotation currently attached to this notion can be ascribed to its reduction either to intellectualism or to legalism. This reduction can be obviated by rediscovering the integrative character of dogma that characterised the praesymbola in the New Testament and is furthermore implied by the Reformed doctrine of the clarity of Holy Scripture.

  3. Asthma myths, controversies, and dogma.

    Science.gov (United States)

    Rubin, Bruce K

    2015-03-01

    Although the symptom complex we call asthma has been well described since antiquity, our understanding of the causes and therapy of asthma has evolved. Even with this evolution in our understanding, there are persistent myths (widely held but false beliefs) and dogma (entrenched beliefs) regarding the causes, classification, and therapy of asthma. It is sobering that some of the knowledge we hold dear today, will become the mythology of tomorrow. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Historia y dogma. Sobre el valor histdrico del dogma. [Reseña

    OpenAIRE

    Alonso, J. (Juan)

    2005-01-01

    Reseña de Maurice BLONDEL, Historia y dogma. Sobre el valor histdrico del dogma, Ediciones Cristiandad (Biblioteca Teoldgica «Cldsicos del siglo XX»), Madrid 2004, 184 pp., 13 X 20, ISBN 84- 7057-492-2.

  5. Die betekenis van die kerklike dogma

    African Journals Online (AJOL)

    Because dogmatic decisions of the past are not guaran teed to remain relevant for contemporary temptations and attacks, and because the dogma is by intrinsically relative to the Word of God, this article argues that a critical interpretation of the dogma is essential. The purpose of such a critical interpretation must be to keep.

  6. The Central Dogma of Molecular Biology

    Indian Academy of Sciences (India)

    Srimath

    Since that tim e,m any disciplines have m im icked ... of religion, he considered dogm as sim ply as bold hy- p oth eses ... Form any students,now fam iliarw ith the C entralD ogm a since their ..... m olecules,R N A s and proteins,existed initially,and D N A .... B J Strasser, A world in one dimension: Linus Pauling, Francis Crick.

  7. NSAIDs: the Emperor’s new dogma?

    Science.gov (United States)

    Bjarnason, I; Takeuchi, K; Simpson, R

    2003-01-01

    The spectacular marketing success of the selective cyclooxygenase 2 (COX-2) inhibitors is largely based on efficacy comparable with conventional non-steroidal anti-inflammatory drugs (NSAIDs) with vastly improved gastrointestinal safety. The additional key to the marketing success is the purity and simplicity of the message—that is, COX-1 inhibition causes the gastrointestinal side effects of NSAIDs (COX-1 dogma) while COX-2 blocking confers the therapeutic benefits (COX-2 dogma). Adherence to the COX dogmas with development of COX-2 selective agents has undoubtedly benefited many patients, but ironically their scientific basis is now seriously challenged by experimentation. PMID:12912873

  8. Micropatterning stretched and aligned DNA for sequence-specific nanolithography

    Science.gov (United States)

    Petit, Cecilia Anna Paulette

    -mediated sequence-specific nanolithography. In this process, particles are assembled via molecular recognition with functionalized probes previously hybridized to the stretched DNA template. We have used this approach to pattern proteins, metal colloids, and semiconductor quantum dots. We also demonstrate the co-assembly of two types of particles---metals and semiconductors---on single strands of DNA via the sequence-specific hybridization of two types of functional probes.

  9. Molecular design of sequence specific DNA alkylating agents.

    Science.gov (United States)

    Minoshima, Masafumi; Bando, Toshikazu; Shinohara, Ken-ichi; Sugiyama, Hiroshi

    2009-01-01

    Sequence-specific DNA alkylating agents have great interest for novel approach to cancer chemotherapy. We designed the conjugates between pyrrole (Py)-imidazole (Im) polyamides and DNA alkylating chlorambucil moiety possessing at different positions. The sequence-specific DNA alkylation by conjugates was investigated by using high-resolution denaturing polyacrylamide gel electrophoresis (PAGE). The results showed that polyamide chlorambucil conjugates alkylate DNA at flanking adenines in recognition sequences of Py-Im polyamides, however, the reactivities and alkylation sites were influenced by the positions of conjugation. In addition, we synthesized conjugate between Py-Im polyamide and another alkylating agent, 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI). DNA alkylation reactivies by both alkylating polyamides were almost comparable. In contrast, cytotoxicities against cell lines differed greatly. These comparative studies would promote development of appropriate sequence-specific DNA alkylating polyamides against specific cancer cells.

  10. Sobre la credibilidad del dogma cristiano

    Directory of Open Access Journals (Sweden)

    Juan Noemi

    2004-01-01

    Full Text Available Lo más decisivo de la credibilidad del dogma cristiano solo se aborda cuando se supera la dicotomía entre sujeto creyente y objeto creíble y se piensa la unidad de la diferencia que media entre ambos. En esta perspectiva, que no aísla la soteriología de la creación ni reduce la cristología a una jesuología es más adecuado hablar de condiciones existenciales y proexistenciales de credibilidad. Las primeras se perfilan en referencia a la índole evangélica, personal, histórico-escatológica y orgánica del dogma cristiano. Según estas el dogma cristiano para ser creíble debe articularse en dependencia y transparencia al ser y acontecer de Jesucristo reconocido como verdaderamente Dios y verdaderamente hombre. Las condiciones proexistenciales de credibilidad se hacen eco del diagnóstico de la situación cultural de Chile según el Informe 2002 del Programa de las Naciones Unidas. Tal diagnóstico confirmaría que solo tiene sentido hablar de credibilidad en materia religiosa cuando el recurso a una instancia trascendente propio de toda religión no se articula disociado de la dimensión inmanente que inevitablemente supone. Se concluye, aludiendo al planteo de N. Luhmann, que el dogma cristiano se sostiene como creíble en la medida que remite retrospectiva y prospectivamente a la persona de Jesucristo como a la unidad de la diferencia de inmanencia y trascendencia y así clave de la desparadojización de su propio códigoThe most significant aspect of the credibility of the Christian dogma, can only be undertaken when one overcomes the dichotomy between the believer and what is believed, and one thinks about the unity of the difference that spans between them. From this point of view _wich does not isolate soteriology from creation nor reduce Christology to Jesusology_ it is more appropriate to speak of existential and proexistential conditions of credibility. The former are outlined with reference to the evangelical, personal

  11. Descartes' dogma and damage to Western psychiatry.

    Science.gov (United States)

    Ventriglio, A; Bhugra, D

    2015-10-01

    René Descartes described the concept of mind-body dualism in the 16th century. This concept has been called his error but we prefer to call it his dogma because the error was recognised much later. We studied the original writings translated by various scholars. We believe that his dogma has caused tremendous amount of damage to Western psychiatry. This dualism has created boundaries between mind and body but as we know they are inextricably interlinked and influence each other. This has affected clinical practice and has increased the dichotomy between psychiatric services and the physical health care services in the West at least. This dualism has also contributed to stigma against mental illness, the mentally ill and the psychiatric services. We propose that it is time to abandon this mind-body dualism and to look at the whole patient and their illness experiences as is done in some other health care systems such as Ayurveda.

  12. An extended sequence specificity for UV-induced DNA damage.

    Science.gov (United States)

    Chung, Long H; Murray, Vincent

    2018-01-01

    The sequence specificity of UV-induced DNA damage was determined with a higher precision and accuracy than previously reported. UV light induces two major damage adducts: cyclobutane pyrimidine dimers (CPDs) and pyrimidine(6-4)pyrimidone photoproducts (6-4PPs). Employing capillary electrophoresis with laser-induced fluorescence and taking advantages of the distinct properties of the CPDs and 6-4PPs, we studied the sequence specificity of UV-induced DNA damage in a purified DNA sequence using two approaches: end-labelling and a polymerase stop/linear amplification assay. A mitochondrial DNA sequence that contained a random nucleotide composition was employed as the target DNA sequence. With previous methodology, the UV sequence specificity was determined at a dinucleotide or trinucleotide level; however, in this paper, we have extended the UV sequence specificity to a hexanucleotide level. With the end-labelling technique (for 6-4PPs), the consensus sequence was found to be 5'-GCTC*AC (where C* is the breakage site); while with the linear amplification procedure, it was 5'-TCTT*AC. With end-labelling, the dinucleotide frequency of occurrence was highest for 5'-TC*, 5'-TT* and 5'-CC*; whereas it was 5'-TT* for linear amplification. The influence of neighbouring nucleotides on the degree of UV-induced DNA damage was also examined. The core sequences consisted of pyrimidine nucleotides 5'-CTC* and 5'-CTT* while an A at position "1" and C at position "2" enhanced UV-induced DNA damage. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  13. From heresy to dogma in accounts of opposition to Howard Temin's DNA provirus hypothesis.

    Science.gov (United States)

    Marcum, James A

    2002-01-01

    In 1964 the Wisconsin virologist Howard Temin proposed the DNA provirus hypothesis to explain the mechanism by which a cancer-producing virus containing only RNA infects and transforms cells. His hypothesis reversed the flow of genetic information, as ordained by the central dogma of molecular biology. Although there was initial opposition to his hypothesis it was widely accepted, after the discovery of reverse transcriptase in 1970. Most accounts of Temin's hypothesis after the discovery portray the hypothesis as heretical, because it challenged the central dogma. Temin himself in his Nobel Prize speech of 1975 narrates a similar story about its reception. But are these accounts warranted? I argue that members of the virology community opposed Temin's provirus hypothesis not simply because it was a counterexample to the central dogma, but more importantly because his experimental evidence for supporting it was inconclusive. Furthermore, I propose that these accounts of opposition to the DNA provirus hypothesis as heretical, written by Temin and others after the discovery of reverse transcriptase, played a significant role in establishing retrovirology as a specialized field.

  14. Die betekenis van die kerklike dogma | Koekemoer | HTS ...

    African Journals Online (AJOL)

    Because dogmatic decisions of the past are not guaranteed to remain relevant for contemporary temptations and attacks, and because the dogma is by intrinsically relative to the Word of God, this article argues that a critical interpre tation of the dogma is essential. The purpose of such a critical interpretation must be to keep ...

  15. Cystic fibrosis: myths. mistakes, and dogma.

    Science.gov (United States)

    Rubin, Bruce K

    2014-03-01

    As a student I recall being told that half of what we would learn in medical school would be proven to be wrong. The challenges were to identify the incorrect half and, often more challenging, be willing to give up our entrenched ideas. Myths have been defined as traditional concepts or practice with no basis in fact. A misunderstanding is a mistaken approach or incomplete knowledge that can be resolved with better evidence, while firmly established misunderstandings can become dogma; a point of view put forth as authoritative without basis in fact. In this paper, I explore a number of myths, mistakes, and dogma related to cystic fibrosis disease and care. Many of these are myths that have long been vanquished and even forgotten, while others are controversial. In the future, many things taken as either fact or "clinical experience" today will be proven wrong. Let us examine these myths with an open mind and willingness to change our beliefs when justified. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Hume e o "dogma do reducionismo"

    Directory of Open Access Journals (Sweden)

    Silvio Seno Chibeni

    2011-12-01

    Full Text Available Neste trabalho examina-se uma das principais acusações que Quine faz a Hume, quanto às características de seu empirismo: a de que Hume teria adotado o dogma do "reducionismo radical" e, ainda mais, em uma versão "naïve" e "intoleravelmente restritiva", na qual ele assume a forma de um "impossível empirismo termo-a-termo". Argumenta-se que a teoria humeana do conhecimento não parece justificar tal imputação. Indica-se também que não apenas Hume não adotou as teses empiristas problemáticas que Quine aponta, mas, ao contrário, parece mesmo ter antecipado algumas das posições hoje atribuídas a Quine, entre as quais o holismo e o naturalismo epistemológicos, em versões apropriadas ao contexto de sua filosofia.This work examines the charge made by Quine on Hume, that he adopted the "dogma" of "radical reductionism", in its "naïve" and "intolerably restrictive version", involving "an impossible term-by-term empiricism". It is argued that Hume's theory of knowledge does not seem to justify this serious imputation. Furthermore, it is indicated that Hume not only did not adopt these problematic epistemological theses, but also, on the contrary, effectively anticipated some of the philosophical positions usually attributed to Quine, such as epistemological holism and naturalism.

  17. Termontography and DOGMA for Knowledge Engineering within PROLIX

    Science.gov (United States)

    de Baer, Peter; Meersman, Robert; Temmerman, Rita

    In this article, we describe our ongoing research to combine two approaches, i.e. Termontography and DOGMA, for knowledge engineering. Both approaches have in common that they mainly rely on natural language to describe meaning. Termontography is a special form of terminography that results in an ontologically structured terminological resource. DOGMA is an abbreviation of Developing Ontology Guided Mediation for Agents. The DOGMA approach results in a scalable and modular ontology that can easily be (re)used for different domains and applications. Both Termontography and DOGMA have already been used separately during several research projects. In this article we explain how both approaches are being combined within the PROLIX project, and what the advantages of this combination are. The goal of PROLIX is to develop an open, integrated reference architecture for process-oriented learning and information exchange.

  18. Cell formation by myxozoan species is not explained by dogma

    Science.gov (United States)

    Morris, David J.

    2010-01-01

    Eukaryotes form new cells through the replication of nuclei followed by cytokinesis. A notable exception is reported from the class Myxosporea of the phylum Myxozoa. This assemblage of approximately 2310 species is regarded as either basal bilaterian or cnidarian, depending on the phylogenetic analysis employed. For myxosporeans, cells have long been regarded as forming within other cells by a process referred to as endogenous budding. This would involve a nucleus forming endoplasmic reticulum around it, which transforms into a new plasma membrane, thus enclosing and separating it from the surrounding cell. This remarkable process, unique within the Metazoa, is accepted as occurring within stages found in vertebrate hosts, but has only been inferred from those stages observed within invertebrate hosts. Therefore, I conducted an ultrastructural study to examine how internal cells are formed by a myxosporean parasitizing an annelid. In this case, actinospore parasite stages clearly internalized existing cells; a process with analogies to the acquisition of endosymbiotic algae by cnidarian species. A subsequent examination of the myxozoan literature did not support endogenous budding, indicating that this process, which has been a central tenet of myxozoan developmental biology for over a century, is dogma. PMID:20392735

  19. Cell formation by myxozoan species is not explained by dogma.

    Science.gov (United States)

    Morris, David J

    2010-08-22

    Eukaryotes form new cells through the replication of nuclei followed by cytokinesis. A notable exception is reported from the class Myxosporea of the phylum Myxozoa. This assemblage of approximately 2310 species is regarded as either basal bilaterian or cnidarian, depending on the phylogenetic analysis employed. For myxosporeans, cells have long been regarded as forming within other cells by a process referred to as endogenous budding. This would involve a nucleus forming endoplasmic reticulum around it, which transforms into a new plasma membrane, thus enclosing and separating it from the surrounding cell. This remarkable process, unique within the Metazoa, is accepted as occurring within stages found in vertebrate hosts, but has only been inferred from those stages observed within invertebrate hosts. Therefore, I conducted an ultrastructural study to examine how internal cells are formed by a myxosporean parasitizing an annelid. In this case, actinospore parasite stages clearly internalized existing cells; a process with analogies to the acquisition of endosymbiotic algae by cnidarian species. A subsequent examination of the myxozoan literature did not support endogenous budding, indicating that this process, which has been a central tenet of myxozoan developmental biology for over a century, is dogma.

  20. Wild dogma II: The role and implications of wild dogma for wild dog management in Australia

    Directory of Open Access Journals (Sweden)

    Benjamin L. ALLEN, Richard M. ENGEMAN, Lee R. ALLEN

    2011-12-01

    Full Text Available The studies of Allen (2011 and Allen et al. (2011 recently examined the methodology underpinning claims that dingoes provide net benefits to biodiversity by suppressing foxes and cats. They found most studies to have design flaws and/or observational methods that preclude valid interpretations from the data, describing most of the current literature as ‘wild dogma’. In this short supplement, we briefly highlight the roles and implications of wild dogma for wild dog management in Australia. We discuss nomenclature, and the influence that unreliable science can have on policy and practice changes related to apex predator management [Current Zoology 57 (6: 737–740, 2011].

  1. Endocrine Disrupting Contaminants—Beyond the Dogma

    Science.gov (United States)

    Guillette, Louis J.

    2006-01-01

    Descriptions of endocrine disruption have largely been associated with wildlife and driven by observations documenting estrogenic, androgenic, antiandrogenic, and antithyroid actions. These actions, in response to exposure to ecologically relevant concentrations of various environmental contaminants, have now been established in numerous vertebrate species. However, many potential mechanisms and endocrine actions have not been studied. For example, the DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] metabolite, p,p′-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] is known to disrupt prostaglandin synthesis in the uterus of birds, providing part of the explanation for DDT-induced egg shell thinning. Few studies have examined prostaglandin synthesis as a target for endocrine disruption, yet these hormones are active in reproduction, immune responses, and cardiovascular physiology. Future studies must broaden the basic science approach to endocrine disruption, thereby expanding the mechanisms and endocrine end points examined. This goal should be accomplished even if the primary influence and funding continue to emphasize a narrower approach based on regulatory needs. Without this broader approach, research into endocrine disruption will become dominated by a narrow dogma, focusing on a few end points and mechanisms. PMID:16818240

  2. The sentence wrap-up dogma.

    Science.gov (United States)

    Stowe, Laurie A; Kaan, Edith; Sabourin, Laura; Taylor, Ryan C

    2018-03-30

    Current sentence processing research has focused on early effects of the on-line incremental processes that are performed at each word or constituent during processing. However, less attention has been devoted to what happens at the end of the clause or sentence. More specifically, over the last decade and a half, a lot of effort has been put into avoiding measuring event-related brain potentials (ERPs) at the final word of a sentence, because of the possible effects of sentence wrap-up. This article reviews the evidence on how and when sentence wrap-up impacts behavioral and ERP results. Even though the end of the sentence is associated with a positive-going ERP wave, thus far this effect has not been associated with any factors hypothesized to affect wrap-up. In addition, ERP responses to violations have not been affected by this positivity. "Sentence-final" negativities reported in the literature are not unique to sentence final positions, nor do they obscure or distort ERP effects associated with linguistic manipulations. Finally, the empirical evidence used to argue that sentence-final ERPs are different from those recorded at sentence-medial positions is weak at most. Measuring ERPs at sentence-final positions is therefore certainly not to be avoided at all costs, especially not in cases where the structure of the language under investigation requires it. More importantly, researchers should follow rigorous method in their experimental design, avoid decision tasks which may induce ERP confounds, and ensure all other possible explanations for results are considered. Although this article is directed at a particular dogma from a particular literature, this review shows that it is important to reassess what is regarded as "general knowledge" from time to time. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Collective dose: Dogma, tool, or trauma?

    International Nuclear Information System (INIS)

    Becker, K.

    1996-01-01

    In Europe as well as in the United States, the argument continues in the radiation protection community between the open-quotes fundamentalists,close quotes who firmly believe in the linear no-threshold (LNT) hypothesis and the closely related concept of collective dose, and open-quotes pragmatists,close quotes who have serious doubts about these concepts for both radiobiological and socioeconomic reasons. The latter view is reflected in many recent compilations in the scientific literature, in particular in the books by G. Walinder and S. Kondo. The fundamentalist view has been expressed in other recent publications. What has been described as the good old boys' network of the establishment threatens nonbelievers with excommunication: in his 1996 Sievert lecture, D. Beninson described doubts about the LNT hypothesis as open-quotes arrogant ignoranceclose quotes; A. Gonzales, in a 1995 letter to the author, described them as open-quotes intellectual lazinessclose quotes; and R. Clarke, chairman of the International Commission on Radiological Protection (ICRP), during the 1996 IRPA Congress, described them as open-quotes seriously misguided.close quotes Threshold or no threshold, that is the question - the most important one for this and the next generation of health physicists. Corrections of the current dogmas are needed soon and should be initiated not only by the nuclear community (which may be blamed by opinion makers for a biased view) but by those members of the radiation protection community, who are not only interested in order to 'keep the hazard alive' for reasons of publicity, research funding, and sales of instruments and services. The International Atomic Energy Agency will devote a symposium to these questions next year. The results should be interesting

  4. DOGMA: domain-based transcriptome and proteome quality assessment.

    Science.gov (United States)

    Dohmen, Elias; Kremer, Lukas P M; Bornberg-Bauer, Erich; Kemena, Carsten

    2016-09-01

    Genome studies have become cheaper and easier than ever before, due to the decreased costs of high-throughput sequencing and the free availability of analysis software. However, the quality of genome or transcriptome assemblies can vary a lot. Therefore, quality assessment of assemblies and annotations are crucial aspects of genome analysis pipelines. We developed DOGMA, a program for fast and easy quality assessment of transcriptome and proteome data based on conserved protein domains. DOGMA measures the completeness of a given transcriptome or proteome and provides information about domain content for further analysis. DOGMA provides a very fast way to do quality assessment within seconds. DOGMA is implemented in Python and published under GNU GPL v.3 license. The source code is available on https://ebbgit.uni-muenster.de/domainWorld/DOGMA/ CONTACTS: e.dohmen@wwu.de or c.kemena@wwu.de Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Skill and Physical Activity: A Central Dogma for Kinesiology

    Science.gov (United States)

    Zelaznik, Howard N.; Harper, William A.

    2007-01-01

    Kinesiology has a long and storied tradition and history. The growth of our discipline and what might be called our subdisciplines has been the shining achievement of the 1970-2006 era, spurred on by Henry's (1964) call for an academic discipline. In this short thought paper, we argue that we have lost sight of the discipline in a quest to become…

  6. Teaching the Central Dogma of Molecular Biology using Jewelry †

    OpenAIRE

    DeBruyn, Jennifer M.

    2012-01-01

    ”Cracking the Code” is an activity developed to demonstrate the processes of transcription and translation. This hands-on activity helps students understand the relationship between form (base pairing) and function (information storage and transfer) of nucleic acids. In this activity, students go through the processes of transcription and translation of a DNA molecule to create jewelry; a beaded bracelet or necklace is used as a tactile representation of a chain of amino acids. To dete...

  7. Rethinking the central dogma: noncoding RNAs are biologically relevant.

    Science.gov (United States)

    Robinson, Victoria L

    2009-01-01

    Non-coding RNAs (ncRNAs) are a large class of functional molecules with over 100 unique classes described to date. ncRNAs are diverse in terms of their function and size. A relatively new class of small ncRNA, called microRNAs (miRNA), have received a great deal of attention in the literature in recent years. miRNAs are endogenously encoded gene families that demonstrate striking evolutionary conservation. miRNAs serve essential and diverse physiological functions such as differentiation and development, proliferation, maintaining cell type phenotypes, and many others. The discovery and ongoing investigation of miRNAs is part of a revolution in biology that is changing the basic concepts of gene expression and RNA functionality. A single miRNA can participate in controlling the expression of up to several hundred protein-coding genes by interacting with mRNAs, generally in 3' untranslated regions. Our new and developing understanding of miRNAs, and other ncRNAs, promises to lead to significant contributions to medicine. Specifically, miRNAs are likely to serve as the basis for novel therapies and diagnostic tools.

  8. Teaching the Central Dogma of Molecular Biology using Jewelry

    Directory of Open Access Journals (Sweden)

    Jennifer M. DeBruyn

    2012-02-01

    Full Text Available ”Cracking the Code” is an activity developed to demonstrate the processes of transcription and translation. This hands-on activity helps students understand the relationship between form (base pairing and function (information storage and transfer of nucleic acids. In this activity, students go through the processes of transcription and translation of a DNA molecule to create jewelry; a beaded bracelet or necklace is used as a tactile representation of a chain of amino acids. To determine the correct order of “amino acid” beads, students must first decode a strand of DNA using complementary base pairing rules. The decoding is a two-step process that illustrates transcription (the copying of DNA to RNA and translation (using tRNAs to match the genetic code to the correct amino acid. This teaches the relationship between structure (base pairs and function (information storage and transfer in nucleic acids.

  9. Beyond the Central Dogma: Bringing Epigenetics into the Classroom

    Science.gov (United States)

    Drits-Esser, Dina; Malone, Molly; Barber, Nicola C.; Stark, Louisa A.

    2014-01-01

    Epigenetics is the study of how external factors and internal cellular signals can lead to changes in the packaging and processing of DNA sequences, thereby altering the expression of genes and traits. Exploring the epigenome introduces students to environmental influences on our genes and the complexities of gene expression. A supplemental…

  10. De verleidelijkheid van het grote gebaar : Het werk van Dogma

    NARCIS (Netherlands)

    Teerds, P.J.

    2013-01-01

    In vier portacabins op het parkeerterrein van de Delftse Faculteit Bouwkunde is nog tot volgende week de tentoonstelling 11+1 projects te zien, een overzichtstentoonstelling van het intrigerende werk van het Brusselse bureau Dogma. Met de tentoonstelling zet de faculteit na de brand in 2008 weer een

  11. Recently published papers: Changing bandwagons, innovations and questioning dogma

    Science.gov (United States)

    Ball, Jonathan

    2009-01-01

    This issue's Recently published papers commentary considers the popular and muddy waters of glycaemic control, stops briefly to ponder the incidence of pulmonary embolus in acute exacerbations of chronic obstructive pulmonary disease, promotes novel studies in the areas of traumatic brain injury and extracorporeal circuits, and rounds off with a potentially dogma-challenging study in cardiac arrest. PMID:19591641

  12. Dogmas in the assessment of usability evaluation methods

    DEFF Research Database (Denmark)

    Hornbæk, Kasper

    2010-01-01

    Usability evaluation methods (UEMs) are widely recognised as an essential part of systems development. Assessments of the performance of UEMs, however, have been criticised for low validity and limited reliability. The present study extends this critique by describing seven dogmas in recent work ...... research approaches that may help move beyond the dogmas. In particular, we emphasise detailed studies of evaluation processes, assessments of the impact of UEMs on design carried out in real-world systems development and analyses of how UEMs may be combined......Usability evaluation methods (UEMs) are widely recognised as an essential part of systems development. Assessments of the performance of UEMs, however, have been criticised for low validity and limited reliability. The present study extends this critique by describing seven dogmas in recent work...... on UEMs. The dogmas include using inadequate procedures and measures for assessment, focusing on win-lose outcomes, holding simplistic models of how usability evaluators work, concentrating on evaluation rather than on design and working from the assumption that usability problems are real. We discuss...

  13. Public Libraries and the Decline of the Democratic Dogma

    Science.gov (United States)

    Harris, Michael H.

    1976-01-01

    We are now witnessing what I prefer to call the decline of the democratic dogma in this country; the people seem to be losing their unmitigated faith in the basic and most cherished of American beliefs; their faith in the value of universal public enlightenment. (Author)

  14. Mechanism of sequence-specific template binding by the DNA primase of bacteriophage T7

    KAUST Repository

    Lee, Seung-Joo; Zhu, Bin; Hamdan, Samir; Richardson, Charles C.

    2010-01-01

    DNA primases catalyze the synthesis of the oligoribonucleotides required for the initiation of lagging strand DNA synthesis. Biochemical studies have elucidated the mechanism for the sequence-specific synthesis of primers. However, the physical

  15. One-year retention of general and sequence-specific skills in a probabilistic, serial reaction time task.

    Science.gov (United States)

    Romano, Jennifer C; Howard, James H; Howard, Darlene V

    2010-05-01

    Procedural skills such as riding a bicycle and playing a musical instrument play a central role in daily life. Such skills are learned gradually and are retained throughout life. The present study investigated 1-year retention of procedural skill in a version of the widely used serial reaction time task (SRTT) in young and older motor-skill experts and older controls in two experiments. The young experts were college-age piano and action video-game players, and the older experts were piano players. Previous studies have reported sequence-specific skill retention in the SRTT as long as 2 weeks but not at 1 year. Results indicated that both young and older experts and older non-experts revealed sequence-specific skill retention after 1 year with some evidence that general motor skill was retained as well. These findings are consistent with theoretical accounts of procedural skill learning such as the procedural reinstatement theory as well as with previous studies of retention of other motor skills.

  16. Against dogma: On superluminal propagation in classical electromagnetism

    Science.gov (United States)

    Weatherall, James Owen

    2014-11-01

    It is deeply entrenched dogma that relativity theory prohibits superluminal propagation. It is also experimentally well-established that under some circumstances, classical electromagnetic fields propagate through a dielectric medium with superluminal group velocities and superluminal phase velocities. But it is usually claimed that these superluminal velocities do not violate the relativistic prohibition. Here I analyze electromagnetic fields in a dielectric medium within a framework for understanding superluminal propagation recently developed by Geroch (1996, 2011) and elaborated by Earman (2014). I will argue that for some parameter values, electromagnetic fields do propagate superluminally in the Geroch-Earman sense.

  17. Sequence-specific bias correction for RNA-seq data using recurrent neural networks.

    Science.gov (United States)

    Zhang, Yao-Zhong; Yamaguchi, Rui; Imoto, Seiya; Miyano, Satoru

    2017-01-25

    The recent success of deep learning techniques in machine learning and artificial intelligence has stimulated a great deal of interest among bioinformaticians, who now wish to bring the power of deep learning to bare on a host of bioinformatical problems. Deep learning is ideally suited for biological problems that require automatic or hierarchical feature representation for biological data when prior knowledge is limited. In this work, we address the sequence-specific bias correction problem for RNA-seq data redusing Recurrent Neural Networks (RNNs) to model nucleotide sequences without pre-determining sequence structures. The sequence-specific bias of a read is then calculated based on the sequence probabilities estimated by RNNs, and used in the estimation of gene abundance. We explore the application of two popular RNN recurrent units for this task and demonstrate that RNN-based approaches provide a flexible way to model nucleotide sequences without knowledge of predetermined sequence structures. Our experiments show that training a RNN-based nucleotide sequence model is efficient and RNN-based bias correction methods compare well with the-state-of-the-art sequence-specific bias correction method on the commonly used MAQC-III data set. RNNs provides an alternative and flexible way to calculate sequence-specific bias without explicitly pre-determining sequence structures.

  18. Sequence-specific protection of duplex DNA against restriction and methylation enzymes by pseudocomplementary PNAs

    DEFF Research Database (Denmark)

    Izvolsky, K I; Demidov, V V; Nielsen, P E

    2000-01-01

    I restriction endonuclease and dam methylase. The pcPNA-assisted protection against enzymatic methylation is more efficient when the PNA-binding site embodies the methylase-recognition site rather than overlaps it. We conclude that pcPNAs may provide the robust tools allowing to sequence-specifically manipulate...... DNA duplexes in a virtually sequence-unrestricted manner....

  19. Nostoc PCC7524, a cyanobacterium which contains five sequence-specific deoxyribonucleases

    NARCIS (Netherlands)

    Reaston, J.; Duybesteyn, M.G.C.; Waard, Adrian de

    1982-01-01

    Five nucleotide sequence-specific deoxyribonucleases present in cell-free extracts of the filamentous cyanobacterium Nostoc PCC7524 have been purified and characterized. One of these enzymes, designated Nsp(7524)I cleaves at a new kind of nucleotide sequence i.e. 5'-PuCATG λ Py-3'. The other four

  20. Die Bybel in die geding: Teks versus dogma

    Directory of Open Access Journals (Sweden)

    Lina Spies

    2004-12-01

    This article concentrates on one of the great achievements of postmodernism regarding theology: the highlighting of the inseparable relation between religion and poetry. The article argues that, as we are unable to fashion a dependable representation of our world and of God, we have to return to the text and to the language of belief as sole way of expressing our thoughts about God and about belief. The language of belief is not the language of dogma, but that of poetry, and the language of poetry is figurative language. In illustration of this, the text of Samson is reread not as factually-true history, but as the tragic story of a person whose God-given calling and talents are in conflict with his natural drives and gifts, but whose heroic death nevertheless ultimately serves to glorify God. In conclusion the article pleads for the liberation of the Bible from the Greek-Roman construction of it, so that it may again begin to tell stories through which the reader may learn to comprehend something of God. So, too, the Jewishness of Jesus, which has been eroded by dogma and preaching, may be rediscovered.

  1. Exploiting CRISPR-Cas nucleases to produce sequence-specific antimicrobials.

    Science.gov (United States)

    Bikard, David; Euler, Chad W; Jiang, Wenyan; Nussenzweig, Philip M; Goldberg, Gregory W; Duportet, Xavier; Fischetti, Vincent A; Marraffini, Luciano A

    2014-11-01

    Antibiotics target conserved bacterial cellular pathways or growth functions and therefore cannot selectively kill specific members of a complex microbial population. Here, we develop programmable, sequence-specific antimicrobials using the RNA-guided nuclease Cas9 (refs.1,2) delivered by a bacteriophage. We show that Cas9, reprogrammed to target virulence genes, kills virulent, but not avirulent, Staphylococcus aureus. Reprogramming the nuclease to target antibiotic resistance genes destroys staphylococcal plasmids that harbor antibiotic resistance genes and immunizes avirulent staphylococci to prevent the spread of plasmid-borne resistance genes. We also show that CRISPR-Cas9 antimicrobials function in vivo to kill S. aureus in a mouse skin colonization model. This technology creates opportunities to manipulate complex bacterial populations in a sequence-specific manner.

  2. Sequence-specific RNA Photocleavage by Single-stranded DNA in Presence of Riboflavin

    Science.gov (United States)

    Zhao, Yongyun; Chen, Gangyi; Yuan, Yi; Li, Na; Dong, Juan; Huang, Xin; Cui, Xin; Tang, Zhuo

    2015-10-01

    Constant efforts have been made to develop new method to realize sequence-specific RNA degradation, which could cause inhibition of the expression of targeted gene. Herein, by using an unmodified short DNA oligonucleotide for sequence recognition and endogenic small molecue, vitamin B2 (riboflavin) as photosensitizer, we report a simple strategy to realize the sequence-specific photocleavage of targeted RNA. The DNA strand is complimentary to the target sequence to form DNA/RNA duplex containing a G•U wobble in the middle. The cleavage reaction goes through oxidative elimination mechanism at the nucleoside downstream of U of the G•U wobble in duplex to obtain unnatural RNA terminal, and the whole process is under tight control by using light as switch, which means the cleavage could be carried out according to specific spatial and temporal requirements. The biocompatibility of this method makes the DNA strand in combination with riboflavin a promising molecular tool for RNA manipulation.

  3. Rapid detection and purification of sequence specific DNA binding proteins using magnetic separation

    Directory of Open Access Journals (Sweden)

    TIJANA SAVIC

    2006-02-01

    Full Text Available In this paper, a method for the rapid identification and purification of sequence specific DNA binding proteins based on magnetic separation is presented. This method was applied to confirm the binding of the human recombinant USF1 protein to its putative binding site (E-box within the human SOX3 protomer. It has been shown that biotinylated DNA attached to streptavidin magnetic particles specifically binds the USF1 protein in the presence of competitor DNA. It has also been demonstrated that the protein could be successfully eluted from the beads, in high yield and with restored DNA binding activity. The advantage of these procedures is that they could be applied for the identification and purification of any high-affinity sequence-specific DNA binding protein with only minor modifications.

  4. Automated sequence-specific protein NMR assignment using the memetic algorithm MATCH

    International Nuclear Information System (INIS)

    Volk, Jochen; Herrmann, Torsten; Wuethrich, Kurt

    2008-01-01

    MATCH (Memetic Algorithm and Combinatorial Optimization Heuristics) is a new memetic algorithm for automated sequence-specific polypeptide backbone NMR assignment of proteins. MATCH employs local optimization for tracing partial sequence-specific assignments within a global, population-based search environment, where the simultaneous application of local and global optimization heuristics guarantees high efficiency and robustness. MATCH thus makes combined use of the two predominant concepts in use for automated NMR assignment of proteins. Dynamic transition and inherent mutation are new techniques that enable automatic adaptation to variable quality of the experimental input data. The concept of dynamic transition is incorporated in all major building blocks of the algorithm, where it enables switching between local and global optimization heuristics at any time during the assignment process. Inherent mutation restricts the intrinsically required randomness of the evolutionary algorithm to those regions of the conformation space that are compatible with the experimental input data. Using intact and artificially deteriorated APSY-NMR input data of proteins, MATCH performed sequence-specific resonance assignment with high efficiency and robustness

  5. Sequence-specific DNA alkylation by tandem Py-Im polyamide conjugates.

    Science.gov (United States)

    Taylor, Rhys Dylan; Kawamoto, Yusuke; Hashiya, Kaori; Bando, Toshikazu; Sugiyama, Hiroshi

    2014-09-01

    Tandem N-methylpyrrole-N-methylimidazole (Py-Im) polyamides with good sequence-specific DNA-alkylating activities have been designed and synthesized. Three alkylating tandem Py-Im polyamides with different linkers, which each contained the same moiety for the recognition of a 10 bp DNA sequence, were evaluated for their reactivity and selectivity by DNA alkylation, using high-resolution denaturing gel electrophoresis. All three conjugates displayed high reactivities for the target sequence. In particular, polyamide 1, which contained a β-alanine linker, displayed the most-selective sequence-specific alkylation towards the target 10 bp DNA sequence. The tandem Py-Im polyamide conjugates displayed greater sequence-specific DNA alkylation than conventional hairpin Py-Im polyamide conjugates (4 and 5). For further research, the design of tandem Py-Im polyamide conjugates could play an important role in targeting specific gene sequences. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Lifelong Persistence of Toxoplasma Cysts: A Questionable Dogma?

    Science.gov (United States)

    Rougier, Solène; Montoya, Jose G; Peyron, François

    2017-02-01

    It is believed that infection by Toxoplasma gondii triggers a lifelong protective immunity due to the persistence of parasitic cysts which induce immunoprotection against reinfection. A review of the scientific literature since the 1950s did not yield any definitive data regarding the duration of cysts in the host or the presence of lifelong protective immunity, which led us to question this dogma. We put forward the hypothesis that sustained immunity to T. gondii requires repeated antigenic stimulations. The decline of seroprevalence recently observed in many countries might contribute to explain the loss of immunity. We address the potential consequences of this phenomenon, should it persist and worsen. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Variations in the Incidence of Schizophrenia: Data Versus Dogma

    Science.gov (United States)

    McGrath, John J

    2006-01-01

    The schizophrenia research community has shared a belief that the incidence of schizophrenia shows little variation. This belief is related to the dogma that schizophrenia affects all individuals equally, regardless of sex, race, or nationality. However, there is now robust evidence that the incidence of schizophrenia is characterized by substantial variability. There is prominent variation in the incidence of schizophrenia between sites. The incidence of schizophrenia is significantly higher in males than in females (male:female ratio = 1.4). Migrants and those living in urban areas have a higher incidence of schizophrenia. The incidence of schizophrenia has fluctuations across time. In addition, the prevalence of schizophrenia is also characterized by prominent variation. The realization that schizophrenia is characterized by rich and informative gradients will serve as a catalyst for future research. PMID:16135560

  8. Antitumor activity of sequence-specific alkylating agents: pyrolle-imidazole CBI conjugates with indole linker.

    Science.gov (United States)

    Shinohara, Ken-ichi; Bando, Toshikazu; Sasaki, Shunta; Sakakibara, Yogo; Minoshima, Masafumi; Sugiyama, Hiroshi

    2006-03-01

    DNA-targeting agents, including cisplatin, bleomycin and mitomycin C, are used routinely in cancer treatments. However, these drugs are extremely toxic, attacking normal cells and causing severe side effects. One important question to consider in designing anticancer agents is whether the introduction of sequence selectivity to DNA-targeting agents can improve their efficacy as anticancer agents. In the present study, the growth inhibition activities of an indole-seco 1,2,9,9a-tetrahydrocyclopropa[1,2-c]benz[1,2-e]indol-4-one (CBI) (1) and five conjugates with hairpin pyrrole-imidazole polyamides (2-6), which have different sequence specificities for DNA alkylation, were compared using 10 different cell lines. The average values of -log GI50 (50% growth inhibition concentration) for compounds 1-6 against the 10 cell lines were 8.33, 8.56, 8.29, 8.04, 8.23 and 8.83, showing that all of these compounds strongly inhibit cell growth. Interestingly, each alkylating agent caused significantly different growth inhibition patterns with each cell line. In particular, the correlation coefficients between the -log GI50 of compound 1 and its conjugates 2-6 showed extremely low values (Ralkylation lead to marked differences in biological activity. Comparison of the correlation coefficients between compounds 6 and 7, with the same sequence specificity as 6, and MS-247, with sequence specificity different from 6, when used against a panel of 37 human cancer cell lines further confirmed the above hypothesis.

  9. The sequence specificity of UV-induced DNA damage in a systematically altered DNA sequence.

    Science.gov (United States)

    Khoe, Clairine V; Chung, Long H; Murray, Vincent

    2018-06-01

    The sequence specificity of UV-induced DNA damage was investigated in a specifically designed DNA plasmid using two procedures: end-labelling and linear amplification. Absorption of UV photons by DNA leads to dimerisation of pyrimidine bases and produces two major photoproducts, cyclobutane pyrimidine dimers (CPDs) and pyrimidine(6-4)pyrimidone photoproducts (6-4PPs). A previous study had determined that two hexanucleotide sequences, 5'-GCTC*AC and 5'-TATT*AA, were high intensity UV-induced DNA damage sites. The UV clone plasmid was constructed by systematically altering each nucleotide of these two hexanucleotide sequences. One of the main goals of this study was to determine the influence of single nucleotide alterations on the intensity of UV-induced DNA damage. The sequence 5'-GCTC*AC was designed to examine the sequence specificity of 6-4PPs and the highest intensity 6-4PP damage sites were found at 5'-GTTC*CC nucleotides. The sequence 5'-TATT*AA was devised to investigate the sequence specificity of CPDs and the highest intensity CPD damage sites were found at 5'-TTTT*CG nucleotides. It was proposed that the tetranucleotide DNA sequence, 5'-YTC*Y (where Y is T or C), was the consensus sequence for the highest intensity UV-induced 6-4PP adduct sites; while it was 5'-YTT*C for the highest intensity UV-induced CPD damage sites. These consensus tetranucleotides are composed entirely of consecutive pyrimidines and must have a DNA conformation that is highly productive for the absorption of UV photons. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  10. Chromatin accessibility data sets show bias due to sequence specificity of the DNase I enzyme.

    Directory of Open Access Journals (Sweden)

    Hashem Koohy

    Full Text Available DNase I is an enzyme which cuts duplex DNA at a rate that depends strongly upon its chromatin environment. In combination with high-throughput sequencing (HTS technology, it can be used to infer genome-wide landscapes of open chromatin regions. Using this technology, systematic identification of hundreds of thousands of DNase I hypersensitive sites (DHS per cell type has been possible, and this in turn has helped to precisely delineate genomic regulatory compartments. However, to date there has been relatively little investigation into possible biases affecting this data.We report a significant degree of sequence preference spanning sites cut by DNase I in a number of published data sets. The two major protocols in current use each show a different pattern, but for a given protocol the pattern of sequence specificity seems to be quite consistent. The patterns are substantially different from biases seen in other types of HTS data sets, and in some cases the most constrained position lies outside the sequenced fragment, implying that this constraint must relate to the digestion process rather than events occurring during library preparation or sequencing.DNase I is a sequence-specific enzyme, with a specificity that may depend on experimental conditions. This sequence specificity is not taken into account by existing pipelines for identifying open chromatin regions. Care must be taken when interpreting DNase I results, especially when looking at the precise locations of the reads. Future studies may be able to improve the sensitivity and precision of chromatin state measurement by compensating for sequence bias.

  11. Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms.

    Science.gov (United States)

    Mattick, John S

    2003-10-01

    The central dogma of biology holds that genetic information normally flows from DNA to RNA to protein. As a consequence it has been generally assumed that genes generally code for proteins, and that proteins fulfil not only most structural and catalytic but also most regulatory functions, in all cells, from microbes to mammals. However, the latter may not be the case in complex organisms. A number of startling observations about the extent of non-protein-coding RNA (ncRNA) transcription in the higher eukaryotes and the range of genetic and epigenetic phenomena that are RNA-directed suggests that the traditional view of the structure of genetic regulatory systems in animals and plants may be incorrect. ncRNA dominates the genomic output of the higher organisms and has been shown to control chromosome architecture, mRNA turnover and the developmental timing of protein expression, and may also regulate transcription and alternative splicing. This paper re-examines the available evidence and suggests a new framework for considering and understanding the genomic programming of biological complexity, autopoietic development and phenotypic variation. Copyright 2003 Wiley Periodicals, Inc.

  12. Mechanism of sequence-specific template binding by the DNA primase of bacteriophage T7

    KAUST Repository

    Lee, Seung-Joo

    2010-03-28

    DNA primases catalyze the synthesis of the oligoribonucleotides required for the initiation of lagging strand DNA synthesis. Biochemical studies have elucidated the mechanism for the sequence-specific synthesis of primers. However, the physical interactions of the primase with the DNA template to explain the basis of specificity have not been demonstrated. Using a combination of surface plasmon resonance and biochemical assays, we show that T7 DNA primase has only a slightly higher affinity for DNA containing the primase recognition sequence (5\\'-TGGTC-3\\') than for DNA lacking the recognition site. However, this binding is drastically enhanced by the presence of the cognate Nucleoside triphosphates (NTPs), Adenosine triphosphate (ATP) and Cytosine triphosphate (CTP) that are incorporated into the primer, pppACCA. Formation of the dimer, pppAC, the initial step of sequence-specific primer synthesis, is not sufficient for the stable binding. Preformed primers exhibit significantly less selective binding than that observed with ATP and CTP. Alterations in subdomains of the primase result in loss of selective DNA binding. We present a model in which conformational changes induced during primer synthesis facilitate contact between the zinc-binding domain and the polymerase domain. The Author(s) 2010. Published by Oxford University Press.

  13. A novel family of sequence-specific endoribonucleases associated with the clustered regularly interspaced short palindromic repeats.

    Science.gov (United States)

    Beloglazova, Natalia; Brown, Greg; Zimmerman, Matthew D; Proudfoot, Michael; Makarova, Kira S; Kudritska, Marina; Kochinyan, Samvel; Wang, Shuren; Chruszcz, Maksymilian; Minor, Wladek; Koonin, Eugene V; Edwards, Aled M; Savchenko, Alexei; Yakunin, Alexander F

    2008-07-18

    Clustered regularly interspaced short palindromic repeats (CRISPRs) together with the associated CAS proteins protect microbial cells from invasion by foreign genetic elements using presently unknown molecular mechanisms. All CRISPR systems contain proteins of the CAS2 family, suggesting that these uncharacterized proteins play a central role in this process. Here we show that the CAS2 proteins represent a novel family of endoribonucleases. Six purified CAS2 proteins from diverse organisms cleaved single-stranded RNAs preferentially within U-rich regions. A representative CAS2 enzyme, SSO1404 from Sulfolobus solfataricus, cleaved the phosphodiester linkage on the 3'-side and generated 5'-phosphate- and 3'-hydroxyl-terminated oligonucleotides. The crystal structure of SSO1404 was solved at 1.6A resolution revealing the first ribonuclease with a ferredoxin-like fold. Mutagenesis of SSO1404 identified six residues (Tyr-9, Asp-10, Arg-17, Arg-19, Arg-31, and Phe-37) that are important for enzymatic activity and suggested that Asp-10 might be the principal catalytic residue. Thus, CAS2 proteins are sequence-specific endoribonucleases, and we propose that their role in the CRISPR-mediated anti-phage defense might involve degradation of phage or cellular mRNAs.

  14. Sequence specificity and biological consequences of drugs that bind covalently in the minor groove of DNA

    International Nuclear Information System (INIS)

    Hurley, L.H.; Needham-VanDevanter, D.R.

    1986-01-01

    DNA ligands which bind within the minor groove of DNA exhibit varying degrees of sequence selectivity. Factors which contribute to nucleotide sequence recognition by minor groove ligands have been extensively investigated. Electrostatic interactions, ligand and DNA dehydration energies, hydrophobic interactions and steric factors all play significant roles in sequence selectivity in the minor groove. Interestingly, ligand recognition of nucleotide sequence in the minor groove does not involve significant hydrogen bonding. This is in sharp contrast to cellular enzyme and protein recognition of nucleotide sequence, which is achieved in the major groove via specific hydrogen bond formation between individual bases and the ligand. The ability to read nucleotide sequence via hydrogen bonding allows precise binding of proteins to specific DNA sequences. Minor groove ligands examined to date exhibit a much lower sequence specificity, generally binding to a subset of possible sequences, rather than a single sequence. 19 refs., 7 figs

  15. Thermodynamic Molecular Switch in Sequence-Specific Hydrophobic Interaction: Two Computational Models Compared

    Directory of Open Access Journals (Sweden)

    Paul Chun

    2003-01-01

    Full Text Available We have shown in our published work the existence of a thermodynamic switch in biological systems wherein a change of sign in ΔCp°(Treaction leads to a true negative minimum in the Gibbs free energy change of reaction, and hence, a maximum in the related Keq. We have examined 35 pair-wise, sequence-specific hydrophobic interactions over the temperature range of 273–333 K, based on data reported by Nemethy and Scheraga in 1962. A closer look at a single example, the pair-wise hydrophobic interaction of leucine-isoleucine, will demonstrate the significant differences when the data are analyzed using the Nemethy-Scheraga model or treated by the Planck-Benzinger methodology which we have developed. The change in inherent chemical bond energy at 0 K, ΔH°(T0 is 7.53 kcal mol-1 compared with 2.4 kcal mol-1, while ‹ts› is 365 K as compared with 355 K, for the Nemethy-Scheraga and Planck-Benzinger model, respectively. At ‹tm›, the thermal agitation energy is about five times greater than ΔH°(T0 in the Planck-Benzinger model, that is 465 K compared to 497 K in the Nemethy-Scheraga model. The results imply that the negative Gibbs free energy minimum at a well-defined ‹ts›, where TΔS° = 0 at about 355 K, has its origin in the sequence-specific hydrophobic interactions, which are highly dependent on details of molecular structure. The Nemethy-Scheraga model shows no evidence of the thermodynamic molecular switch that we have found to be a universal feature of biological interactions. The Planck-Benzinger method is the best known for evaluating the innate temperature-invariant enthalpy, ΔH°(T0, and provides for better understanding of the heat of reaction for biological molecules.

  16. Sequence-Specific Model for Peptide Retention Time Prediction in Strong Cation Exchange Chromatography.

    Science.gov (United States)

    Gussakovsky, Daniel; Neustaeter, Haley; Spicer, Victor; Krokhin, Oleg V

    2017-11-07

    The development of a peptide retention prediction model for strong cation exchange (SCX) separation on a Polysulfoethyl A column is reported. Off-line 2D LC-MS/MS analysis (SCX-RPLC) of S. cerevisiae whole cell lysate was used to generate a retention dataset of ∼30 000 peptides, sufficient for identifying the major sequence-specific features of peptide retention mechanisms in SCX. In contrast to RPLC/hydrophilic interaction liquid chromatography (HILIC) separation modes, where retention is driven by hydrophobic/hydrophilic contributions of all individual residues, SCX interactions depend mainly on peptide charge (number of basic residues at acidic pH) and size. An additive model (incorporating the contributions of all 20 residues into the peptide retention) combined with a peptide length correction produces a 0.976 R 2 value prediction accuracy, significantly higher than the additive models for either HILIC or RPLC. Position-dependent effects on peptide retention for different residues were driven by the spatial orientation of tryptic peptides upon interaction with the negatively charged surface functional groups. The positively charged N-termini serve as a primary point of interaction. For example, basic residues (Arg, His, Lys) increase peptide retention when located closer to the N-terminus. We also found that hydrophobic interactions, which could lead to a mixed-mode separation mechanism, are largely suppressed at 20-30% of acetonitrile in the eluent. The accuracy of the final Sequence-Specific Retention Calculator (SSRCalc) SCX model (∼0.99 R 2 value) exceeds all previously reported predictors for peptide LC separations. This also provides a solid platform for method development in 2D LC-MS protocols in proteomics and peptide retention prediction filtering of false positive identifications.

  17. Using sequence-specific chemical and structural properties of DNA to predict transcription factor binding sites.

    Directory of Open Access Journals (Sweden)

    Amy L Bauer

    2010-11-01

    Full Text Available An important step in understanding gene regulation is to identify the DNA binding sites recognized by each transcription factor (TF. Conventional approaches to prediction of TF binding sites involve the definition of consensus sequences or position-specific weight matrices and rely on statistical analysis of DNA sequences of known binding sites. Here, we present a method called SiteSleuth in which DNA structure prediction, computational chemistry, and machine learning are applied to develop models for TF binding sites. In this approach, binary classifiers are trained to discriminate between true and false binding sites based on the sequence-specific chemical and structural features of DNA. These features are determined via molecular dynamics calculations in which we consider each base in different local neighborhoods. For each of 54 TFs in Escherichia coli, for which at least five DNA binding sites are documented in RegulonDB, the TF binding sites and portions of the non-coding genome sequence are mapped to feature vectors and used in training. According to cross-validation analysis and a comparison of computational predictions against ChIP-chip data available for the TF Fis, SiteSleuth outperforms three conventional approaches: Match, MATRIX SEARCH, and the method of Berg and von Hippel. SiteSleuth also outperforms QPMEME, a method similar to SiteSleuth in that it involves a learning algorithm. The main advantage of SiteSleuth is a lower false positive rate.

  18. A novel analysis strategy for HLA typing using a sequence-specific oligonucleotide probe method.

    Science.gov (United States)

    Won, D I

    2017-11-01

    The technique of reverse sequence-specific oligonucleotide probes (SSOPs) is commonly used in human leukocyte antigen (HLA) typing. In the conventional method for data analysis (exact pattern matching, EPM), the larger is the number of mismatched probes, the longer the time for final typing assignment. A novel strategy, filtering and scoring (FnS), has been developed to easily assign the best-fit allele pair. In the FnS method, candidate alleles and allele pairs were filtered based on (1) subject's ethnicity, and (2) the measured partial reaction pattern with only definitely negative or positive probes. Then, the complete reaction pattern for all probes (CRPoAPs) were compared between the raw sample and expected residual allele pairs to obtain mismatch scores. To compare the FnS and EPM methods, each analysis time (minutes:seconds) for reverse SSOP HLA typing with intermediate resolution (n = 507) was measured. The analysis time with FnS method was shorter than that of the EPM method [00:21 (00:08-01:47) and 01:04 (00:15-23:45), respectively, P typing in a comprehensive and quantitative comparison between measured and expected CRPoAPs of candidate allele pairs. Therefore, this analysis strategy might be useful in a clinical setting. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Sequence specific electronic conduction through polyion-stabilized double-stranded DNA in nanoscale break junctions

    International Nuclear Information System (INIS)

    Mahapatro, Ajit K; Jeong, Kyung J; Lee, Gil U; Janes, David B

    2007-01-01

    This paper presents a study of sequence specific electronic conduction through short (15-base-pair) double-stranded (ds) DNA molecules, measured by immobilizing 3 ' -thiol-derivatized DNAs in nanometre scale gaps between gold electrodes. The polycation spermidine was used to stabilize the ds-DNA structure, allowing electrical measurements to be performed in a dry state. For specific sequences, the conductivity was observed to scale with the surface density of immobilized DNA, which can be controlled by the buffer concentration. A series of 15-base DNA oligonucleotide pairs, in which the centre sequence of five base pairs was changed from G:C to A:T pairs, has been studied. The conductivity per molecule is observed to decrease exponentially with the number of adjacent A:T pairs replacing G:C pairs, consistent with a barrier at the A:T sites. Conductance-based devices for short DNA sequences could provide sensing approaches with direct electrical readout, as well as label-free detection

  20. Sequence-specific capture of protein-DNA complexes for mass spectrometric protein identification.

    Directory of Open Access Journals (Sweden)

    Cheng-Hsien Wu

    Full Text Available The regulation of gene transcription is fundamental to the existence of complex multicellular organisms such as humans. Although it is widely recognized that much of gene regulation is controlled by gene-specific protein-DNA interactions, there presently exists little in the way of tools to identify proteins that interact with the genome at locations of interest. We have developed a novel strategy to address this problem, which we refer to as GENECAPP, for Global ExoNuclease-based Enrichment of Chromatin-Associated Proteins for Proteomics. In this approach, formaldehyde cross-linking is employed to covalently link DNA to its associated proteins; subsequent fragmentation of the DNA, followed by exonuclease digestion, produces a single-stranded region of the DNA that enables sequence-specific hybridization capture of the protein-DNA complex on a solid support. Mass spectrometric (MS analysis of the captured proteins is then used for their identification and/or quantification. We show here the development and optimization of GENECAPP for an in vitro model system, comprised of the murine insulin-like growth factor-binding protein 1 (IGFBP1 promoter region and FoxO1, a member of the forkhead rhabdomyosarcoma (FoxO subfamily of transcription factors, which binds specifically to the IGFBP1 promoter. This novel strategy provides a powerful tool for studies of protein-DNA and protein-protein interactions.

  1. Sequence-specific procedural learning deficits in children with specific language impairment.

    Science.gov (United States)

    Hsu, Hsinjen Julie; Bishop, Dorothy V M

    2014-05-01

    This study tested the procedural deficit hypothesis of specific language impairment (SLI) by comparing children's performance in two motor procedural learning tasks and an implicit verbal sequence learning task. Participants were 7- to 11-year-old children with SLI (n = 48), typically developing age-matched children (n = 20) and younger typically developing children matched for receptive grammar (n = 28). In a serial reaction time task, the children with SLI performed at the same level as the grammar-matched children, but poorer than age-matched controls in learning motor sequences. When tested with a motor procedural learning task that did not involve learning sequential relationships between discrete elements (i.e. pursuit rotor), the children with SLI performed comparably with age-matched children and better than younger grammar-matched controls. In addition, poor implicit learning of word sequences in a verbal memory task (the Hebb effect) was found in the children with SLI. Together, these findings suggest that SLI might be characterized by deficits in learning sequence-specific information, rather than generally weak procedural learning. © 2014 The Authors. Developmental Science Published by John Wiley & Sons Ltd.

  2. A survey of the sequence-specific interaction of damaging agents with DNA: emphasis on antitumor agents.

    Science.gov (United States)

    Murray, V

    1999-01-01

    This article reviews the literature concerning the sequence specificity of DNA-damaging agents. DNA-damaging agents are widely used in cancer chemotherapy. It is important to understand fully the determinants of DNA sequence specificity so that more effective DNA-damaging agents can be developed as antitumor drugs. There are five main methods of DNA sequence specificity analysis: cleavage of end-labeled fragments, linear amplification with Taq DNA polymerase, ligation-mediated polymerase chain reaction (PCR), single-strand ligation PCR, and footprinting. The DNA sequence specificity in purified DNA and in intact mammalian cells is reviewed for several classes of DNA-damaging agent. These include agents that form covalent adducts with DNA, free radical generators, topoisomerase inhibitors, intercalators and minor groove binders, enzymes, and electromagnetic radiation. The main sites of adduct formation are at the N-7 of guanine in the major groove of DNA and the N-3 of adenine in the minor groove, whereas free radical generators abstract hydrogen from the deoxyribose sugar and topoisomerase inhibitors cause enzyme-DNA cross-links to form. Several issues involved in the determination of the DNA sequence specificity are discussed. The future directions of the field, with respect to cancer chemotherapy, are also examined.

  3. Generating quantitative models describing the sequence specificity of biological processes with the stabilized matrix method

    Directory of Open Access Journals (Sweden)

    Sette Alessandro

    2005-05-01

    Full Text Available Abstract Background Many processes in molecular biology involve the recognition of short sequences of nucleic-or amino acids, such as the binding of immunogenic peptides to major histocompatibility complex (MHC molecules. From experimental data, a model of the sequence specificity of these processes can be constructed, such as a sequence motif, a scoring matrix or an artificial neural network. The purpose of these models is two-fold. First, they can provide a summary of experimental results, allowing for a deeper understanding of the mechanisms involved in sequence recognition. Second, such models can be used to predict the experimental outcome for yet untested sequences. In the past we reported the development of a method to generate such models called the Stabilized Matrix Method (SMM. This method has been successfully applied to predicting peptide binding to MHC molecules, peptide transport by the transporter associated with antigen presentation (TAP and proteasomal cleavage of protein sequences. Results Herein we report the implementation of the SMM algorithm as a publicly available software package. Specific features determining the type of problems the method is most appropriate for are discussed. Advantageous features of the package are: (1 the output generated is easy to interpret, (2 input and output are both quantitative, (3 specific computational strategies to handle experimental noise are built in, (4 the algorithm is designed to effectively handle bounded experimental data, (5 experimental data from randomized peptide libraries and conventional peptides can easily be combined, and (6 it is possible to incorporate pair interactions between positions of a sequence. Conclusion Making the SMM method publicly available enables bioinformaticians and experimental biologists to easily access it, to compare its performance to other prediction methods, and to extend it to other applications.

  4. Screening for sequence-specific RNA-BPs by comprehensive UV crosslinking

    Directory of Open Access Journals (Sweden)

    Le Meuth-Metzinger Valerie

    2002-06-01

    Full Text Available Abstract Background Specific cis-elements and the associated trans-acting factors have been implicated in the post-transcriptional regulation of gene expression. In the era of genome wide analyses identifying novel trans-acting factors and cis-regulatory elements is a step towards understanding coordinated gene expression. UV-crosslink analysis is a standard method used to identify RNA-binding proteins. Uridine is traditionally used to radiolabel substrate RNAs, however, proteins binding to cis-elments particularly uridine poor will be weakly or not detected. We evaluate here the possibility of using UV-crosslinking with RNA substrates radiolabeled with each of the four ribonucleotides as an approach for screening for novel sequence specific RNA-binding proteins. Results The radiolabeled RNA substrates were derived from the 3'UTRs of the cloned Eg and c-mos Xenopus laevis maternal mRNAs. Specific, but not identical, uv-crosslinking signals were obtained, some of which corresponded to already identified proteins. A signal for a novel 90 kDa protein was observed with the c-mos 3'UTR radiolabeled with both CTP and GTP but not with UTP. The binding site of the 90 kDa RNA-binding protein was localised to a 59-nucleotide portion of the c-mos 3'UTR. Conclusion That the 90 kDa signal was detected with RNAs radiolabeled with CTP or GTP but not UTP illustrates the advantage of radiolabeling all four nucleotides in a UV-crosslink based screen. This method can be used for both long and short RNAs and does not require knowledge of the cis-acting sequence. It should be amenable to high throughput screening for RNA binding proteins.

  5. Sequence specific motor performance gains after memory consolidation in children and adolescents.

    Directory of Open Access Journals (Sweden)

    Shoshi Dorfberger

    Full Text Available Memory consolidation for a trained sequence of finger opposition movements, in 9- and 12-year-old children, was recently found to be significantly less susceptible to interference by a subsequent training experience, compared to that of 17-year-olds. It was suggested that, in children, the experience of training on any sequence of finger movements may affect the performance of the sequence elements, component movements, rather than the sequence as a unit; the latter has been implicated in the learning of the task by adults. This hypothesis implied a possible childhood advantage in the ability to transfer the gains from a trained to the reversed, untrained, sequence of movements. Here we report the results of transfer tests undertaken to test this proposal in 9-, 12-, and 17-year-olds after training in the finger-to-thumb opposition sequence (FOS learning task. Our results show that the performance gains in the trained sequence partially transferred from the left, trained hand, to the untrained hand at 48-hours after a single training session in the three age-groups tested. However, there was very little transfer of the gains from the trained to the untrained, reversed, sequence performed by either hand. The results indicate sequence specific post-training gains in FOS performance, as opposed to a general improvement in performance of the individual, component, movements that comprised both the trained and untrained sequences. These results do not support the proposal that the reduced susceptibility to interference, in children before adolescence, reflects a difference in movement syntax representation after training.

  6. CaMV-35S promoter sequence-specific DNA methylation in lettuce.

    Science.gov (United States)

    Okumura, Azusa; Shimada, Asahi; Yamasaki, Satoshi; Horino, Takuya; Iwata, Yuji; Koizumi, Nozomu; Nishihara, Masahiro; Mishiba, Kei-ichiro

    2016-01-01

    We found 35S promoter sequence-specific DNA methylation in lettuce. Additionally, transgenic lettuce plants having a modified 35S promoter lost methylation, suggesting the modified sequence is subjected to the methylation machinery. We previously reported that cauliflower mosaic virus 35S promoter-specific DNA methylation in transgenic gentian (Gentiana triflora × G. scabra) plants occurs irrespective of the copy number and the genomic location of T-DNA, and causes strong gene silencing. To confirm whether 35S-specific methylation can occur in other plant species, transgenic lettuce (Lactuca sativa L.) plants with a single copy of the 35S promoter-driven sGFP gene were produced and analyzed. Among 10 lines of transgenic plants, 3, 4, and 3 lines showed strong, weak, and no expression of sGFP mRNA, respectively. Bisulfite genomic sequencing of the 35S promoter region showed hypermethylation at CpG and CpWpG (where W is A or T) sites in 9 of 10 lines. Gentian-type de novo methylation pattern, consisting of methylated cytosines at CpHpH (where H is A, C, or T) sites, was also observed in the transgenic lettuce lines, suggesting that lettuce and gentian share similar methylation machinery. Four of five transgenic lettuce lines having a single copy of a modified 35S promoter, which was modified in the proposed core target of de novo methylation in gentian, exhibited 35S hypomethylation, indicating that the modified sequence may be the target of the 35S-specific methylation machinery.

  7. Sequence specific motor performance gains after memory consolidation in children and adolescents.

    Science.gov (United States)

    Dorfberger, Shoshi; Adi-Japha, Esther; Karni, Avi

    2012-01-01

    Memory consolidation for a trained sequence of finger opposition movements, in 9- and 12-year-old children, was recently found to be significantly less susceptible to interference by a subsequent training experience, compared to that of 17-year-olds. It was suggested that, in children, the experience of training on any sequence of finger movements may affect the performance of the sequence elements, component movements, rather than the sequence as a unit; the latter has been implicated in the learning of the task by adults. This hypothesis implied a possible childhood advantage in the ability to transfer the gains from a trained to the reversed, untrained, sequence of movements. Here we report the results of transfer tests undertaken to test this proposal in 9-, 12-, and 17-year-olds after training in the finger-to-thumb opposition sequence (FOS) learning task. Our results show that the performance gains in the trained sequence partially transferred from the left, trained hand, to the untrained hand at 48-hours after a single training session in the three age-groups tested. However, there was very little transfer of the gains from the trained to the untrained, reversed, sequence performed by either hand. The results indicate sequence specific post-training gains in FOS performance, as opposed to a general improvement in performance of the individual, component, movements that comprised both the trained and untrained sequences. These results do not support the proposal that the reduced susceptibility to interference, in children before adolescence, reflects a difference in movement syntax representation after training.

  8. Molecular-Level Thermodynamic Switch Controls Chemical Equilibrium in Sequence-Specific Hydrophobic Interaction of 35 Dipeptide Pairs

    OpenAIRE

    Chun, Paul W.

    2003-01-01

    Applying the Planck-Benzinger methodology, the sequence-specific hydrophobic interactions of 35 dipeptide pairs were examined over a temperature range of 273–333 K, based on data reported by Nemethy and Scheraga in 1962. The hydrophobic interaction in these sequence-specific dipeptide pairs is highly similar in its thermodynamic behavior to that of other biological systems. The results imply that the negative Gibbs free energy change minimum at a well-defined stable temperature, 〈Ts〉, where t...

  9. Prevalence of Misconceptions, Dogmas, and Popular Views about Giftedness and Intelligence: A Case from Turkey

    Science.gov (United States)

    Sak, Ugur

    2011-01-01

    The purpose of this study was to investigate the prevalence of misconceptions, dogmas and popular views about giftedness and intelligence among Turkish lay people. A survey questionnaire consisting of 12 forced-choice items about global misconceptions, dogmatic beliefs and popular views related to giftedness and intelligence was used to collect…

  10. Structural basis for sequence-specific recognition of DNA by TAL effectors

    KAUST Repository

    Deng, Dong; Yan, Chuangye; Pan, Xiaojing; Mahfouz, Magdy M.; Wang, Jiawei; Zhu, Jiankang; Shi, Yi Gong; Yan, Nieng

    2012-01-01

    TAL (transcription activator-like) effectors, secreted by phytopathogenic bacteria, recognize host DNA sequences through a central domain of tandem repeats. Each repeat comprises 33 to 35 conserved amino acids and targets a specific base pair

  11. Sequence-specific high mobility group box factors recognize 10-12-base pair minor groove motifs

    DEFF Research Database (Denmark)

    van Beest, M; Dooijes, D; van De Wetering, M

    2000-01-01

    Sequence-specific high mobility group (HMG) box factors bind and bend DNA via interactions in the minor groove. Three-dimensional NMR analyses have provided the structural basis for this interaction. The cognate HMG domain DNA motif is generally believed to span 6-8 bases. However, alignment...

  12. Unnatural base pair systems toward the expansion of the genetic alphabet in the central dogma.

    Science.gov (United States)

    Hirao, Ichiro; Kimoto, Michiko

    2012-01-01

    Toward the expansion of the genetic alphabet of DNA, several artificial third base pairs (unnatural base pairs) have been created. Synthetic DNAs containing the unnatural base pairs can be amplified faithfully by PCR, along with the natural A-T and G-C pairs, and transcribed into RNA. The unnatural base pair systems now have high potential to open the door to next generation biotechnology. The creation of unnatural base pairs is a consequence of repeating "proof of concept" experiments. In the process, initially designed base pairs were modified to address their weak points. Some of them were artificially evolved to ones with higher efficiency and selectivity in polymerase reactions, while others were eliminated from the analysis. Here, we describe the process of unnatural base pair development, as well as the tests of their applications.

  13. From DNA to RNA to disease and back: The 'central dogma' of regulatory disease variation

    Directory of Open Access Journals (Sweden)

    Stranger Barbara E

    2006-06-01

    Full Text Available Abstract Much of the focus of human disease genetics is directed towards identifying nucleotide variants that contribute to disease phenotypes. This is a complex problem, often involving contributions from multiple loci and their interactions, as well as effects due to environmental factors. Although some diseases with a genetic basis are caused by nucleotide changes that alter an amino acid sequence, in other cases, disease risk is associated with altered gene regulation. This paper focuses on how studies of gene expression variation might complement disease studies and provide crucial links between genotype and phenotype.

  14. Beyond the Central Dogma: Model-Based Learning of How Genes Determine Phenotypes

    Science.gov (United States)

    Reinagel, Adam; Speth, Elena Bray

    2016-01-01

    In an introductory biology course, we implemented a learner-centered, model-based pedagogy that frequently engaged students in building conceptual models to explain how genes determine phenotypes. Model-building tasks were incorporated within case studies and aimed at eliciting students' understanding of 1) the origin of variation in a population…

  15. A world in one dimension: Linus Pauling, Francis Crick and the central dogma of molecular biology.

    Science.gov (United States)

    Strasser, Bruno J

    2006-01-01

    In 1957, Francis Crick outlined a startling vision of life in which the great diversity of forms and shapes of macromolecules was encoded in the one-dimensional sequence of nucleic acids. This paper situates Crick's new vision in the debates of the 1950s about protein synthesis and gene action. After exploring the reception of Crick's ideas, it shows how they differed radically from a different model of protein synthesis which enjoyed wide currency in that decade. In this alternative model, advocated by Linus Pauling and other luminaries, three-dimensional templates directed the folding of proteins. Even though it was always considered somewhat speculative, this theory was supported by a number of empirical results originating in different experimental systems. It was eventually replaced by a model in which the forms and shapes of macromolecules resulted solely from their amino acid sequence, dramatically simplifying the problem of protein synthesis which Crick was attempting to solve in 1957.

  16. The discovery of viruses: advancing science and medicine by challenging dogma.

    Science.gov (United States)

    Artenstein, Andrew W

    2012-07-01

    The discovery of viruses in the final years of the nineteenth century represented the culmination of two decades of work on tobacco mosaic disease by three botanical scientists. Eventually their discovery led to a paradigm shift in scientific thought, but it took more than 20 years to appreciate its implications because it was inconsistent with the prevailing dogma of the time-Koch's postulates. Although these 'rules' were actually conceived of as guidelines upon which to establish microbial causality and their implementation resulted in many new discoveries, they also had the unintended effect of limiting the interpretation of novel findings. However, by challenging existing dogma through rigorous scientific observation and sheer persistence, the investigators advanced medicine and heralded new areas of discovery. Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  17. ;Every dogma has its day': a personal look at carbon metabolism in photosynthetic bacteria.

    Science.gov (United States)

    Ormerod, John

    2003-01-01

    Dogmas are unscientific. What is perhaps the greatest biological dogma of all time, the 'unity of biochemistry' is, in the main, still having its day. According to present knowledge, the exceptions to this dogma are mere details when seen in relation to the biosystem as a whole. Nevertheless the exceptions are scientifically interesting and the understanding of them has led to a better comprehension of photosynthesis and ecology. Until the discovery of (14)C, photosynthetic CO(2) fixation was like a slightly opened black box. With (14)C in hand scientists mapped out the path of carbon in green plant photosynthesis in the course of a few years. The impressive reductive pentose phosphate cycle was almost immediately assumed to be universal in autotrophs, including anoxygenic phototrophs, in spite of the odd observation to the contrary. A new dogma was born and held the field for about two decades. Events began to turn when green sulfur bacteria were found to contain ferredoxin-coupled ketoacid-oxidoreductases. This led to the formulation of a novel CO(2)-fixing pathway, the reductive citric acid cycle, but its general acceptance required much work by many investigators. However, the ice had now been broken and after some years a third mechanism of CO(2) fixation was discovered, this time in Chloroflexus,and then a fourth in the same genus. One consequence of these discoveries is that it has become apparent that oxygen is an important factor that determines the kind of CO(2)-fixing mechanism an organism uses. With the prospect of the characterization of hordes of novel bacteria forecast by molecular ecologists we can expect further distinctive CO(2) fixation mechanisms to turn up.

  18. Structural basis for sequence-specific recognition of DNA by TAL effectors

    KAUST Repository

    Deng, Dong

    2012-01-05

    TAL (transcription activator-like) effectors, secreted by phytopathogenic bacteria, recognize host DNA sequences through a central domain of tandem repeats. Each repeat comprises 33 to 35 conserved amino acids and targets a specific base pair by using two hypervariable residues [known as repeat variable diresidues (RVDs)] at positions 12 and 13. Here, we report the crystal structures of an 11.5-repeat TAL effector in both DNA-free and DNA-bound states. Each TAL repeat comprises two helices connected by a short RVD-containing loop. The 11.5 repeats form a right-handed, superhelical structure that tracks along the sense strand of DNA duplex, with RVDs contacting the major groove. The 12th residue stabilizes the RVD loop, whereas the 13th residue makes a base-specific contact. Understanding DNA recognition by TAL effectors may facilitate rational design of DNA-binding proteins with biotechnological applications.

  19. Molecular Simulations of Sequence-Specific Association of Transmembrane Proteins in Lipid Bilayers

    Science.gov (United States)

    Doxastakis, Manolis; Prakash, Anupam; Janosi, Lorant

    2011-03-01

    Association of membrane proteins is central in material and information flow across the cellular membranes. Amino-acid sequence and the membrane environment are two critical factors controlling association, however, quantitative knowledge on such contributions is limited. In this work, we study the dimerization of helices in lipid bilayers using extensive parallel Monte Carlo simulations with recently developed algorithms. The dimerization of Glycophorin A is examined employing a coarse-grain model that retains a level of amino-acid specificity, in three different phospholipid bilayers. Association is driven by a balance of protein-protein and lipid-induced interactions with the latter playing a major role at short separations. Following a different approach, the effect of amino-acid sequence is studied using the four transmembrane domains of the epidermal growth factor receptor family in identical lipid environments. Detailed characterization of dimer formation and estimates of the free energy of association reveal that these helices present significant affinity to self-associate with certain dimers forming non-specific interfaces.

  20. Sequence-specific assignments in the 1H NMR spectrum of the human inflammatory protein C5a

    International Nuclear Information System (INIS)

    Zuiderweg, E.R.P.; Mollison, K.W.; Henkin, J.; Carter, G.W.

    1988-01-01

    Full sequence-specific assignments for the 1 H NMR lines of the backbone protons of the human complement factor C5a are described and documented. The results were obtained by largely following the methodology developed by Wuethrich et al. Assignments for the majority of the amino acid side chain protons were obtained by using a comparison of double- and triple-quantum-filtered two-dimensional correlated experiments together with the analysis of relayed coherence transfer spectra. The assignments provide the basis for the determination of the thus far unknown three-dimensional structure of C5a from nuclear Overhauser enhancement distance constraints

  1. Sequence-specific validation of LAMP amplicons in real-time optomagnetic detection of Dengue serotype 2 synthetic DNA

    DEFF Research Database (Denmark)

    Minero, Gabriel Khose Antonio; Nogueira, Catarina; Rizzi, Giovanni

    2017-01-01

    We report on an optomagnetic technique optimised for real-time molecular detection of Dengue fever virus under ideal as well as non-ideal laboratory conditions using two different detection approaches. The first approach is based on the detection of the hydrodynamic volume of streptavidin coated...... magnetic nanoparticles attached to biotinylated LAMP amplicons. We demonstrate detection of sub-femtomolar Dengue DNA target concentrations in the ideal contamination-free lab environment within 20 min. The second detection approach is based on sequence-specific binding of functionalised magnetic...... claim detection of down to 100 fM of Dengue target after 20 min of LAMP with a contamination background....

  2. DNA minor groove electrostatic potential: influence of sequence-specific transitions of the torsion angle gamma and deoxyribose conformations.

    Science.gov (United States)

    Zhitnikova, M Y; Shestopalova, A V

    2017-11-01

    The structural adjustments of the sugar-phosphate DNA backbone (switching of the γ angle (O5'-C5'-C4'-C3') from canonical to alternative conformations and/or C2'-endo → C3'-endo transition of deoxyribose) lead to the sequence-specific changes in accessible surface area of both polar and non-polar atoms of the grooves and the polar/hydrophobic profile of the latter ones. The distribution of the minor groove electrostatic potential is likely to be changing as a result of such conformational rearrangements in sugar-phosphate DNA backbone. Our analysis of the crystal structures of the short free DNA fragments and calculation of their electrostatic potentials allowed us to determine: (1) the number of classical and alternative γ angle conformations in the free B-DNA; (2) changes in the minor groove electrostatic potential, depending on the conformation of the sugar-phosphate DNA backbone; (3) the effect of the DNA sequence on the minor groove electrostatic potential. We have demonstrated that the structural adjustments of the DNA double helix (the conformations of the sugar-phosphate backbone and the minor groove dimensions) induce changes in the distribution of the minor groove electrostatic potential and are sequence-specific. Therefore, these features of the minor groove sizes and distribution of minor groove electrostatic potential can be used as a signal for recognition of the target DNA sequence by protein in the implementation of the indirect readout mechanism.

  3. 1H NMR studies of plastocyanin from Scenedesmus obliquus: Complete sequence-specific assignment, secondary structure analysis, and global fold

    International Nuclear Information System (INIS)

    Moore, J.M.; Chazin, W.J.; Wright, P.E.; Powls, R.

    1988-01-01

    Two-dimensional 1 H NMR methods have been used to make sequence-specific resonance assignments for the 97 amino acid residues of the plastocyanin from the green alga Scenedesmus obliquus. Assignments were obtained for all backbone protons and the majority of the side-chain protons. Spin system identification relied heavily on the observation of relayed connectivities to the backbone amide proton. Sequence-specific assignments were made by using the sequential assignment procedure. During this process, an extra valine residue was identified that had not been detected in the original amino acid sequence. Elements of regular secondary structure were identified from characteristic NOE connectivities between backbone protons, coupling constant values, and the observation of slowly exchanging amide protons. The protein in solution contains eight β-strands, one short segment of helix, five reverse turns, and five loops. The β-strands may be arranged into two βsheets on the basis of extensive cross-strand NOE connectivities. The chain-folding topology determined from the NMR experiments is that of a Greek key β-barrel and is similar to that observed for French bean plastocyanin in solution and poplar plastocyanin in the crystalline state. While the overall structures are similar, several differences in local structure between the S. obliquus and higher plant plastocyanins have been identified

  4. Breaking Free of Sample Size Dogma to Perform Innovative Translational Research

    Science.gov (United States)

    Bacchetti, Peter; Deeks, Steven G.; McCune, Joseph M.

    2011-01-01

    Innovative clinical and translational research is often delayed or prevented by reviewers’ expectations that any study performed in humans must be shown in advance to have high statistical power. This supposed requirement is not justifiable and is contradicted by the reality that increasing sample size produces diminishing marginal returns. Studies of new ideas often must start small (sometimes even with an N of 1) because of cost and feasibility concerns, and recent statistical work shows that small sample sizes for such research can produce more projected scientific value per dollar spent than larger sample sizes. Renouncing false dogma about sample size would remove a serious barrier to innovation and translation. PMID:21677197

  5. Challenging the Cancer Molecular Stratification Dogma: Intratumoral Heterogeneity Undermines Consensus Molecular Subtypes and Potential Diagnostic Value in Colorectal Cancer.

    Science.gov (United States)

    Dunne, Philip D; McArt, Darragh G; Bradley, Conor A; O'Reilly, Paul G; Barrett, Helen L; Cummins, Robert; O'Grady, Tony; Arthur, Ken; Loughrey, Maurice B; Allen, Wendy L; McDade, Simon S; Waugh, David J; Hamilton, Peter W; Longley, Daniel B; Kay, Elaine W; Johnston, Patrick G; Lawler, Mark; Salto-Tellez, Manuel; Van Schaeybroeck, Sandra

    2016-08-15

    A number of independent gene expression profiling studies have identified transcriptional subtypes in colorectal cancer with potential diagnostic utility, culminating in publication of a colorectal cancer Consensus Molecular Subtype classification. The worst prognostic subtype has been defined by genes associated with stem-like biology. Recently, it has been shown that the majority of genes associated with this poor prognostic group are stromal derived. We investigated the potential for tumor misclassification into multiple diagnostic subgroups based on tumoral region sampled. We performed multiregion tissue RNA extraction/transcriptomic analysis using colorectal-specific arrays on invasive front, central tumor, and lymph node regions selected from tissue samples from 25 colorectal cancer patients. We identified a consensus 30-gene list, which represents the intratumoral heterogeneity within a cohort of primary colorectal cancer tumors. Using a series of online datasets, we showed that this gene list displays prognostic potential HR = 2.914 (confidence interval 0.9286-9.162) in stage II/III colorectal cancer patients, but in addition, we demonstrated that these genes are stromal derived, challenging the assumption that poor prognosis tumors with stem-like biology have undergone a widespread epithelial-mesenchymal transition. Most importantly, we showed that patients can be simultaneously classified into multiple diagnostically relevant subgroups based purely on the tumoral region analyzed. Gene expression profiles derived from the nonmalignant stromal region can influence assignment of colorectal cancer transcriptional subtypes, questioning the current molecular classification dogma and highlighting the need to consider pathology sampling region and degree of stromal infiltration when employing transcription-based classifiers to underpin clinical decision making in colorectal cancer. Clin Cancer Res; 22(16); 4095-104. ©2016 AACRSee related commentary by Morris and

  6. �Nie waar nie?� Opmerkinge oor geloofservaring, dogma en die (eskatologiese aard van teologiese besinning

    Directory of Open Access Journals (Sweden)

    D P Veldsman

    2008-05-01

    Full Text Available �Not true?� Remarks on the experience of faith, dogma and the (eschatological nature of theological reflection�Not true?� is a characteristic saying of Conrad Wethmar. In this article of appreciation for his academic contribution, this saying as a �polite questioning and affirmation� (as I understand it, is explored within the context of viewpoints on the experience of faith and in reference to his understanding of dogma in order to highlight the way in which this saying actually gives expression to his understanding of the nature of theological reflection.

  7. A modified strategy for sequence specific assignment of protein NMR spectra based on amino acid type selective experiments

    International Nuclear Information System (INIS)

    Schubert, Mario; Labudde, Dirk; Leitner, Dietmar; Oschkinat, Hartmut; Schmieder, Peter

    2005-01-01

    The determination of the three-dimensional structure of a protein or the study of protein-ligand interactions requires the assignment of all relevant nuclei as an initial step. This is nowadays almost exclusively performed using triple-resonance experiments. The conventional strategy utilizes one or more pairs of three dimensional spectra to obtain redundant information and thus reliable assignments. Here, a modified strategy for obtaining sequence specific assignments based on two dimensional amino acid type selective triple-resonance experiments is proposed. These experiments can be recorded with good resolution in a relatively short time. They provide very specific and redundant information, in particular on sequential connectivities, that drastically increases the ease and reliability of the assignment procedure, done either manually or in an automated fashion. The new strategy is demonstrated with the protein domain PB1 from yeast CDC24p

  8. CRISPR-Cas9 technology: applications in genome engineering, development of sequence-specific antimicrobials, and future prospects.

    Science.gov (United States)

    de la Fuente-Núñez, César; Lu, Timothy K

    2017-02-20

    The development of CRISPR-Cas9 technology has revolutionized our ability to edit DNA and to modulate expression levels of genes of interest, thus providing powerful tools to accelerate the precise engineering of a wide range of organisms. In addition, the CRISPR-Cas system can be harnessed to design "precision" antimicrobials that target bacterial pathogens in a DNA sequence-specific manner. This capability will enable killing of drug-resistant microbes by selectively targeting genes involved in antibiotic resistance, biofilm formation and virulence. Here, we review the origins and mechanistic basis of CRISPR-Cas systems, discuss how this technology can be leveraged to provide a range of applications in both eukaryotic and prokaryotic systems, and finish by outlining limitations and future prospects.

  9. Sequence specific DNA binding by P53 is enhanced by ionizing radiation and is mediated via DNA-PK activity

    International Nuclear Information System (INIS)

    Kachnic, L.A.; Wunsch, H.; Mekeel, K.L.; De Frank, J.S.; Powell, S.N.

    1996-01-01

    Purpose: P53 is known to be involved in the cellular response to DNA damage. It mediates many of its effects by acting as a transcription factor via sequence-specific DNA binding. The half-life of p53 is prolonged following DNA damage, and this results in elevated levels of p53 for a period of 2-8 hours. The increase in p53 is often relatively small, but this produces significant stimulation of a downstream gene such as p21(WAF1/cip1). We investigated post-translational modification of p53 following ionizing radiation damage. Materials and Methods: The response of normal Balb-C mouse fibroblasts (FC) to ionizing radiation (IR, 8 Gy) was measured at 0,3,6,9 and 24 hours, by the levels of p53, p21, flow cytometry and the electrophoretic mobility shift assay (EMSA). EMSA utilized a 26 bp consensus sequence end-labeled oligonucleotide to measure sequence-specific p53 binding. P53 specificity was confirmed by an enhanced mobility shift (retardation) when using p53 antibody. Comparison was made with scid fibroblasts (FS) and FC cells transfected with a plasmid (CX3) containing mutant p53 (alanine-143) or infected with a retrovirus containing the E6 protein of human papilloma virus type 16. Results: The response of p53 to DNA damage shows a 3-fold increase at 3-6 hours, and was not significantly different between FC and FS. FC-CX3 showed detectable basal levels of p53, and a 2-fold further induction of p53 after IR. FC-E6 showed no detectable levels of p53 before or after IR. No induction of p21 or G1/S arrest was seen in FC-CX3 or FC-E6, as has been observed previously. The induction of p21 in FS cells was attenuated and delayed: a 2-3-fold increase seen maximally at 9 hours, compared with a 5-fold increase seen maximally at 3-6 hours in FC cells. The accumulation of cells at the G1/S junction after IR showed the same kinetics as p21 induction: the peak of cells in G1 occurs at 3-6 hours in FC, but not until 9-24 hours in FS. The response is reminiscent of that seen in

  10. Protocols for 16S rDNA Array Analyses of Microbial Communities by Sequence-Specific Labeling of DNA Probes

    Directory of Open Access Journals (Sweden)

    Knut Rudi

    2003-01-01

    Full Text Available Analyses of complex microbial communities are becoming increasingly important. Bottlenecks in these analyses, however, are the tools to actually describe the biodiversity. Novel protocols for DNA array-based analyses of microbial communities are presented. In these protocols, the specificity obtained by sequence-specific labeling of DNA probes is combined with the possibility of detecting several different probes simultaneously by DNA array hybridization. The gene encoding 16S ribosomal RNA was chosen as the target in these analyses. This gene contains both universally conserved regions and regions with relatively high variability. The universally conserved regions are used for PCR amplification primers, while the variable regions are used for the specific probes. Protocols are presented for DNA purification, probe construction, probe labeling, and DNA array hybridizations.

  11. Infant circumcision: the last stand for the dead dogma of parental (sovereignal) rights.

    Science.gov (United States)

    Van Howe, Robert S

    2013-07-01

    J S Mill used the term 'dead dogma' to describe a belief that has gone unquestioned for so long and to such a degree that people have little idea why they accept it or why they continue to believe it. When wives and children were considered chattel, it made sense for the head of a household to have a 'sovereignal right' to do as he wished with his property. Now that women and children are considered to have the full complement of human rights and slavery has been abolished, it is no longer acceptable for someone to have a 'right' to completely control the life of another human being. Revealingly, parental rights tend to be invoked only when parents want to do something that is arguably not in their child's best interest. Infant male circumcision is a case in point. Instead of parental rights, I claim that parents have an obligation to protect their children's rights as well as to preserve the future options of those children so far as possible. In this essay, it is argued that the notion that parents have a right to make decisions concerning their children's bodies and minds-irrespective of the child's best interests-is a dead dogma. The ramifications of this argument for the circumcision debate are then spelled out and discussed.

  12. Design of Tail-Clamp Peptide Nucleic Acid Tethered with Azobenzene Linker for Sequence-Specific Detection of Homopurine DNA

    Directory of Open Access Journals (Sweden)

    Shinjiro Sawada

    2017-10-01

    Full Text Available DNA carries genetic information in its sequence of bases. Synthetic oligonucleotides that can sequence-specifically recognize a target gene sequence are a useful tool for regulating gene expression or detecting target genes. Among the many synthetic oligonucleotides, tail-clamp peptide nucleic acid (TC-PNA offers advantages since it has two homopyrimidine PNA strands connected via a flexible ethylene glycol-type linker that can recognize complementary homopurine sequences via Watson-Crick and Hoogsteen base pairings and form thermally-stable PNA/PNA/DNA triplex structures. Here, we synthesized a series of TC-PNAs that can possess different lengths of azobenzene-containing linkers and studied their binding behaviours to homopurine single-stranded DNA. Introduction of azobenzene at the N-terminus amine of PNA increased the thermal stability of PNA-DNA duplexes. Further extension of the homopyrimidine PNA strand at the N-terminus of PNA-AZO further increased the binding stability of the PNA/DNA/PNA triplex to the target homopurine sequence; however, it induced TC-PNA/DNA/TC-PNA complex formation. Among these TC-PNAs, 9W5H-C4-AZO consisting of nine Watson-Crick bases and five Hoogsteen bases tethered with a beta-alanine conjugated azobenzene linker gave a stable 1:1 TC-PNA/ssDNA complex and exhibited good mismatch recognition. Our design for TC-PNA-AZO can be utilized for detecting homopurine sequences in various genes.

  13. A duplex DNA-gold nanoparticle probe composed as a colorimetric biosensor for sequence-specific DNA-binding proteins.

    Science.gov (United States)

    Ahn, Junho; Choi, Yeonweon; Lee, Ae-Ree; Lee, Joon-Hwa; Jung, Jong Hwa

    2016-03-21

    Using duplex DNA-AuNP aggregates, a sequence-specific DNA-binding protein, SQUAMOSA Promoter-binding-Like protein 12 (SPL-12), was directly determined by SPL-12-duplex DNA interaction-based colorimetric actions of DNA-Au assemblies. In order to prepare duplex DNA-Au aggregates, thiol-modified DNA 1 and DNA 2 were attached onto the surface of AuNPs, respectively, by the salt-aging method and then the DNA-attached AuNPs were mixed. Duplex-DNA-Au aggregates having the average size of 160 nm diameter and the maximum absorption at 529 nm were able to recognize SPL-12 and reached the equivalent state by the addition of ∼30 equivalents of SPL-12 accompanying a color change from red to blue with a red shift of the maximum absorption at 570 nm. As a result, the aggregation size grew to about 247 nm. Also, at higher temperatures of the mixture of duplex-DNA-Au aggregate solution and SPL-12, the equivalent state was reached rapidly. On the contrary, in the control experiment using Bovine Serum Albumin (BSA), no absorption band shift of duplex-DNA-Au aggregates was observed.

  14. The future of bioethics: three dogmas and a cup of hemlock.

    Science.gov (United States)

    Dawson, Angus

    2010-06-01

    In this paper I argue that bioethics is in crisis and that it will not have a future unless it begins to embrace a more Socratic approach to its leading assumptions. The absence of a critical and sceptical spirit has resulted in little more than a dominant ideology. I focus on three key issues. First, that too often bioethics collapses into medical ethics. Second, that medical ethics itself is beset by a lack of self-reflection that I characterize here as a commitment to three dogmas. Third, I offer a more positive perspective by suggesting how bioethics may benefit from looking towards public health ethics as a new source of inspiration and direction.

  15. Cholesterol Autoxidation Revisited: Debunking the Dogma Associated with the Most Vilified of Lipids.

    Science.gov (United States)

    Zielinski, Zosia A M; Pratt, Derek A

    2016-06-08

    The longstanding dogma that cholesterol (chol) autoxidation gives chol 7-hydroperoxide (7-OOH) as the sole primary product is shown to be invalid. In fact, the epimers of each of chol 4-OOH, 6-OOH, and 7-OOH are readily formed. Although the C4-H bond that must be cleaved to produce the chol 4-OOH and 6-OOH products is significantly stronger than the C7-H bond, H-atom abstraction from C4 is facilitated by H-bond formation between the attacking peroxyl radical and the 3β-OH. Chol 5α-OOH is also formed, but only in the presence of a good H-atom donor. Chol 5α-OOH and 6-OOH undergo Hock fragmentation to yield the secosterols implicated in cardiovascular and neurodegenerative diseases, suggesting that they are likely to arise simply from autoxidation and not from reactions with O3 or (1)O2.

  16. Overturning dogma: tolerance of insects to mixed-sterol diets is not universal.

    Science.gov (United States)

    Behmer, Spencer T

    2017-10-01

    Insects cannot synthesize sterols de novo, but like all eukaryotes they use them as cell membrane inserts where they influence membrane fluidity and rigidity. They also use a small amount for metabolic purposes, most notably as essential precursors for steroid hormones. It has been a long-held view that most insects require a small amount of specific sterol (often cholesterol) for metabolic purposes, but for membrane purposes (where the bulk of sterols are used) specificity in sterol structure was less important. Under this model, it was assumed that insects could tolerate mixed-sterol diets as long as a small amount of cholesterol was available. In the current paper this dogma is overturned, using data from plant-feeding insects that were fed mixed-sterol diets with different amounts and ratios of dietary sterols. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Linking maternal and somatic 5S rRNA types with different sequence-specific non-LTR retrotransposons.

    Science.gov (United States)

    Locati, Mauro D; Pagano, Johanna F B; Ensink, Wim A; van Olst, Marina; van Leeuwen, Selina; Nehrdich, Ulrike; Zhu, Kongju; Spaink, Herman P; Girard, Geneviève; Rauwerda, Han; Jonker, Martijs J; Dekker, Rob J; Breit, Timo M

    2017-04-01

    5S rRNA is a ribosomal core component, transcribed from many gene copies organized in genomic repeats. Some eukaryotic species have two 5S rRNA types defined by their predominant expression in oogenesis or adult tissue. Our next-generation sequencing study on zebrafish egg, embryo, and adult tissue identified maternal-type 5S rRNA that is exclusively accumulated during oogenesis, replaced throughout the embryogenesis by a somatic-type, and thus virtually absent in adult somatic tissue. The maternal-type 5S rDNA contains several thousands of gene copies on chromosome 4 in tandem repeats with small intergenic regions, whereas the somatic-type is present in only 12 gene copies on chromosome 18 with large intergenic regions. The nine-nucleotide variation between the two 5S rRNA types likely affects TFIII binding and riboprotein L5 binding, probably leading to storage of maternal-type rRNA. Remarkably, these sequence differences are located exactly at the sequence-specific target site for genome integration by the 5S rRNA-specific Mutsu retrotransposon family. Thus, we could define maternal- and somatic-type MutsuDr subfamilies. Furthermore, we identified four additional maternal-type and two new somatic-type MutsuDr subfamilies, each with their own target sequence. This target-site specificity, frequently intact maternal-type retrotransposon elements, plus specific presence of Mutsu retrotransposon RNA and piRNA in egg and adult tissue, suggest an involvement of retrotransposons in achieving the differential copy number of the two types of 5S rDNA loci. © 2017 Locati et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  18. Human Platelet Antigen Alleles in 998 Taiwanese Blood Donors Determined by Sequence-Specific Primer Polymerase Chain Reaction

    Directory of Open Access Journals (Sweden)

    Shun-Chung Pai

    2013-01-01

    Full Text Available Polymorphism of human platelet antigens (HPAs leads to alloimmunizations and immune-mediated platelet disorders including fetal-neonatal alloimmune thrombocytopenia (FNAIT, posttransfusion purpura (PTP, and platelet transfusion refractoriness (PTR. HPA typing and knowledge of antigen frequency in a population are important in particular for the provision of HPA-matched blood components for patients with PTR. We have performed allele genotyping for HPA-1 through -6 and -15 among 998 platelet donors from 6 blood centers in Taiwan using sequence-specific primer polymerase chain reaction. The HPA allele frequency was 99.55, and 0.45% for HPA-1a and -1b; 96.49, and 3.51% for HPA-2a and -2b; 55.81, and 44.19% for HPA-3a and -3b; 99.75, and 0.25% for HPA-4a and -4b; 98.50, and 1.50% for HPA-5a and -5b; 97.75 and 2.25% for HPA-6a and -6b; 53.71 and 46.29% for HPA-15a and -15b. HPA-15b and HPA-3a, may be considered the most important, followed by HPA-2, -6, -1, -5, and -4 systems, as a cause of FNAIT, PTP, and PTR based on allele frequency. HPA-4b and HPA-5b role cannot be excluded based on their immunogenicity. A larger-scale study will now be conducted to confirm these hypotheses and to establish an apheresis donor database for the procurement of HPA-matched apheresis platelets for patients with PTR.

  19. Sequence-specific DNA binding by MYC/MAX to low-affinity non-E-box motifs.

    Directory of Open Access Journals (Sweden)

    Michael Allevato

    Full Text Available The MYC oncoprotein regulates transcription of a large fraction of the genome as an obligatory heterodimer with the transcription factor MAX. The MYC:MAX heterodimer and MAX:MAX homodimer (hereafter MYC/MAX bind Enhancer box (E-box DNA elements (CANNTG and have the greatest affinity for the canonical MYC E-box (CME CACGTG. However, MYC:MAX also recognizes E-box variants and was reported to bind DNA in a "non-specific" fashion in vitro and in vivo. Here, in order to identify potential additional non-canonical binding sites for MYC/MAX, we employed high throughput in vitro protein-binding microarrays, along with electrophoretic mobility-shift assays and bioinformatic analyses of MYC-bound genomic loci in vivo. We identified all hexameric motifs preferentially bound by MYC/MAX in vitro, which include the low-affinity non-E-box sequence AACGTT, and found that the vast majority (87% of MYC-bound genomic sites in a human B cell line contain at least one of the top 21 motifs bound by MYC:MAX in vitro. We further show that high MYC/MAX concentrations are needed for specific binding to the low-affinity sequence AACGTT in vitro and that elevated MYC levels in vivo more markedly increase the occupancy of AACGTT sites relative to CME sites, especially at distal intergenic and intragenic loci. Hence, MYC binds diverse DNA motifs with a broad range of affinities in a sequence-specific and dose-dependent manner, suggesting that MYC overexpression has more selective effects on the tumor transcriptome than previously thought.

  20. Direct stacking of sequence-specific nuclease-induced mutations to produce high oleic and low linolenic soybean oil.

    Science.gov (United States)

    Demorest, Zachary L; Coffman, Andrew; Baltes, Nicholas J; Stoddard, Thomas J; Clasen, Benjamin M; Luo, Song; Retterath, Adam; Yabandith, Ann; Gamo, Maria Elena; Bissen, Jeff; Mathis, Luc; Voytas, Daniel F; Zhang, Feng

    2016-10-13

    The ability to modulate levels of individual fatty acids within soybean oil has potential to increase shelf-life and frying stability and to improve nutritional characteristics. Commodity soybean oil contains high levels of polyunsaturated linoleic and linolenic acid, which contribute to oxidative instability - a problem that has been addressed through partial hydrogenation. However, partial hydrogenation increases levels of trans-fatty acids, which have been associated with cardiovascular disease. Previously, we generated soybean lines with knockout mutations within fatty acid desaturase 2-1A (FAD2-1A) and FAD2-1B genes, resulting in oil with increased levels of monounsaturated oleic acid (18:1) and decreased levels of linoleic (18:2) and linolenic acid (18:3). Here, we stack mutations within FAD2-1A and FAD2-1B with mutations in fatty acid desaturase 3A (FAD3A) to further decrease levels of linolenic acid. Mutations were introduced into FAD3A by directly delivering TALENs into fad2-1a fad2-1b soybean plants. Oil from fad2-1a fad2-1b fad3a plants had significantly lower levels of linolenic acid (2.5 %), as compared to fad2-1a fad2-1b plants (4.7 %). Furthermore, oil had significantly lower levels of linoleic acid (2.7 % compared to 5.1 %) and significantly higher levels of oleic acid (82.2 % compared to 77.5 %). Transgene-free fad2-1a fad2-1b fad3a soybean lines were identified. The methods presented here provide an efficient means for using sequence-specific nucleases to stack quality traits in soybean. The resulting product comprised oleic acid levels above 80 % and linoleic and linolenic acid levels below 3 %.

  1. Stem loop sequences specific to transposable element IS605 are found linked to lipoprotein genes in Borrelia plasmids.

    Directory of Open Access Journals (Sweden)

    Nicholas Delihas

    Full Text Available BACKGROUND: Plasmids of Borrelia species are dynamic structures that contain a large number of repetitive genes, gene fragments, and gene fusions. In addition, the transposable element IS605/200 family, as well as degenerate forms of this IS element, are prevalent. In Helicobacter pylori, flanking regions of the IS605 transposase gene contain sequences that fold into identical small stem loops. These function in transposition at the single-stranded DNA level. METHODOLOGY/PRINCIPAL FINDINGS: In work reported here, bioinformatics techniques were used to scan Borrelia plasmid genomes for IS605 transposable element specific stem loop sequences. Two variant stem loop motifs are found in the left and right flanking regions of the transposase gene. Both motifs appear to have dispersed in plasmid genomes and are found "free-standing" and phylogenetically conserved without the associated IS605 transposase gene or the adjacent flanking sequence. Importantly, IS605 specific stem loop sequences are also found at the 3' ends of lipoprotein genes (PFam12 and PFam60, however the left and right sequences appear to develop their own evolutionary patterns. The lipoprotein gene-linked left stem loop sequences maintain the IS605 stem loop motif in orthologs but only at the RNA level. These show mutations whereby variants fold into phylogenetically conserved RNA-type stem loops that contain the wobble non-Watson-Crick G-U base-pairing. The right flanking sequence is associated with the family lipoprotein-1 genes. A comparison of homologs shows that the IS605 stem loop motif rapidly dissipates, but a more elaborate secondary structure appears to develop in its place. CONCLUSIONS/SIGNIFICANCE: Stem loop sequences specific to the transposable element IS605 are present in plasmid regions devoid of a transposase gene and significantly, are found linked to lipoprotein genes in Borrelia plasmids. These sequences are evolutionarily conserved and/or structurally developed in

  2. DNA minor groove targeted alkylating agents based on bisbenzimidazole carriers: synthesis, cytotoxicity and sequence-specificity of DNA alkylation.

    Science.gov (United States)

    Smaill, J B; Fan, J Y; Denny, W A

    1998-12-01

    A series of bisbenzimidazoles bearing a variety of alkylating agents [ortho- and meta-mustards, imidazolebis(hydroxymethyl), imidazolebis(methylcarbamate) and pyrrolebis(hydroxymethyl)], appended by a propyl linker chain, were prepared and investigated for sequence-specificity of DNA alkylation and their cytotoxicity. Previous work has shown that, for para-aniline mustards, a propyl linker is optimal for cytotoxicity. Alkaline cleavage assays using a variety of different labelled oligonucleotides showed that the preferred sequences for adenine alkylation were 5'-TTTANANAANN and 5'-ATTANANAANN (underlined bases show the drug alkylation sites), with AT-rich sequences required on both the 5' and 3' sides of the alkylated adenine. The different aniline mustards showed little variation in alkylation pattern and similar efficiencies of DNA cross-link formation despite the changes in orientation and positioning of the mustard, suggesting that the propyl linker has some flexibility. The imidazole- and pyrrolebis(hydroxymethyl) alkylators showed no DNA strand cleavage following base treatment, indicating that no guanine or adenine N3 or N7 adducts were formed. Using the PCR-based polymerase stop assay, these alkylators showed PCR blocks at 5'-C*G sites (the * nucleotide indicates the blocked site), particularly at 5'-TAC*GA 5'-AGC*GGA, and 5'-AGCC*GGT sequences, caused by guanine 2-NH2 lesions on the opposite strand. Only the (more reactive) imidazolebis(methylcarbamoyl) and pyrrolebis(hydroxymethyl) alkylators demonstrated interstrand cross-linking ability. All of the bifunctional mustards showed large (approximately 100-fold) increases in cytotoxicity over chlorambucil, with the corresponding monofunctional mustards being 20- to 60-fold less cytotoxic. These results suggest that in the mustards the propyl linker provides sufficient flexibility to achieve delivery of the alkylator to favoured (adenine N3) sites in the minor groove, regardless of its exact geometry with

  3. Use of PCR with Sequence-specific Primers for High-Resolution Human Leukocyte Antigen Typing of Patients with Narcolepsy

    Science.gov (United States)

    Woo, Hye In; Joo, Eun Yeon; Lee, Kyung Wha

    2012-01-01

    Background Narcolepsy is a neurologic disorder characterized by excessive daytime sleepiness, symptoms of abnormal rapid eye movement (REM) sleep, and a strong association with HLA-DRB1*1501, -DQA1*0102, and -DQB1*0602. Here, we investigated the clinico-physical characteristics of Korean patients with narcolepsy, their HLA types, and the clinical utility of high-resolution PCR with sequence-specific primers (PCR-SSP) as a simple typing method for identifying DRB1*15/16, DQA1, and DQB1 alleles. Methods The study population consisted of 67 consecutively enrolled patients having unexplained daytime sleepiness and diagnosed narcolepsy based on clinical and neurological findings. Clinical data and the results of the multiple sleep latency test and polysomnography were reviewed, and HLA typing was performed using both high-resolution PCR-SSP and sequence-based typing (SBT). Results The 44 narcolepsy patients with cataplexy displayed significantly higher frequencies of DRB1*1501 (Pc= 0.003), DQA1*0102 (Pc=0.001), and DQB1*0602 (Pc=0.014) than the patients without cataplexy. Among patients carrying DRB1*1501-DQB1*0602 or DQA1*0102, the frequencies of a mean REM sleep latency of less than 20 min in nocturnal polysomnography and clinical findings, including sleep paralysis and hypnagogic hallucination were significantly higher. SBT and PCR-SSP showed 100% concordance for high-resolution typing of DRB1*15/16 alleles and DQA1 and DQB1 loci. Conclusions The clinical characteristics and somnographic findings of narcolepsy patients were associated with specific HLA alleles, including DRB1*1501, DQA1*0102, and DQB1*0602. Application of high-resolution PCR-SSP, a reliable and simple method, for both allele- and locus-specific HLA typing of DRB1*15/16, DQA1, and DQB1 would be useful for characterizing clinical status among subjects with narcolepsy. PMID:22259780

  4. Impact of cadmium, cobalt and nickel on sequence-specific DNA binding of p63 and p73 in vitro and in cells

    Czech Academy of Sciences Publication Activity Database

    Adámik, Matěj; Bažantová, Pavla; Navrátilová, Lucie; Polášková, Alena; Pečinka, Petr; Holanová, L.; Tichý, Vlastimil; Brázdová, Marie

    2015-01-01

    Roč. 456, č. 1 (2015), s. 29-34 ISSN 0006-291X R&D Projects: GA ČR(CZ) GA13-36108S Institutional support: RVO:68081707 Keywords : p53 protein family * Sequence-specific DNA binding * Heavy metals Subject RIV: BO - Biophysics Impact factor: 2.371, year: 2015

  5. Implicit sequence-specific motor learning after sub-cortical stroke is associated with increased prefrontal brain activations: An fMRI study

    Science.gov (United States)

    Meehan, Sean K.; Randhawa, Bubblepreet; Wessel, Brenda; Boyd, Lara A.

    2010-01-01

    Implicit motor learning is preserved after stroke, but how the brain compensates for damage to facilitate learning is unclear. We used a random effects analysis to determine how stroke alters patterns of brain activity during implicit sequence-specific motor learning as compared to general improvements in motor control. Nine healthy participants and 9 individuals with chronic, right focal sub-cortical stroke performed a continuous joystick-based tracking task during an initial fMRI session, over 5 days of practice, and a retention test during a separate fMRI session. Sequence-specific implicit motor learning was differentiated from general improvements in motor control by comparing tracking performance on a novel, repeated tracking sequences during early practice and again at the retention test. Both groups demonstrated implicit sequence-specific motor learning at the retention test, yet substantial differences were apparent. At retention, healthy control participants demonstrated increased BOLD response in left dorsal premotor cortex (BA 6) but decreased BOLD response left dorsolateral prefrontal cortex (DLPFC; BA 9) during repeated sequence tracking. In contrast, at retention individuals with stroke did not show this reduction in DLPFC during repeated tracking. Instead implicit sequence-specific motor learning and general improvements in motor control were associated with increased BOLD response in the left middle frontal gyrus BA 8, regardless of sequence type after stroke. These data emphasize the potential importance of a prefrontal-based attentional network for implicit motor learning after stroke. The present study is the first to highlight the importance of the prefrontal cortex for implicit sequence-specific motor learning after stroke. PMID:20725908

  6. Risks and benefits of hormone therapy: has medical dogma now been overturned?

    Science.gov (United States)

    Shapiro, S; de Villiers, T J; Pines, A; Sturdee, D W; Baber, R J; Panay, N; Stevenson, J C; Mueck, A O; Burger, H G

    2014-06-01

    In an integrated overview of the benefits and risks of menopausal hormone therapy (HT), the Women's Health Initiative (WHI) investigators have claimed that their 'findings … do not support use of this therapy for chronic disease prevention'. In an accompanying editorial, it was claimed that 'the WHI overturned medical dogma regarding menopausal [HT]'. To evaluate those claims. Epidemiological criteria of causation were applied to the evidence. A 'global index' purporting to summarize the overall benefit versus the risk of HT was not valid, and it was biased. For coronary heart disease, an increased risk in users of estrogen plus progestogen (E + P), previously reported by the WHI, was not confirmed. The WHI study did not establish that E+ P increases the risk of breast cancer; the findings suggest that unopposed estrogen therapy (ET) does not increase the risk, and may even reduce it. The findings for stroke and pulmonary embolism were compatible with an increased risk, and among E+ P users there were credible reductions in the risk of colorectal and endometrial cancer. For E+ P and ET users, there were credible reductions in the risk of hip fracture. Under 'worst case' and 'best case' assumptions, the changes in the incidence of the outcomes attributable to HT were minor. Over-interpretation and misrepresentation of the WHI findings have damaged the health and well-being of menopausal women by convincing them and their health professionals that the risks of HT outweigh the benefits.

  7. Is it true that ozone is always toxic? The end of a dogma

    International Nuclear Information System (INIS)

    Bocci, Velio

    2006-01-01

    There are a number of good experimental studies showing that exposure by inhalation to prolonged tropospheric ozone damages the respiratory system and extrapulmonary organs. The skin, if extensively exposed, may also contribute to the damage. The undoubtful strong reactivity of ozone has contributed to establish the dogma that ozone is always toxic and its medical application must be proscribed. Although it is less known, judiciously practiced ozonetherapy is becoming very useful either on its own or applied in combination with orthodox medicine in a broad range of pathologies. The opponents of ozonetherapy base their judgment on the ozone chemistry, and physicians, without any knowledge of the problem, are often skeptical. During the last 15 years, a clear understanding of the action of ozone in biology and medicine has been gained, allowing today to argue if it is true that ozone is always toxic. The fundamental points that are discussed in this paper are: the topography, anatomical and biochemical characteristics of the organs daily exposed to ozone versus the potent antioxidant capacity of blood exposed to a small and precisely calculated dose of ozone only for a few minutes. It is becoming clear how the respiratory system undergoing a chronic oxidative stress can release slowly, but steadily, a huge amount of toxic compounds able to enter the circulation and cause serious damage. The aim of this paper is to objectively evaluate this controversial issue

  8. Challenging the dogma of mitochondrial reactive oxygen species overproduction in diabetic kidney disease.

    Science.gov (United States)

    Coughlan, Melinda T; Sharma, Kumar

    2016-08-01

    The paradigm that high glucose drives overproduction of superoxide from mitochondria as a unifying theory to explain end organ damage in diabetes complications has been tightly held for more than a decade. With the recent development of techniques and probes to measure the production of distinct reactive oxygen species (ROS) in vivo, this widely held dogma is now being challenged with the emerging view that specific ROS moieties are essential for the function of specific intracellular signaling pathways and represent normal mitochondrial function. This review will provide a balanced overview of the dual nature of ROS, detailing current evidence for ROS overproduction in diabetic kidney disease, with a focus on cell types and sources of ROS. The technical aspects of measurement of mitochondrial ROS, both in isolated mitochondria and emerging in vivo methods will be discussed. The counterargument, that mitochondrial ROS production is reduced in diabetic complications, is consistent with a growing recognition that stimulation of mitochondrial biogenesis and oxidative phosphorylation activity reduces inflammation and fibrosis. It is clear that there is an urgent need to fully characterize ROS production paying particular attention to spatiotemporal aspects and to factor in the relevance of ROS in the regulation of cellular signaling in the pathogenesis of diabetic kidney disease. With improved tools and real-time imaging capacity, a greater understanding of the complex role of ROS will be able to guide novel therapeutic regimens. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  9. Death of a dogma: eukaryotic mRNAs can code for more than one protein.

    Science.gov (United States)

    Mouilleron, Hélène; Delcourt, Vivian; Roucou, Xavier

    2016-01-08

    mRNAs carry the genetic information that is translated by ribosomes. The traditional view of a mature eukaryotic mRNA is a molecule with three main regions, the 5' UTR, the protein coding open reading frame (ORF) or coding sequence (CDS), and the 3' UTR. This concept assumes that ribosomes translate one ORF only, generally the longest one, and produce one protein. As a result, in the early days of genomics and bioinformatics, one CDS was associated with each protein-coding gene. This fundamental concept of a single CDS is being challenged by increasing experimental evidence indicating that annotated proteins are not the only proteins translated from mRNAs. In particular, mass spectrometry (MS)-based proteomics and ribosome profiling have detected productive translation of alternative open reading frames. In several cases, the alternative and annotated proteins interact. Thus, the expression of two or more proteins translated from the same mRNA may offer a mechanism to ensure the co-expression of proteins which have functional interactions. Translational mechanisms already described in eukaryotic cells indicate that the cellular machinery is able to translate different CDSs from a single viral or cellular mRNA. In addition to summarizing data showing that the protein coding potential of eukaryotic mRNAs has been underestimated, this review aims to challenge the single translated CDS dogma. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Challenging a dogma: co-mutations exist in MAPK pathway genes in colorectal cancer.

    Science.gov (United States)

    Grellety, Thomas; Gros, Audrey; Pedeutour, Florence; Merlio, Jean-Philippe; Duranton-Tanneur, Valerie; Italiano, Antoine; Soubeyran, Isabelle

    2016-10-01

    Sequencing of genes encoding mitogen-activated protein kinase (MAPK) pathway proteins in colorectal cancer (CRC) has established as dogma that of the genes in a pathway only a single one is ever mutated. We searched for cases with a mutation in more than one MAPK pathway gene (co-mutations). Tumor tissue samples of all patients presenting with CRC, and referred between 01/01/2008 and 01/06/2015 to three French cancer centers for determination of mutation status of RAS/RAF+/-PIK3CA, were retrospectively screened for co-mutations using Sanger sequencing or next-generation sequencing. We found that of 1791 colorectal patients with mutations in the MAPK pathway, 20 had a co-mutation, 8 of KRAS/NRAS, and some even with a third mutation. More than half of the mutations were in codons 12 and 13. We also found 3 cases with a co-mutation of NRAS/BRAF and 9 with a co-mutation of KRAS/BRAF. In 2 patients with a co-mutation of KRAS/NRAS, the co-mutation existed in the primary as well as in a metastasis, which suggests that co-mutations occur early during carcinogenesis and are maintained when a tumor disseminates. We conclude that co-mutations exist in the MAPK genes but with low frequency and as yet with unknown outcome implications.

  11. The peculiar NPQ regulation in the stramenopile Phaeomonas sp. challenges the xanthophyll cycle dogma.

    Science.gov (United States)

    Berne, N; Fabryova, T; Istaz, B; Cardol, P; Bailleul, B

    2018-07-01

    In changing light conditions, photosynthetic organisms develop different strategies to maintain a fine balance between light harvesting, photochemistry, and photoprotection. One of the most widespread photoprotective mechanisms consists in the dissipation of excess light energy in the form of heat in the photosystem II antenna, which participates to the Non Photochemical Quenching (NPQ) of chlorophyll fluorescence. It is tightly related to the reversible epoxidation of xanthophyll pigments, catalyzed by the two enzymes, the violaxanthin deepoxidase and the zeaxanthin epoxidase. In Phaeomonas sp. (Pinguiophyte, Stramenopiles), we show that the regulation of the heat dissipation process is different from that of the green lineage: the NPQ is strictly proportional to the amount of the xanthophyll pigment zeaxanthin and the xanthophyll cycle enzymes are differently regulated. The violaxanthin deepoxidase is already active in the dark, because of a low luminal pH, and the zeaxanthin epoxidase shows a maximal activity under moderate light conditions, being almost inactive in the dark and under high light. This light-dependency mirrors the one of NPQ: Phaeomonas sp. displays a large NPQ in the dark as well as under high light, which recovers under moderate light. Our results pinpoint zeaxanthin epoxidase activity as the prime regulator of NPQ in Phaeomonas sp. and therefore challenge the deepoxidase-regulated xanthophyll cycle dogma. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Sharia Adherence Mosque Survey: Correlations between Sharia Adherence and Violent Dogma in U.S. Mosques

    Directory of Open Access Journals (Sweden)

    Mordechai Kedar

    2011-12-01

    Full Text Available A random survey of 100 representative mosques in the U.S. was conducted to measure the correlation between Sharia adherence and dogma calling for violence against non-believers.  Of the 100 mosques surveyed, 51% had texts on site rated as severely advocating violence; 30% had texts rated as moderately advocating violence; and 19% had no violent texts at all.  Mosques that presented as Sharia adherent were more likely to feature violence-positive texts on site than were their non-Sharia-adherent counterparts.  In 84.5% of the mosques, the imam recommended studying violence-positive texts.  The leadership at Sharia-adherent mosques was more likely to recommend that a worshipper study violence-positive texts than leadership at non-Sharia-adherent mosques.  Fifty-eight percent of the mosques invited guest imams known to promote violent jihad.  The leadership of mosques that featured violence-positive literature was more likely to invite guest imams who were known to promote violent jihad than was the leadership of mosques that did not feature violence-positive literature on mosque premises.  

  13. THE ASH’ARITE DOGMA: THE ROOT OF THE ARAB/MUSLIM ABSOLUTISM

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    Ali Mabrook

    2008-02-01

    Full Text Available There are three major categories upon which all of the world’s civilizations are established, namely, God, Man and World. The differentiation of worldly civilizations and the diversity of systems of knowledge are due to the way of drawing up the relation thereby the three categories are arranged. Some scholars assumed that these categories are communicated and totally correlated each other, in a way that each cannot be realized except in its connectivity to the others. While some others thought that the three categories should be separated and disconnected, in a way that each of the three is realized as an absolute and dominant one while the two others are marginal and dependent ones. Needless to say, while the first perception provokes the values of tolerance and the acceptance of the other, the second one motivates absolutism and the negation of the other. Unfortunately the Ash’arism, not only a dogma but —and more importantly— a stable and dominant way of thinking, is stimulated by the second perception based on an absolutism and the negation of the other. It departs from that historical fact that this paper argues that absolutism, manifested in political, religious and cultural aspects of nowadays Muslims life, can be related to the dominance ofAsh’arism all over the Muslim world.

  14. The Hidden Story of Innovation: Charity Hospital, Angola Prison, and the Challenging of Surgical Dogma.

    Science.gov (United States)

    Greiffenstein, Patrick; Hastings, Paul R

    2017-02-01

    The late 1960s was a period of significant upheaval of social, cultural, and scientific norms. The generally accepted notion of mandatory laparotomy for all penetrating abdominal injuries was among those norms being called into question across the country and many advocated expectant management of selected patients presenting with this type of injury. Leaders of the surgical community published opinions on either side of the argument. The house staff at Charity Hospital during this period was among the busiest in the nation in treating these injuries, many of them inmates of the Louisiana State Penitentiary who used self-inflicted stab wounds to the abdomen as a means of temporary respite from the inhumane conditions in the prison. Inspired, in part, by the overabundance of negative laparotomies among this group, F. Carter Nance went on to systematically challenge the standard of care. This effort constitutes one of the major forces for change of the surgical dogma of mandatory laparotomy for all abdominal stab wounds. It is the first major study to show conclusively that delayed laparotomy for perforated viscous was not significantly detrimental and posed less of a risk than unnecessary laparotomy. The circumstances surrounding this initiative constitute a powerful and heretofore unknown chapter in the history of surgical innovation.

  15. Double-stranded RNA interferes in a sequence-specific manner with the infection of representative members of the two viroid families

    International Nuclear Information System (INIS)

    Carbonell, Alberto; Martinez de Alba, Angel-Emilio; Flores, Ricardo; Gago, Selma

    2008-01-01

    Infection by viroids, non-protein-coding circular RNAs, occurs with the accumulation of 21-24 nt viroid-derived small RNAs (vd-sRNAs) with characteristic properties of small interfering RNAs (siRNAs) associated to RNA silencing. The vd-sRNAs most likely derive from dicer-like (DCL) enzymes acting on viroid-specific dsRNA, the key elicitor of RNA silencing, or on the highly structured genomic RNA. Previously, viral dsRNAs delivered mechanically or agroinoculated have been shown to interfere with virus infection in a sequence-specific manner. Here, we report similar results with members of the two families of nuclear- and chloroplast-replicating viroids. Moreover, homologous vd-sRNAs co-delivered mechanically also interfered with one of the viroids examined. The interference was sequence-specific, temperature-dependent and, in some cases, also dependent on the dose of the co-inoculated dsRNA or vd-sRNAs. The sequence-specific nature of these effects suggests the involvement of the RNA induced silencing complex (RISC), which provides sequence specificity to RNA silencing machinery. Therefore, viroid titer in natural infections might be regulated by the concerted action of DCL and RISC. Viroids could have evolved their secondary structure as a compromise between resistance to DCL and RISC, which act preferentially against RNAs with compact and relaxed secondary structures, respectively. In addition, compartmentation, association with proteins or active replication might also help viroids to elude their host RNA silencing machinery

  16. Iglesias coptas, testimonio silencioso de un dogma trinitario (S. IV-VII

    Directory of Open Access Journals (Sweden)

    María Teresa Viviani

    2007-01-01

    Full Text Available Esta investigación se inscribe dentro de una línea de trabajo que intenta profundizar en las relaciones entre la estética y el dogma en las antiguas comunidades cristianas del Medio Oriente. Ya se ha propuesto y publicado, un marco dogmático que permite identificar las iglesias de las comunidades Arrianas y Capadocias. En esta nueva investigación se propone también una comprensión de la arquitectura y de los programas pictográficos de las iglesias coptas de Egipto, a partir de una aproximación dogmática. Se consideran dos grupos de iglesias: las iglesias del Norte o Bajo Egipto y las del Sur o Alto Egipto. Como referente dogmático, se trabaja preferentemente con el pensamiento de Cirilo de Alejandría (378-444. Se ha seleccionado este autor, considerando que vivió las experiencias de los monjes del desierto, que estudió en una escuela teológica monástica y participó activamente en las controversias contra arríanos y nestorianos. Presidió el Patriarcado de Alejandría por más de 30 años. Desde la perspectiva dogmática, se pone énfasis en el tema de la Trinidad y de las 3 hipóstasis, de la unidad de naturaleza entre el Padre y el Hijo, y de la Virgen como Madre de Dios, TheotokosThis investigation can be regarded as within a line of work attempting to deepen understanding of the relationship between aesthetics and dogma in the ancient Christian communities of the Middle East. A dogmatic framework has already been proposed and published that allows the churches of the Arian and Cappadocian communities to be identified. In this new investigation, an understanding of the architecture and of the pictographic programs of the Coptic churches in Egypt is also proposed, beginning with a dogmatic approximation. Two groups of churches are considered: the churches of North, or Lower Egypt, and those of South, or Higher Egypt. As a dogmatic reference point, the thought of Cyril of Alexandria (378-444 is preferentially dealt with. This

  17. Evaluating the Rule of 10s in Cleft Lip Repair: Do Data Support Dogma?

    Science.gov (United States)

    Chow, Ian; Purnell, Chad A; Hanwright, Philip J; Gosain, Arun K

    2016-09-01

    Cleft lip represents one of the most common birth defects in the world. Although the timing of cleft lip repair is contingent on a number of factors, the "rule of 10s" remains a frequently quoted safety benchmark. Initially reported by Wilhelmsen and Musgrave in 1966 and modified by Millard in 1976, this rule referred to performing surgery once patients had reached cutoffs in weight, hemoglobin, and age/leukocyte count. Despite significant advances in both surgical and anesthetic technique, the oft-quoted "rule of 10s" has not been systematically investigated since its inception. Patients who underwent primary cleft lip repair were identified from the National Surgical Quality Improvement Program Pediatric database. Multivariate logistic regression models were used to determine the independent effect of each rule of 10 metric or violation of the rule of 10s as a whole on postoperative complications, and to determine independent risk factors for complications in cleft lip surgery. One thousand three hundred thirteen patients met inclusion criteria, with a 3.6 percent complication rate. Of the included patients, 151 (11.5 percent) violated at least one facet of the rule of 10s. Other than patient weight, neither the rule of 10s nor any individual metric was significantly predictive of postoperative complications. Since its introduction nearly a half century ago, the risks associated with performing surgery in patients who violate the rule of 10s has undergone dramatic reductions. This analysis highlights the need to continually validate and evaluate dogma as the field continues to advance. Risk, III.

  18. Changing the surgical dogma in frontal sinus trauma: transnasal endoscopic repair.

    Science.gov (United States)

    Grayson, Jessica W; Jeyarajan, Hari; Illing, Elisa A; Cho, Do-Yeon; Riley, Kristen O; Woodworth, Bradford A

    2017-05-01

    Management of frontal sinus trauma includes coronal or direct open approaches through skin incisions to either ablate or obliterate the frontal sinus for posterior table fractures and openly reduce/internally fixate fractured anterior tables. The objective of this prospective case-series study was to evaluate outcomes of frontal sinus anterior and posterior table trauma using endoscopic techniques. Prospective evaluation of patients undergoing surgery for frontal sinus fractures was performed. Data were collected regarding demographics, etiology, technique, operative site, length involving the posterior table, size of skull base defects, complications, and clinical follow-up. Forty-six patients (average age, 42 years) with frontal sinus fractures were treated using endoscopic techniques from 2008 to 2016. Mean follow-up was 26 (range, 0.5 to 79) months. Patients were treated primarily with a Draf IIb frontal sinusotomies. Draf III was used in 8 patients. Average fracture defect (length vs width) was 17.1 × 9.1 mm, and the average length involving the posterior table was 13.1 mm. Skull base defects were covered with either nasoseptal flaps or free tissue grafts. One individual required Draf IIb revision, but all sinuses were patent on final examination and all closed reductions of anterior table defects resulted in cosmetically acceptable outcomes. Frontal sinus trauma has traditionally been treated using open approaches. Our findings show that endoscopic management should become part of the management algorithm for frontal sinus trauma, which challenges current surgical dogma regarding mandatory open approaches. © 2017 ARS-AAOA, LLC.

  19. The routine use of prosthetic mesh in austere environments: dogma vs data.

    Science.gov (United States)

    Kuckelman, John P; Barron, Morgan R; Blair, Kelly; Martin, Matthew J

    2016-05-01

    Mesh repair has become the standard in adult hernia repairs. Mesh infection is an uncommon but potentially devastating complication. Currently, there is widespread dogma against the use of prosthetic mesh (PM) in deployed or austere environments but little available data to support or refute this bias. Retrospective review of all hernia repairs over 1 year in a forward deployed surgical unit in Afghanistan. Demographics, hernia type, repair performed, and mesh type were evaluated. Follow-up was completed up to 6 weeks and then as needed for up to a year, and complications to include infection were recorded. Sixty-six patients were identified, mean age was 38 (range 3 to 80) and 98% were male. Single-dose perioperative antibiotics and standard sterile technique were used in all cases. The majority (70%) had PM placed. The mean operative time was 54 min, and mean estimated blood loss was less than 25 cm(3). The vast majority of our hernias were inguinal (95%) with 1 ventral and 2 umbilical hernias. In the PM group, there were no surgical site infections, no mesh infections, and no mesh explantation or reoperation. There were no recurrences in either group identified at up to 1-year postoperation. There was no statistically significant difference in any outcome measure between the PM and no-PM groups. The use of PM for hernia repairs in the austere or forward environment appears safe and did not increase the risk of wound infection, mesh infections, or recurrence. Published by Elsevier Inc.

  20. Liberalism - neoliberalism - market fundamentalism: from the concept of freedom to the totalitarian dogma

    Directory of Open Access Journals (Sweden)

    V. I. Chelischev

    2016-01-01

    Full Text Available The article further describes the ideological, historical, socio-political and economic circumstances, responsible for the specific direction of a new form of the ideology of liberalism - contemporary liberalism (neo-liberalism. The special attention, along with the analysis of the ideas of the founder of original theory of the state intervention in the economic life of the society of John Maynard Keynes (1883-1946, is given to “neoliberal” economic constructions of an ideological orientation of Friedrich August von Hayek (1899-1992 and Milton Friedman (1912-2006, defenders of a liberal principle of self-regulation of economy, free from any regalements. The author, on the basis of the analysis of primary sources and examples from a political and social life of some States, shows that in theory the resurgence of liberalism in the form of neo-liberalism personified the idea of the priority of the individual to society and the State, the market - before planning and regulation, the human rights - before the power authority and the team. However in practice this revival was accompanied by displacement of accents and growth of ideological tendencies. Thus, theorists and practitioners of neo-liberalism lined up quite utopian model not only of economic, but also of social relations. Article details the mechanisms by which the theoretical constructions of economists-neoliberals were emasculated by politicians who gradually reduced them to the primitive and convenient theses, justifying any actions of the authorities. Over time, these points have become “undeniable truths”, through which neo-liberalism became dogmatic, and its economic credo has got obvious fundamentalist character, having turned to market dogma of totalitarian type.

  1. Optimal surgical approach to thymic malignancies: New trends challenging old dogmas.

    Science.gov (United States)

    Ruffini, Enrico; Filosso, Pier Luigi; Guerrera, Francesco; Lausi, Paolo; Lyberis, Paraskevas; Oliaro, Alberto

    2018-04-01

    Until recently, the surgical approach to thymic tumors has remained basically unchanged. The collaborative effort led by ITMIG with the collaboration of regional and society-based interest groups (ESTS, JART) produced an enthusiastic surge of interest in testing the new technological advances in thoracic surgery and many historical dogmas in thymic surgery have been questioned and challenged. The present review addresses the new trends in the optimal surgical management of thymic tumors based on the review of the current literature. 1. Minimally-invasive techniques (MIT) including video-assisted thoracic surgery (VATS) and robotic-assisted thoracic Surgery (RATS) are now to be considered the standard of care in early-stage thymic tumors. MIT are no inferior to open approaches in terms of postoperative complications, loco-regional recurrence rates and survival. MIT are associated with a shorter length of stay, reduced intraoperative blood loss and better cosmetic results. 2. The adoption of the ITMIG/IASLC TNM staging system for thymic tumors requires a paradigm shift among thoracic surgeons to include regional lymphadenectomy according to the IASLC/ITMIG nodal map in the surgical management of thymic tumors. 3. A limited thymectomy instead of total thymectomy along with the removal of the thymic tumor in nonmyasthenic Stage I-II tumors has been proposed by some authors, although the results are not uniform. Until more mature data is available, adherence to the current guidelines recommending total thymectomy in addition to thymomectomy is always indicated. 4. In locally-advanced Stage IVa patients with pleural involvement, major pleural resections, including pleurectomy/decortication or extrapleural pneumonectomy are indicated, provided a complete resection of the pleural deposits is anticipated, usually in a multidisciplinary setting, with excellent long-term results. The incorporation of these new concepts and techniques in the surgical armamentarium of the

  2. Informing a Learning Progression in Genetics: Which Should Be Taught First, Mendelian Inheritance or the Central Dogma of Molecular Biology?

    Science.gov (United States)

    Duncan, Ravit Golan; Castro-Faix, Moraima; Choi, Jinnie

    2016-01-01

    The Framework for Science Education and the Next Generation Science Standards in the USA emphasize learning progressions (LPs) that support conceptual coherence and the gradual building of knowledge over time. In the domain of genetics there are two independently developed alternative LPs. In essence, the difference between the two progressions…

  3. Phytopythium leanoi sp. nov. and Phytopythium dogmae sp. nov., Phytopythium species associated with mangrove leaf litter from the Philippines

    Directory of Open Access Journals (Sweden)

    Reuel M. Bennett

    2018-02-01

    Full Text Available The genus Phytopythium is a monophyletic taxon of the Peronosporaceae with characteristics intermediate between Phytophthora and Pythium. In the Philippines, reports of Phytopythium are scarce, with the mangrove-swamp-inhabiting species Phytopythium kandeliae being the only species recorded to date. It was the aim of the current study to investigate the diversity of Phytopythium in mangrove habitats in more detail. Based on culture characteristics, morphology, and molecular phylogenetic position, two new species of Phytopythium are described from Philippine mangroves, P. leanoi USTCMS 4102 and P. dogmae USTCMS 4101. Phytopythium leanoi is a species morphologically similar to P. kandeliae, but with the ability to develop gametangia in a homothallic fashion. The other new species, P. dogmae, is characterized by having a short discharge tube, semipapillate to papillate sporangia and frequently exhibiting a clustering of two sporangia per sporangiogenic hypha. With the addition of the two species described in this study, the genus Phytopythium has grown from around 10 to beyond 20 recognized species over the past decade, and it seems likely that several more species of this genus await discovery.

  4. Sequence-specific 1H-NMR assignments for the aromatic region of several biologically active, monomeric insulins including native human insulin.

    Science.gov (United States)

    Roy, M; Lee, R W; Kaarsholm, N C; Thøgersen, H; Brange, J; Dunn, M F

    1990-06-12

    The aromatic region of the 1H-FT-NMR spectrum of the biologically fully-potent, monomeric human insulin mutant, B9 Ser----Asp, B27 Thr----Glu has been investigated in D2O. At 1 to 5 mM concentrations, this mutant insulin is monomeric above pH 7.5. Coupling and amino acid classification of all aromatic signals is established via a combination of homonuclear one- and two-dimensional methods, including COSY, multiple quantum filters, selective spin decoupling and pH titrations. By comparisons with other insulin mutants and with chemically modified native insulins, all resonances in the aromatic region are given sequence-specific assignments without any reliance on the various crystal structures reported for insulin. These comparisons also give the sequence-specific assignments of most of the aromatic resonances of the mutant insulins B16 Tyr----Glu, B27 Thr----Glu and B25 Phe----Asp and the chemically modified species des-(B23-B30) insulin and monoiodo-Tyr A14 insulin. Chemical dispersion of the assigned resonances, ring current perturbations and comparisons at high pH have made possible the assignment of the aromatic resonances of human insulin, and these studies indicate that the major structural features of the human insulin monomer (including those critical to biological function) are also present in the monomeric mutant.

  5. One Day Every 216 Years, Three Days Each Decan. Rebirth Cycle of Pythagoras, Phoenix, Hazon Gabriel, and Christian Dogma of Resurrection Can Be Explained by the Metonic Cycle

    Science.gov (United States)

    Rothwangl, S.

    2009-08-01

    This article explains how the Metonic cycle is at the base of the period of 216 years Pythagoras believed in being reborn after that period. It shows how this period calendrically is related to other mythological worldviews such as the Phoenix myth, the Hebrean Hazon Gabriel, and the Christian dogma of resurrection on the third day.

  6. Geometry of the Valgus Knee: Contradicting the Dogma of a Femoral-Based Deformity.

    Science.gov (United States)

    Eberbach, Helge; Mehl, Julian; Feucht, Matthias J; Bode, Gerrit; Südkamp, Norbert P; Niemeyer, Philipp

    2017-03-01

    Realignment osteotomies of valgus knee deformities are usually performed at the distal femur, as valgus alignment is considered to be a femoral-based deformity. This dogma, however, has not been proven in a large patient population. Valgus malalignment may also be caused by a tibial deformity or a combined tibial and femoral deformity. The purposes of this study were (1) to analyze the coronal geometry of patients with valgus malalignment and identify the location of the underlying deformity and (2) to investigate the proportion of cases that require realignment osteotomy at the tibia, the femur, or both locations to avoid an oblique joint line. Cross-sectional study; Level of evidence, 3. The analysis included 420 standing full-leg radiographs of patients with valgus malalignment (mechanical femorotibial angle [mFTA], ≥4°). A systematic analysis of the coronal leg geometry was performed including the mFTA, mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA), and joint-line convergence angle (JLCA). The localization of the deformity was determined according to the malalignment test described by Paley, and patients were assigned to 1 of 4 groups: femoral-based valgus deformity, tibial-based valgus deformity, femoral- and tibial-based valgus deformity, or intra-articular/ligamentary-based valgus deformity. Subsequently, the ideal osteotomy site was identified with the goal of a postoperative change of the joint line of two different maximum values, ±2° and ±4°, from its physiological varus position of 3°. Measurements of the coronal alignment revealed a mean (±SD) mFTA of 7.4° ± 4.3° (range, 4°-28.2°). The mean mLDFA and mean mMPTA were 84.8° ± 2.4° and 90.9° ± 2.6°, respectively. The mean JLCA was 1.2° ± 3.1°. The majority (41.0%) of valgus deformities were tibial based, 23.6% were femoral based, 26.9% were femoral and tibial based, and 8.6% were intra-articular/ligamentary based. To achieve a

  7. Impact of cadmium, cobalt and nickel on sequence-specific DNA binding of p63 and p73 in vitro and in cells

    International Nuclear Information System (INIS)

    Adámik, Matej; Bažantová, Pavla; Navrátilová, Lucie; Polášková, Alena; Pečinka, Petr; Holaňová, Lucie; Tichý, Vlastimil; Brázdová, Marie

    2015-01-01

    Highlights: • DNA binding of p53 family core domains is inhibited by cadmium, cobalt and nickel. • Binding to DNA protects p53 family core domains from metal induced inhibition. • Cadmium, cobalt and nickel induced inhibition was reverted by EDTA in vitro. - Abstract: Site-specific DNA recognition and binding activity belong to common attributes of all three members of tumor suppressor p53 family proteins: p53, p63 and p73. It was previously shown that heavy metals can affect p53 conformation, sequence-specific binding and suppress p53 response to DNA damage. Here we report for the first time that cadmium, nickel and cobalt, which have already been shown to disturb various DNA repair mechanisms, can also influence p63 and p73 sequence-specific DNA binding activity and transactivation of p53 family target genes. Based on results of electrophoretic mobility shift assay and luciferase reporter assay, we conclude that cadmium inhibits sequence-specific binding of all three core domains to p53 consensus sequences and abolishes transactivation of several promoters (e.g. BAX and MDM2) by 50 μM concentrations. In the presence of specific DNA, all p53 family core domains were partially protected against loss of DNA binding activity due to cadmium treatment. Effective cadmium concentration to abolish DNA–protein interactions was about two times higher for p63 and p73 proteins than for p53. Furthermore, we detected partial reversibility of cadmium inhibition for all p53 family members by EDTA. DTT was able to reverse cadmium inhibition only for p53 and p73. Nickel and cobalt abolished DNA–p53 interaction at sub-millimolar concentrations while inhibition of p63 and p73 DNA binding was observed at millimolar concentrations. In summary, cadmium strongly inhibits p53, p63 and p73 DNA binding in vitro and in cells in comparison to nickel and cobalt. The role of cadmium inhibition of p53 tumor suppressor family in carcinogenesis is discussed

  8. Impact of cadmium, cobalt and nickel on sequence-specific DNA binding of p63 and p73 in vitro and in cells

    Energy Technology Data Exchange (ETDEWEB)

    Adámik, Matej [Institute of Biophysics, Academy of Science of the Czech Republic, v.v.i., Královopolská 135, 612 65 Brno (Czech Republic); Bažantová, Pavla [Institute of Biophysics, Academy of Science of the Czech Republic, v.v.i., Královopolská 135, 612 65 Brno (Czech Republic); Department of Biology and Ecology, Faculty of Science, University of Ostrava, Chittussiho 10, 701 03 Ostrava (Czech Republic); Navrátilová, Lucie; Polášková, Alena [Institute of Biophysics, Academy of Science of the Czech Republic, v.v.i., Královopolská 135, 612 65 Brno (Czech Republic); Pečinka, Petr [Institute of Biophysics, Academy of Science of the Czech Republic, v.v.i., Královopolská 135, 612 65 Brno (Czech Republic); Department of Biology and Ecology, Faculty of Science, University of Ostrava, Chittussiho 10, 701 03 Ostrava (Czech Republic); Holaňová, Lucie [Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackého 1/3, 61242 Brno (Czech Republic); Tichý, Vlastimil [Institute of Biophysics, Academy of Science of the Czech Republic, v.v.i., Královopolská 135, 612 65 Brno (Czech Republic); Brázdová, Marie, E-mail: maruska@ibp.cz [Institute of Biophysics, Academy of Science of the Czech Republic, v.v.i., Královopolská 135, 612 65 Brno (Czech Republic); Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackého 1/3, 61242 Brno (Czech Republic)

    2015-01-02

    Highlights: • DNA binding of p53 family core domains is inhibited by cadmium, cobalt and nickel. • Binding to DNA protects p53 family core domains from metal induced inhibition. • Cadmium, cobalt and nickel induced inhibition was reverted by EDTA in vitro. - Abstract: Site-specific DNA recognition and binding activity belong to common attributes of all three members of tumor suppressor p53 family proteins: p53, p63 and p73. It was previously shown that heavy metals can affect p53 conformation, sequence-specific binding and suppress p53 response to DNA damage. Here we report for the first time that cadmium, nickel and cobalt, which have already been shown to disturb various DNA repair mechanisms, can also influence p63 and p73 sequence-specific DNA binding activity and transactivation of p53 family target genes. Based on results of electrophoretic mobility shift assay and luciferase reporter assay, we conclude that cadmium inhibits sequence-specific binding of all three core domains to p53 consensus sequences and abolishes transactivation of several promoters (e.g. BAX and MDM2) by 50 μM concentrations. In the presence of specific DNA, all p53 family core domains were partially protected against loss of DNA binding activity due to cadmium treatment. Effective cadmium concentration to abolish DNA–protein interactions was about two times higher for p63 and p73 proteins than for p53. Furthermore, we detected partial reversibility of cadmium inhibition for all p53 family members by EDTA. DTT was able to reverse cadmium inhibition only for p53 and p73. Nickel and cobalt abolished DNA–p53 interaction at sub-millimolar concentrations while inhibition of p63 and p73 DNA binding was observed at millimolar concentrations. In summary, cadmium strongly inhibits p53, p63 and p73 DNA binding in vitro and in cells in comparison to nickel and cobalt. The role of cadmium inhibition of p53 tumor suppressor family in carcinogenesis is discussed.

  9. Sequence-specific 1H NMR resonance assignments of Bacillus subtilis HPr: Use of spectra obtained from mutants to resolve spectral overlap

    International Nuclear Information System (INIS)

    Wittekind, M.; Klevit, R.E.; Reizer, J.

    1990-01-01

    On the basis of an analysis of two-dimensional 1 H NMR spectra, the complete sequence-specific 1 H NMR assignments are presented for the phosphocarrier protein HPr from the Gram-positive bacterium Bacillus subtilis. During the assignment procedure, extensive use was made of spectra obtained from point mutants of HPr in order to resolve spectral overlap and to provide verification of assignments. Regions of regular secondary structure were identified by characteristic patterns of sequential backbone proton NOEs and slowly exchanging amide protons. B subtilis HPr contains four β-strands that form a single antiparallel β-sheet and two well-defined α-helices. There are two stretches of extended backbone structure, one of which contains the active site His 15 . The overall fold of the protein is very similar to that of Escherichia coli HPr determined by NMR studies

  10. An intact sequence-specific DNA-binding domain is required for human cytomegalovirus-mediated sequestration of p53 and may promote in vivo binding to the viral genome during infection

    International Nuclear Information System (INIS)

    Rosenke, Kyle; Samuel, Melanie A.; McDowell, Eric T.; Toerne, Melissa A.; Fortunato, Elizabeth A.

    2006-01-01

    The p53 protein is stabilized during infection of primary human fibroblasts with human cytomegalovirus (HCMV). However, the p53 in HCMV-infected cells is unable to activate its downstream targets. HCMV accomplishes this inactivation, at least in part, by sequestering p53 into viral replication centers within the cell's nucleus soon after they are established. In order to better understand the interplay between HCMV and p53 and the mechanism of sequestration, we constructed a panel of mutant p53-GFP fusion constructs for use in transfection/infection experiments. These mutants affected several post-translational modification sites and several sites within the central sequence-specific DNA-binding domain of the protein. Two categories of p53 sequestration were observed when the mutant constructs were transfected into primary fibroblasts and then infected at either high or low multiplicity. The first category, including all of the post-translational modification mutants, showed sequestration comparable to a wild-type (wt) control, while the second category, mutants affecting the DNA-binding core, were not specifically sequestered above control GFP levels. This suggested that the DNA-binding ability of the protein was required for sequestration. When the HCMV genome was analyzed for p53 consensus binding sites, 21 matches were found, which localized either to the promoters or the coding regions of viral proteins involved in DNA replication and processing as well as structural proteins. An analysis of in vivo binding to these identified sites via chromatin immunoprecipitation assays revealed differential binding to several of the sites over the course of infection

  11. Two-dimensional NMR studies of squash family inhibitors. Sequence-specific proton assignments and secondary structure of reactive-site hydrolyzed Cucurbita maxima trypsin inhibitor III

    Energy Technology Data Exchange (ETDEWEB)

    Krisnamoorthi, R.; Yuxi Gong; Chanlan Sun Lin (Kansas State Univ., Manhattan (United States)); VanderVelde, D. (Univ. of Kansas, Lawrence (United States))

    1992-01-28

    The solution structure of reactive-site hydrolyzed Cucurbita maxima trypsin inhibitor III (CMTI-III*) was investigated by two-dimensional proton nuclear magnetic resonance (2D NMR) spectroscopy. CMTI-III*, prepared by reacting CMTI-III with trypsin which cleaved the Arg5-Ile6 peptide bond, had the two fragments held together by a disulfide linkage. Sequence-specific {sup 1}H NMR resonance assignments were made for all the 29 amino acid residues of the protein. The secondary structure of CMTI-III*, as deduced from NOESY cross peaks and identification of slowly exchanging hydrogens, contains two turns, a 3{sub 10}-helix, and a triple-stranded {beta}-sheet. Sequential proton assignments were also made for the virgin inhibitor, CMTI-III, at pH 4.71, 30C. Comparison of backbone hydrogen chemical shifts of CMTI-III and CMTI-III* revealed significant changes for residues located far away from the reactive-site region as well as for those located near it, indicating tertiary structural changes that are transmitted through most of the 29 residues of the inhibitor protein. These chemical shift changes were relatively small compared to changes that occurred upon hydrolysis of the reactive-site peptide bond between Arg 5 and Ile6 in CMTI-III.

  12. Sequence- and structure-dependent DNA base dynamics: Synthesis, structure, and dynamics of site and sequence specifically spin-labeled DNA

    International Nuclear Information System (INIS)

    Spaltenstein, A.; Robinson, B.H.; Hopkins, P.B.

    1989-01-01

    A nitroxide spin-labeled analogue of thymidine (1a), in which the methyl group is replaced by an acetylene-tethered nitroxide, was evaluated as a probe for structural and dynamics studies of sequence specifically spin-labeled DNA. Residue 1a was incorporated into synthetic deoxyoligonucleotides by using automated phosphite triester methods. 1 H NMR, CD, and thermal denaturation studies indicate that 1a (T) does not significantly alter the structure of 5'-d(CGCGAATT*CGCG) from that of the native dodecamer. EPR studies on monomer, single-stranded, and duplexed DNA show that 1a readily distinguishes environments of different rigidity. Comparison of the general line-shape features of the observed EPR spectra of several small duplexes (12-mer, 24-mer) with simulated EPR spectra assuming isotropic motion suggests that probe 1a monitors global tumbling of small duplexes. Increasing the length of the DNA oligomers results in significant deviation from isotropic motion, with line-shape features similar to those of calculated spectra of objects with isotropic rotational correlation times of 20-100 ns. EPR spectra of a spin-labeled GT mismatch and a T bulge in long DNAs are distinct from those of spin-labeled Watson-Crick paired DNAs, further demonstrating the value of EPR as a tool in the evaluation of local dynamic and structural features in macromolecules

  13. Integrated analysis of RNA-binding protein complexes using in vitro selection and high-throughput sequencing and sequence specificity landscapes (SEQRS).

    Science.gov (United States)

    Lou, Tzu-Fang; Weidmann, Chase A; Killingsworth, Jordan; Tanaka Hall, Traci M; Goldstrohm, Aaron C; Campbell, Zachary T

    2017-04-15

    RNA-binding proteins (RBPs) collaborate to control virtually every aspect of RNA function. Tremendous progress has been made in the area of global assessment of RBP specificity using next-generation sequencing approaches both in vivo and in vitro. Understanding how protein-protein interactions enable precise combinatorial regulation of RNA remains a significant problem. Addressing this challenge requires tools that can quantitatively determine the specificities of both individual proteins and multimeric complexes in an unbiased and comprehensive way. One approach utilizes in vitro selection, high-throughput sequencing, and sequence-specificity landscapes (SEQRS). We outline a SEQRS experiment focused on obtaining the specificity of a multi-protein complex between Drosophila RBPs Pumilio (Pum) and Nanos (Nos). We discuss the necessary controls in this type of experiment and examine how the resulting data can be complemented with structural and cell-based reporter assays. Additionally, SEQRS data can be integrated with functional genomics data to uncover biological function. Finally, we propose extensions of the technique that will enhance our understanding of multi-protein regulatory complexes assembled onto RNA. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Protease activity of PprI facilitates DNA damage response: Mn2+-dependence and substrate sequence-specificity of the proteolytic reaction.

    Directory of Open Access Journals (Sweden)

    Yunguang Wang

    Full Text Available The extremophilic bacterium Deinococcus radiodurans exhibits an extraordinary resistance to ionizing radiation. Previous studies established that a protein named PprI, which exists only in the Deinococcus-Thermus family, acts as a general switch to orchestrate the expression of a number of DNA damage response (DDR proteins involved in cellular radio-resistance. Here we show that the regulatory mechanism of PprI depends on its Mn(2+-dependent protease activity toward DdrO, a transcription factor that suppresses DDR genes' expression. Recognition sequence-specificity around the PprI cleavage site is essential for DNA damage repair in vivo. PprI and DdrO mediate a novel DNA damage response pathway differing from the classic LexA-mediated SOS response system found in radiation-sensitive bacterium Escherichia coli. This PprI-mediated pathway in D. radiodurans is indispensable for its extreme radio-resistance and therefore its elucidation significantly advances our understanding of the DNA damage repair mechanism in this amazing organism.

  15. Molecular beacon based biosensor for the sequence-specific detection of DNA using DNA-capped gold nanoparticles-streptavidin conjugates for signal amplification

    International Nuclear Information System (INIS)

    Fang, Xian; Jiang, Wei; Han, Xiaowei; Zhang, Yuzhong

    2013-01-01

    We describe a highly sensitive and selective molecular beacon-based electrochemical impedance biosensor for the sequence-specific detection of DNA. DNA-capped conjugates between gold nanoparticles (Au-NPs) and streptavidin are used for signal amplification. The molecular beacon was labeled with a thiol at its 5′ end and with biotin at its 3′ end, and then immobilized on the surface of a bare gold electrode through the formation of Au-S bonds. Initially, the molecular beacon is present in the “closed” state, and this shields the biotin from being approached by streptavidin due to steric hindrance. In the presence of the target DNA, the target DNA molecules hybridize with the loop and cause a conformational change that moves the biotin away from the surface of the electrode. The biotin thereby becomes accessible for the reporter (the DNA-streptavidin capped Au-NPs), and this results in a distinct increase in electron transfer resistance. Under optimal conditions, the increase in resistance is linearly related to the logarithm of the concentration of complementary target DNA in the range from 1.0 fM to 0.1 μM, with a detection limit of 0.35 fM (at an S/N of 3). This biosensor exhibits good selectivity, and acceptable stability and reproducibility. (author)

  16. Molecular dynamics simulations shed light on the enthalpic and entropic driving forces that govern the sequence specific recognition between netropsin and DNA.

    Science.gov (United States)

    Dolenc, Jozica; Gerster, Sarah; van Gunsteren, Wilfred F

    2010-09-02

    With the aim to gain a better understanding of the various driving forces that govern sequence specific DNA minor groove binding, we performed a thermodynamic analysis of netropsin binding to an AT-containing and to a set of six mixed AT/GC-containing binding sequences in the DNA minor groove. The relative binding free energies obtained using molecular dynamics simulations and free energy calculations show significant variations with the binding sequence. While the introduction of a GC base pair in the middle or close to the middle of the binding site is unfavorable for netropsin binding, a GC base pair at the end of the binding site appears to have no negative influence on the binding. The results of the structural and energetic analyses of the netropsin-DNA complexes reveal that the differences in the calculated binding affinities cannot be explained solely in terms of netropsin-DNA hydrogen-bonding or interaction energies. In addition, solvation effects and entropic contributions to the relative binding free energy provide a more complete picture of the various factors determining binding. Analysis of the relative binding entropy indicates that its magnitude is highly sequence-dependent, with the ratio |TDeltaDeltaS|/|DeltaDeltaH| ranging from 0.07 for the AAAGA to 1.7 for the AAGAG binding sequence, respectively.

  17. Localized sequence-specific release of a chemopreventive agent and an anticancer drug in a time-controllable manner to enhance therapeutic efficacy.

    Science.gov (United States)

    Pan, Wen-Yu; Lin, Kun-Ju; Huang, Chieh-Cheng; Chiang, Wei-Lun; Lin, Yu-Jung; Lin, Wei-Chih; Chuang, Er-Yuan; Chang, Yen; Sung, Hsing-Wen

    2016-09-01

    Combination chemotherapy with multiple drugs commonly requires several injections on various schedules, and the probability that the drug molecules reach the diseased tissues at the proper time and effective therapeutic concentrations is very low. This work elucidates an injectable co-delivery system that is based on cationic liposomes that are adsorbed on anionic hollow microspheres (Lipos-HMs) via electrostatic interaction, from which the localized sequence-specific release of a chemopreventive agent (1,25(OH)2D3) and an anticancer drug (doxorubicin; DOX) can be thermally driven in a time-controllable manner by an externally applied high-frequency magnetic field (HFMF). Lipos-HMs can greatly promote the accumulation of reactive oxygen species (ROS) in tumor cells by reducing their cytoplasmic expression of an antioxidant enzyme (superoxide dismutase) by 1,25(OH)2D3, increasing the susceptibility of cancer cells to the cytotoxic action of DOX. In nude mice that bear xenograft tumors, treatment with Lipos-HMs under exposure to HFMF effectively inhibits tumor growth and is the most effective therapeutic intervention among all the investigated. These empirical results demonstrate that the synergistic anticancer effects of sequential release of 1,25(OH)2D3 and DOX from the Lipos-HMs may have potential for maximizing DOX cytotoxicity, supporting more effective cancer treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Concordance of the ForenSeq™ system and characterisation of sequence-specific autosomal STR alleles across two major population groups.

    Science.gov (United States)

    Devesse, Laurence; Ballard, David; Davenport, Lucinda; Riethorst, Immy; Mason-Buck, Gabriella; Syndercombe Court, Denise

    2018-05-01

    By using sequencing technology to genotype loci of forensic interest it is possible to simultaneously target autosomal, X and Y STRs as well as identity, ancestry and phenotypic informative SNPs, resulting in a breadth of data obtained from a single run that is considerable when compared to that generated with standard technologies. It is important however that this information aligns with the genotype data currently obtained using commercially available kits for CE-based investigations such that results are compatible with existing databases and hence can be of use to the forensic community. In this work, 400 samples were typed using commercially available STR kits and CE, as well as using the Ilumina ForenSeq™ DNA Signature Prep Kit and MiSeq ® FGx to assess concordance of autosomal STRs and population variability. Results show a concordance rate between the two technologies exceeding 99.98% while numerous novel sequence based alleles are described. In order to make use of the sequence variation observed, sequence specific allele frequencies were generated for White British and British Chinese populations. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Challenging the Wigglesworthia, Sodalis, Wolbachia symbiosis dogma in tsetse flies: Spiroplasma is present in both laboratory and natural populations.

    Science.gov (United States)

    Doudoumis, V; Blow, F; Saridaki, A; Augustinos, A; Dyer, N A; Goodhead, I; Solano, P; Rayaisse, J-B; Takac, P; Mekonnen, S; Parker, A G; Abd-Alla, A M M; Darby, A; Bourtzis, K; Tsiamis, G

    2017-07-05

    Profiling of wild and laboratory tsetse populations using 16S rRNA gene amplicon sequencing allowed us to examine whether the "Wigglesworthia-Sodalis-Wolbachia dogma" operates across species and populations. The most abundant taxa, in wild and laboratory populations, were Wigglesworthia (the primary endosymbiont), Sodalis and Wolbachia as previously characterized. The species richness of the microbiota was greater in wild than laboratory populations. Spiroplasma was identified as a new symbiont exclusively in Glossina fuscipes fuscipes and G. tachinoides, members of the palpalis sub-group, and the infection prevalence in several laboratory and natural populations was surveyed. Multi locus sequencing typing (MLST) analysis identified two strains of tsetse-associated Spiroplasma, present in G. f. fuscipes and G. tachinoides. Spiroplasma density in G. f. fuscipes larva guts was significantly higher than in guts from teneral and 15-day old male and female adults. In gonads of teneral and 15-day old insects, Spiroplasma density was higher in testes than ovaries, and was significantly higher density in live versus prematurely deceased females indicating a potentially mutualistic association. Higher Spiroplasma density in testes than in ovaries was also detected by fluorescent in situ hybridization in G. f. fuscipes.

  20. Treating all fields in every radiotherapy session? - Questioning the old dogma (or, pelvis radiotherapy: speculations on fractioning)

    International Nuclear Information System (INIS)

    Faria, S.L.; Ferrigno, R.; Osti, N.

    1995-01-01

    Twenty years ago Wilson and Hall published paper on the advisability of treating all fields at each radiotherapy session. That was based on the widely accepted method for calculating the biological effect of fractionated treatment in terms of a single quantity: the concept of a nominal standard dose (NSD). It was the beginning of an old dogma in radiation oncology: treating all fields every day. The basis megavoltage units of treatment in Brazil are cobalt and low energy linacs. The country is poor and it is not rare to have patients waiting lines. Due to that situation since five years ago we have been treating pelvic tumors with four fields (box technique) but irradiating only two fields per day. After treating hundreds of patients this way we have found no increased late complications, particularly subcutaneous tissue fibrosis. Previous data showed that TDE factors equal or lower than 90 were not related to any kind of fibrosis. treating pelvic tumors with the box technique but irradiating only two fields per day gives TDF values little greater than doing all four fields per day, but still lower than 90. That may explain why we have found no fibrosis. The impression is that not to treat all fields at each radiotherapy session may be possible with no increased rate of late complications. (author). 10 refs, 3 tabs, 2 figs

  1. α-transforming growth factor secreted by untransformed bovine anterior pituitary cells in culture. II. Identification using a sequence-specific monoclonal antibody

    International Nuclear Information System (INIS)

    Kobrin, M.S.; Samsoondar, J.; Kudlow, J.E.

    1986-01-01

    Untransformed bovine anterior pituitary cells cultured in serum-free defined medium secrete an epidermal growth factor (EGF)-like peptide with an amino acid composition similar to rat or human α-transforming growth factor (αTGF). To further characterize the bovine pituitary αTGF, it was compared to a human αTGF partially purified from the conditioned medium of a human melanoma cell line. An anti-αTGF monoclonal antibody, MF9, was produced from hybridomas derived from mice immunized with a 17-residue synthetic peptide corresponding to the carboxyl-terminal sequence of rat αTGF. The hybridoma supernatants were initially screened for the ability to immunoprecipitate 125 I-peptide and then tested for recognition of human αTGF. Only 2 of 36 antipeptide antibodies recognized the native αTGF. The binding of 125 I-peptide to MF9 was displaced by human αTGF but not by EGF. Bovine pituitary αTGF also displaced the binding of 125 I-peptide to MF9 in a similar manner to human αTGF. Both iodinated human and bovine pituitary αTGF were immunoprecipitated by MF9 whereas 125 I-EGF was not. Tryptic digests of both 125 I-αTGFs chromatographed to give a single, indistinguishable peak of iodinated material on a reverse-phase C 18 high performance liquid chromatography column when eluted with two different solvent systems, suggesting the generation of a single and identical tyrosine-containing tryptic peptide from both αTGFs. The comparisons of the bovine pituitary and human melanoma αTGF using a sequence-specific monoclonal antibody and peptide mapping suggest that these αTGFs are related and that αTGF production is not limited to transformed or fetal sources

  2. Two-dimensional NMR studies of squash family inhibitors. Sequence-specific proton assignments and secondary structure of reactive-site hydrolyzed Cucurbita maxima trypsin inhibitor III.

    Science.gov (United States)

    Krishnamoorthi, R; Gong, Y X; Lin, C L; VanderVelde, D

    1992-01-28

    The solution structure of reactive-site hydrolyzed Cucurbita maxima trypsin inhibitor III (CMTI-III*) was investigated by two-dimensional proton nuclear magnetic resonance (2D NMR) spectroscopy. CMTI-III*, prepared by reacting CMTI-III with trypsin which cleaved the Arg5-Ile6 peptide bond, had the two fragments held together by a disulfide linkage. Sequence-specific 1H NMR resonance assignments were made for all the 29 amino acid residues of the protein. The secondary structure of CMTI-III*, as deduced from NOESY cross peaks and identification of slowly exchanging hydrogens, contains two turns (residues 8-12 and 24-27), a 3(10)-helix (residues 13-16), and a triple-stranded beta-sheet (residues 8-10, 29-27, and 21-25). This secondary structure is similar to that of CMTI-I [Holak, T. A., Gondol, D., Otlewski, J., & Wilusz, T. (1989) J. Mol. Biol. 210, 635-648], which has a Glu instead of a Lys at position 9. Sequential proton assignments were also made for the virgin inhibitor, CMTI-III, at pH 4.71, 30 degrees C. Comparison of backbone hydrogen chemical shifts of CMTI-III and CMTI-III* revealed significant changes for residues located far away from the reactive-site region as well as for those located near it, indicating tertiary structural changes that are transmitted through most of the 29 residues of the inhibitor protein. Many of these residues are functionally important in that they make contact with atoms of the enzyme in the trypsin-inhibitor complex, as revealed by X-ray crystallography [Bode, W., Greyling, H. J., Huber, R., Otlewski, J., & Wilusz, T. (1989) FEBS Lett. 242, 285-292].(ABSTRACT TRUNCATED AT 250 WORDS)

  3. DNA sequence-specific dimeric bisbenzimidazoles DBP(n) and DBPA(n) as inhibitors of H-NS silencing in bacterial cells.

    Science.gov (United States)

    Melkina, Olga E; Koval, Vasilii S; Ivanov, Alexander A; Zhuze, Alexei L; Zavilgelsky, Gennadii B

    2018-03-01

    DNA sequence-specific fluorescent dimeric bisbenzimidazoles DBP(n) and DBPA(n), noncovalently interacting with A-T pairs in the minor groove of double-stranded DNA were used for studying and monitoring the expression of histone-like H-NS-dependent promoters. Histone-like H-NS selectively binds to AT-rich segments of DNA and silences a large number of genes in bacterial chromosomes. The H-NS-dependent promoters of Quorum Sensing (QS)-regulated lux operons of the marine bacteria mesophilic Aliivibrio fischeri, psychrophilic Aliivibrio logei were used. Escherichia coli lux biosensors were constructed by cloning fragments bearing QS-regulated promoters into the vector, thereby placing each fragment upstream of the promoterless Photorhabdus luminescens luxCDABE genes. It was shown that the dimeric bisbenzimidazoles DBP(n) and DBPA(n) counteract the H-NS silencing activity. Thus, the presence of DBP(n) or DBPA(n) in the medium leads to an approximately 10-100-fold increase in the level of transcription of QS promoters in E. coli hns + . The largest decrease in the level of H-NS repression was observed using ligands containing a linker with a length of ca. 18Å, such as DBP(2) and DBPA(2). Ligands containing linkers with n=1 and 3 are an order of magnitude less active; ligands with n=4 are inactive. DBPA(2) exhibits activity starting with a concentration of 0.5μM; the minimum concentration of DBP(2) is 5-7 times higher. It is suggested that A-T pairs located at five nucleotide pair intervals, which correspond to the linker length in highly active ligands with n=2, play a key role in the structure of H-NS-binding sites in QS-regulated promoters. Copyright © 2017 Elsevier GmbH. All rights reserved.

  4. Label-Free Detection of Sequence-Specific DNA Based on Fluorescent Silver Nanoclusters-Assisted Surface Plasmon-Enhanced Energy Transfer.

    Science.gov (United States)

    Ma, Jin-Liang; Yin, Bin-Cheng; Le, Huynh-Nhu; Ye, Bang-Ce

    2015-06-17

    We have developed a label-free method for sequence-specific DNA detection based on surface plasmon enhanced energy transfer (SPEET) process between fluorescent DNA/AgNC string and gold nanoparticles (AuNPs). DNA/AgNC string, prepared by a single-stranded DNA template encoded two emitter-nucleation sequences at its termini and an oligo spacer in the middle, was rationally designed to produce bright fluorescence emission. The proposed method takes advantage of two strategies. The first one is the difference in binding properties of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) toward AuNPs. The second one is SPEET process between fluorescent DNA/AgNC string and AuNPs, in which fluorescent DNA/AgNC string can be spontaneously adsorbed onto the surface of AuNPs and correspondingly AuNPs serve as "nanoquencher" to quench the fluorescence of DNA/AgNC string. In the presence of target DNA, the sensing probe hybridized with target DNA to form duplex DNA, leading to a salt-induced AuNP aggregation and subsequently weakened SPEET process between fluorescent DNA/AgNC string and AuNPs. A red-to-blue color change of AuNPs and a concomitant fluorescence increase were clearly observed in the sensing system, which had a concentration dependent manner with specific DNA. The proposed method achieved a detection limit of ∼2.5 nM, offering the following merits of simple design, convenient operation, and low experimental cost because of no chemical modification, organic dye, enzymatic reaction, or separation procedure involved.

  5. Sequence-specific 1H NMR assignments and secondary structure of the Arc repressor of bacteriophage P22, as determined by two-dimensional 1H NMR spectroscopy

    International Nuclear Information System (INIS)

    Breg, J.N.; Boelens, R.; George, A.V.E.; Kaptein, R.

    1989-01-01

    The Arc repressor of bacteriophage P22 is a DNA binding protein that does not belong to any of the known classes of such proteins. The authors have undertaken a 1 H NMR study of the protein with the aim of elucidating its three-dimensional structure in solution and its mode of binding of operator DNA. Here the authors present the 1 H nuclear magnetic resonance (NMR) assignments of all backbone protons an most of the side-chain protons of Arc repressor. Elements of secondary structure have been identified on the basis of networks of characteristics sequential and medium-range nuclear Overhauser enhancements (NOEs). Two α-helical regions have been found in the peptide regions 16-29 and 35-45. The ends of the helices could not yet be firmly established and could extend to residue 31 for the first helix and to residue 49 for the second. Immediately before the first helix, between residues 8 and 14, a region is present with β-sheet characteristics dominated by a close proximity of the α-protons of residues 9 and 13. Because of the dimeric nature of the protein there are still two possible ways in which the NOEs in the β-sheet region can be interpreted. While the data presently do not allow an unambiguous choice between these two possibilities, some evidence is discussed that favors the latter (β-sheet between monomers). Since the N-terminal region of Arc is responsible for the sequence-specific recognition of its operator, the findings suggest the existence of a DNA binding motif in which a β-sheet region is present

  6. The dogma of bacteriology and other events as spearheads of virology Dogma de la bacteriología y otros eventos como puntas de lanza de la virología

    Directory of Open Access Journals (Sweden)

    Charles Volcy

    2009-11-01

    Full Text Available

    This review analyzes some of the main events during the twentieth century that led to the birth of virology. In the literature of the time, a relationship of causality was established between virus and disease, and within this pathological context, the notions of fixed virus, volatile virus, contagium vivum fluidum and contagium fixum were formed. The transformation of the virus concept as a technoscientific object took place based on the criterion of filterability and on the methodology devised for the bacteriology dogma. Studies on tobacco mosaic virus are highlighted, as well as those on viral diseases of human beings and animals, which led to the discovery of these submicroscopic agents through the appropriation of technologies and the impulse triggered by political and economic factors.

    Esta investigación analiza algunos de los eventos principales del siglo XIX que condujeron hacia la cristalización de la virología. En los documentos de esta investigación analiza algunos de los eventos principales del siglo XIX que condujeron hacia la cristalización de la virología. En los documentos de aquella época, se plasmó una relación de causalidad entre virus y enfermedad o contagio, y en este contexto patológico, se elaboraron las nociones de virus fijo, virus volátil, contagium vivum fluidum y contagium fixum. De otro lado, la transformación conceptual hacia el virus como objeto tecnocientífico tuvo lugar con base en el criterio de filtrabilidad y en la metodología trazada por la bacteriología convertida en dogma. Asimismo, se

  7. Dogma disputed: potential endemic heterosexual transmission of human immunodeficiency virus in Australia.

    Science.gov (United States)

    Chapman, S

    1992-06-01

    The concept of tertiary sexual transmission of human immunodeficiency virus (HIV) has been central to government efforts to communicate notions of risk to heterosexuals in Australia. Data on heterosexually transmitted acquired immune deficiency syndrome (AIDS) and HIV for Australia are reviewed with emphasis given to the probability of misclassification bias in the heterosexually acquired and 'other/undetermined' categories. Tertiary cases are almost certainly rare in Australia, with little evidence of any increase in their incidence since the first cases were recorded. Three factors (low probability of exposure, the infectivity of HIV and a comparatively low rate of sexual partner change) make it improbable that Australian heterosexuals with no risk factors will experience endemic HIV infection, with a caveat to this conclusion lying in the potential of Australian sex tourism to Southeast Asia for introducing HIV into the Australian heterosexual population. Four hegemonic factors which have acted to suppress any serious debate of the notion that HIV in Australia is unlikely to become endemic among heterosexuals are discussed: the political 'democratization' of risk inspired by concerns that gay men should not be further vilified as a victim group; the preventive imperative; a reluctance among health educators to question the very foundations of the message they are employed to deliver; and a reluctance to curtail 'Trojan horse' benefits to sexually transmissible disease prevention engendered by HIV education promoting safe sex messages.

  8. Limb remote-preconditioning protects against focal ischemia in rats and contradicts the dogma of therapeutic time windows for preconditioning

    Science.gov (United States)

    Ren, Chuancheng; Gao, Xuwen; Steinberg, Gary K.; Zhao, Heng

    2009-01-01

    Remote ischemic preconditioning is an emerging concept for stroke treatment, but its protection against focal stroke has not been established. We tested whether remote preconditioning, performed in the ipsilateral hind limb, protects against focal stroke and explored its protective parameters. Stroke was generated by a permanent occlusion of the left distal middle cerebral artery (MCA) combined with a 30 minute occlusion of the bilateral common carotid arteries (CCA) in male rats. Limb preconditioning was generated by 5 or 15 minute occlusion followed with the same period of reperfusion of the left hind femoral artery, and repeated for 2 or 3 cycles. Infarct was measured 2 days later. The results showed that rapid preconditioning with 3 cycles of 15 minutes performed immediately before stroke reduced infarct size from 47.7±7.6% of control ischemia to 9.8±8.6%; at 2 cycles of 15 minutes, infarct was reduced to 24.7±7.3%; at 2 cycles of 5 minutes, infarct was not reduced. Delayed preconditioning with 3 cycles of 15 minutes conducted 2 days before stroke also reduced infarct to 23.0 ±10.9%, but with 2 cycles of 15 minutes it offered no protection. The protective effects at these two therapeutic time windows of remote preconditioning are consistent with those of conventional preconditioning, in which the preconditioning ischemia is induced in the brain itself. Unexpectedly, intermediate preconditioning with 3 cycles of 15 minutes performed 12 hours before stroke also reduced infarct to 24.7±4.7%, which contradicts the current dogma for therapeutic time windows for the conventional preconditioning that has no protection at this time point. In conclusion, remote preconditioning performed in one limb protected against ischemic damage after focal cerebral ischemia. PMID:18201834

  9. Dispelling dogma and misconceptions regarding the most pharmacologically targetable source of reactive species in inflammatory disease, xanthine oxidoreductase.

    Science.gov (United States)

    Kelley, Eric E

    2015-08-01

    Xanthine oxidoreductase (XOR), the molybdoflavin enzyme responsible for the terminal steps of purine degradation in humans, is also recognized as a significant source of reactive species contributory to inflammatory disease. In animal models and clinical studies, inhibition of XOR has resulted in diminution of symptoms and enhancement of function in a number of pathologies including heart failure, diabetes, sickle cell anemia, hypertension and ischemia-reperfusion injury. For decades, XOR involvement in pathologic processes has been established by salutary outcomes attained from treatment with the XOR inhibitor allopurinol. This has served to frame a working dogma that elevation of XOR-specific activity is associated with enhanced rates of reactive species generation that mediate negative outcomes. While adherence to this narrowly focused practice of designating elevated XOR activity to be "bad" has produced some benefit, it has also led to significant underdevelopment of the processes mediating XOR regulation, identification of alternative reactants and products as well as micro-environmental factors that alter enzymatic activity. This is exemplified by recent reports: (1) identifying XOR as a nitrite reductase and thus a source of beneficial nitric oxide ((•)NO) under in vivo conditions similar to those where XOR inhibition has been assumed an optimal treatment choice, (2) describing XOR-derived uric acid (UA) as a critical pro-inflammatory mediator in vascular and metabolic disease and (3) ascribing an antioxidant/protective role for XOR-derived UA. When taken together, these proposed and countervailing functions of XOR affirm the need for a more comprehensive evaluation of product formation as well as the factors that govern product identity. As such, this review will critically evaluate XOR-catalyzed oxidant, (•)NO and UA formation as well as identify factors that mediate their production, inhibition and the resultant impact on inflammatory disease.

  10. The ICE hypothesis stands: How the dogma of late Cenozoic tectonic uplift can no longer be sustained in the light of data and physical laws

    Science.gov (United States)

    Nielsen, S. B.; Clausen, O. R.; Jacobsen, B. H.; Thomsen, E.; Huuse, M.; Gallagher, K.; Balling, N.; Egholm, D.

    2010-08-01

    In this reply, we address the issues raised by the comment of Chalmers et al. (2010) regarding our ICE hypothesis for the evolution of western Scandinavia. We reject their conjectures as based, uncritically and without consideration of physical mechanisms, on the long-standing dogma of late Cenozoic tectonic uplift. Our hypothesis, in contrast, honours well-documented physical laws and the present wealth of actual data constraints (as opposed to dogma-biased inferences). After careful consideration of the points raised by Chalmers et al. (2010) we maintain our simple explanation for the evolution of Scandinavian topography, as it honours well-documented actual data constraints, such as crustal structure (including its spatio-temporal variability), thermal history in the eastern North Sea, global and regional climatic change (including eustacy) and sedimentation in the adjacent basins. The inevitable conclusion is that, although more data constraints are desirable, the current best fit hypothesis, is that the Scandinavian topography is of Caledonide origin, and has been shaped by fluvial and glacial buzzsaw and periglacial processes, and most recently (last few Myr) been re-invigorated by extensive glacial erosion in the fjords and on the shelf.

  11. Infantile wheeze: rethinking dogma.

    Science.gov (United States)

    de Benedictis, Fernando Maria; Bush, Andrew

    2017-04-01

    Wheeze is a common symptom in young children and is usually associated with viral illnesses. It is a major source of morbidity and is responsible for a high consumption of healthcare and economic resources worldwide. A few children have a condition resembling classical asthma. Rarer specific conditions may have a wheezy component and should be considered in the differential diagnosis. Over the last half century, there have been many circular discussions about the best way of managing preschool wheeze. In general, intermittent wheezing should be treated with intermittent bronchodilator therapy, and a controller therapy should be prescribed for a young child with recurrent wheezing only if positively indicated, and only then if carefully monitored for efficacy. Good multidisciplinary support, attention to environmental exposition and education are essential in managing this common condition. This article analyses the pathophysiological basis of wheezing in infancy and critically discusses the evolution of the scientific progress over time in this unique field of respiratory medicine. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  12. The Dogma of Transformation

    Science.gov (United States)

    Newkirk, Thomas

    2004-01-01

    This essay examines the writing done at the University of New Hampshire in the period between 1928 and 1942. It argues that while there was extensive writing from personal experience, this writing did not perform the "turn" where the writer claims a new form of self-understanding. It goes on to suggest that work with this largely observational…

  13. El dogma de la competitividad frente a la utopía de la sustentabilidad: análisis crítico del ethos desarrollista y economicista

    OpenAIRE

    Ochoa Fonseca, Fredy Alfonso; Universidad Externado de Colombia

    2016-01-01

    A través del análisis de discursos y la dialéctica, este artículo tiene como objetivo argumentar de manera crítica el ethos que orienta la apuesta por la competitividad. Se encuentra que como dogma, fruto de una sociedad mercantilizada y de una visión economizada del mundo y de la vida, la competitividad desconoce las bases epistemológicas de la economía, pone todas las apuestas bajo la óptica de la maximización del beneficio y el aumento de la rentabilidad, no tiene en cuenta la ética, confu...

  14. Sequence-specific 1H NMR assignments, secondary structure, and location of the calcium binding site in the first epidermal growth factor like domain of blood coagulation factor IX

    International Nuclear Information System (INIS)

    Huang, L.H.; Cheng, H.; Sweeney, W.V.; Pardi, A.; Tam, J.P.

    1991-01-01

    Factor IX is a blood clotting protein that contains three regions, including a γ-carboxyglutamic acid (Gla) domain, two tandemly connected epidermal growth factor like (EGF-like) domains, and a serine protease region. The protein exhibits a high-affinity calcium binding site in the first EGF0like domain, in addition to calcium binding in the Gla domain. The first EGF-like domain, factor IX (45-87), has been synthesized. Sequence-specific resonance assignment of the peptide has been made by using 2D NMR techniques, and its secondary structure has been determined. The protein is found to have two antiparallel β-sheets, and preliminary distance geometry calculations indicate that the protein has two domains, separated by Trp 28 , with the overall structure being similar to that of EGF. An NMR investigation of the calcium-bound first EGF-like domain indicates the presence and location of a calcium binding site involving residues on both strands of one of the β-sheets as well as the N-terminal region of the peptide. These results suggest that calcium binding in the first EGF-like domain could induce long-range (possibly interdomain) conformational changes in factor IX, rather than causing structural alterations in the EGF-like domain itself

  15. Realismo e Vanguardismo no Dogma 95: o lugar do movimento na história do cinema e suas implicações estéticas e tecnológicas

    OpenAIRE

    Silva, Márcio Corino Lantelme da

    2010-01-01

    O trabalho, um estudo sobre o Dogma 95, tem como objetivo principal situar esse movimento na história do cinema a partir da consideração de três matrizes de linguagem cinematográfica: A matriz Realista, a Vanguardista e a Clássica, propondo para ele um lugar entre o Realismo e o Vanguardismo, a partir do estudo centrado em dois de seus filmes: Festa de Família, de Thomas Vinterberg (1998); e Os Idiotas, de Lars Von Trier (1998). Aspectos como a corporeidade da câmera dv, o papel da dramaturgi...

  16. Phenotypic silencing of cytoplasmic genes using sequence-specific double-stranded short interfering RNA and its application in the reverse genetics of wild type negative-strand RNA viruses

    Directory of Open Access Journals (Sweden)

    Barik Sailen

    2001-12-01

    Full Text Available Abstract Background Post-transcriptional gene silencing (PTGS by short interfering RNA has opened up new directions in the phenotypic mutation of cellular genes. However, its efficacy on non-nuclear genes and its effect on the interferon pathway remain unexplored. Since directed mutation of RNA genomes is not possible through conventional mutagenesis, we have tested sequence-specific 21-nucleotide long double-stranded RNAs (dsRNAs for their ability to silence cytoplasmic RNA genomes. Results Short dsRNAs were generated against specific mRNAs of respiratory syncytial virus, a nonsegmented negative-stranded RNA virus with a cytoplasmic life cycle. At nanomolar concentrations, the dsRNAs specifically abrogated expression of the corresponding viral proteins, and produced the expected mutant phenotype ex vivo. The dsRNAs did not induce an interferon response, and did not inhibit cellular gene expression. The ablation of the viral proteins correlated with the loss of the specific mRNAs. In contrast, viral genomic and antigenomic RNA, which are encapsidated, were not directly affected. Conclusions Synthetic inhibitory dsRNAs are effective in specific silencing of RNA genomes that are exclusively cytoplasmic and transcribed by RNA-dependent RNA polymerases. RNA-directed RNA gene silencing does not require cloning, expression, and mutagenesis of viral cDNA, and thus, will allow the generation of phenotypic null mutants of specific RNA viral genes under normal infection conditions and at any point in the infection cycle. This will, for the first time, permit functional genomic studies, attenuated infections, reverse genetic analysis, and studies of host-virus signaling pathways using a wild type RNA virus, unencumbered by any superinfecting virus.

  17. Development of a multiplex polymerase chain reaction-sequence-specific primer method for NKG2D and NKG2F single-nucleotide polymorphism typing using isothermal multiple displacement amplification products.

    Science.gov (United States)

    Kaewmanee, M; Phoksawat, W; Romphruk, A; Romphruk, A V; Jumnainsong, A; Leelayuwat, C

    2013-06-01

    Natural killer group 2 member D (NKG2D) on immune effector cells recognizes multiple stress-inducible ligands. NKG2D single-nucleotide polymorphism (SNP) haplotypes were related to the levels of cytotoxic activity of peripheral blood mononuclear cells. Indeed, these polymorphisms were also located in NKG2F. Isothermal multiple displacement amplification (IMDA) is used for whole genome amplification (WGA) that can amplify very small genomic DNA templates into microgram with whole genome coverage. This is particularly useful in the cases of limited amount of valuable DNA samples requiring multi-locus genotyping. In this study, we evaluated the quality and applicability of IMDA to genetic studies in terms of sensitivity, efficiency of IMDA re-amplification and stability of IMDA products. The smallest amount of DNA to be effectively amplified by IMDA was 200 pg yielding final DNA of approximately 16 µg within 1.5 h. IMDA could be re-amplified only once (second round of amplification), and could be kept for 5 months at 4°C and more than a year at -20°C without loosing genome coverage. The amplified products were used successfully to setup a multiplex polymerase chain reaction-sequence-specific primer for SNP typing of the NKG2D/F genes. The NKG2D/F multiplex polymerase chain reaction (PCR) contained six PCR mixtures for detecting 10 selected SNPs, including 8 NKG2D/F SNP haplotypes and 2 additional NKG2D coding SNPs. This typing procedure will be applicable in both clinical and research laboratories. Thus, our data provide useful information and limitations for utilization of genome-wide amplification using IMDA and its application for multiplex NKG2D/F typing. © 2013 John Wiley & Sons Ltd.

  18. Central Chile

    Science.gov (United States)

    2002-01-01

    The beginning of spring in central Chile looked like this to SeaWiFS. The snow-covered Andes mark the country's eastern border, and phytoplankton blooms and river sediment plumes fill the waters off its west coast. A large eddy due west of Concepcion is highlighted by the phytoplankton it contains.

  19. Afrique Centrale

    African Journals Online (AJOL)

    PR BOKO

    (Afrique Centrale) : peuplement de protozoaires ciliés et macro invertébrés ... Le lac d'Obili est un écosystème aquatique situé en plein cœur de Yaoundé en ...... électrique des eaux est assez stable, autour de 200 ; ce qui suppose que la ...

  20. Challenging surgical dogma in the management of proximal esophageal atresia with distal tracheoesophageal fistula: Outcomes from the Midwest Pediatric Surgery Consortium.

    Science.gov (United States)

    Lal, Dave R; Gadepalli, Samir K; Downard, Cynthia D; Ostlie, Daniel J; Minneci, Peter C; Swedler, Ruth M; Chelius, Thomas H; Cassidy, Laura; Rapp, Cooper T; Billmire, Deborah; Bruch, Steven; Burns, R Carland; Deans, Katherine J; Fallat, Mary E; Fraser, Jason D; Grabowski, Julia; Hebel, Ferdynand; Helmrath, Michael A; Hirschl, Ronald B; Kabre, Rashmi; Kohler, Jonathan; Landman, Matthew P; Leys, Charles M; Mak, Grace Z; Raque, Jessica; Rymeski, Beth; Saito, Jacqueline M; St Peter, Shawn D; von Allmen, Daniel; Warner, Brad W; Sato, Thomas T

    2017-06-01

    Perioperative management of infants with esophageal atresia and tracheoesophageal fistula (EA/TEF) is frequently based on surgeon experience and dogma rather than evidence-based guidelines. This study examines whether commonly perceived important aspects of practice affect outcome in a contemporary multi-institutional cohort of patients undergoing primary repair for the most common type of esophageal atresia anomaly, proximal EA with distal TEF. The Midwest Pediatric Surgery Consortium conducted a multicenter, retrospective study examining selected outcomes on infants diagnosed with proximal EA with distal TEF who underwent primary repair over a 5-year period (2009-2014), with a minimum 1-year follow up, across 11 centers. 292 patients with proximal EA and distal TEF who underwent primary repair were reviewed. The overall mortality was 6% and was significantly associated with the presence of congenital heart disease (OR 4.82, p=0.005). Postoperative complications occurred in 181 (62%) infants, including: anastomotic stricture requiring intervention (n=127; 43%); anastomotic leak (n=54; 18%); recurrent fistula (n=15; 5%); vocal cord paralysis/paresis (n=14; 5%); and esophageal dehiscence (n=5; 2%). Placement of a transanastomotic tube was associated with an increase in esophageal stricture formation (OR 2.2, p=0.01). Acid suppression was not associated with altered rates of stricture, leak or pneumonia (all p>0.1). Placement of interposing prosthetic material between the esophageal and tracheal suture lines was associated with an increased leak rate (OR 4.7, p24h were used in 193 patients (66%) with no difference in rates of infection, shock or death when compared to antibiotic use ≤24h (all p>0.3). Hospital volume was not associated with postoperative complication rates (p>0.08). Routine postoperative esophagram obtained on day 5 resulted in no delayed/missed anastomotic leaks or a difference in anastomotic leak rate as compared to esophagrams obtained on day 7

  1. Revisiting a dogma: similar survival of patients with small bowel and gastric GIST. A population-based propensity score SEER analysis.

    Science.gov (United States)

    Guller, Ulrich; Tarantino, Ignazio; Cerny, Thomas; Ulrich, Alexis; Schmied, Bruno M; Warschkow, Rene

    2017-01-01

    The objective of the present analysis was to assess whether small bowel gastrointestinal stromal tumor (GIST) is associated with worse cancer-specific survival (CSS) and overall survival (OS) compared with gastric GIST on a population-based level. Data on patients aged 18 years or older with histologically proven GIST was extracted from the SEER database from 1998 to 2011. OS and CSS for small bowel GIST were compared with OS and CSS for gastric GIST by application of adjusted and unadjusted Cox regression analyses and propensity score analyses. GIST were located in the stomach (n = 3011, 59 %), duodenum (n = 313, 6 %), jejunum/ileum (n = 1288, 25 %), colon (n = 139, 3 %), rectum (n = 172, 3 %), and extraviscerally (n = 173, 3 %). OS and CSS of patients with GIST in the duodenum [OS, HR 0.95, 95 % confidence interval (CI) 0.76-1.19; CSS, HR 0.99, 95 % CI 0.76-1.29] and in the jejunum/ileum (OS, HR 0.97, 95 % CI 0.85-1.10; CSS, HR = 0.95, 95 % CI 0.81-1.10) were similar to those of patients with gastric GIST in multivariate analyses. Conversely, OS and CSS of patients with GIST in the colon (OS, HR 1.40; 95 % CI 1.07-1.83; CSS, HR 1.89, 95 % CI 1.41-2.54) and in an extravisceral location (OS, HR 1.42, 95 % CI 1.14-1.77; CSS, HR = 1.43, 95 % CI 1.11-1.84) were significantly worse than those of patients with gastric GIST. Contrary to common belief, OS and CSS of patients with small bowel GIST are not statistically different from those of patients with gastric GIST when adjustment is made for confounding variables on a population-based level. The prognosis of patients with nongastric GIST is worse because of a colonic and extravisceral GIST location. These findings have implications regarding adjuvant treatment of GIST patients. Hence, the dogma that small bowel GIST patients have worse prognosis than gastric GIST patients and therefore should receive adjuvant treatment to a greater extent must be revisited.

  2. Europa central

    Directory of Open Access Journals (Sweden)

    Karel BARTOSEK

    2010-02-01

    Full Text Available La investigación francesa continúa interesándose por Europa Central. Desde luego, hay límites a este interés en el ambiente general de mi nueva patria: en la ignorancia, producto del largo desinterés de Francia por este espacio después de la Segunda Guerra Mundial, y en el comportamiento y la reflexión de la clase política y de los medios de comunicación (una anécdota para ilustrar este ambiente: durante la preparación de nuestro coloquio «Refugiados e inmigrantes de Europa Central en el movimiento antifascista y la Resistencia en Francia, 1933-1945», celebrado en París en octubre de 1986, el problema de la definición fue planteado concreta y «prácticamente». ¡Y hubo entonces un historiador eminente, para quién Alemania no formaría parte de Europa Central!.

  3. The Simplest Flowchart Stating the Mechanisms for Organic Xenobiotics-induced Toxicity: Can it Possibly be Accepted as a “Central Dogma” for Toxic Mechanisms?

    Science.gov (United States)

    Lee, Sundong; Cho, Myung-Haing

    2014-01-01

    Xenobiotics causing a variety of toxicity in biological systems could be classified as two types, inorganic and organic chemicals. It is estimated that the organic xenobiotics are responsible for approximately 80~90% of chemical-induced toxicity in human population. In the class for toxicology, we have encountered some difficulties in explaining the mechanisms of toxicity caused especially by organic chemicals. Here, a simple flowchart was introduced for explaining the mechanism of toxicity caused by organic xenobiotics, as the central dogma of molecular biology. This flowchart, referred to as a central dogma, was described based on a view of various aspects as follows: direct-acting chemicals vs. indirect-acting chemicals, cytochrome P450-dependent vs. cytochrome P450-independent biotransformation, reactive intermediates, reactivation, toxicokinetics vs. toxicodynamics, and reversibility vs. irreversibility. Thus, the primary objective of this flowchart is to help better understanding of the organic xenobiotics-induced toxic mechanisms, providing a major pathway for toxicity occurring in biological systems. PMID:25343011

  4. central t

    Directory of Open Access Journals (Sweden)

    Manuel R. Piña Monarrez

    2007-01-01

    Full Text Available Dado que la Regresión Ridge (RR, es una estimación sesgada que parte de la solución de la regresión de Mínimos Cuadrados (MC, es vital establecer las condiciones para las que la distribución central t de Student que se utiliza en la prueba de hipótesis en MC, sea también aplicable a la regresión RR. La prueba de este importante resultado se presenta en este artículo.

  5. Central sleep apnea

    Science.gov (United States)

    Sleep apnea - central; Obesity - central sleep apnea; Cheyne-Stokes - central sleep apnea; Heart failure - central sleep apnea ... Central sleep apnea results when the brain temporarily stops sending signals to the muscles that control breathing. The condition ...

  6. Central hypothyroidism

    Directory of Open Access Journals (Sweden)

    Vishal Gupta

    2011-01-01

    Full Text Available Central hypothyroidism is defined as hypothyroidism due to insufficient stimulation by thyroid stimulating hormone (TSH of an otherwise normal thyroid gland. It has an estimated prevalence of approximately 1 in 80,000 to 1 in 120,000. It can be secondary hypothyroidism (pituitary or tertiary hypothyroidism (hypothalamus in origin. In children, it is usually caused by craniopharyngiomas or previous cranial irradiation for brain tumors or hematological malignancies. In adults, it is usually due to pituitary macroadenomas, pituitary surgeries or post-irradiation. Fatigue and peripheral edema are the most specific clinical features. Diagnosis is established by the presence of normal to low-normal TSH on the background of low-normal thyroid hormones, confirmed by the thyrotropin releasing hormone stimulation test. Therapy includes use of levothyroxine titrated to improvement in symptomology and keeping free T4 in the upper limit of normal reference range.

  7. Central Nervous System Vasculitis

    Science.gov (United States)

    ... of Vasculitis / Central Nervous System (CNS) Vasculitis Central Nervous System (CNS) Vasculitis Swap out your current Facebook Profile ... Facebook personal page. Replace with this image. Central nervous system (CNS) vasculitis is inflammation of blood vessel walls ...

  8. An operational perspective of challenging statistical dogma while establishing a modern, secure distributed data management and imaging transport system: the Pediatric Brain Tumor Consortium phase I experience.

    Science.gov (United States)

    Onar, Arzu; Ramamurthy, Uma; Wallace, Dana; Boyett, James M

    2009-04-01

    The Pediatric Brain Tumor Consortium (PBTC) is a multidisciplinary cooperative research organization devoted to the study of correlative tumor biology and new therapies for primary central nervous system (CNS) tumors of childhood. The PBTC was created in 1999 to conduct early-phase studies in a rapid fashion in order to provide sound scientific foundation for the Children's Oncology Group to conduct definitive trials. The Operations and Biostatistics Center (OBC) of the PBTC is responsible for centrally administering study design and trial development, study conduct and monitoring, data collection and management as well as various regulatory and compliance processes. The phase I designs utilized for the consortium trials have accommodated challenges unique to pediatric trials such as body surface area (BSA)-based dosing in the absence of pediatric formulations of oral agents. Further during the past decade, the OBC has developed and implemented a state-of-the-art secure and efficient internet-based paperless distributed data management system. Additional web-based systems are also in place for tracking and distributing correlative study data as well as neuroimaging files. These systems enable effective communications among the members of the consortium and facilitate the conduct and timely reporting of multi-institutional early-phase clinical trials.

  9. Sequence specificity of DNA cleavage by Micrococcus luteus γ endonuclease

    International Nuclear Information System (INIS)

    Hentosh, P.; Henner, W.D.; Reynolds, R.J.

    1985-01-01

    DNA fragments of defined sequence have been used to determine the sites of cleavage by γ-endonuclease activity in extracts prepared from Micrococcus luteus. End-labeled DNA restriction fragments of pBR322 DNA that had been irradiated under nitrogen in the presence of potassium iodide or t-butanol were treated with M. luteus γ endonuclease and analyzed on irradiated DNA preferentially at the positions of cytosines and thymines. DNA cleavage occurred immediately to the 3' side of pyrimidines in irradiated DNA and resulted in fragments that terminate in a 5'-phosphoryl group. These studies indicate that both altered cytosines and thymines may be important DNA lesions requiring repair after exposure to γ radiation

  10. Sequence specific inhibition of DNA restriction enzyme cleavage by PNA

    DEFF Research Database (Denmark)

    Nielsen, P.E.; Egholm, M.; Berg, R.H.

    1993-01-01

    Plasmids containing double-stranded 10-mer PNA (peptide nucleic acid chimera) targets proximally flanked by two restriction enzyme sites were challenged with the complementary PNA or PNAs having one or two mismatches, and the effect on the restriction enzyme cleavage of the flanking sites was ass...

  11. Chimeric TALE recombinases with programmable DNA sequence specificity.

    Science.gov (United States)

    Mercer, Andrew C; Gaj, Thomas; Fuller, Roberta P; Barbas, Carlos F

    2012-11-01

    Site-specific recombinases are powerful tools for genome engineering. Hyperactivated variants of the resolvase/invertase family of serine recombinases function without accessory factors, and thus can be re-targeted to sequences of interest by replacing native DNA-binding domains (DBDs) with engineered zinc-finger proteins (ZFPs). However, imperfect modularity with particular domains, lack of high-affinity binding to all DNA triplets, and difficulty in construction has hindered the widespread adoption of ZFPs in unspecialized laboratories. The discovery of a novel type of DBD in transcription activator-like effector (TALE) proteins from Xanthomonas provides an alternative to ZFPs. Here we describe chimeric TALE recombinases (TALERs): engineered fusions between a hyperactivated catalytic domain from the DNA invertase Gin and an optimized TALE architecture. We use a library of incrementally truncated TALE variants to identify TALER fusions that modify DNA with efficiency and specificity comparable to zinc-finger recombinases in bacterial cells. We also show that TALERs recombine DNA in mammalian cells. The TALER architecture described herein provides a platform for insertion of customized TALE domains, thus significantly expanding the targeting capacity of engineered recombinases and their potential applications in biotechnology and medicine.

  12. Thermodynamics of sequence-specific binding of PNA to DNA

    DEFF Research Database (Denmark)

    Ratilainen, T; Holmén, A; Tuite, E

    2000-01-01

    For further characterization of the hybridization properties of peptide nucleic acids (PNAs), the thermodynamics of hybridization of mixed sequence PNA-DNA duplexes have been studied. We have characterized the binding of PNA to DNA in terms of binding affinity (perfectly matched duplexes) and seq......For further characterization of the hybridization properties of peptide nucleic acids (PNAs), the thermodynamics of hybridization of mixed sequence PNA-DNA duplexes have been studied. We have characterized the binding of PNA to DNA in terms of binding affinity (perfectly matched duplexes...

  13. Cyclodextrin-peptide conjugates for sequence specific DNA binding

    Czech Academy of Sciences Publication Activity Database

    García, Y. R.; Zelenka, Jan; Pabon, Y. V.; Iyer, A.; Buděšínský, Miloš; Kraus, Tomáš; Smith, C. I. E.; Madder, A.

    2015-01-01

    Roč. 13, č. 18 (2015), s. 5273-5278 ISSN 1477-0520 R&D Projects: GA MŠk LD12019 Institutional support: RVO:61388963 Keywords : crystal structure * inclusion complex * click chemistry Subject RIV: CC - Organic Chemistry Impact factor: 3.559, year: 2015

  14. Observations of central stars

    International Nuclear Information System (INIS)

    Lutz, J.H.

    1978-01-01

    Difficulties occurring in the observation of central stars of planetary nebulae are reviewed with emphasis on spectral classifications and population types, and temperature determination. Binary and peculiar central stars are discussed. (U.M.G.)

  15. Gangs in Central America

    National Research Council Canada - National Science Library

    Ribando, Clare

    2005-01-01

    ... activities of Central American gangs. Citizens in several Central American countries have identified crime and gang violence among the top issues of popular concern, and Honduras and El Salvador have recently enacted tough anti-gang legislation...

  16. NIDDK Central Repository

    Data.gov (United States)

    U.S. Department of Health & Human Services — The NIDDK Central Repository stores biosamples, genetic and other data collected in designated NIDDK-funded clinical studies. The purpose of the NIDDK Central...

  17. Is banking supervision central to central banking?

    OpenAIRE

    Joe Peek; Eric S. Rosengren; Geoffrey M. B. Tootell

    1997-01-01

    Whether central banks should play an active role in bank supervision and regulation is being debated both in the United States and abroad. While the Bank of England has recently been stripped of its supervisory responsibilities and several proposals in the United States have advocated removing bank supervision from the Federal Reserve System, other countries are considering enhancing central bank involvement in this area. Many of the arguments for and against these proposals hinge on the effe...

  18. HLA-A, -B, -DRB1 allele and haplotype frequencies of 920 cord blood units from Central Chile.

    Science.gov (United States)

    Schäfer, Christian; Sauter, Jürgen; Riethmüller, Tobias; Kashi, Zahra Mehdizadeh; Schmidt, Alexander H; Barriga, Francisco J

    2016-08-01

    We present human leukocyte antigen (HLA) haplotype and allele/antigenic group frequencies derived from a data set of 920 umbilical cord blood units collected in Central Chile. HLA-A and -B genotypes were typed using sequence specific oligonucleotide probe methods while HLA-DRB1 genotypes were obtained from sequencing-based typing. The most frequent haplotype is A*29~B*44~DRB1*07:01 with an estimated frequency of 2.1%. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  19. Central Laboratories Services

    Data.gov (United States)

    Federal Laboratory Consortium — The TVA Central Laboratories Services is a comprehensive technical support center, offering you a complete range of scientific, engineering, and technical services....

  20. Central Pain Syndrome

    Science.gov (United States)

    ... such as neurontin (gabapentin) can be useful. Lowering stress levels appears to reduce pain. View Full Treatment Information Definition Central pain syndrome is a neurological condition caused ...

  1. Central Diabetes Insipidus, Central Hypothyroidism, Renal Tubular ...

    African Journals Online (AJOL)

    readmitted to the hospital because of jaundice and failure to thrive, for which he was investigated and diagnosed to have central congenital hypothyroidism. Shortly thereafter, he was admitted to our institute with a history of vomiting, decreased oral intake, polyuria, and dehydration having lasted 5 days. He was investigated ...

  2. Optimal Central Bank Transparency

    NARCIS (Netherlands)

    van der Cruijsen, C.A.B.; Eijffinger, S.C.W.; Hoogduin, L.H.

    2008-01-01

    Should central banks increase their degree of transparency any further? We show that there is likely to be an optimal intermediate degree of central bank transparency. Up to this optimum more transparency is desirable: it improves the quality of private sector inflation forecasts. But beyond the

  3. Optimal central bank transparency

    NARCIS (Netherlands)

    van der Cruijsen, C.A.B.; Eijffinger, S.C.W.; Hoogduin, L.

    2008-01-01

    Should central banks increase their degree of transparency any further? We show that there is likely to be an optimal intermediate degree of central bank transparency. Up to this optimum more transparency is desirable: it improves the quality of private sector inflation forecasts. But beyond the

  4. Optimal central bank transparency

    NARCIS (Netherlands)

    van der Cruijsen, C.A.B.; Eijffinger, S.C.W.; Hoogduin, L.H.

    2010-01-01

    Should central banks increase their degree of transparency any further? We show that there is likely to be an optimal intermediate degree of central bank transparency. Up to this optimum more transparency is desirable: it improves the quality of private sector inflation forecasts. But beyond the

  5. Idiopathic central diabetes Insipidus.

    Science.gov (United States)

    Grace, Mary; Balachandran, Venu; Menon, Sooraj

    2011-10-01

    Idiopathic central diabetes insipidus (CDI) is a rare disorder characterized clinically by polyuria and polydipsia, and an abnormal urinary concentration without any identified etiology. We report a case of central diabetes insipidus in a 60-year-old lady in the absence of secondary causes like trauma, infection, and infiltrative disorders of brain.

  6. Central Diffraction in ALICE

    CERN Document Server

    Schicker, R

    2012-01-01

    The ALICE experiment at the Large Hadron Collider (LHC) at CERN consists of a central barrel, a muon spectrometer and of additional detectors for trigger and event classification purposes. The low transverse momentum threshold of the central barrel gives ALICE a unique opportunity to study the low mass sector of central production at the LHC. I will report on first analysis results of meson production in double gap events in minimum-bias proton-proton collisions at sqrt{s} = 7 TeV, and will describe a dedicated double gap trigger for future data taking.

  7. Crustal Growth: In Defense of the Dogma

    Science.gov (United States)

    Albarede, F.; Blichert-Toft, J.; Guitreau, M.

    2012-12-01

    Plate tectonics was not even in its teens when Armstrong suggested that mantle and crust have interacted at steady-state over Earth's history. With the help of new geochemical tools and large-scale compilations, the concept of steady-state crust (as opposed to continuous crustal growth) is being revived with the implications that the equivalent of several volumes of present-day crust (PDCV) may have been subducted through geological times. Here we argue --or recall-- that four different lines of evidence invalidate this model. (i) The subduction filter must be particularly efficient for argon, even more so than for LILE and most other volatile elements. Atmosphere collects 40Ar degassed from both the extant crust and the crust dragged down at subduction zones over geological time. Regardless of the residence time of the crust at the surface, the amount of atmospheric 40Ar limits subduction of continental crust into the mantle to < 30% of the PDCV [1]. (ii) EM II, the only component that undoubtedly represents subducted continental crust in oceanic basalts, is extremely uncommon. (iii) Crustal age histograms are irrepressibly episodic. It has been argued that erosion selectively removes the crust with the elusive ages [2]. Ages of detrital zircons, which in the selective erosion conjecture should fill the voids, do not support this view [3]. Episodicity is difficult to reconcile with a continental protolith isolated by the common geological processes working either at mid-ocean ridges or subduction zones. A role may be recognized for Wilson cycles, if they can be shown to have prevailed for the entire history of the Earth. Geochemistry demonstrates that superplume material makes up the crustal protolith of all the major juvenile provinces. (iv) The residence time in the mantle of the elements distinctive of the crust is similar to the age of the Earth or even longer [4]. Continental crust finds its source in the instabilities of the lower mantle and the irreversible extraction of its low-melting point components, not in the steady-state processing of the rather barren upper mantle. This is why we surmise that steady-state does not provide an adequate account of crustal dynamics. [1] Coltice, N. et al. Science 288 (2000) 845 [2] Gurnies, M. & Davies, G. J. Geol. 14 (1986) 396 [3] Guitreau, M. et al., Earth Planet. Sci. Lettes 337-338 (2012) 211 [4] Albarede, F. AGU Monogr. 160 (2005) 25.

  8. Homogenising time series: beliefs, dogmas and facts

    Science.gov (United States)

    Domonkos, P.

    2011-06-01

    In the recent decades various homogenisation methods have been developed, but the real effects of their application on time series are still not known sufficiently. The ongoing COST action HOME (COST ES0601) is devoted to reveal the real impacts of homogenisation methods more detailed and with higher confidence than earlier. As a part of the COST activity, a benchmark dataset was built whose characteristics approach well the characteristics of real networks of observed time series. This dataset offers much better opportunity than ever before to test the wide variety of homogenisation methods, and analyse the real effects of selected theoretical recommendations. Empirical results show that real observed time series usually include several inhomogeneities of different sizes. Small inhomogeneities often have similar statistical characteristics than natural changes caused by climatic variability, thus the pure application of the classic theory that change-points of observed time series can be found and corrected one-by-one is impossible. However, after homogenisation the linear trends, seasonal changes and long-term fluctuations of time series are usually much closer to the reality than in raw time series. Some problems around detecting multiple structures of inhomogeneities, as well as that of time series comparisons within homogenisation procedures are discussed briefly in the study.

  9. Avoiding measurement dogma: a response to Rossiter

    NARCIS (Netherlands)

    Rigdon, E.E.; Preacher, K.J.; Lee, N.; Howell, R.D.; Franke, G.R.; Borsboom, D.

    2011-01-01

    Purpose - This paper aims to respond to John Rossiter's call for a "Marketing measurement revolution" in the current issue of EJM, as well as providing broader comment on Rossiter's C-OAR-SE framework, and measurement practice in marketing in general. Design/methodology/approach - The paper is

  10. Wnt signaling: Ig-norrin the dogma.

    Science.gov (United States)

    Clevers, Hans

    2004-06-08

    Secreted Wnt proteins trigger the intracellular Wnt signaling cascade upon engagement of dedicated Frizzled-Lrp receptor complexes. Unexpectedly, a non-Wnt ligand for this receptor complex has now been discovered. This novel ligand, Norrin, is mutated in the hereditary ocular Norrie syndrome. Copyright 2004 Elsevier Ltd.

  11. Austin and Quine on the Dogmas

    Czech Academy of Sciences Publication Activity Database

    Tomeček, Marek

    2016-01-01

    Roč. 17, č. 1 (2016), s. 36-48 ISSN 1212-9097 R&D Projects: GA ČR(CZ) GAP401/11/0371 Institutional support: RVO:67985955 Keywords : analytic * a priori * Austin * Quine * reductionism * synthetic Subject RIV: AA - Philosophy ; Religion http://www.phil.muni.cz/journals/index.php/profil/article/view/1452

  12. Upper blepharoplasty : Defying dogmas and clarifying uncertainties

    NARCIS (Netherlands)

    Pool, Shariselle Mirna Wietske

    2016-01-01

    Upper blepharoplasty is one of the most commonly performed procedures by (oculo)plastic surgeons and it is generally recognized as a relatively easy technical procedure. However, seemingly minor aspects before, during and after surgery can be identified that significantly contribute to surgical

  13. "Central Station" Londonis

    Index Scriptorium Estoniae

    2000-01-01

    Londoni galeriis Milch seitsme läti, leedu ja eesti kunstniku projekt "Central Station". Kuraatorid Lisa Panting, Sally Tallant. Eestist osalevad Hanno Soans (Catarina Campinoga koostöös valminud video), Kiwa, Kai Kaljo

  14. The central noradrenergic system

    African Journals Online (AJOL)

    2006-07-27

    Jul 27, 2006 ... recognition of a direct influence of the central noradrenergic system on peripheral ... influences on cerebral function and behavior it is impossible to imagine ... stimuli and to speed-up information processing.4. The influence of ...

  15. Central Asian Republic Info

    Data.gov (United States)

    US Agency for International Development — CAR Info is designed and managed by the Central Asian Republic Mission to fill in the knowledge and reporting gaps in existing agency systems for that Mission. It...

  16. Outsourcing central banking

    DEFF Research Database (Denmark)

    Khoury, Sarkis Joseph; Wihlborg, Clas

    2005-01-01

    The literature on Currency Boards (CB) stops at the water edge in terms of dealing with the totality of the functions of a central bank. Monetary policy, and banking supervisioncan be "outsourced" in an open economy with substantial foreign direct investment (FDI)in the banking sector if political...... nationalism does not trump economic rationality. An orthodox CB renders the central banking function redundant in terms of interest rate and exchange rate determination. FDI in banking could perform the same role for the supervisory function of central banks. We use the case of Estonia to illustrate...... the feasibility of, and constraints on, outsourcing of central bank functions. A brief discussion of the Argentinian experience is used for contrast.Key words: Currency Board, Foreign Banks, Supervision, Regional Integration,outsourcing....

  17. Central nervous system resuscitation

    DEFF Research Database (Denmark)

    McIntosh, T K; Garde, E; Saatman, K E

    1997-01-01

    Traumatic injury to the central nervous system induces delayed neuronal death, which may be mediated by acute and chronic neurochemical changes. Experimental identification of these injury mechanisms and elucidation of the neurochemical cascade following trauma may provide enhanced opportunities...

  18. Central nervous system

    Science.gov (United States)

    The central nervous system is composed of the brain and spinal cord. Your brain and spinal cord serve as the main "processing center" for your entire nervous system. They control all the workings of your body.

  19. Central Pontine Myelinolysis

    Science.gov (United States)

    ... Clinical Trials Organizations Publications Definition Central pontine myelinolysis (CPM) is a neurological disorder that most frequently occurs ... Experts estimate that 10 percent of those with CPM will also have areas of EPM. The initial ...

  20. Central banks: Paradise lost

    OpenAIRE

    Issing, Otmar

    2012-01-01

    The focus of the paper is to analyze how the concept behind central bank policy developed over time and how the recent financial crisis and its consequences will have an influence. While the principles of the institutional arrangement for central banks (independence, clear mandate, prohibition of monetary financing) are relevant as ever, pre- crisis consensus strategies of monetary policy have been revealed as flawed. The close monitoring of money and credit developments, a key lesson to be d...

  1. CENTRAL PLATEAU REMEDIATION

    International Nuclear Information System (INIS)

    ROMINE, L.D.

    2006-01-01

    A systematic approach to closure planning is being implemented at the Hanford Site's Central Plateau to help achieve the goal of closure by the year 2035. The overall objective of Central Plateau remediation is to protect human health and the environment from the significant quantity of contaminated material that resulted from decades of plutonium production in support of the nation's defense. This goal will be achieved either by removing contaminants or placing the residual contaminated materials in a secure configuration that minimizes further migration to the groundwater and reduces the potential for inadvertent intrusion into contaminated sites. The approach to Central Plateau cleanup used three key concepts--closure zones, closure elements, and closure process steps--to create an organized picture of actions required to complete remediation. These actions were merged with logic ties, constraints, and required resources to produce an integrated time-phased schedule and cost profile for Central Plateau closure. Programmatic risks associated with implementation of Central Plateau closure were identified and analyzed. Actions to mitigate the most significant risks are underway while high priority remediation projects continue to make progress

  2. The Naive Central Banker

    Directory of Open Access Journals (Sweden)

    Marcelo de Carvalho Griebeler

    2015-09-01

    Full Text Available There has been in some countries a trend of assigning other functions to central banks besides price stability. The most suggested function to be added to monetary authority’s obligations is to pursue economic growth or full employment. In this paper we characterize the behavior and analyse the optimal monetary policy of, what we call, a naive central banker. We describe the naive behavior as one that does face the inflation-unemployment trade-off, but it tries to minimize both variables simultaneously. Our findings, both under discretion and commitment, indicate that the naive central banker delivers lower expected inflation and inflation variance than the benchmark behavior whenever the economy is rigid enough. However, the degree of conservativeness also affects this result, such that the less conservative the naive policymaker, the more rigidity is necessary.

  3. Colloquium on Central Asia

    International Nuclear Information System (INIS)

    2005-01-01

    This colloquium on Azerbaijan was organized by the direction of international relations of the French Senate and the French center of foreign trade (CFCE). This document gathers the interventions of the participants and the debates with the audience following these interventions. The topics treated concern: - the present day political-economical situation of Central Asia countries (problem of borders, relations with Russia and China); - the economies of Central Asia countries: short term problems and medium-term perspectives; - the relations with the European Union (political, economical, trade and investments, perspectives); - the European energy stakes of Caspian sea (oil and gas reserves, development of hydrocarbon resources, exploitation and transport constraints, stakes for Europe and France); - TotalFinaElf company in Central Asia (Kazakhstan, Azerbaijan, enclavement problem); - the economical impacts of the TRACECA pathway (Transport Corridor Europe Caucasus Asia). (J.S.)

  4. Central Station Design Options

    DEFF Research Database (Denmark)

    2011-01-01

    . The work identifies the architecture, sizing and siting of prospective Central Stations in Denmark, which can be located at shopping centers, large car parking lots or gas stations. Central Stations are planned to be integrated in the Danish distribution grid. The Danish island of Bornholm, where a high...... overloading, more reference points might be necessary to represent various transformer loading levels. The subject of safety in Central Station is also addressed. A number of safety rules based on European standards apply to AC charging equipment up to 44 kW. The connection interlock and the automatic de......-energization are identified as fundamental requirements for safety in such a charging station. The connection interlock is a solution which ensures that no power is applied to the DC cable when the EV connector is not connected. The automatic de-energization device ensures that whenever a strain on the cable is detected, e...

  5. The central nervous system

    International Nuclear Information System (INIS)

    Holmes, R.A.

    1984-01-01

    The first section presents a comprehensive evaluation of radionuclide imaging of the central nervous system and provides a comparison of the detection accuracies of radionuclide imaging (RNI) and XCT in certain lesions, realizing that the XCT results may vary when radiocontrast or newer generation XCT scanners are used. Although conventional radionuclide imaging of the central nervous system has experienced no significant changes over the last 7 years except for mild refinements, a new section has been added on positron emission tomography (PET). Most positron radiopharmaceuticals passively cross the intact blood-brain barrier, and their localization has catalyzed renewed interest in our ability to metabolically study and obtain images of the central nervous system. The section on radionuclide cisternography has been rewritten to reflect present day practice and the wider application of XCT in describing conditions affecting the ventricular system

  6. Atmospheres of central stars

    International Nuclear Information System (INIS)

    Hummer, D.G.

    1978-01-01

    The author presents a brief summary of atmospheric models that are of possible relevance to the central stars of planetary nebulae, and then discusses the extent to which these models accord with the observations of both nebulae and central stars. Particular attention is given to the significance of the very high Zanstra temperature implied by the nebulae He II lambda 4686 A line, and to the discrepancy between the Zanstra He II temperature and the considerably lower temperatures suggested by the appearance of the visual spectrum for some of these objects. (Auth.)

  7. Central Bank independence

    Directory of Open Access Journals (Sweden)

    Vasile DEDU

    2012-08-01

    Full Text Available In this paper we present the key aspects regarding central bank’s independence. Most economists consider that the factor which positively influences the efficiency of monetary policy measures is the high independence of the central bank. We determined that the National Bank of Romania (NBR has a high degree of independence. NBR has both goal and instrument independence. We also consider that the hike of NBR’s independence played an important role in the significant disinflation process, as headline inflation dropped inside the targeted band of 3% ± 1 percentage point recently.

  8. Several Centuries of Centrality

    OpenAIRE

    Dana L. Roth

    2015-01-01

    As Carolyn Bertozzi mentioned in her inaugural editorial, the relationship of “Central Science” to “Chemistry” became popularized over 40 years ago with the publication of the first edition of Brown and LeMay’s Chemistry: The Central Science, now in its 13th edition. Yet as late as 2003, Prof. Sason Shaik at The Hebrew University claimed “popularization of chemistry remains scant.” He goes on to share [his] “own experience of popularizing chemistry by delivering the following universal messag...

  9. Central Venous Access

    International Nuclear Information System (INIS)

    Ganeshan, Arul; Warakaulle, Dinuke R.; Uberoi, Raman

    2007-01-01

    Central venous access plays an important role in the management of an ever-increasing population of patients ranging from those that are critically ill to patients with difficult clinical access. Interventional radiologists are key in delivering this service and should be familiar with the wide range of techniques and catheters now available to them. A comprehensive description of these catheters with regard to indications, technical aspects of catheterization, success rates, and associated early and late complications, as well as a review of various published guidelines on central venous catheter insertion are given in this article

  10. Centralized mouse repositories.

    Science.gov (United States)

    Donahue, Leah Rae; Hrabe de Angelis, Martin; Hagn, Michael; Franklin, Craig; Lloyd, K C Kent; Magnuson, Terry; McKerlie, Colin; Nakagata, Naomi; Obata, Yuichi; Read, Stuart; Wurst, Wolfgang; Hörlein, Andreas; Davisson, Muriel T

    2012-10-01

    Because the mouse is used so widely for biomedical research and the number of mouse models being generated is increasing rapidly, centralized repositories are essential if the valuable mouse strains and models that have been developed are to be securely preserved and fully exploited. Ensuring the ongoing availability of these mouse strains preserves the investment made in creating and characterizing them and creates a global resource of enormous value. The establishment of centralized mouse repositories around the world for distributing and archiving these resources has provided critical access to and preservation of these strains. This article describes the common and specialized activities provided by major mouse repositories around the world.

  11. Hydrogen peroxide and central redox theory for aerobic life: A tribute to Helmut Sies: Scout, trailblazer, and redox pioneer.

    Science.gov (United States)

    Jones, Dean P

    2016-04-01

    When Rafael Radi and I wrote about Helmut Sies for the Redox Pioneer series, I was disappointed that the Editor restricted us to the use of "Pioneer" in the title. My view is that Helmut was always ahead of the pioneers: He was a scout discovering paths for exploration and a trailblazer developing strategies and methods for discovery. I have known him for nearly 40 years and greatly enjoyed his collegiality as well as brilliance in scientific scholarship. He made monumental contributions to 20th century physiological chemistry beginning with his first measurement of H2O2 in rat liver. While continuous H2O2 production is dogma today, the concept of H2O2 production in mammalian tissues was largely buried for half a century. He continued this leadership in research on oxidative stress, GSH, selenium, and singlet oxygen, during the timeframe when physiological chemistry and biochemistry transitioned to contemporary 21st century systems biology. His impact has been extensive in medical and health sciences, especially in nutrition, aging, toxicology and cancer. I briefly summarize my interactions with Helmut, stressing our work together on the redox code, a set of principles to link mitochondrial respiration, bioenergetics, H2O2 metabolism, redox signaling and redox proteomics into central redox theory. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

  12. Centralized vs. de-centralized multinationals and taxes

    OpenAIRE

    Nielsen, Søren Bo; Raimondos-Møller, Pascalis; Schjelderup, Guttorm

    2005-01-01

    The paper examines how country tax differences affect a multinational enterprise's choice to centralize or de-centralize its decision structure. Within a simple model that emphasizes the multiple conflicting roles of transfer prices in MNEs – here, as a strategic pre-commitment device and a tax manipulation instrument –, we show that (de-)centralized decisions are more profitable when tax differentials are (small) large. Keywords: Centralized vs. de-centralized decisions, taxes, MNEs. ...

  13. CMS Central Hadron Calorimeter

    OpenAIRE

    Budd, Howard S.

    2001-01-01

    We present a description of the CMS central hadron calorimeter. We describe the production of the 1996 CMS hadron testbeam module. We show the results of the quality control tests of the testbeam module. We present some results of the 1995 CMS hadron testbeam.

  14. Ecodesign in Central America

    NARCIS (Netherlands)

    Crul, M.R.M.

    2003-01-01

    This PhD thesis describes and analyses the change process started by the Ecodesign project in Central America, executed between 1998 and 2002. The project started using the concept and praxis developed in Europe. Nine ecodesign projects were performed in industry, and ecodesign was introduced to

  15. NCEP Central Operations

    Science.gov (United States)

    ) NCO Organizational Chart NOAA's Weather and Climate Operational Supercomputing System is known as Climate Climate Prediction Climate Archives Weather Safety Storm Ready NOAA Central Library Photo Library NCO's MISSION * Execute the NCEP operational model suite - Create climate, weather, ocean, space and

  16. Central oxygen pipeline failure

    African Journals Online (AJOL)

    surgical intensive care unit (ICU), with two patients on full ventilation and ... uncertainty around the cause of the failure and the restoration, .... soon as its level also falls below three tons. Should ... (properly checked and closed prior to each anaesthetic). ... in use at the time of the central oxygen pipeline failure at Tygerberg.

  17. Central American Climatology

    Science.gov (United States)

    1985-04-01

    Central America, as where mean temperatures are relatively warm throughout the year de- so spite seasonal rainfall changes. 75 Elevation, solar angle...November 1982 Control Hidalgo Anos.1952-1963, Republica de Nicaragua, Ministerio de Formento Y O0.PP, Comision Nacional de Energia . Craig, Richard A., The

  18. Centrality and Creativity:

    DEFF Research Database (Denmark)

    Andersen, Kristina Vaarst; Lorenzen, Mark

    2009-01-01

    To provide new insights into urban hierarchy, this article brings together one of economic geography’s oldest and most well-established notions with one of its newest and most disputed notions: Christäller’s centrality and Florida’s creative class. Using a novel original database, the article...... compares the distribution of the general population and the creative class across 444 city regions in 8 European countries. It finds that the two groups are both distributed according to the rank-size rule, but exhibit different distinct phases with different slopes. The article argues that the two...... distributions are different because market thresholds for creative services and jobs are lower than thresholds for less specialized services and jobs. The article hence concludes that centrality exerts a strong influence upon urban hierarchies of creativity and that the study of creative urban city hierarchies...

  19. Central American Flying Weather

    Science.gov (United States)

    1985-12-01

    CEILING; VISIBILITY; WIND, PRECIPITATIDNc’--." HAZE, SMOKE, TEMPORALE ; MOUNTAIN WAVE; MILITARY METEOROLOGY. 4k- / ’A. bstract; Asummary of~ing weather...1 The " Temporale " ....................................1 Mountain Waves ......................I...............1 Severe Thunderstorms...charts. The for any part of Central America lies in having: Tactical Pilota.e Chart series , produced by the Df -.nse Mapping Agency, is * A good, basic

  20. The European Central Bank

    OpenAIRE

    Binder, Michael; Wieland, Volker

    2006-01-01

    The establishment of the ECB and with it the launch of the euro has arguably been a unique endeavor in economic history, representing an important experiment in central banking. This note aims to summarize some of the main lessons learned from this experiment and sketch some of the prospects for the ECB. It is written for "The New Palgrave Dictionary of Economics", 2nd edition. JEL Classification: E52, E58

  1. FNAL central email systems

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Jack; Lilianstrom, Al; Pasetes, Ray; Hill, Kevin; /Fermilab

    2004-10-01

    The FNAL Email System is the primary point of entry for email destined for an employee or user at Fermilab. This centrally supported system is designed for reliability and availability. It uses multiple layers of protection to help ensure that: (1) SPAM messages are tagged properly; (2) All mail is inspected for viruses; and (3) Valid mail gets delivered. This system employs numerous redundant subsystems to accomplish these tasks.

  2. Centrally Banked Cryptocurrencies

    OpenAIRE

    Danezis, George; Meiklejohn, Sarah

    2015-01-01

    Current cryptocurrencies, starting with Bitcoin, build a decentralized blockchain-based transaction ledger, maintained through proofs-of-work that also generate a monetary supply. Such decentralization has benefits, such as independence from national political control, but also significant limitations in terms of scalability and computational cost. We introduce RSCoin, a cryptocurrency framework in which central banks maintain complete control over the monetary supply, but rely on a distribut...

  3. Centrally Banked Cryptocurrencies

    OpenAIRE

    Danezis, G.; Meiklejohn, S.

    2016-01-01

    Current cryptocurrencies, starting with Bitcoin, build a decentralized blockchain-based transaction ledger, maintained through proofs-of-work that also serve to generate a monetary supply. Such decentralization has benefits, such as independence from national political control, but also significant limitations in terms of computational costs and scalability. We introduce RSCoin, a cryptocurrency framework in which central banks maintain complete control over the monetary supply, but rely on...

  4. Centralized vs decentralized contests

    OpenAIRE

    Beviá, Carmen; Corchón, Luis C.

    2015-01-01

    We compare two contests, decentralized in which there are several independent contests with non overlapping contestants and centralized in which all contestants fight for a unique prize which is the sum of all prizes in the small contests. We study the relationship between payoffs and efforts between these two contests. The first author acknowledges financial support from ECO2008-04756 (Grupo Consolidado-C), SGR2014-515 and PROMETEO/2013/037. The second author acknowledges financial suppor...

  5. Centralized versus distributed propulsion

    Science.gov (United States)

    Clark, J. P.

    1982-01-01

    The functions and requirements of auxiliary propulsion systems are reviewed. None of the three major tasks (attitude control, stationkeeping, and shape control) can be performed by a collection of thrusters at a single central location. If a centralized system is defined as a collection of separated clusters, made up of the minimum number of propulsion units, then such a system can provide attitude control and stationkeeping for most vehicles. A distributed propulsion system is characterized by more numerous propulsion units in a regularly distributed arrangement. Various proposed large space systems are reviewed and it is concluded that centralized auxiliary propulsion is best suited to vehicles with a relatively rigid core. These vehicles may carry a number of flexible or movable appendages. A second group, consisting of one or more large flexible flat plates, may need distributed propulsion for shape control. There is a third group, consisting of vehicles built up from multiple shuttle launches, which may be forced into a distributed system because of the need to add additional propulsion units as the vehicles grow. The effects of distributed propulsion on a beam-like structure were examined. The deflection of the structure under both translational and rotational thrusts is shown as a function of the number of equally spaced thrusters. When two thrusters only are used it is shown that location is an important parameter. The possibility of using distributed propulsion to achieve minimum overall system weight is also examined. Finally, an examination of the active damping by distributed propulsion is described.

  6. Solar thermal central receivers

    International Nuclear Information System (INIS)

    Vant-Hull, L.L.

    1993-01-01

    Market issues, environmental impact, and technology issues related to the Solar Central Receiver concept are addressed. The rationale for selection of the preferred configuration and working fluid are presented as the result of a joint utility-industry analysis. A $30 million conversion of Solar One to an external molten salt receiver would provide the intermediate step to a commercial demonstration plant. The first plant in this series could produce electricity at 11.2 cents/kWhr and the seventh at 8.2 cents/kWhr, completely competitive with projected costs of new utility plants in 1992

  7. Central osteosclerosis with trichothiodystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Wakeling, Emma L.; Brady, Angela F. [North West Thames Regional Genetics Service, Kennedy-Galton Centre, Level 8 V, North West London Hospitals NHS Trust, Watford Road, HAI 3UJ, Harrow, Middlesex (United Kingdom); Cruwys, Michele [Department of Paediatrics, Hillingdon Hospital, Hillingdon, Middlesex (United Kingdom); Suri, Mohnish [Clinical Genetics Service, City Hospital, Nottingham (United Kingdom); Aylett, Sarah E. [Neurosciences Unit, Great Ormond Street Hospital for Children NHS Trust, London (United Kingdom); Hall, Christine [Department of Radiology, Great Ormond Street Hospital for Children NHS Trust, London (United Kingdom)

    2004-07-01

    Trichothiodystrophy (TTD) is a rare, autosomal recessive, multisystem disorder associated with defects in nucleotide excision repair. We report a 7-year-old boy with TTD due to mutation in the XPD gene. The patient has classic features of this condition, including brittle, sulphur-deficient hair, ichthyosis, growth retardation and developmental delay. In addition, he has radiological evidence of progressive central osteosclerosis. Although similar radiological findings have previously been reported in a small number of patients, this association is not widely recognised. We review the radiological findings in this and other similar cases and discuss the natural history of these bony changes. (orig.)

  8. Central nervous system tumors

    International Nuclear Information System (INIS)

    Curran, W.J. Jr.

    1991-01-01

    Intrinsic tumors of the central nervous system (CNS) pose a particularly challenging problem to practicing oncologists. These tumors rarely metastasize outside the CNS, yet even histologically benign tumors can be life-threatening due to their local invasiveness and strategic location. The surrounding normal tissues of the nervous system is often incapable of full functional regeneration, therefore prohibiting aggressive attempts to use either complete surgical resection or high doses of irradiation. Despite these limitations, notable achievements have recently been recorded in the management of these tumors

  9. Decentralized central heating

    Energy Technology Data Exchange (ETDEWEB)

    Savic, S.; Hudjera, A.

    1994-08-04

    The decentralized central heating is essentially based on new technical solutions for an independent heating unit, which allows up to 20% collectible energy savings and up to 15% savings in built-in-material. These savings are already made possible by the fact that the elements described under point A are thus eliminated from the classical heating. The thus superfluous made elements are replaced by new technical solutions described under point B - technical problem - and point E - patent claim. The technical solutions described in detail under point B and point E form together a technical unit and are essential parts of the invention protected by the patent. (author)

  10. Central Hypothyroidism in Miniature Schnauzers

    NARCIS (Netherlands)

    Voorbij, Annemarie M W Y; Leegwater, Peter A J; Buijtels, Jenny J C W M; Daminet, Sylvie; Kooistra, Hans S

    2016-01-01

    BACKGROUND: Primary hypothyroidism is a common endocrinopathy in dogs. In contrast, central hypothyroidism is rare in this species. OBJECTIVES: The objective of this article is to describe the occurrence and clinical presentation of central hypothyroidism in Miniature Schnauzers. Additionally, the

  11. Central Banking after the Crisis

    OpenAIRE

    Frederick S. Mishkin

    2013-01-01

    This paper explores where central banking is heading after the recent financial crisis. First it discusses the central bank consensus before the crisis and then outlines the key facts learned from the crisis that require changes in the way central banks conduct their business. Finally, it discusses four main areas in which central banks are altering their policy frameworks: 1) the interaction between monetary and financial stability policies, 2) nonconventional monetary policy, 3) risk manage...

  12. Central ignition scenarios for TFTR

    International Nuclear Information System (INIS)

    Zweben, S.J.; Redi, M.H.; Bateman, G.

    1986-03-01

    The possibility of obtaining ignition in TFTR by means of very centrally peaked density profiles is examined. It is shown that local central alpha heating can be made to exceed local central energy losses (''central ignition'') under global conditions for which Q greater than or equal to 1. Time dependent 1-D transport simulations show that the normal global ignition requirements are substantially relaxed for plasmas with peaked density profiles. 18 refs., 18 figs

  13. The central Iowa project.

    Science.gov (United States)

    Allen, H M

    1994-10-01

    This project developed and tested a population-based survey, the HS Form, to examine health and health care in the Central Iowa community. Data from this new collection of proven sets of items were used to compare competing health plans, doctor offices, hospitals, and to develop preliminary norms of the community's insured, in two areas: system performance and health burden. The results showed that the survey: (1) was both feasible and efficient in delivering a comprehensive and generic assessment of consumers and patients; (2) revealed consistent, noteworthy differences between plans and between providers across both sets of criteria; and (3) indicated that there is substantial room for improvement in Central Iowa's health care delivery system from the public's perspective. Recommendations for next steps include: (1) following through on the June 1993 community forum (held to discuss the project's methods and results with local decision makers); (2) broadening the evaluation design to increase sample representativeness; and (3) implementing a pre/post approach to measure changes in plan and provider performance.

  14. Alpha current flow betweenness centrality

    NARCIS (Netherlands)

    Avrachenkov, K.; Litvak, Nelli; Medyanikov, V.; Sokol, M.

    2013-01-01

    A class of centrality measures called betweenness centralities reflects degree of participation of edges or nodes in communication between different parts of the network. The original shortest-path betweenness centrality is based on counting shortest paths which go through a node or an edge. One of

  15. Orden monetario y bancos centrales Monetary order and Central Banks

    Directory of Open Access Journals (Sweden)

    Aglietta Michel

    1996-06-01

    Full Text Available Con el enfoque evolucionista e institucionalista de la economía de las convenciones francesa, este trabajo analiza el surgimiento histórico de la banca central y la creación institucional del 'arte de la banca central'. El artículo estudia los modelos formales del orden monetario, la banca libre y la banca central, y analiza los eventos históricos que llevaron a que el Banco de Inglaterra inventara el arte de manejar los bancos centrales en conjunción con el aprendizaje colectivo e institucional que lo hizo posible. Aglietta muestra que la banca central no es una creación del Estado sino una creación institucional endógena al sistema de mercado.With the evolutionist and institutionalist focus of the economics of the French conventions, this paper analyzes the historical rise of the central bank and the institutional creation of the 'art of the central bank'. The article studies formal models of the monetary order, free banking and the central bank, and analyzes the historie events that led to the Bank of England inventing the art of managing the central banks, in conjunction with the collective and institutional learning that made it possible. Aglietta shows that the central bank is not a creation of the State, but rather aninstitutional creation endogenous to the market system.

  16. Adult central nervous system

    International Nuclear Information System (INIS)

    Sutton, M.L.

    1985-01-01

    Historically, the adult central nervous system (CNS) was regarded as relatively immune to the effects of ionising radiation, and the recognition of the CNS as a radio-vulnerable structure occurred later than was the case for many other tissues. Increasingly precise knowledge of the time-dose-volume relationships for CNS tolerance has had two important consequences: (1) it has permitted the avoidance of catastrophic and usually lethal late effects in the brain and spinal cord when these tissues are unavoidably irradiated during the treatment of adjacent non-CNS tumours, and (2) it has encouraged referral for irradiation of certain technically benign lesions which, although compatible with prolonged survival, represent a continuing threat to the patient - for example arteriovenous malformations, pituitary adenomas, and some meningiomas. Many of these can now be controlled for very long periods following radiation doses consistent with the long-term functional integrity of the CNS

  17. UA2 central calorimeter

    CERN Multimedia

    The UA2 central calorimeter measured the energy of individual particles created in proton-antiproton collisions. Accurate calibration allowed the W and Z masses to be measured with a precision of about 1%. The calorimeter had 24 slices like this one, each weighing 4 tons. The slices were arranged like orange segments around the collision point. Incoming particles produced showers of secondary particles in the layers of heavy material. These showers passed through the layers of plastic scintillator, generating light which was taken by light guides (green) to the data collection electronics. The amount of light was proportional to the energy of the original particle. The inner 23 cm of lead and plastic sandwiches measured electrons and photons; the outer 80 cm of iron and plastic sandwiches measured strongly interacting hadrons. The detector was calibrated by injecting light through optical fibres or by placing a radioactive source in the tube on the bottom edge.

  18. CENTRAL EUROPE: Austron

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    For many of the countries of Central and Eastern Europe access to international research centres such as CERN, the European Space Agency (ESA), the Institut Laue-Langevin (ILL) or to national centres such as the Rutherford Appleton Laboratory in the UK or DESY in Germany, is hindered by the absence of intermediate research institutions. Since mid-1990 this question has been studied by an 'Austron' Study Group set up under the auspices of the Austrian Academy of Sciences and which cooperates with the so-called 'Pentagonal' initiative of Austria, Czechoslovakia, Hungary, Italy and Yugoslavia to promote cooperation in the area, with which Poland is now associated

  19. Central Accountability System (CLAS)

    International Nuclear Information System (INIS)

    Hairston, L.A.

    1991-01-01

    The Central Accountability System (CLAS) is a high level accountability system that consolidates data from the site's 39 material balance areas (MBA) for reporting to Westinghouse Savannah River Company (WSRC) management, Department of Energy (DOE) and the Nuclear Materials Management and Safeguards System (NMMSS) in Oak Ridge, TN. Development of the system began in 1989 and became operational in April, 1991. The CLAS system enhances data accuracy and accountability records, resulting in increased productivity and time and cost savings. This paper reports that the system is in compliance with DOE Orders and meets NMMSS reporting requirements. WSRC management is provided with the overall status of the site's nuclear material inventory. CLAS gives WSRC a leading edge in accounting technology and enhances good accounting practices

  20. Central America's shrinking forests.

    Science.gov (United States)

    1992-01-01

    This news brief reports that 66% of deforestation in Central America has happened in the past 40 years, based on World Conservation Union (WCU) data. Deforestation is expected to continue. The population of Central America and Mexico grew by 28% between 1977 and 1987. Growth is decreasing but remains high at 2.5% in all countries of the region except Panama. 29 million was the regional population in 1990; the projection is for 63 million by 2025. Population is migrating to urban centers. Forests declined by 13% and croplands increased from 4% to 13% of total land area and pasture land from 2% to 37%. There was an increase in unproductive land from 145 to 24%, i.e., 50% of El Salvador's land had soil degradation as does 30% of Guatemala's. In addition to deforestation and soil degradation, there has been soil erosion leading to sedimentation buildup near dam sites and in rivers, which diminishes hydroelectric power capability. Silting also affects groundwater resources, which impact on a safe drinking water supply. Population growth results in increased demand for fuelwood, urban land, and agricultural land. New techniques practiced widely are needed in order to meet the region's needs or demands. Slowing population growth buys time for adjusting to the necessary changes needed for sustaining the region's population. WCU urges conservation organizations to raise awareness about the role population plays in environmental degradation, and to support efforts to reduce birth rates. Women's status needs to be improved through income-generating projects, for instance, and cooperation is needed between conservation groups and organizations involved with improving maternal and child health.

  1. Central control of thermogenesis.

    Science.gov (United States)

    Clapham, John C

    2012-07-01

    In mammals and birds, conservation of body heat at around 37 °C is vital to life. Thermogenesis is the production of this heat which can be obligatory, as in basal metabolic rate, or it can be facultative such as the response to cold. A complex regulatory system has evolved which senses environmental or core temperature and integrates this information in hypothalamic regions such as the preoptic area and dorsomedial hypothalamus. These areas then send the appropriate signals to generate and conserve heat (or dissipate it). In this review, the importance of the sympathetic nervous system is discussed in relation to its role in basal metabolic rate and adaptive thermogenesis with a particular emphasis to human obesity. The efferent sympathetic pathway does not uniformly act on all tissues; different tissues can receive different levels of sympathetic drive at the same time. This is an important concept in the discussion of the pharmacotherapy of obesity. Despite decades of work the medicine chest contains only one pill for the long term treatment of obesity, orlistat, a lipase inhibitor that prevents the absorption of lipid from the gut and is itself not systemically absorbed. The central controlling system for thermogenesis has many potential intervention points. Several drugs, previously marketed, awaiting approval or in the earlier stages of development may have a thermogenic effect via activation of the sympathetic nervous system at some point in the thermoregulatory circuit and are discussed in this review. If the balance is weighted to the "wrong" side there is the burden of increased cardiovascular risk while a shift to the "right" side, if possible, will afford a thermogenic benefit that is conducive to weight loss maintenance. This article is part of a Special Issue entitled 'Central Control Food Intake' Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. SECURITY THREATS IN CENTRAL ASIA

    Directory of Open Access Journals (Sweden)

    Çağla Gül Yesevi

    2013-07-01

    Full Text Available This study will analyze main security threats in Central Asia. It is obvious thatsince the end of Cold War, there have been many security threats in Central Asiaas internal weakness of Central Asian states, terrorism, transnational crime,economic insecurity, environmental issues, drug trafficking, ethnic violence,regional instability. This study will propose thatwith increasing interdependence,states need each other to solve these global security problems. In that sense,regional and sub-regional cooperation between Central Asian states and with otherregional actors has been witnessed. It is clear that the withdrawal of NATO fromAfghanistan will destabilize Central Asia. This study will investigate overallsecurity situation in Central Asia and affects andcontributions of regionalorganizations to Eurasian security

  3. Mexico and Central America.

    Science.gov (United States)

    Bronfman, M

    1998-01-01

    This article reviews the literature on migration and HIV/AIDS in Mexico and Central America, including Belize, Costa Rica, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, and Panama. Most migrants travel to the US through Mexico. US-Mexico trade agreements created opportunities for increased risk of HIV transmission. The research literature focuses on Mexico. Most countries, with the exception of Belize and Costa Rica, are sending countries. Human rights of migrants are violated in transit and at destination. Migration policies determine migration processes. The Mexican-born population in the US is about 3% of US population and 8% of Mexico's population. About 22% arrived during 1992-97, and about 500,000 are naturalized US citizens. An additional 11 million have a Mexican ethnic background. Mexican migrants are usually economically active men who had jobs before leaving and were urban people who settled in California, Texas, Illinois, and Arizona. Most Mexican migrants enter illegally. Many return to Mexico. The main paths of HIV transmission are homosexual, heterosexual, and IV-drug-injecting persons. Latino migrants frequently use prostitutes, adopt new sexual practices including anal penetration among men, greater diversity of sexual partners, and use of injectable drugs.

  4. CENTRAL EUROPE: Role models

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1993-12-15

    Hungary is one of the newcomers to the CERN fold, having joined in 1992. The country's contributions are naturally in line with its slender resources and are not as immediately visible as those of the major Western European Member States. However the approach used and its consequent successes provide a good role model for a smaller nation in an international research environment. This was reflected on 24 September at a meeting of the European Committee for Future Accelerators (ECFA) convened in Budapest, continuing an ECFA tradition of holding meetings in national centres to learn more about the physics programmes of different countries. This tradition started with visits to major West European Centres, but last year ECFA held a meeting in Warsaw, its first in a central European country. By far the largest Hungarian population centre, Budapest is also a hub for national research in this sector, with university centres and the KFKI Research Institute for Particle and Nuclear Physics of the National Academy of Sciences. However important research work is also carried out in the eastern city of Debrecen. Hungarians look back to the classic investigations of Eotvos early this century as the starting point of their national tradition in fundamental physics. (In the mid-80s, these experiments briefly came back into vogue when there was a suggestion of an additional 'fifth force' contribution to nuclear masses.)

  5. CENTRAL EUROPE: Role models

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    Hungary is one of the newcomers to the CERN fold, having joined in 1992. The country's contributions are naturally in line with its slender resources and are not as immediately visible as those of the major Western European Member States. However the approach used and its consequent successes provide a good role model for a smaller nation in an international research environment. This was reflected on 24 September at a meeting of the European Committee for Future Accelerators (ECFA) convened in Budapest, continuing an ECFA tradition of holding meetings in national centres to learn more about the physics programmes of different countries. This tradition started with visits to major West European Centres, but last year ECFA held a meeting in Warsaw, its first in a central European country. By far the largest Hungarian population centre, Budapest is also a hub for national research in this sector, with university centres and the KFKI Research Institute for Particle and Nuclear Physics of the National Academy of Sciences. However important research work is also carried out in the eastern city of Debrecen. Hungarians look back to the classic investigations of Eotvos early this century as the starting point of their national tradition in fundamental physics. (In the mid-80s, these experiments briefly came back into vogue when there was a suggestion of an additional 'fifth force' contribution to nuclear masses.)

  6. Big Data and central banks

    OpenAIRE

    David Bholat

    2015-01-01

    This commentary recaps a Centre for Central Banking Studies event held at the Bank of England on 2–3 July 2014. The article covers three main points. First, it situates the Centre for Central Banking Studies event within the context of the Bank’s Strategic Plan and initiatives. Second, it summarises and reflects on major themes from the event. Third, the article links central banks’ emerging interest in Big Data approaches with their broader uptake by other economic agents.

  7. Centralized vs. De-centralized Multinationals and Taxes

    DEFF Research Database (Denmark)

    Nielsen, Søren Bo; Raimondos-Møller, Pascalis; Schjelderup, Guttorm

    2005-01-01

    The paper examines how country tax differences affect a multinational enterprise's choice to centralize or de-centralize its decision structure. Within a simple model that emphasizes the multiple conflicting roles of transfer prices in MNEs - here, as a strategic pre-commitment device and a tax...

  8. The Regional Centrality of Vietnam’s Central Highlands

    DEFF Research Database (Denmark)

    Salemink, Oscar

    2018-01-01

    strategic value turned it into a battleground among various Vietnamese parties, France, and the United States. It was here that the outcome of the Indochina wars was determined, but at a terrible price for the local population. After the adoption of economic reforms in reunified Vietnam the Central......Vietnam’s Central Highlands—or Tây Nguyên—area is usually described as remote, backward, and primitive, but this region has played a central role in the history of the surrounding states and the wider East and Southeast Asia region. Far from isolated, the Central Highlands engaged in trade...... various rivalrous polities now known as Vietnam, Champa, Cambodia, Laos, and Thailand, the area occupied a strategic position in the wider mainland Southeast Asia region. With the emergence of a unified, neo-Confucianist Vietnamese state the region lost its centrality until the late colonial era, when its...

  9. Central nervous system tumors

    International Nuclear Information System (INIS)

    Gavin, P.R.; Fike, J.R.; Hoopes, P.J.

    1995-01-01

    Central nervous system (CNS) tumors are relatively common in veterinary medicine, with most diagnoses occurring in the canine and feline species. Numerous tumor types from various cells or origins have been identified with the most common tumors being meningiomas and glial cell tumors. Radiation therapy is often used as an aid to control the clinical signs associated with these neoplasms. In general, these tumors have a very low metastatic potential, such that local control offers substantial benefit. Experience in veterinary radiation oncology would indicate that many patients benefit from radiation treatment. Current practice indicates the need for computed tomography or magnetic resonance imaging studies. These highly beneficial studies are used for diagnosis, treatment planning, and to monitor treatment response. Improvements in treatment planning and radiation delivered to the tumor, while sparing the normal tissues, should improve local control and decrease potential radiation related problems to the CNS. When possible, multiple fractions of 3 Gy or less should be used. The tolerance dose to the normal tissue with this fractionation schedule is 50 to 55 Gy. The most common and serious complications of radiation for CNS tumors is delayed radiation myelopathy and necrosis. Medical management of the patient during radiation therapy requires careful attention to anesthetic protocols, and medications to reduce intracranial pressure that is often elevated in these patients. Canine brain tumors have served as an experimental model to test numerous new treatments. Increased availability of advanced imaging modalities has spawned increased detection of these neoplasms. Early detection of these tumors with appropriate aggressive therapy should prove beneficial to many patients

  10. Dublin South Central (DSC)

    LENUS (Irish Health Repository)

    O'Gorman, Clodagh S M

    2010-12-01

    Children who appear healthy, even if they have one or more recognized cardiovascular risk factors, do not generally have outcomes of cardiovascular or other vascular disease during childhood. Historically, pediatric medicine has not aggressively screened for or treated cardiovascular risk factors in otherwise healthy children. However, studies such as the P-Day Study (Pathobiological Determinants of Atherosclerosis in Youth), and the Bogalusa Heart Study, indicate that healthy children at remarkably young ages can have evidence of significant atherosclerosis. With the increasing prevalence of pediatric obesity, can we expect more health problems related to the consequences of pediatric dyslipidemia, hypertriglyceridemia, and atherosclerosis in the future? For many years, medications have been available and used in adult populations to treat dyslipidemia. In recent years, reports of short-term safety of some of these medications in children have been published. However, none of these studies have detailed long-term follow-up, and therefore none have described potential late side-effects of early cholesterol-lowering therapy, or potential benefits in terms of reduction of or delay in cardiovascular or other vascular end-points. In 2007, the American Heart Association published a scientific statement on the use of cholesterol-lowering therapy in pediatric patients. In this review paper, we discuss some of the current literature on cholesterol-lowering therapy in children, including the statins that are currently available for use in children, and some of the cautions with using these and other cholesterol-lowering medications. A central tenet of this review is that medications are not a substitute for dietary and lifestyle interventions, and that even in children on cholesterol-lowering medications, physicians should take every opportunity to encourage children and their parents to make healthy diet and lifestyle choices.

  11. Central African Republic.

    Science.gov (United States)

    1989-11-01

    The Central African Republic contains 242,000 square miles, which rolling terrain almost 2000 feet above sea level. The climate is tropical, and it has a population of 2.8 million people with a 2.5% growth rate. There are more than 80 ethnic groups including Baya 34%, Banda 28%, Sara 10%, Mandja 9%, Mboum 9%, and M'Baka 7%. The religions are traditional African 35%, protestant 25%, Roman Catholic 25%, and Muslim 15%, and the languages are French and Sangho. The infant mortality rate is 143/1000, with expectancy at 49 years and a 40% literacy rate. The work force of 1 million is 70% agricultural, industry 6% and commerce and service 6% and government 3%. The government consists of a president assisted by cabinet ministers and a single party. Natural resources include diamonds, uranium, timber, gold, and oil, and major industries are beverages, textiles, and soap. Agricultural products feature coffee, cotton, peanuts, tobacco, food crops and livestock. Most of the population live in rural areas and most of the 80 ethnic groups have their own language. This is one of the world's least developed countries, with a per capita income of $375/year. The main problems with development are the poor transportation infrastructure, and the weak internal and international marketing systems. The US and various international organizations have aided in agriculture development, health programs, and family planning. US investment is mainly in diamond and gold mining, and although oil drilling has been successful it is not economically feasible at current prices.

  12. O dogma da formalidade visível e inoperante ante a constatação necessária de medidas reais ao combate da violência contra a mulher: Lei Maria da Penha (da igualdade formal à igualdade real-material

    Directory of Open Access Journals (Sweden)

    Denigelson da Rosa Ismael

    2010-12-01

    Full Text Available A violência contra a mulher no Brasil é um mal que atravessa os séculos. Está enraizada em uma retrógrada imagem em que a mulher era fantoche do homem, e, mesmo com a Declaração dos Direitos Humanos, o advento da Constituição Federal de 1988 e com tantos Tratados e Convenções Internacionais ratificados pelo Brasil, o quadro continua inerte. No intuito de inibir a violência afetiva, familiar e doméstica contra a mulher, foi promulgada, em 2006, a Lei Maria da Penha, caracterizada, principalmente, pela sua dúplice função proteção/coibição. Todavia, como se trata de uma lei amparada em uma ação afirmativa que impõe medidas de diferenciação, muito se tem discutido a respeito de sua constitucionalidade. Portanto, o presente estudo propõe-se a construir uma reflexão, analisando os mecanismos de proteção à mulher inseridos no corpo da Lei Maria da Penha, como institutos reais de combate ao dogma da igualdade formal visível (existente e inoperante, possibilitando alcançar à mulher um esboço da igualdade real-material. Palavras-chave: Violência contra mulher. Lei Maria da Penha. Igualdade formal. Igualdade real-material. Constitucionalidade.

  13. Geometric origin of central charges

    International Nuclear Information System (INIS)

    Lukierski, J.; Rytel, L.

    1981-05-01

    The complete set of N(N-1) central charge generators for D=4 N-extended super Poincare algebra is obtained by suitable contraction of OSp (2N; 4) superalgebra. The superspace realizations of the spinorial generators with central charges are derived. The conjugate set of N(N-1) additional bosonic superspace coordinates is introduced in an unique and geometric way. (author)

  14. Controlling centrality in complex networks

    Science.gov (United States)

    Nicosia, V.; Criado, R.; Romance, M.; Russo, G.; Latora, V.

    2012-01-01

    Spectral centrality measures allow to identify influential individuals in social groups, to rank Web pages by popularity, and even to determine the impact of scientific researches. The centrality score of a node within a network crucially depends on the entire pattern of connections, so that the usual approach is to compute node centralities once the network structure is assigned. We face here with the inverse problem, that is, we study how to modify the centrality scores of the nodes by acting on the structure of a given network. We show that there exist particular subsets of nodes, called controlling sets, which can assign any prescribed set of centrality values to all the nodes of a graph, by cooperatively tuning the weights of their out-going links. We found that many large networks from the real world have surprisingly small controlling sets, containing even less than 5 – 10% of the nodes. PMID:22355732

  15. Central presbycusis: an emerging view.

    Science.gov (United States)

    Gates, George A

    2012-07-01

    Age-related dysfunction of the central auditory system (central presbycusis) is common but rarely looked for by those who provide aural rehabilitation. Patients who complain of difficulty hearing in noise--the key symptom of central presbycusis--are generally disadvantaged with conventional rehabilitation. This symptom should be documented with commercially available speech-in-noise tests, which use materials that are uncomplicated to administer. Those patients who perform poorly on such tests should have a customized rehabilitation program aimed at optimizing their remaining communication abilities. Otolaryngologists who provide auditory rehabilitation may wish to consider expanding their practices to meet the communication needs of older patients with central presbycusis. Central presbycusis is an emerging area for basic and clinical research in auditory neurotology, particularly in the relation of cognitive dysfunction to impaired auditory processing.

  16. Central control of body temperature.

    Science.gov (United States)

    Morrison, Shaun F

    2016-01-01

    Central neural circuits orchestrate the behavioral and autonomic repertoire that maintains body temperature during environmental temperature challenges and alters body temperature during the inflammatory response and behavioral states and in response to declining energy homeostasis. This review summarizes the central nervous system circuit mechanisms controlling the principal thermoeffectors for body temperature regulation: cutaneous vasoconstriction regulating heat loss and shivering and brown adipose tissue for thermogenesis. The activation of these thermoeffectors is regulated by parallel but distinct efferent pathways within the central nervous system that share a common peripheral thermal sensory input. The model for the neural circuit mechanism underlying central thermoregulatory control provides a useful platform for further understanding of the functional organization of central thermoregulation, for elucidating the hypothalamic circuitry and neurotransmitters involved in body temperature regulation, and for the discovery of novel therapeutic approaches to modulating body temperature and energy homeostasis.

  17. DNA → RNA: What Do Students Think the Arrow Means?

    OpenAIRE

    Wright, L. Kate; Fisk, J. Nick; Newman, Dina L.

    2014-01-01

    The central dogma of molecular biology, a model that has remained intact for decades, describes the transfer of genetic information from DNA to protein though an RNA intermediate. While recent work has illustrated many exceptions to the central dogma, it is still a common model used to describe and study the relationship between genes and protein products. We investigated understanding of central dogma concepts and found that students are not primed to think about information when presented w...

  18. [Central diabetes insipidus: diagnostic difficulties].

    Science.gov (United States)

    Matoussi, N; Aissa, K; Fitouri, Z; Hajji, M; Makni, S; Bellagha, I; Ben Becher, S

    2008-06-01

    Central diabetes insipidus is rare in children. Characteristic features include polyuria and polydipsia due to arginine vasopressin deficiency. The differential diagnosis of polyuric states may be difficult. Etiologic diagnosis of central diabetes insipidus may be an equally difficult task. To specify the difficulties encountered in the diagnosis of central diabetes insipidus and to point out features of the etiologic work-up and of long-term follow-up of children with idiopathic central diabetes insipidus. A retrospective study of 12 children admitted with a polyuria/polydipsia syndrome to the pediatric - consultation and emergency unit of the children's hospital of Tunis between 1988 and 2005. Children with acquired nephrogenic central diabetes insipidus were excluded. Fourteen-hour fluid restriction test and/or desmopressin test were used without plasma vasopressin measurement. Eight patients were classified as having central diabetes insipidus, which was severe in seven children and partial in one girl. One patient was classified as having primary polydipsia. The diagnosis remains unclear in three patients. The etiological work-up in eight patients with central diabetes insipidus enabled the identification of Langerhan's-cell histiocytosis in two patients and neurosurgical trauma in one. The cause was considered idiopathic in five patients. The median follow-up of the five patients with idiopathic central diabetes insipidus was five years two months plus or minus six years seven months (range five months, 14.5 years). During this follow-up, neither brain magnetic resonance imaging scans findings nor anterior pituitary function have changed. Fluid restriction and desmopressin tests did not enable an accurate distinction between partial diabetes insipidus and primary polydipsia. Regular surveillance is warranted in patients with idiopathic central diabetes insipidus to identify potential etiologies.

  19. Centralized digital control of accelerators

    International Nuclear Information System (INIS)

    Melen, R.E.

    1983-09-01

    In contrasting the title of this paper with a second paper to be presented at this conference entitled Distributed Digital Control of Accelerators, a potential reader might be led to believe that this paper will focus on systems whose computing intelligence is centered in one or more computers in a centralized location. Instead, this paper will describe the architectural evolution of SLAC's computer based accelerator control systems with respect to the distribution of their intelligence. However, the use of the word centralized in the title is appropriate because these systems are based on the use of centralized large and computationally powerful processors that are typically supported by networks of smaller distributed processors

  20. Central European gas market perspectives

    International Nuclear Information System (INIS)

    Vanous, Jan

    1999-01-01

    This presentation deals with (1) Definition of the Central European market, (2) Factors driving up consumption of natural gas in Central and Eastern Europe, (3) Role of natural gas in regional energy consumption, (4) Position of natural gas in individual country markets, (5) Future sources of imported natural gas into the region. The Central European market are the eleven countries Albania, Bulgaria, Croatia, Czech Republic, Hungary, Macedonia, Poland, Romania, Serbia and Montenegro, Slovakia, and Slovenia, with a total population of 121 million. This market is comparable to combined France and Italy in terms of population, but only 30% of its size in terms of GDP

  1. Big Data and central banks

    Directory of Open Access Journals (Sweden)

    David Bholat

    2015-04-01

    Full Text Available This commentary recaps a Centre for Central Banking Studies event held at the Bank of England on 2–3 July 2014. The article covers three main points. First, it situates the Centre for Central Banking Studies event within the context of the Bank’s Strategic Plan and initiatives. Second, it summarises and reflects on major themes from the event. Third, the article links central banks’ emerging interest in Big Data approaches with their broader uptake by other economic agents.

  2. Demographic tensions in Central America.

    Science.gov (United States)

    1986-08-01

    This discussion of Central America focuses on the rapid growth of its population, its stagnating economy, and those countries that are socioeconomically advanced. Between 1950-85 the population of Central America tripled, from 9.1 million to 26. 4 million, due to marked mortality declines and the absence of off-setting fertility declines. The distribution of Central Americas's growing populations sets its population growth apart from that of other developing regions. Currently, almost half of all Central Americans live in cities. Although the average growth rate for Central American countries has fallen and is expected to drop further, the decline does not counterbalance the effect of the absolute rise in population numbers. The average annual growth rate of more than 3% annually in the 1960s fell to about 2.6% in recent years, but this decline is due primarily to socioeconomically advanced Costa Rica and Panama. Central America's age structure further complicates the population crisis. About 43% of Central Americans are under the age of 15. When the increasingly larger young population group enters it reproductive years, the potential for future growth (albeit the falling rate of population increase) is unparalleled. UN population projections show the region's population at 40 million by the year 2000. The 1973 oil crisis began a downward spiral for the buoyant post World War II Central American economy. Between 1950-79, real per capita income growth in Central America doubled, with Central American economies growing an average of 5.3% annually. By the early 1980s, overseas markets of the trade-dependent countries of Central America had dried up due to protectionism abroad and slumping basic commodity prices. These and other factors plunged Central America into its current economic malaise of falling real per capita income, rising unemployment, curtailed export led economic growth, and a rising cost of living. In general, economic growth in Central America

  3. The Central Trigger Processor (CTP)

    CERN Multimedia

    Franchini, Matteo

    2016-01-01

    The Central Trigger Processor (CTP) receives trigger information from the calorimeter and muon trigger processors, as well as from other sources of trigger. It makes the Level-1 decision (L1A) based on a trigger menu.

  4. Central Exclusive Production at LHCb

    CERN Document Server

    INSPIRE-00106463

    2015-01-01

    Central Exclusive Production is a unique QCD process in which particles are produced via colourless propagators. Several results have been obtained at LHCb for the production of single charmonia, pairs of charmonia, and single bottomonia.

  5. Hepatostomy for central hepatic hematomas

    International Nuclear Information System (INIS)

    Gewertz, B.L.; Olsen, W.R.

    1975-01-01

    Two patients with central hepatic hematomas are presented. Hepatostomy tube drainage provided prompt healing of the cavities without complications. The technique is presented as a safe and effective alternative to hepatic resection without compromising the established principles of management

  6. Payments and Central Bank Policy

    DEFF Research Database (Denmark)

    Korsgaard, Søren

    This thesis consists of three chapters. The rst, "Paying for Payments", examines the role of interchange fees in payment card networks. The second, "Bank Liquidity and the Interbank Market" (co-authored with Mikael Reimer Jensen), investigates how banks' liquidity holdings at the central bank a ect...... outcomes in the money market. The third, "Collateralized Lending and Central Bank Collateral Policy", considers the emergence of credit constraints under collateralized lending, and how central banks use collateral policy to mitigate these constraints. While the chapters can be read independently......, they share common themes. Each chapter is concerned with payments in one way or another, each is concerned with the e ciency of market outcomes, and, to the extent that there is scope for improving these outcomes, each discusses the appropriate role for policy, in particular central bank policy....

  7. CENTRAL PLATEAU REMEDIATION OPTIMIZATION STUDY

    Energy Technology Data Exchange (ETDEWEB)

    BERGMAN, T. B.; STEFANSKI, L. D.; SEELEY, P. N.; ZINSLI, L. C.; CUSACK, L. J.

    2012-09-19

    THE CENTRAL PLATEAU REMEDIATION OPTIMIZATION STUDY WAS CONDUCTED TO DEVELOP AN OPTIMAL SEQUENCE OF REMEDIATION ACTIVITIES IMPLEMENTING THE CERCLA DECISION ON THE CENTRAL PLATEAU. THE STUDY DEFINES A SEQUENCE OF ACTIVITIES THAT RESULT IN AN EFFECTIVE USE OF RESOURCES FROM A STRATEGIC PERSPECTIVE WHEN CONSIDERING EQUIPMENT PROCUREMENT AND STAGING, WORKFORCE MOBILIZATION/DEMOBILIZATION, WORKFORCE LEVELING, WORKFORCE SKILL-MIX, AND OTHER REMEDIATION/DISPOSITION PROJECT EXECUTION PARAMETERS.

  8. Human GW182 Paralogs Are the Central Organizers for RNA-Mediated Control of Transcription.

    Science.gov (United States)

    Hicks, Jessica A; Li, Liande; Matsui, Masayuki; Chu, Yongjun; Volkov, Oleg; Johnson, Krystal C; Corey, David R

    2017-08-15

    In the cytoplasm, small RNAs can control mammalian translation by regulating the stability of mRNA. In the nucleus, small RNAs can also control transcription and splicing. The mechanisms for RNA-mediated nuclear regulation are not understood and remain controversial, hindering the effective application of nuclear RNAi and investigation of its natural regulatory roles. Here, we reveal that the human GW182 paralogs TNRC6A/B/C are central organizing factors critical to RNA-mediated transcriptional activation. Mass spectrometry of purified nuclear lysates followed by experimental validation demonstrates that TNRC6A interacts with proteins involved in protein degradation, RNAi, the CCR4-NOT complex, the mediator complex, and histone-modifying complexes. Functional analysis implicates TNRC6A, NAT10, MED14, and WDR5 in RNA-mediated transcriptional activation. These findings describe protein complexes capable of bridging RNA-mediated sequence-specific recognition of noncoding RNA transcripts with the regulation of gene transcription. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Chapter 1. Central nervous system

    International Nuclear Information System (INIS)

    Planiol, T.; Veyre, A.; Plagne, R.

    1975-01-01

    The present situation with regard to explorations of the central nervous system by radioactive compounds is reviewed. For the sake of clarity the brain and cerebrospinal fluid examinations are described separately, with emphasis nevertheless on their complementarity. The tracers used in each of these examinations are listed, together with the criteria governing their choice. The different techniques employed are described. Scintigraphy is presented apart from gamma-angio-encephalography since it is not possible with rectilinear scintigraphs to observe the circulatory phase. The results are interpreted by an analysis of normal and pathological aspects of the different stages of the central nervous system [fr

  10. Design of multi-phase dynamic chemical networks

    Science.gov (United States)

    Chen, Chenrui; Tan, Junjun; Hsieh, Ming-Chien; Pan, Ting; Goodwin, Jay T.; Mehta, Anil K.; Grover, Martha A.; Lynn, David G.

    2017-08-01

    Template-directed polymerization reactions enable the accurate storage and processing of nature's biopolymer information. This mutualistic relationship of nucleic acids and proteins, a network known as life's central dogma, is now marvellously complex, and the progressive steps necessary for creating the initial sequence and chain-length-specific polymer templates are lost to time. Here we design and construct dynamic polymerization networks that exploit metastable prion cross-β phases. Mixed-phase environments have been used for constructing synthetic polymers, but these dynamic phases emerge naturally from the growing peptide oligomers and create environments suitable both to nucleate assembly and select for ordered templates. The resulting templates direct the amplification of a phase containing only chain-length-specific peptide-like oligomers. Such multi-phase biopolymer dynamics reveal pathways for the emergence, self-selection and amplification of chain-length- and possibly sequence-specific biopolymers.

  11. Educated Cities and Regional Centralization

    DEFF Research Database (Denmark)

    Eriksen, Jesper

    centralization where the shares of students rose significantly more in urban municipalities than non-urban municipalities. The highest shares of students as well as fastest increases were seen in the municipalities of the four largest cities, Copenhagen, Århus, Odense, and Aalborg. At the national level...

  12. Fire management in central America

    Science.gov (United States)

    Andrea L. Koonce; Armando González-Cabán

    1992-01-01

    Information on fire management operations in Central America is scant. To evaluate the known level of fire occurrence in seven countries in that area, fire management officers were asked to provide information on their fire control organizations and on any available fire statistics. The seven countries surveyed were Guatemala, Belize, Honduras, El Salvador, Nicaragua,...

  13. Central amygdala, stress and adaption

    NARCIS (Netherlands)

    Roozendaal, Benno

    1992-01-01

    In this thesis the results were presented of studies that were designed to provide more insight in the role of the central nucleus of the amygdala (CEA) in the adaptation to environmental demands. The experiments were performed in several situations, in which rats react either directly to aversive

  14. Central African Journal of Medicine

    African Journals Online (AJOL)

    The Central African Journal of Medicine is a quarterly refereed general medical journal which seeks to promote the practice and science of medicine in Africa. Emphasis is placed on general medical topics, reflecting common and important conditions in the region. The journal also covers related medical fields. Submissions ...

  15. Shared breastfeeding in central Africa

    NARCIS (Netherlands)

    Ramharter, Michael; Chai, Sanders K.; Adegnika, Ayola A.; Klöpfer, Anna; Längin, Matthias; Agnandji, Selidji T.; Oyakhirome, Sunny; Schwarz, Norbert G.; Grobusch, Martin P.; Issifou, Saadon; Kremsner, Peter G.

    2004-01-01

    In this study, shared breastfeeding is described asa novel risk factor for vertical HIV transmission. This cross-sectional survey conducted in the central African country Gabon found that 40% of lactating mothers also breastfed other children than their own, and as many children were additionally

  16. Music Libraries: Centralization versus Decentralization.

    Science.gov (United States)

    Kuyper-Rushing, Lois

    2002-01-01

    Considers the decision that branch libraries, music libraries in particular, have struggled with concerning a centralized location in the main library versus a decentralized collection. Reports on a study of the Association of Research Libraries that investigated the location of music libraries, motivation for the location, degrees offered,…

  17. Central New York's New Workforce

    Science.gov (United States)

    Center for an Urban Future, 2009

    2009-01-01

    Conducted in late 2008 in partnership with the Greater Syracuse Chamber of Commerce and the Mohawk Valley Chamber of Commerce, this is the largest survey ever taken of Central New York businesses regarding the English language skills of the area workforce. The online survey was emailed to several hundred local businesses; 126 responses were…

  18. Central index of dose information

    International Nuclear Information System (INIS)

    1991-01-01

    The Central Index of Dose Information (CIDI) is a national database of occupational exposure to radiation operated by the NRPB as agent for the Health and Safety Executive. It receives summarised information on the radiation doses to classified persons in Great Britain annually from Approved Dosimetry Services. This document is the first annual CIDI summary of the data, giving statistics for 1986. (UK)

  19. Copycats of the Central Himalayas

    NARCIS (Netherlands)

    P.A. Arora (Payal)

    2009-01-01

    textabstractThis case study highlights practices of a rarely documented group of neo-users of the Internet or newbies from Central Himalayas, serving as a catalyst for delving deeply into the act of ‘plagiarism’ in online learning By looking at such ‘learning’ practices away from schools, namely

  20. Central Libraries in Uncertain Times.

    Science.gov (United States)

    Kenney, Brian J.

    2001-01-01

    Discusses security and safety issues for public libraries, especially high-profile central facilities, in light of the September 11 terrorist attacks. Highlights include inspecting bags as patrons enter as well as exit; the need for security guidelines for any type of disaster or emergency; building design; and the importance of communication.…

  1. Central and eastern European activities

    International Nuclear Information System (INIS)

    Rea, J.L.

    1993-01-01

    The Florida State University/Technical University of Budapest environmental research center, Center for Hungarian/American Environmental Research, Studies and Exchanges (CHAERSE), provides a resource base for information and technologies that is used to address near- and long-term environmental problems within the Department of Energy (DOE) complex and in Central and Eastern Europe. The CHAERSE is used as a technology transfer conduit for environmental restoration and waste management (ER/WM) problems and solutions. The International Technology Exchange Division (ITED) used the CHAERSE as one source of information for the identification of international ER/WM technologies being developed in Central and Eastern Europe. This was accomplished by matching high-priority problems in that region to high-priority problems in the DOE Complex; conducting symposia, meetings and workshops with international environmental experts; and identifying innovative technologies

  2. A centralized audio presentation manager

    Energy Technology Data Exchange (ETDEWEB)

    Papp, A.L. III; Blattner, M.M.

    1994-05-16

    The centralized audio presentation manager addresses the problems which occur when multiple programs running simultaneously attempt to use the audio output of a computer system. Time dependence of sound means that certain auditory messages must be scheduled simultaneously, which can lead to perceptual problems due to psychoacoustic phenomena. Furthermore, the combination of speech and nonspeech audio is examined; each presents its own problems of perceptibility in an acoustic environment composed of multiple auditory streams. The centralized audio presentation manager receives abstract parameterized message requests from the currently running programs, and attempts to create and present a sonic representation in the most perceptible manner through the use of a theoretically and empirically designed rule set.

  3. A Randomized Central Limit Theorem

    International Nuclear Information System (INIS)

    Eliazar, Iddo; Klafter, Joseph

    2010-01-01

    The Central Limit Theorem (CLT), one of the most elemental pillars of Probability Theory and Statistical Physics, asserts that: the universal probability law of large aggregates of independent and identically distributed random summands with zero mean and finite variance, scaled by the square root of the aggregate-size (√(n)), is Gaussian. The scaling scheme of the CLT is deterministic and uniform - scaling all aggregate-summands by the common and deterministic factor √(n). This Letter considers scaling schemes which are stochastic and non-uniform, and presents a 'Randomized Central Limit Theorem' (RCLT): we establish a class of random scaling schemes which yields universal probability laws of large aggregates of independent and identically distributed random summands. The RCLT universal probability laws, in turn, are the one-sided and the symmetric Levy laws.

  4. Centrality in earthquake multiplex networks

    Science.gov (United States)

    Lotfi, Nastaran; Darooneh, Amir Hossein; Rodrigues, Francisco A.

    2018-06-01

    Seismic time series has been mapped as a complex network, where a geographical region is divided into square cells that represent the nodes and connections are defined according to the sequence of earthquakes. In this paper, we map a seismic time series to a temporal network, described by a multiplex network, and characterize the evolution of the network structure in terms of the eigenvector centrality measure. We generalize previous works that considered the single layer representation of earthquake networks. Our results suggest that the multiplex representation captures better earthquake activity than methods based on single layer networks. We also verify that the regions with highest seismological activities in Iran and California can be identified from the network centrality analysis. The temporal modeling of seismic data provided here may open new possibilities for a better comprehension of the physics of earthquakes.

  5. Perihelium shifts in central potentials

    International Nuclear Information System (INIS)

    Amorim, A.E.A.; Ferreira, P.L.

    1987-01-01

    Motivated by the rigorous results on level ordering for arbitrary central potentials recently derived in the literature a classical treatment of the perihelium shifts is presented, based on the consideration of those orbits which lie in the vicinity of a circular orbit. The role played by the Laplacian of the potential is emphasized. By the same approach Bertrand's theorem is also discussed, in connection with Arnold's proof. (Author) [pt

  6. Information from the central stores

    CERN Multimedia

    GS Department

    2010-01-01

    All items sold in the CERN shop (Bldg. 33) are now available in the central stores (Bldg. 73) and can be purchased on-line via EDH “Material Request” or at the “Emergency Desk” of the stores on the ground floor of Bldg. 73. These items are visible in the CERN catalogue under the “SCEM” codes beginning with 92. Department of General Infrastructure Services (GS) GS-SEM Group

  7. Central Exclusive Production at LHCb

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00392425

    2017-01-01

    The LHCb detector, with its excellent momentum resolution and flexible trigger strategy, is ideally suited for measuring particles produced exclusively. In addition, a new system of forward shower counters has been installed upstream and downstream of the detector, and has been used to facilitate studies of Central Exclusive Production. Such measurements of integrated and differential cross-section in both Run 1 and Run 2 of the LHC, are summarised here.

  8. Volcanic hazards in Central America

    Science.gov (United States)

    Rose, William I.; Bluth, Gregg J.S.; Carr, Michael J.; Ewert, John W.; Patino, Lina C.; Vallance, James W.

    2006-01-01

    This volume is a sampling of current scientific work about volcanoes in Central America with specific application to hazards. The papers reflect a variety of international and interdisciplinary collaborations and employ new methods. The book will be of interest to a broad cross section of scientists, especially volcanologists. The volume also will interest students who aspire to work in the field of volcano hazards mitigation or who may want to work in one of Earth’s most volcanically active areas.

  9. Barter Economies and Centralized Merchants

    OpenAIRE

    Jose Noguera

    2000-01-01

    The main goal of this essay is to analyze the emergence of a barter economy, and the rise of centralized merchants and a barter redistribution system out of a primitive barter system. The environment is a spatial general equilibrium model where exchange is costly. Since exchange becomes more complicated as the scope of the economy increases, we prove that, after the economy reaches a critical size, the cost of trade expansion surpasses its benefits. This imposes limitations on the scope of th...

  10. Seismotectonic model of Central Europe

    International Nuclear Information System (INIS)

    Prochazkova, D.; Roth, Z.

    1994-01-01

    Earthquakes belong to natural disasters which are associated with tectonic processes in the interior of the Earth. They are extremely devastating in populated areas; they cause human losses and damage personal estates and the environment. To mitigate the potential effects of earthquakes it is necessary that relief and mitigation structures operate following an earthquake, but it is also essential to stimulate and enhance preparedness and prevention. Prevention includes the development of scenarios of potential earthquakes, hazard mapping, formulation of regulations, etc. Preparedness includes the installation and operation of warning systems, establishing communication networks to operate before, during, and after earthquakes. As nuclear technology belongs to high-risk technologies with regard to human health and the environment and its hazard substantially increases in consequence of earthquakes, in the siting of a nuclear plant engineering solutions are generally available to mitigate the potential vibratory effects through design. For the choice of a suitable engineering solution, reliable data must be processed by reliable techniques. The IAEA safety guide of the safety series No. 50-SG-S1(Rev. 1) specifies the demands on data and on their processing and also on the regional seismotectonic model. With a view of this the regional seismotectonic model of Central Europe was created. The paper presents regional geological characteristics of Central Europe and a chronological model of neotectonic movements in Central Europe with specification of neotectonic regional units and their present movements. Moreover, it contains earthquake characteristics for Central Europe and the specification of seismogenic movements. It was found that the genesis of local regions with occurrence of the strongest earthquakes is connected with several movement trends in the last 5 Ma. Six more or less tectonically separate regional units were revealed. The earthquake epicenters often

  11. MR findings of central nerocytoma

    International Nuclear Information System (INIS)

    Lee, Chang Hoon; Kim, Dong Ik; Lee, Byung Hee; Kim, Myung Soon

    1997-01-01

    Central neurocytoma is a reae neuronal differentiated intraventricular tomor of young adults. The purpose of this study was to evaluate the characteristic MR appearance of central neurocytoma. We retrospectively reviewed MR images of 12 patients with central neurocytoma, confirmed by ultrastructural and immunohistochemical study. We analyzed patient age, and on all sequences, tumor location, extension into the third ventricle, involvement of brain parenchyma, cyst, hemorrhage, vascular signal void and signal intensity ; and egree of Gd-enhancement was examined on MR images, pattern of calcification on CT, and neovascularity, tumor staining on angiography. Age distribution was wide ranging from 26 to 64 years ; the most frequent age group was the fourth decade (five patients). All tumors except one (in the third ventricle) were located in the lateral ventricle and most were seen in the region of the foramen of Monro (10 cases). Tumors showed extension into the third ventricle and involvement of parenchyma in three cases. The internal architecture of the tumor was heterogenous and consisted of cysts (83%), hemorrhage (25%) and vascular signal void (25%). The solid portion of the tumor showed variable signal intensity on T1-weighted images and iso or high signal intensity on T2- and proton density-weighted images. On MR imaging, mild to moderate heterogenous Gd-enhancement was seen in ten cases (83%), and on CT, a spotted, amorphous, nodular pattern of calcifications was seen in seven cases (63%). On angiography, neovasevlarity and tumor staining was seen in three cases (100%). The typical location of the lateral and third ventricles and MR imaging characteristics including variable signal intensity and heterogenous internal architecture are helpful in the diagnosis of central neurocytoma in young adults

  12. Central nervous system mesenchymal chondrosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Salvati, M.; Frati, A.; Piccirilli, M.; Agrillo, A.; Brogna, C.; Occhiogrosso, G.; Giangaspero, F. [INM Neuromed IRCCS, Pozzilli (Italy). Dept. of Neurosurgery; Caroli, E. [Policlinico S. Andrea, Rome (Italy). Dept. of Neurological Sciences, Neurosurgery

    2005-06-15

    Central nervous system mesenchymal chondrosarcomas are rare malignant tumors that constitute a separate entity from the classical chondrosarcoma and myxoid variant. Clinical behaviour of central nervous system chondrosarcomas is still unknown. We describe two rare examples of intracranial mesenchymal chondrosarcoma with a review of the literature, in an attempt to clarify the clinical characteristics, prognosis and treatment of choice of these unusual tumors. Among the 55 reported cases, 23 had postoperative radiotherapy. Although there is no statistical significance according to the Log-Rank test (p=0.7), the patients treated with radiation therapy seem to have a better chance of survival. Patients who had adjuvant chemotherapy (only 5) showed survival times similar to those patients who had none. Although clinical behaviour of central nervous system chondrosarcomas remains to be defined, data from our series as well as literature show that radical removal is the best therapeutic choice. In addition, patients treated with postoperative radiotherapy seem to show a trend toward increased survival.

  13. Central nervous system mesenchymal chondrosarcoma

    International Nuclear Information System (INIS)

    Salvati, M.; Frati, A.; Piccirilli, M.; Agrillo, A.; Brogna, C.; Occhiogrosso, G.; Giangaspero, F.; Caroli, E.

    2005-01-01

    Central nervous system mesenchymal chondrosarcomas are rare malignant tumors that constitute a separate entity from the classical chondrosarcoma and myxoid variant. Clinical behaviour of central nervous system chondrosarcomas is still unknown. We describe two rare examples of intracranial mesenchymal chondrosarcoma with a review of the literature, in an attempt to clarify the clinical characteristics, prognosis and treatment of choice of these unusual tumors. Among the 55 reported cases, 23 had postoperative radiotherapy. Although there is no statistical significance according to the Log-Rank test (p=0.7), the patients treated with radiation therapy seem to have a better chance of survival. Patients who had adjuvant chemotherapy (only 5) showed survival times similar to those patients who had none. Although clinical behaviour of central nervous system chondrosarcomas remains to be defined, data from our series as well as literature show that radical removal is the best therapeutic choice. In addition, patients treated with postoperative radiotherapy seem to show a trend toward increased survival

  14. MR appearance of central neurocytoma

    International Nuclear Information System (INIS)

    Chang, K.H.; Han, M.H.; Kim, D.G.; Chi, J.G.; Suh, D.C.; Kim, S.J.; Cha, S.H.; Han, M.C.

    1993-01-01

    To provide a detailed description of the MR appearances of central neurocytoma, MR images of 13 patients with central neurocytoma were retrospectively reviewed and compared with CT examinations. The histology was confirmed by ultrastructural and immunohistochemical studies. In 12 patients the tumors were histologically benign and located in the anterior part of the lateral ventricle, 6 of which extended to the 3rd ventricle. There was one case of a histologically malignant variant involving the thalamus and lateral ventricle. The tumors were primarily solid, but contained cysts (85%, 11/13), calcifications (69%, 9/13), and signal void from tumor vessels (62%, 8/13), frequently producing heterogeneous signal intensity on both T1- and T2-weighted images. Most of the solid portion appeared isointense or slightly hyperintense relative to the cerebral cortex on all MR pulse sequences. Calcifications were iso- or hypointense on MR, making them difficult to characterize with MR alone. Intratumoral hemorrhage was seen in 2 patients on MR but not on CT. Contrast enhancement was variable in degree and pattern. Coronal and sagittal MR images were valuable in evaluating the tumor extent and origin site, and in planning the surgical approach. It is concluded that MR imaging appears to be more useful than CT in the overall evaluation of central neurocytoma, even though calcification is better characterized with CT. (orig.)

  15. Concept of the central clip

    DEFF Research Database (Denmark)

    Alegria-Barrero, Eduardo; Chan, Pak Hei; Foin, Nicolas

    2014-01-01

    AIMS: Percutaneous edge-to-edge mitral valve repair with the MitraClip(®) was shown to be a safe and feasible alternative compared to conventional surgical mitral valve repair. We analyse the concept of the central clip and the predictors for the need of more than one MitraClip(®) in our high.......8±10.7 years (30 males, 13 females; mean logistic EuroSCORE 24.1±11, mean LVEF 47.5±18.5%; mean±SD) were treated. Median follow-up was 385 days (104-630; Q1-Q3). Device implantation success was 93%. All patients were treated following the central clip concept: 52.5% of MR was degenerative in aetiology and 47....... The presence of a restricted posterior mitral valve leaflet (PML) was inversely correlated with the need for more than one clip (p=0.02). A cut-off value of ≥7.5 mm for vena contracta predicted the need for a second clip (sensitivity 83%, specificity 90%, p=0.01). CONCLUSIONS: The central MitraClip(®) concept...

  16. Centralized digital control of accelerators

    International Nuclear Information System (INIS)

    Melen, R.E.

    1984-01-01

    Upon careful examination of the architecture of SLAC's computer control systems, it becomes evident that the distribution of the systems' intelligence generally falls into tree-like layers. The first layer typically consists of a central computer complex incorporating one or more relatively large and powerful processors. The more modern systems use state-of-the-art 32-bit processors with several megabytes of RAM and several hundreds of megabytes of disk memory. Further, they support extensive user-friendly operating systems and program development facilities. The second layer typically consists of several smaller processors which are downloaded from the central complex and whose primary task is to provide data acquisition and distribution. The more modern systems are 16-bit processors with several hundred kilobytes of RAM and no disk memory. The third layer typically consists of several tens or hundreds of micro-processors, each dedicated to a single device. The micro-processors for these ''dedicated intelligent controllers'' are small and inexpensive and typically require less than 32 kilobytes of RAM or EPROM memory. Their hardware may be general purpose in nature or may be built into the architecture of the device itself. Figure 5 illustrates several of the relevant features of each of these layers. This paper serves to illustrate that SLAC is commited to the centralized digital control of its accelerators

  17. Sequence-specific inhibition of duck hepatitis B virus reverse transcription by peptide nucleic acids (PNA)

    DEFF Research Database (Denmark)

    Robaczewska, Magdalena; Narayan, Ramamurthy; Seigneres, Beatrice

    2005-01-01

    BACKGROUND/AIMS: Peptide nucleic acids (PNAs) appear as promising new antisense agents, that have not yet been examined as hepatitis B virus (HBV) inhibitors. Our aim was to study the ability of PNAs targeting the duck HBV (DHBV) encapsidation signal epsilon to inhibit reverse transcription (RT...... in primary duck hepatocytes (PDH). RESULTS: Both PNAs reproducibly inhibited DHBV RT in a dose-dependent manner with IC(50) of 10nM, whereas up to 600-fold higher concentration of S-ODNs was required for similar inhibition. The PNA targeting the bulge and upper stem of epsilon appeared as more efficient RT...

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

    Directory of Open Access Journals (Sweden)

    Artyom A Alekseyenko

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

  19. Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases.

    Science.gov (United States)

    Citorik, Robert J; Mimee, Mark; Lu, Timothy K

    2014-11-01

    Current antibiotics tend to be broad spectrum, leading to indiscriminate killing of commensal bacteria and accelerated evolution of drug resistance. Here, we use CRISPR-Cas technology to create antimicrobials whose spectrum of activity is chosen by design. RNA-guided nucleases (RGNs) targeting specific DNA sequences are delivered efficiently to microbial populations using bacteriophage or bacteria carrying plasmids transmissible by conjugation. The DNA targets of RGNs can be undesirable genes or polymorphisms, including antibiotic resistance and virulence determinants in carbapenem-resistant Enterobacteriaceae and enterohemorrhagic Escherichia coli. Delivery of RGNs significantly improves survival in a Galleria mellonella infection model. We also show that RGNs enable modulation of complex bacterial populations by selective knockdown of targeted strains based on genetic signatures. RGNs constitute a class of highly discriminatory, customizable antimicrobials that enact selective pressure at the DNA level to reduce the prevalence of undesired genes, minimize off-target effects and enable programmable remodeling of microbiota.

  20. Sequence-specific unusual (1-->2)-type helical turns in alpha/beta-hybrid peptides.

    Science.gov (United States)

    Prabhakaran, Panchami; Kale, Sangram S; Puranik, Vedavati G; Rajamohanan, P R; Chetina, Olga; Howard, Judith A K; Hofmann, Hans-Jörg; Sanjayan, Gangadhar J

    2008-12-31

    This article describes novel conformationally ordered alpha/beta-hybrid peptides consisting of repeating l-proline-anthranilic acid building blocks. These oligomers adopt a compact, right-handed helical architecture determined by the intrinsic conformational preferences of the individual amino acid residues. The striking feature of these oligomers is their ability to display an unusual periodic pseudo beta-turn network of nine-membered hydrogen-bonded rings formed in the forward direction of the sequence by 1-->2 amino acid interactions both in solid-state and in solution. Conformational investigations of several of these oligomers by single-crystal X-ray diffraction, solution-state NMR, and ab initio MO theory suggest that the characteristic steric and dihedral angle restraints exerted by proline are essential for stabilizing the unusual pseudo beta-turn network found in these oligomers. Replacing proline by the conformationally flexible analogue alanine (Ala) or by the conformationally more constrained alpha-amino isobutyric acid (Aib) had an adverse effect on the stabilization of this structural architecture. These findings increase the potential to design novel secondary structure elements profiting from the steric and dihedral angle constraints of the amino acid constituents and help to augment the conformational space available for synthetic oligomer design with diverse backbone structures.

  1. Single-cell mRNA cytometry via sequence-specific nanoparticle clustering and trapping

    Science.gov (United States)

    Labib, Mahmoud; Mohamadi, Reza M.; Poudineh, Mahla; Ahmed, Sharif U.; Ivanov, Ivaylo; Huang, Ching-Lung; Moosavi, Maral; Sargent, Edward H.; Kelley, Shana O.

    2018-05-01

    Cell-to-cell variation in gene expression creates a need for techniques that can characterize expression at the level of individual cells. This is particularly true for rare circulating tumour cells, in which subtyping and drug resistance are of intense interest. Here we describe a method for cell analysis—single-cell mRNA cytometry—that enables the isolation of rare cells from whole blood as a function of target mRNA sequences. This approach uses two classes of magnetic particles that are labelled to selectively hybridize with different regions of the target mRNA. Hybridization leads to the formation of large magnetic clusters that remain localized within the cells of interest, thereby enabling the cells to be magnetically separated. Targeting specific intracellular mRNAs enablescirculating tumour cells to be distinguished from normal haematopoietic cells. No polymerase chain reaction amplification is required to determine RNA expression levels and genotype at the single-cell level, and minimal cell manipulation is required. To demonstrate this approach we use single-cell mRNA cytometry to detect clinically important sequences in prostate cancer specimens.

  2. Torque measurements reveal sequence-specific cooperative transitions in supercoiled DNA

    Science.gov (United States)

    Oberstrass, Florian C.; Fernandes, Louis E.; Bryant, Zev

    2012-01-01

    B-DNA becomes unstable under superhelical stress and is able to adopt a wide range of alternative conformations including strand-separated DNA and Z-DNA. Localized sequence-dependent structural transitions are important for the regulation of biological processes such as DNA replication and transcription. To directly probe the effect of sequence on structural transitions driven by torque, we have measured the torsional response of a panel of DNA sequences using single molecule assays that employ nanosphere rotational probes to achieve high torque resolution. The responses of Z-forming d(pGpC)n sequences match our predictions based on a theoretical treatment of cooperative transitions in helical polymers. “Bubble” templates containing 50–100 bp mismatch regions show cooperative structural transitions similar to B-DNA, although less torque is required to disrupt strand–strand interactions. Our mechanical measurements, including direct characterization of the torsional rigidity of strand-separated DNA, establish a framework for quantitative predictions of the complex torsional response of arbitrary sequences in their biological context. PMID:22474350

  3. Multicolour probes for sequence-specific DNA detection based on graphene oxide.

    Science.gov (United States)

    Zhu, Qing; Xiang, Dongshan; Zhang, Cuiling; Ji, Xinghu; He, Zhike

    2013-09-21

    The bifunctionality of graphene oxide (GO) which can highly adsorb single-stranded DNA (ssDNA) and effectively quench the emission of organic dyes is reasonably utilized in a multiplexed DNA detection system, achieving sensitive and selective detection of HIV, VV and EV, respectively.

  4. Molecular Design of Antifouling Polymer Brushes Using Sequence-Specific Peptoids.

    Science.gov (United States)

    Lau, King Hang Aaron; Sileika, Tadas S; Park, Sung Hyun; Sousa, Ana Maria Leal; Burch, Patrick; Szleifer, Igal; Messersmith, Phillip B

    2015-01-07

    Material systems that can be used to flexibly and precisely define the chemical nature and molecular arrangement of a surface would be invaluable for the control of complex biointerfacial interactions. For example, progress in antifouling polymer biointerfaces that prevent non-specific protein adsorption and cell attachment, which can significantly improve the performance of an array of biomedical and industrial applications, is hampered by a lack of chemical models to identify the molecular features conferring their properties. Poly(N-substituted glycine) "peptoids" are peptidomimetic polymers that can be conveniently synthesized with specific monomer sequences and chain lengths, and are presented as a versatile platform for investigating the molecular design of antifouling polymer brushes. Zwitterionic antifouling polymer brushes have captured significant recent attention, and a targeted library of zwitterionic peptoid brushes with a different charge densities, hydration, separations between charged groups, chain lengths, and grafted chain densities, is quantitatively evaluated for their antifouling properties through a range of protein adsorption and cell attachment assays. Specific zwitterionic brush designs were found to give rise to distinct but subtle differences in properties. The results also point to the dominant roles of the grafted chain density and chain length in determining the performance of antifouling polymer brushes.

  5. Non coding RNA: sequence-specific guide for chromatin modification and DNA damage signaling

    Directory of Open Access Journals (Sweden)

    Sofia eFrancia

    2015-11-01

    Full Text Available Chromatin conformation shapes the environment in which our genome is transcribed into RNA. Transcription is a source of DNA damage, thus it often occurs concomitantly to DNA damage signaling. Growing amounts of evidence suggest that different types of RNAs can, independently from their protein-coding properties, directly affect chromatin conformation, transcription and splicing, as well as promote the activation of the DNA damage response (DDR and DNA repair. Therefore, transcription paradoxically functions to both threaten and safeguard genome integrity. On the other hand, DNA damage signaling is known to modulate chromatin to suppress transcription of the surrounding genetic unit. It is thus intriguing to understand how transcription can modulate DDR signaling while, in turn, DDR signaling represses transcription of chromatin around the DNA lesion. An unexpected player in this field is the RNA interference (RNAi machinery, which play roles in transcription, splicing and chromatin modulation in several organisms. Non-coding RNAs (ncRNAs and several protein factors involved in the RNAi pathway are well known master regulators of chromatin while only recent reports suggest that ncRNAs are involved in DDR signaling and homology-mediated DNA repair. Here, we discuss the experimental evidence supporting the idea that ncRNAs act at the genomic loci from which they are transcribed to modulate chromatin, DDR signaling and DNA repair.

  6. RNA-Mediated Gene Duplication and Retroposons: Retrogenes, LINEs, SINEs, and Sequence Specificity

    Science.gov (United States)

    2013-01-01

    A substantial number of “retrogenes” that are derived from the mRNA of various intron-containing genes have been reported. A class of mammalian retroposons, long interspersed element-1 (LINE1, L1), has been shown to be involved in the reverse transcription of retrogenes (or processed pseudogenes) and non-autonomous short interspersed elements (SINEs). The 3′-end sequences of various SINEs originated from a corresponding LINE. As the 3′-untranslated regions of several LINEs are essential for retroposition, these LINEs presumably require “stringent” recognition of the 3′-end sequence of the RNA template. However, the 3′-ends of mammalian L1s do not exhibit any similarity to SINEs, except for the presence of 3′-poly(A) repeats. Since the 3′-poly(A) repeats of L1 and Alu SINE are critical for their retroposition, L1 probably recognizes the poly(A) repeats, thereby mobilizing not only Alu SINE but also cytosolic mRNA. Many flowering plants only harbor L1-clade LINEs and a significant number of SINEs with poly(A) repeats, but no homology to the LINEs. Moreover, processed pseudogenes have also been found in flowering plants. I propose that the ancestral L1-clade LINE in the common ancestor of green plants may have recognized a specific RNA template, with stringent recognition then becoming relaxed during the course of plant evolution. PMID:23984183

  7. IDENTIFICATION OF PUTATIVE SEQUENCE SPECIFIC PCR PRIMERS FOR DETECTION OF THE TOXIGENIC FUNGAL SPECIES STACHYBOTRYS CHARTARUM

    Science.gov (United States)

    The nucleotide sequence of a c 936 bp segment of the nuclear rRNA gene operon was determined for the toxigenic fungal species Stachybotrys chartarum and for other species of Stachbotrys and the related genus Memnoniella. This information was used to infer the phylogenetic relatio...

  8. IDENTIFICATION OF SEQUENCE SPECIFIC PCR PRIMERS FOR DETECTION OF THE TOXIGENIC FUNGAL SPECIES STACHYBOTRYS CHARTARUM

    Science.gov (United States)

    The nucleotide sequence of a 936 bp segment of the nuclear rRNA gene operon was determined for the toxigenic fungal species Stachybotrys chartarum and for other species of Stachybotrys and the related genus Memnoniella. This information was used to infer the phylogenitic relati...

  9. Synthesis and evaluation of sequence-specific DNA alkylating agents: effect of alkylation subunits.

    Science.gov (United States)

    Shimizu, Tatsuhiko; Sasaki, Shunta; Minoshima, Masafumi; Shinohara, Ken-ichi; Bando, Toshikazu; Sugiyama, Hiroshi

    2006-01-01

    We have demonstrated that hairpin pyrrole (Py)- imidazole (Im) polyamide-CBI conjugates selectively alkylate predetermined sequences. In this study, we investigated the effect of alkylation subunits, for example conjugates 1-4 with three types of DNA alkylating units, and Py-Im polyamides with indole linker. Conjugate 3 and 4 selectively alkylated the predetermined sequences as described previously, while conjugates 1 and 2 alkylate at mismatched sites.

  10. Sequence specificity of mutagenesis in the cI gene of bacteriophage lambda

    International Nuclear Information System (INIS)

    Skopek, T.R.; Wood, R.D.; Hutchinson, F.

    1985-01-01

    Studies of DNA base sequence alterations have shown that for every agent the mutagenic process is specific with respect to the types of base changes induced and the location of the changes in the DNA. Analysis of the types of mutations produced by mutagenic agents can provide insight into the mechanism of mutation and can suggest which DNA lesions may be involved in the actual mutagenic event. We have developed a system for the analysis of chemically induced base sequence alterations in the cI repressor gene of bacteriophage lambda using DNA sequencing techniques. To illustrate the utility of this type of analysis, we present the results obtained with ultraviolet light (UV). Irradiation of target DNA with UV alone, or UV followed by photoreactivating light (which removes dimers), produces mostly transitions at pyrimidine-pyrimidine sites. Conversely, irradiation with 313 nm light plus acetophenone (which produces only thymine dimers) produces mostly transversions at low efficiency. This and other evidence suggests that the actual premutagenic UV lesion in E. coli may not be pyrimidine-pyrimidine dimers, but rather pyr(6-4)pyo photoproducts

  11. Templated Chemistry for Sequence-Specific Fluorogenic Detection of Duplex DNA

    Science.gov (United States)

    Li, Hao; Franzini, Raphael M.; Bruner, Christopher; Kool, Eric T.

    2015-01-01

    We describe the development of templated fluorogenic chemistry for detection of specific sequences of duplex DNA in solution. In this approach, two modified homopyrimidine oligodeoxynucleotide probes are designed to bind by triple helix formation at adjacent positions on a specific purine-rich target sequence of duplex DNA. One fluorescein-labeled probe contains an α-azidoether linker to a fluorescence quencher; the second (trigger) probe carries a triarylphosphine, designed to reduce the azide and cleave the linker. The data showed that at pH 5.6 these probes yielded a strong fluorescence signal within minutes on addition to a complementary homopurine duplex DNA target. The signal increased by a factor of ca. 60, and was completely dependent on the presence of the target DNA. Replacement of cytosine in the probes with pseudoisocytosine allowed the templated chemistry to proceed readily at pH 7. Single nucleotide mismatches in the target oligonucleotide slowed the templated reaction considerably, demonstrating high sequence selectivity. The use of templated fluorogenic chemistry for detection of duplex DNAs has not been previously reported and may allow detection of double stranded DNA, at least for homopurine-homopyrimidine target sites, under native, non-disturbing conditions. PMID:20859985

  12. Sequence-specific inhibition of Dicer measured with a force-based microarray for RNA ligands.

    Science.gov (United States)

    Limmer, Katja; Aschenbrenner, Daniela; Gaub, Hermann E

    2013-04-01

    Malfunction of protein translation causes many severe diseases, and suitable correction strategies may become the basis of effective therapies. One major regulatory element of protein translation is the nuclease Dicer that cuts double-stranded RNA independently of the sequence into pieces of 19-22 base pairs starting the RNA interference pathway and activating miRNAs. Inhibiting Dicer is not desirable owing to its multifunctional influence on the cell's gene regulation. Blocking specific RNA sequences by small-molecule binding, however, is a promising approach to affect the cell's condition in a controlled manner. A label-free assay for the screening of site-specific interference of small molecules with Dicer activity is thus needed. We used the Molecular Force Assay (MFA), recently developed in our lab, to measure the activity of Dicer. As a model system, we used an RNA sequence that forms an aptamer-binding site for paromomycin, a 615-dalton aminoglycoside. We show that Dicer activity is modulated as a function of concentration and incubation time: the addition of paromomycin leads to a decrease of Dicer activity according to the amount of ligand. The measured dissociation constant of paromomycin to its aptamer was found to agree well with literature values. The parallel format of the MFA allows a large-scale search and analysis for ligands for any RNA sequence.

  13. Complete sequence-specific 1H NMR assignments for human insulin

    International Nuclear Information System (INIS)

    Kline, A.D.; Justice, R.M. Jr.

    1990-01-01

    Solvent conditions where human insulin could be studied by high-resolution NMR were determined. Both low pH and addition of acetonitrile were required to overcome the protein's self-association and to obtain useful spectra. Two hundred eighty-six 1 H resonances were located and assigned to specific sites on the protein by using two-dimensional NMR methods. The presence and position of numerous d NN sequential NOE's indicate that the insulin conformation seen in crystallographic studies is largely retained under these solution conditions. Slowly exchanging protons were observed for seven backbone amide protons and were assigned to positions A15 and A16 and to positions B15-B19. These amides all occur within helical regions of the protein

  14. Sequence-specific electrochemical recognition of multiple species using nanoparticle labels

    International Nuclear Information System (INIS)

    Cai Hong; Shang, Chii; Hsing, I.-Ming

    2004-01-01

    In this work, we report an electrochemical methodology that enables the rapid identification of different DNA sequences on the microfabricated electrodes. Our approach starts with an electropolymerization process on a patterned indium tin oxide (ITO)-coated glass electrode, followed by a selective immobilization of biotin-tagged probes on individually addressable spots via the biotin-streptavidin linkage. An exemplary target mixture containing E. coli and Stachybotrys Chartarum, an airborne pathogen, is then introduced. Recognition of the DNA hybridization event of the immobilized probes with the target pathogen PCR products or synthetic oligonucleotides is achieved by a novel electrochemistry-based technique utilizing the preferential catalytic silver electrodeposition process on the DNA-linked nanogold shells. The ability to selectively immobilize different oligonucleotide probes together with a sensitive electrochemistry-based detection for multiple species, as demonstrated in this study, is an important step forward for the realization of a portable bioanalytical microdevice for the rapid detection of pathogens

  15. An algorithm and program for finding sequence specific oligo-nucleotide probes for species identification

    Directory of Open Access Journals (Sweden)

    Tautz Diethard

    2002-03-01

    Full Text Available Abstract Background The identification of species or species groups with specific oligo-nucleotides as molecular signatures is becoming increasingly popular for bacterial samples. However, it shows also great promise for other small organisms that are taxonomically difficult to tract. Results We have devised here an algorithm that aims to find the optimal probes for any given set of sequences. The program requires only a crude alignment of these sequences as input and is optimized for performance to deal also with very large datasets. The algorithm is designed such that the position of mismatches in the probes influences the selection and makes provision of single nucleotide outloops. Program implementations are available for Linux and Windows.

  16. Sequence specificity for uridylylation of the viral peptide linked to the genome (VPg) of enteroviruses.

    Science.gov (United States)

    Schein, Catherine H; Ye, Mengyi; Paul, Aniko V; Oberste, M Steven; Chapman, Nora; van der Heden van Noort, Gerbrand J; Filippov, Dmitri V; Choi, Kyung H

    2015-10-01

    Enteroviruses (EV) uridylylate a peptide, VPg, as the first step in their replication. VPgpUpU, found free in infected cells, serves as the primer for RNA elongation. The abilities of four polymerases (3D(pol)), from EV-species A-C, to uridylylate VPgs that varied by up to 60% of their residues were compared. Each 3D(pol) was able to uridylylate all five VPgs using polyA RNA as template, while showing specificity for its own genome encoded peptide. All 3D(pol) uridylylated a consensus VPg representing the physical chemical properties of 31 different VPgs. Thus the residues required for uridylylation and the enzymatic mechanism must be similar in diverse EV. As VPg-binding sites differ in co-crystal structures, the reaction is probably done by a second 3D(pol) molecule. The conservation of polymerase residues whose mutation reduces uridylylation but not RNA elongation is compared. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Alteration of Sequence Specificity of the Type IIS Restriction Endonuclease BtsI

    OpenAIRE

    Guan, Shengxi; Blanchard, Aine; Zhang, Penghua; Zhu, Zhenyu

    2010-01-01

    The Type IIS restriction endonuclease BtsI recognizes and digests at GCAGTG(2/0). It comprises two subunits: BtsIA and BtsIB. The BtsIB subunit contains the recognition domain, one catalytic domain for bottom strand nicking and part of the catalytic domain for the top strand nicking. BtsIA has the rest of the catalytic domain that is responsible for the DNA top strand nicking. BtsIA alone has no activity unless it mixes with BtsIB to reconstitute the BtsI activity. During characterization of ...

  18. Sequence-Specific Targeting of Bacterial Resistance Genes Increases Antibiotic Efficacy

    Science.gov (United States)

    Wong, Michael; Daly, Seth M.; Greenberg, David E.; Toprak, Erdal

    2016-01-01

    The lack of effective and well-tolerated therapies against antibiotic-resistant bacteria is a global public health problem leading to prolonged treatment and increased mortality. To improve the efficacy of existing antibiotic compounds, we introduce a new method for strategically inducing antibiotic hypersensitivity in pathogenic bacteria. Following the systematic verification that the AcrAB-TolC efflux system is one of the major determinants of the intrinsic antibiotic resistance levels in Escherichia coli, we have developed a short antisense oligomer designed to inhibit the expression of acrA and increase antibiotic susceptibility in E. coli. By employing this strategy, we can inhibit E. coli growth using 2- to 40-fold lower antibiotic doses, depending on the antibiotic compound utilized. The sensitizing effect of the antisense oligomer is highly specific to the targeted gene’s sequence, which is conserved in several bacterial genera, and the oligomer does not have any detectable toxicity against human cells. Finally, we demonstrate that antisense oligomers improve the efficacy of antibiotic combinations, allowing the combined use of even antagonistic antibiotic pairs that are typically not favored due to their reduced activities. PMID:27631336

  19. Potential clinical usefulness of new glandular and circulating parathyroid peptides illuminated by sequence specific radioimmunoassay

    International Nuclear Information System (INIS)

    Lindall, A.W.; Cecchettin, M.

    1981-01-01

    It is now well known that human PTH peptides constitute a heterogeneous population of fragments of the eighty-four amino acid molecules. Over the years, considerable confusion has resulted from measurements made in both clinical and experimental settings with radioimmunoassays of either undefined or partially-defined specificity for a particular region of the intact molecule. The approach of the authors has been to make use of modern technology to synthesize peptide fragments that mimic portions of native molecules, and to use these fragments in RIA. A more detailed description of a portion of this work will appear in the Journal of Clinical Endocrinology and Metabolism. (Auth.)

  20. Sequence specificity of alkali-labile DNA damage photosensitized by suprofen.

    Science.gov (United States)

    Starrs, S M; Davies, R J

    2000-09-01

    On irradiation at UVB wavelengths, in aerated neutral aqueous solution, the anti-inflammatory drug suprofen (SP) photosensitizes the production of alkali-labile cleavage sites in DNA much more efficiently than direct strand breaks. It is active at submillimolar concentrations despite having no significant binding affinity for DNA. Gel sequencing studies utilizing 32P-end-labeled oligonucleotides have revealed that piperidine-sensitive lesions are formed predominantly at the positions of guanine (G) bases, with the extent of modification being UV dose- and SP concentration-dependent. Quite distinct patterns of G-specific damage are observed in single-stranded and duplex DNA molecules. The uniform attack at all G residues in single-stranded DNA, which is enhanced in D2O, is compatible with a Type-II mechanism. SP is a known generator of singlet oxygen whose participation in the reaction is supported by the effects of quenchers and scavengers. In duplex DNA, piperidine-induced cleavage occurs with high selectivity at the 5'-G of GG and (less prominently) GA doublets. This behavior is characteristic of a Type-I process involving electron transfer from DNA to photoexcited SP molecules. The ability of SP to sensitize the formation of Type-I and Type-II photo-oxidation products from 2'-deoxyguanosine attests to the feasibility of competing mechanisms in DNA.

  1. AAPT Diagnostic Criteria for Central Neuropathic Pain

    DEFF Research Database (Denmark)

    Widerstrom-Noga, Eva; Loeser, John D.; Jensen, Troels Staehelin

    2017-01-01

    Central neuropathic pain, which is pain caused by a lesion or disease of the central somatosensory nervous system, is a serious consequence of spinal cord injury, stroke, multiple sclerosis, and other conditions affecting the central nervous system. A collaborative effort between the Analgesic....... This article focuses on central neuropathic pain associated with spinal cord injury, stroke, and multiple sclerosis, but the AAPT framework can be extended to central pain due to other causes such as traumatic brain injury. The classification of central neuropathic pain is organized according to the AAPT...

  2. DNA?RNA: What Do Students Think the Arrow Means?

    Science.gov (United States)

    Wright, L. Kate; Fisk, J. Nick; Newman, Dina L.

    2014-01-01

    The central dogma of molecular biology, a model that has remained intact for decades, describes the transfer of genetic information from DNA to protein though an RNA intermediate. While recent work has illustrated many exceptions to the central dogma, it is still a common model used to describe and study the relationship between genes and protein…

  3. Crustal structure of Central Sicily

    Science.gov (United States)

    Giustiniani, Michela; Tinivella, Umberta; Nicolich, Rinaldo

    2018-01-01

    We processed crustal seismic profile SIRIPRO, acquired across Central Sicily. To improve the seismic image we utilized the wave equation datuming technique, a process of upward or downward continuation of the wave-field between two arbitrarily shaped surfaces. Wave equation datuming was applied to move shots and receivers to a given datum plane, removing time shifts related to topography and to near-surface velocity variations. The datuming procedure largely contributed to attenuate ground roll, enhance higher frequencies, increase resolution and improve the signal/noise ratio. Processed data allow recognizing geometries of crust structures differentiating seismic facies and offering a direct image of ongoing tectonic setting within variable lithologies characterizing the crust of Central Sicily. Migrated sections underline distinctive features of Hyblean Plateau foreland and above all a crustal thinning towards the Caltanissetta trough, to the contact with a likely deep Permo-Triassic rifted basin or rather a zone of a continent to oceanic transition. Inhomogeneity and fragmentation of Sicily crust, with a distinct separation of Central Sicily basin from western and eastern blocks, appear to have guided the tectonic transport inside the Caltanissetta crustal scale syncline and the accumulation of allochthonous terrains with south and north-verging thrusts. Major tectonic stack operated on the construction of a wide anticline of the Maghrebian chain in northern Sicily. Sequential south-verging imbrications of deep elements forming the anticline core denote a crust wedge indenting foreland structures. Deformation processes involved multiple detachment planes down to decoupling levels located near crust/mantle transition, supporting a presence of high-density lenses beneath the chain, interrelated to a southwards push of Tyrrhenian mantle and asthenosphere.

  4. 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

  5. Neurocitoma no sistema nervoso central

    Directory of Open Access Journals (Sweden)

    José Torquato Severo

    1973-03-01

    Full Text Available É relatado o caso de uma paciente com 6 anos de idade, hospitalizada com síndrome de hipertensão intracraniana. Após o exame neuro-radiológico que evidenciou processo expansivo frontal direito, a paciente foi submetida à cirurgia, durante a qual ocorreu o óbito. O exame histo-patológico do material retirado durante o ato operatório, permitiu o diagnóstico de neurocitoma, tumor raro no sistema nervoso central.

  6. Biomass energy in Central America

    Energy Technology Data Exchange (ETDEWEB)

    Blanco, J M [Biomass Users` Network, Regional Office for Central America and the Caribbean, San Jose (Costa Rica)

    1995-12-01

    The objective of this paper is to introduce the concept of biomass to energy issues and opportunities in Central America. In this region, made up of seven countries (Belize, Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua and Panama), the biomass sector has the potential to play a crucial role in alleviating the environmental and development predicaments faced by all economies of the region. This paper assesses the available biomass resources at the regional and country levels and gives an overview of the current utilization of biomass fuels. It also describes the overall context in which the biomass-to-energy initiatives are immersed. At the regional level, biomass energy consumption accounts for more than 50% of total energy consumption. In regard to the utilization of biomass for energy purposes, it is clear that Central America faces a critical juncture at two levels, both mainly in rural areas: in the productive sector and at the household level. The absence of sustainable development policies and practices has jeopardized the availability of biomass fuels, particularly wood. Firewood is an important source of energy for rural industries such as coffee processing, which is one of the largest productive activities in the region. This paper comments on some of the most successful technological innovations already in place in the region, for instance, the rapid development of co-generation projects by the sugar cane industry, especially in El Salvador and Guatemala, the substitution of coffee husks for firewood in coffee processing plants in Costa Rica and El Salvador and the sustainable use of pine forests for co-generation in Honduras. Only one out of every two inhabitants in Central America now has access to electricity from the public grid. Biomass fuels, mainly firewood but also, to a lesser extent, other crop residues such as corn stalks, are the main source of energy for cooking and heating by most of the population. (It is foreseen that by the end

  7. Central precocious puberty in girls

    International Nuclear Information System (INIS)

    Argyropoulou, M.; Malandry, F.; Perignon, F.; Brunelle, F.; Brauner, R.; Rappaport, R.

    1990-01-01

    The treatment of central precocious puberty (CPP) in girls depends on its etiology and evolution, the latter based on the degree of accelerated bone maturation. The goal of this paper is to assess the diagnostic value of MR imaging in studying CPP in girls. Thirty-four girls with CPP were studied with MR imaging. Pituitary gland height (PGH) was measured on a sagittal midline image and compared with normal measurements. Correlations among clinical presentation, PGH, estradiol levels, and LH/FSH ratio were evaluated

  8. Biomass energy in Central America

    International Nuclear Information System (INIS)

    Blanco, J.M.

    1995-01-01

    The objective of this paper is to introduce the concept of biomass to energy issues and opportunities in Central America. In this region, made up of seven countries (Belize, Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua and Panama), the biomass sector has the potential to play a crucial role in alleviating the environmental and development predicaments faced by all economies of the region. This paper assesses the available biomass resources at the regional and country levels and gives an overview of the current utilization of biomass fuels. It also describes the overall context in which the biomass-to-energy initiatives are immersed. At the regional level, biomass energy consumption accounts for more than 50% of total energy consumption. In regard to the utilization of biomass for energy purposes, it is clear that Central America faces a critical juncture at two levels, both mainly in rural areas: in the productive sector and at the household level. The absence of sustainable development policies and practices has jeopardized the availability of biomass fuels, particularly wood. Firewood is an important source of energy for rural industries such as coffee processing, which is one of the largest productive activities in the region. This paper comments on some of the most successful technological innovations already in place in the region, for instance, the rapid development of co-generation projects by the sugar cane industry, especially in El Salvador and Guatemala, the substitution of coffee husks for firewood in coffee processing plants in Costa Rica and El Salvador and the sustainable use of pine forests for co-generation in Honduras. Only one out of every two inhabitants in Central America now has access to electricity from the public grid. Biomass fuels, mainly firewood but also, to a lesser extent, other crop residues such as corn stalks, are the main source of energy for cooking and heating by most of the population. (It is foreseen that by the end

  9. Vulnerability in north- central Vietnam

    DEFF Research Database (Denmark)

    Casse, Thorkil; Milhøj, Anders; Nguyen, Thao Phuong

    2015-01-01

    This article examines changes in livelihood strategies in response to flooding. It does so on the basis of a household survey which was undertaken in three provinces in north central Vietnam. All households in the survey were regularly affected by flooding, but only poor households experience a l...... the impact of flooding in the provinces. The article ends by looking at the vulnerability-resilience debate concluding that the poorer households could enter a vulnerability loop, unless new strategies to cope with natural hazards are suggested....

  10. Central collisions of heavy ions

    International Nuclear Information System (INIS)

    Fung, Sun-yiu.

    1991-10-01

    This report describes the activities of the Heavy Ion Physics Group at the University of California, Riverside from October 1, 1990 to September 30, 1991. During this period, our program focuses on particle production at AGS energies, and correlation studies at the Bevalac in nucleus central collisions. We participated in the preparation of letters of intent for two RHIC experiments -- the OASIS proposal and the Di-Muon proposal -- and worked on two RHIC R ampersand D efforts -- a silicon strip detector project and a muon-identifier project. A small fraction of time was also devoted to physics programs outside the realm of heavy ion reactions by several individuals

  11. The European Central Bank and the Eurosystem

    OpenAIRE

    Carol C. Bertaut

    2002-01-01

    The Eurosystem comprises the European Central Bank at its center as well as the national central banks of the twelve countries currently participating in monetary union. The European Central Bank was established in July 1998, six months before the beginning of Stage Three of economic and monetary union. Although decisions regarding monetary policy are made centrally by the Governing Council of the Eurosystem, the operational aspects of monetary policy-including open market operations, adminis...

  12. RELATION BETWEEN ISLAMIC BANK AND CENTRAL BANK

    OpenAIRE

    PAKSOY, H. Mustafa; ABAROSS, Nour

    2015-01-01

    This study deals with the nature of Islamic banks and their features, and requirements of these features in terms of control tools and methods appropriate with the particularity of their business and their relation with the traditional central bank. At the same time aims to view the relationship between Islamic bank and central bank. To explain this relation the researcher started to explain what is the central bank, objectives of central bank, and characteristics, what is Islamic bank and ob...

  13. Accountability of central banks: aspects and quantification

    Directory of Open Access Journals (Sweden)

    J. DE HAAN

    1999-06-01

    Full Text Available The work examines the relationship between central bank independence and accountability. The authors do this by using an indicator for central bank accountability based on the laws of 16 central banks. Central bank accountability is identified as having three distinct features, namely, the explicit definition and ranking of the objectives of monetary policy, the transparency of the actual monetary policy, and the final responsibility to monetary policy.

  14. Distributed trace using central performance counter memory

    Science.gov (United States)

    Satterfield, David L.; Sexton, James C.

    2013-01-22

    A plurality of processing cores, are central storage unit having at least memory connected in a daisy chain manner, forming a daisy chain ring layout on an integrated chip. At least one of the plurality of processing cores places trace data on the daisy chain connection for transmitting the trace data to the central storage unit, and the central storage unit detects the trace data and stores the trace data in the memory co-located in with the central storage unit.

  15. The Meat Dogma Project: Exploring Nitrogen Mitigation in Denmark

    DEFF Research Database (Denmark)

    Andersen, Sandy; Graversgaard, Morten

    2017-01-01

    and consumption of meat has in this issue. Publication of relevant studies, strategies and discussions is needed. Our research analyzes both methodologies and social themes which are pertinent for developing custom-based strategies aimed at reducing the current level of meat usage in Denmark, a country...... with a high production meat industry and heavy meat consumption per capita. Along with our qualitative research, we are utilizing quantitative calculations of N-Footprint size in terms of food consumption. We conclude by discussing certain strategies which with broader implementation could result in a more...

  16. Positivist Dogmas, Rhetoric, and the Education Science Question

    Science.gov (United States)

    Howe, Kenneth R.

    2009-01-01

    Explicit versions of positivism were cast off some time ago in philosophy, but a tacit form continues to thrive in education research, exemplified by the "new scientific orthodoxy" codified in the National Research Council's "Scientific Research in Education" (2002) and reinforced in the American Educational Research Association's "Standards for…

  17. Beyond the dogma of the fixed book price agreement

    NARCIS (Netherlands)

    van der Ploeg, F.

    2004-01-01

    After describing the essential features of the book market, a welfare analysisof the fixed book price agreement is given. Allowance is made for theopportunity cost of reading. Theoretically such an agreement pushes up bookprices and depresses book sales. However, more titles will be

  18. Sõnavabaduse dogma Hollandi moodi / Kaspar Näf

    Index Scriptorium Estoniae

    Näf, Kaspar

    2008-01-01

    Šveitsi ajaloolane ja ajakirjanik leiab Hollandi parlamendisaadiku Geert Wildersi islami-vastase filmi ja ENPA endise presidendi Rene van der Lindeni arvamusavaldustega seoses, et kui sõnavabadus ja arvamuse väljendamine on eesmärk iseenesest, siis on see eriti neil juhtudel absurdne, kui seab teisi inimesi ohtu

  19. Area, length and thickness conservation: Dogma or reality?

    Science.gov (United States)

    Moretti, Isabelle; Callot, Jean Paul

    2012-08-01

    The basic assumption of quantitative structural geology is the preservation of material during deformation. However the hypothesis of volume conservation alone does not help to predict past or future geometries and so this assumption is usually translated into bed length in 2D (or area in 3D) and thickness conservation. When subsurface data are missing, geologists may extrapolate surface data to depth using the kink-band approach. These extrapolations, preserving both thicknesses and dips, lead to geometries which are restorable but often erroneous, due to both disharmonic deformation and internal deformation of layers. First, the Bolivian Sub-Andean Zone case is presented to highlight the evolution of the concepts on which balancing is based, and the important role played by a decoupling level in enhancing disharmony. Second, analogue models are analyzed to test the validity of the balancing techniques. Chamberlin's excess area approach is shown to be on average valid. However, neither the length nor the thicknesses are preserved. We propose that in real cases, the length preservation hypothesis during shortening could also be a wrong assumption. If the data are good enough to image the decollement level, the Chamberlin excess area method could be used to compute the bed length changes.

  20. 45 Gy - tolerance dose spinal cord - dogma or the facts?

    International Nuclear Information System (INIS)

    Maciejewski, B.; Hliniak, A.; Danczak-Ginalska, Z.; Meder, M.; Skolyszewski, J.; Reinfuss, M.; Korzeniowski, S.; Peszynski, J.; Jassem, J.

    1993-01-01

    Dose of 45 Gy as a tolerance dose for spinal cord was questioned based on review of clinical data. Some data show that for conventional fractionation with the dose per fraction of less than 2.0 Gy spinal cord tolerance dose may arise up to 50-55 Gy. This was the base for round-table discussion and the importance of clinical and physical risk factors of postirradiation spinal cord injury was discussed and previous diseases of spinal cord, size of dose per fraction and length of irradiated spinal cord were pointed out as high risk factors. It was concluded that from clinical point of view there is no reason and on need to verify and to increase tolerance dose for spinal cord. (author)

  1. Allergenicity of vertebrate tropomyosins: Challenging an immunological dogma.

    Science.gov (United States)

    González-Fernández, J; Daschner, A; Cuéllar, C

    With the exception of tilapia tropomyosin, other anecdotic reports of tropomyosin recognition of vertebrate origin are generally not accompanied by clinical significance and a dogmatic idea is generally accepted about the inexistence of allergenicity of vertebrate tropomyosins, based mainly on sequence similarity evaluations with human tropomyosins. Recently, a specific work-up of a tropomyosin sensitised patient with seafood allergy, demonstrated that the IgE-recognition of tropomyosin from different fish species can be clinically relevant. We hypothesise that some vertebrate tropomyosins could be relevant allergens. The hypothesis is based on the molecular evolution of the proteins and it was tested by in silico methods. Fish, which are primitive vertebrates, could have tropomyosins similar to those of invertebrates. If the hypothesis is confirmed, tropomyosin should be included in different allergy diagnosis tools to improve the medical protocols and management of patients with digestive or cutaneous symptoms after fish intake. Copyright © 2016 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

  2. Endocrine disruptors: Revisiting concepts and dogma in toxicology.

    Science.gov (United States)

    Barouki, Robert

    During the last decades, a large number of observations have shown that some exogenous substances could interfere with hormone levels or hormone action and could induce toxic effects. This has led to the identification of endocrine disruptors more than 25 years ago as a new class of toxic agents (Zoeller et al., 2014). Those widely used agents correspond to a variety of chemical classes, are not identified by their chemical structure or by a specific type of usage, but rather by their mechanisms of action; this is not unprecedented in toxicology since genotoxicants have also been identified by their mechanism of action, i.e. their ability to alter DNA structure and function. Copyright © 2017 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

  3. Eesti tants ühines Dogma-manifestiga / Tiit Tuumalu

    Index Scriptorium Estoniae

    Tuumalu, Tiit, 1971-

    2001-01-01

    "1=3 õige või vale" (idee autor ja lavastaja Jarmo Karing), kunstnik Liina Tepand, esietendus 1. märtsil Tartu Teatrilaboris; "1973. Võrrand kolme muutuja ja ühe puudujaga" ( idee autor Tiina Mölder), esietendus 1. aprillil Mustpeade Majas

  4. Six-Hours-Rule - A Dogma for Military Surgery?

    National Research Council Canada - National Science Library

    Gerngross, Heinz; Kahle, Wilhelm

    2004-01-01

    Today, the six-hours-rule is a delicate item for military logistics and it is a great challenge for medical services to provide an adequate treatment during the first hours after wounding. DEFINITION: Six-hour-rule...

  5. DOGMA AND ANTINOMY IN THE PHILOSOPHY OF SERGEY BULGAKOV

    Directory of Open Access Journals (Sweden)

    Natalya Vaganova

    2013-08-01

    Full Text Available This article examines the thought of Bulgakov as regards the dogmatic formulation of the council of Chalcedon as well as his thoughts on the Holy Eucharist. The author wishes to describe the difficult path which Bulgakov followed to arrive at his understanding of the most fundamental points of Christian doctrine and during the course of which he was initially fascinated and later disenchanted by Roman Catholicism. This rather short period, usually known by the name of the Crimean Philosophy of Bulgakov, is one of the key moments in the whole of his activity and provided the final impetus for his turn to Sophiology. The author of this article describes how the return of Bulgakov to Russian Orthodoxy was accompanied by the philosopher’s rediscovery of Sophiology. Sophiology was interpreted by Bulgakov as relieving the existing antinomy between two opposing principles in both the mystery of the Eucharist and the mystery of the Incarnation, between the divine and the mortal. The problem of the consecration of the holy gifts was met and resolved by Bulgakov in the domain of Christology and more precisely in the doctrine of the body of Christ: the earthly or material body and the glorifi ed body, the reality of Christ’s body up until the Resurrection and after the Resurrection. This teaching about the relationship between the two realities of the corporality of Christ was little studied in Orthodoxy Theology before Bulgakov. It was interpreted by Bulgakov in the light of his Sophiology: the Incarnation as the absolute realization in human form of the divine sophiological prototype. The author of this article concludes that Bulgakov’s use of Sophiology provided him with a way to oppose and overcome Kant’s transcendentalism. Thus, it became one of the major facets of Russian Philosophy

  6. Seksualiteit in de islam tussen dogma en dagelijks praktijk.

    NARCIS (Netherlands)

    Ajouaou, M.

    2016-01-01

    In the Islamic tradition, sexuality is deemed dangerous, because of its socially disruptive potential. On the other hand, however, sexual desires and pleasures are acknowledged, even apart from procreation. A key concept is ‘chastity’, which should not be equated with the requirement that women

  7. No more this than that: skeptical impression or Pyrrhonian dogma?

    Directory of Open Access Journals (Sweden)

    Necip Fikri Alican

    2017-01-01

    Full Text Available This is a defense of Pyrrhonian skepticism against the charge that the suspension of judgment based on equipollence is vitiated by the assent given to the equipollence in question. The apparent conflict has a conceptual side as well as a practical side, examined here as separate challenges with a section devoted to each. The conceptual challenge is that the skeptical transition from an equipollence of arguments to a suspension of judgment is undermined either by a logical contradiction or by an epistemic inconsistency, perhaps by both, because the determination and affirmation of equipollence is itself a judgment of sorts, one that is not suspended. The practical challenge is that, independently of any conceptual confusion or contradiction, suspending judgment in reaction to equipollence evinces doxastic commitment to equipollence, if only because human beings are not capable of making assessments requiring rational determination without believing the corresponding premises and conclusions to be true. The two analytic sections addressing these challenges are preceded by two prefatory sections, one laying out the epistemic process, the other reviewing the evidentiary context. The response from the conceptual perspective is that the suspension of judgment based on equipollence is not a reasoned conclusion adopted as the truth of the matter but a natural reaction to an impression left by the apparently equal weight of opposing arguments. The response from the practical perspective is that the acknowledgment of equipollence is not just an affirmation of the equal weight of arguments but also an admission of inability to decide, suggesting that any assent, express or implied, is thrust upon the Pyrrhonist in a state of epistemic paralysis affecting the will and the intellect on the matter being investigated. This just leaves a deep disagreement, if any, regarding whether equipollence is an inference based on discursive activity or an impression coming from passive receptivity. But this, even if resolved in favor of the critic (which it need not and ought not be, is not the same as confusion or inconsistency on the part of the Pyrrhonist, the demonstration of which is the primary aim of this paper.

  8. Transparency and Legitimacy in Chinese Criminal Procedure : Beyond Adversarial Dogmas

    NARCIS (Netherlands)

    Zhang, S.

    2017-01-01

    In recent years, the legitimacy of China's criminal justice system has been increasingly challenged by the Chinese populace, in part due to the numerous exposed miscarriages of justice. The Chinese academic mainstream as well as the political and judicial authorities have looked towards the

  9. The Chesty Puller Paragon: Leadership Dogma or Model Doctrine

    National Research Council Canada - National Science Library

    Quintrall, Mickey

    1997-01-01

    In this study, I examine whether or not the United States Marine Corps senior warrior leaders should continue to use heroic warriors from the 1942-52 era as contemporary paragons of tactical leadership...

  10. Hexoses as phloem transport sugars: the end of a dogma?

    Science.gov (United States)

    van Bel, Aart J E; Hess, Paul H

    2008-01-01

    According to most textbooks, only non-reducing carbohydrate species such as sucrose, sugar alcohols, and raffinose-family sugars function as phloem translocates. Occasional abundance of reducing sugar species (such as hexoses) in sieve-tube sap has been discarded as an experimental artefact. This study, however, discloses a widespread occurrence of hexoses in the sieve-tube sap. Phloem exudation facilitated by EDTA provided evidence that many of the members of two plant families (Ranunculaceae and Papaveraceae) investigated translocate >80% of carbohydrates in the form of hexoses. Representatives of other families also appear to translocate appreciable amounts of hexoses in the sieve tubes. Promoting effects of EDTA, activities of sucrose-degrading enzymes, and sugar uptake by micro-organisms on hexose contents of phloem exudates were checked. The rate of sucrose degradation is far too low to explain the large proportions of hexoses measured in phloem exudates; nor did other factors tested seem to stimulate the occurrence of hexoses. The validity of the approach is further supported by the virtual absence of hexoses in exudates from species that were known as exclusive sucrose transporters. This study urges a rethink of the existing views on carbohydrate transport species in the phloem stream. Hexose translocation is to be regarded as a normal mode of carbohydrate transfer by the phloem equivalent to that of sucrose, raffinose-family sugars, or sugar alcohols.

  11. Occupational health in Central America.

    Science.gov (United States)

    Wesseling, Catharina; Aragón, Aurora; Morgado, Hugo; Elgstrand, Kaj; Hogstedt, Christer; Partanen, Timo

    2002-01-01

    The 12.4 million economically active population (EAP) of the seven Central American countries includes a large informal sector. Social security covers only 14-60%. No surveillance of occupational safety and health (OSH) hazards or accidents exists. Extrapolating the incidence of occupational accidents among insured Costa Rican workers to the Central American EAP yields two million accidents yearly, still a gross underestimate. Occupational diseases are underreported, misdiagnosed, and not recognized as such. A number of regional OSH programs aim at modernization of the labor administrations and address the formal sector, in particular textile maquila, in connection with free trade agreements. The weak role of the ministries of health is expected to strengthen under the Pan American Health Organization OSH program. Employers largely influence new policies. Workers' influence on OSH policies has been weak, with only about 10% unionization rate and scarce resources and OSH knowledge. Informal workers, however, are getting organized. OSH research is underdeveloped and not linked to policy making. Construction, agriculture, and general un/underemployment are considered priorities for intervention. The informal sector needs to be included in national and regional OSH policies. Regional collaboration and international development support are of strategic importance to achieve sustainable improvement in OSH.

  12. Central Equatorial Pacific Experiment (CEPEX)

    Energy Technology Data Exchange (ETDEWEB)

    1993-01-01

    The Earth's climate has varied significantly in the past, yet climate records reveal that in the tropics, sea surface temperatures seem to have been remarkably stable, varying by less than a few degrees Celsius over geologic time. Today, the large warm pool of the western Pacific shows similar characteristics. Its surface temperature always exceeds 27[degree]C, but never 31[degree]C. Heightened interest in this observation has been stimulated by questions of global climate change and the exploration of stabilizing climate feedback processes. Efforts to understand the observed weak sensitivity of tropical sea surface temperatures to climate forcing has led to a number of competing ideas about the nature of this apparent thermostat. Although there remains disagreement on the processes that regulate tropical sea surface temperature, most agree that further progress in resolving these differences requires comprehensive field observations of three-dimensional water vapor concentrations, solar and infrared radiative fluxes, surface fluxes of heat and water vapor, and cloud microphysical properties. This document describes the Central Equatorial Pacific Experiment (CEPEX) plan to collect such observations over the central equatorial Pacific Ocean during March of 1993.

  13. Central and forward tracking collaboration

    International Nuclear Information System (INIS)

    Foster, R.; Hanson, G.; Luehring, F.; Luo, X.; Martin, B.; Ogren, H.; Rust, D.R.; Wente, E.; Adrian, B.; Alexander, D.; Ells, F.; Erdos, E.; Ford, W.T.; Johnson, D.; Lohner, M.; Rankin, P.; Schultz, G.; Newcomer, F.M.; Van Berg, R.; Williams, H.H.; Arai, Y.; Hess, D.; Kadyk, J.A.; Palounek, A.P.T.; Wise, J.; Chapman, J.W.; Dunn, A.; Edwards, M.; Hiddleston, J.W.; Payne, B.T.; Amery, C.A.; Bailey, J.M.; Dainton, J.B.; Gabathuler, E.; Maxfield, S.J.; Morton, J.M.; Muir, A.; Patel, G.D.; Sanders, P.; Raine, C.; Saxon, D.H.; Hackworth, D.T.; Swensrud, R.L.; Newfield, S.; Sadler, C.; Va'vra, J.

    1991-01-01

    The goal of this subsystem R ampersand D project is to carry out a detailed study and design of a complete wire chamber tracking system covering pseudorapidity |η| ≤ 2.5 in a solenoidal detector for the SSC. Most of our group are now part of the Solenoidal Detector Collaboration (SDC), so the work has evolved into developing a tracking system conceptual design for the SDC detector. The design discussed in this report uses straw tube drift chambers for the central tracking region. Because of the high rates in the SSC environment, a small cell design is needed for wire chambers in the central region. Straw tubes as small cells offer many advantages because the sense wire is enclosed in a continuous cathode, and the wire tension due to the sense wire only can be supported without a massive structure. The straw tubes are grouped together to form superlayers in order to provide local track segments. The superlayers are composed of modules consisting of about two hundred straw tubes enclosed in a carbon fiber composite shell. Straw tubes have been used in previous experiments for small vertex drift chambers. However, they have never before been used for a large tracking system

  14. Central bank independence and inflation revisited

    NARCIS (Netherlands)

    Klomp, Jeroen; de Haan, Jakob

    We re-examine the relationship between central bank independence (CBI), proxied by the central bank governor's turnover rate and an indicator based on central bank laws in place, and inflation using a random coefficient model with the Hildreth-Houck estimator for more than 100 countries in the

  15. Central bank independence and inflation revisited

    NARCIS (Netherlands)

    Klomp, J.G.; Haan, de J.

    2010-01-01

    We re-examine the relationship between central bank independence (CBI), proxied by the central bank governor's turnover rate and an indicator based on central bank laws in place, and inflation using a random coefficient model with the Hildreth-Houck estimator for more than 100 countries in the

  16. "Christofest" New Yorgi Central Parkis / Rael Artel

    Index Scriptorium Estoniae

    Artel, Rael, 1980-

    2004-01-01

    12. II 2005. a. avatakse Christo ja Jeanne-Claude'i keskkonnainstallatsioon "The Gates" New Yorgi Central Parkis. Paralleelselt toimub Metropolitan Muuseumis näitus "Christo and Jeanne-Claude : The Gates, Central Park, New York", kus eksponeeritakse Central Parki installatsiooni ettevalmistavaid materjale: joonistusi, diagramme, fotosid jne

  17. Accountability of Central Banks : Aspects and Quantification

    NARCIS (Netherlands)

    de Haan, J.; Amtenbrink, F.; Eijffinger, S.C.W.

    1998-01-01

    This paper starts with a discussion of the various aspects of accountability of central banks. On the basis of this discussion we construct an indicator for accountability for 16 central banks, including the European Central Bank. It is shown that the degree of accountability differs considerably

  18. Central Solenoid Insert Technical Specification

    Energy Technology Data Exchange (ETDEWEB)

    Martovetsky, Nicolai N [ORNL; Smirnov, Alexandre [ORNL

    2011-09-01

    The US ITER Project Office (USIPO) is responsible for the ITER central solenoid (CS) contribution to the ITER project. The Central Solenoid Insert (CSI) project will allow ITER validation the appropriate lengths of the conductors to be used in the full-scale CS coils under relevant conditions. The ITER Program plans to build and test a CSI to verify the performance of the CS conductor. The CSI is a one-layer solenoid with an inner diameter of 1.48 m and a height of 4.45 m between electric terminal ends. The coil weight with the terminals is approximately 820 kg without insulation. The major goal of the CSI is to measure the temperature margin of the CS under the ITER direct current (DC) operating conditions, including determining sensitivity to load cycles. Performance of the joints, ramp rate sensitivity, and stability against thermal or electromagnetic disturbances, electrical insulation, losses, and instrumentation are addressed separately and therefore are not major goals in this project. However, losses and joint performance will be tested during the CSI testing campaign. The USIPO will build the CSI that will be tested at the Central Solenoid Model Coil (CSMC) Test Facility at the Japan Atomic Energy Agency (JAEA), Naka, Japan. The industrial vendors (the Suppliers) will report to the USIPO (the Company). All approvals to proceed will be issued by the Company, which in some cases, as specified in this document, will also require the approval of the ITER Organization. Responsibilities and obligations will be covered by respective contracts between the USIPO, called Company interchangeably, and the industrial Prime Contractors, called Suppliers. Different stages of work may be performed by more than one Prime Contractor, as described in this specification. Technical requirements of the contract between the Company and the Prime Contractor will be covered by the Fabrication Specifications developed by the Prime Contractor based on this document and approved by

  19. Performance contracting in central government in Denmark

    DEFF Research Database (Denmark)

    Kristiansen, Mads Bøge

    2015-01-01

    ) are observed across central government agencies, when the content of the performance contracts is compared. This makes it interesting to examine how variation in the content of the performance contracts across agencies can be explained? Based on a broad theoretical framework in which variation......This paper looks into performance contracting in Danish central government. Management by Objectives and Results (MBOR) was adopted in central government in Denmark during the 1980s and early 1990s. In 1991, performance contracts between parent ministries and their agencies were introduced...... in Danish central government. Since their introduction, performance contracts have become central elements in the steering and management of agencies in central government in Denmark, and today they are nearly universally adopted in central government. In Denmark, the Ministry of Finance is responsible...

  20. WINE MARKETS IN CENTRAL EUROPE

    Directory of Open Access Journals (Sweden)

    Š BOJNEC

    2007-04-01

    Full Text Available This paper analyses the tendencies of grapes growing, wine trading and wine price competitiveness in Central European region. Croatia is net exporter of wines, Hungary is net exporter of grapes and wines, and Austria, Slovakia, and Slovenia are net importers of grapes and wines. Reductions in vineyards and increase in yields are found for Austria, Hungary, and Slovakia. More stable developments in vineyards, but decline in yields, are found for Croatia and Slovenia. Grape production increases in Austria, remains stable in Croatia, explores annual oscillations in Hungary, and declines in Slovakia and Slovenia. Export-to-import wine prices deteriorate for Austria and Hungary with most recent stabilization and price similarity, which hold also for Slovakia. Slovenian export-to-import wine prices are unstable, while Croatia experiences a bit higher export than import wine prices. Wine marketing, wine brand image of quality, and wine tourism are seen as tools to improve competitiveness in the wine sector.

  1. Central nervous system in leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Phair, J P; Anderson, R E; Namiki, Hideo

    1964-03-12

    The present report summarizes the pertinent clinical and pathologic findings in 165 cases of leukemia in atomic bomb exposed victims autopsied during the period 1949 to 1962 at ABCC in Hiroshima and Nagasaki, Japan. Significant parenchymal hemorrhage occurred most often in acute myelogenous leukemia and was markedly increased in patients dying with high terminal white blood cell counts. Possible mechanisms involved in the pathogenesis of cerebral hemorrhage in leukemia are discussed. Subarachnoid hemorrhage and subdural hematoma were not related to leukocytosis but appeared to be influenced by marked thrombocytopenia. Leukemic infiltrates of a diffuse nature involving the meninges were paradoxically increased in patients receiving adequate chemotherapy. Meningeal tumors did not show this peculiar relationship to therapy and were not found in association with lymphatic leukemia. Infections involving the central nervous system were confined to patients receiving chemotherapy including steroids. 39 references, 3 figures, 4 tables.

  2. Central myofibroma of the maxilla

    Directory of Open Access Journals (Sweden)

    Paramjeet Kaur

    2016-01-01

    Full Text Available Myofibroma is a rare benign localized or generalized proliferation of myofibroblastic tissue occurring mostly in infants or children. In the oral region, most lesions occur in the mandible, lip, buccal mucosa, and tongue; however, the lesions arising in the maxilla are very rare. Myofibroma has an aggressive clinical presentation and is often treated aggressively because of an inappropriate diagnosis. A unique feature of central myofibroma of the jaws is the potential for teeth and other odontogenic structures to be involved by tumor. We report a case of myofibroma arising in the left side of the maxilla of a 12-year-old girl and describe the differential diagnosis from other spindle cell lesions of neural and smooth muscle origin. We treated the case using surgical excision under general anesthesia. Immunohistochemical staining was done for establishing the diagnosis since histopathological diagnosis with conventional staining could not distinguish myofibroma from spindle cell tumors.

  3. Approximating centrality in evolving graphs: toward sublinearity

    Science.gov (United States)

    Priest, Benjamin W.; Cybenko, George

    2017-05-01

    The identification of important nodes is a ubiquitous problem in the analysis of social networks. Centrality indices (such as degree centrality, closeness centrality, betweenness centrality, PageRank, and others) are used across many domains to accomplish this task. However, the computation of such indices is expensive on large graphs. Moreover, evolving graphs are becoming increasingly important in many applications. It is therefore desirable to develop on-line algorithms that can approximate centrality measures using memory sublinear in the size of the graph. We discuss the challenges facing the semi-streaming computation of many centrality indices. In particular, we apply recent advances in the streaming and sketching literature to provide a preliminary streaming approximation algorithm for degree centrality utilizing CountSketch and a multi-pass semi-streaming approximation algorithm for closeness centrality leveraging a spanner obtained through iteratively sketching the vertex-edge adjacency matrix. We also discuss possible ways forward for approximating betweenness centrality, as well as spectral measures of centrality. We provide a preliminary result using sketched low-rank approximations to approximate the output of the HITS algorithm.

  4. Central gain control in tinnitus and hyperacusis

    Directory of Open Access Journals (Sweden)

    Benjamin D Auerbach

    2014-10-01

    Full Text Available Sensorineural hearing loss induced by noise or ototoxic drug exposure reduces the neural activity transmitted from the cochlea to the central auditory system. Despite a reduced cochlear output, neural activity from more central auditory structures is paradoxically enhanced at suprathreshold intensities. This compensatory increase in the central auditory activity in response to the loss of sensory input is referred to as central gain enhancement. Enhanced central gain is hypothesized to be a potential mechanism that gives rise to hyperacusis and tinnitus, two debilitating auditory perceptual disorders that afflict millions of individuals. This review will examine the evidence for gain enhancement in the central auditory system in response to cochlear damage. Further, it will address the potential cellular and molecular mechanisms underlying this enhancement and discuss the contribution of central gain enhancement to tinnitus and hyperacusis. Current evidence suggests that multiple mechanisms with distinct temporal and spectral profiles are likely to contribute to central gain enhancement. Dissecting the contributions of these different mechanisms at different levels of the central auditory system is essential for elucidating the role of central gain enhancement in tinnitus and hyperacusis and, most importantly, the development of novel treatments for these disorders.

  5. Central Gain Control in Tinnitus and Hyperacusis

    Science.gov (United States)

    Auerbach, Benjamin D.; Rodrigues, Paulo V.; Salvi, Richard J.

    2014-01-01

    Sensorineural hearing loss induced by noise or ototoxic drug exposure reduces the neural activity transmitted from the cochlea to the central auditory system. Despite a reduced cochlear output, neural activity from more central auditory structures is paradoxically enhanced at suprathreshold intensities. This compensatory increase in the central auditory activity in response to the loss of sensory input is referred to as central gain enhancement. Enhanced central gain is hypothesized to be a potential mechanism that gives rise to hyperacusis and tinnitus, two debilitating auditory perceptual disorders that afflict millions of individuals. This review will examine the evidence for gain enhancement in the central auditory system in response to cochlear damage. Further, it will address the potential cellular and molecular mechanisms underlying this enhancement and discuss the contribution of central gain enhancement to tinnitus and hyperacusis. Current evidence suggests that multiple mechanisms with distinct temporal and spectral profiles are likely to contribute to central gain enhancement. Dissecting the contributions of these different mechanisms at different levels of the central auditory system is essential for elucidating the role of central gain enhancement in tinnitus and hyperacusis and, most importantly, the development of novel treatments for these disorders. PMID:25386157

  6. Banco Central de Costa Rica

    Directory of Open Access Journals (Sweden)

    Sauter, Franz

    1963-06-01

    Full Text Available This new building is intended to house the various services of the Central Bank of Costa Rica. It has a prestressed concrete structure, and consists of a basement parking space for 105 vehicles, and nine storeys, providing altogether a floor surface of 12,000 ms2. The building rests on a ground area of 40 by 60 ms, and the main structure occupies 22 by 45 ms. This Bank is located in a district of narrow streets, but its main side overlooks a green open space, which will improve its visibility and appearance. The building structure is made up of a framework of prestressed beams and columns. The beams have been concreted at the site, and the joists, which are also prestressed, are factory made. This framework, at each floor level, constitutes the basis of a continuous slab, which renders the total structure exceedingly stiff. The main continuous girders span 11.22 ms spaces, and vary in cross section. The prestressing reinforcements consist of 6 Loeba type cables. This is an original design by Dr. Leonhardt, in which the cables are placed on three horizontal layers, of parabolic outline. Each cable is made up of 12 x 5.4 mm wires, with a breaking stress of 180 kg/mm2 The tensioning stress was 108 kg/mm2, and the total prestress load is 29,700 kgs. The cables run in corrugated metal tubes, and these were kept in precise position with the aid of distance pieces.El nuevo edificio, destinado a agrupar los servicios del Banco Central de Costa Rica, está constituido por una estructura de hormigón pretensado. El inmueble dispone de un sótano, estacionamiento propio para 105 vehículos y nueve plantas, con una superficie total de 12.000 metros cuadrados. Se asienta sobre una base de 40x60 m, donde se levanta un núcleo central de 22x45 metros. Está situado en un barrio de calles estrechas, pero tiene su fachada, principal frente a una zona verde que le proporcionará mayor categoría y visibilidad. La estructura se compone de una retícula de vigas

  7. ITER Central Solenoid Module Fabrication

    Energy Technology Data Exchange (ETDEWEB)

    Smith, John [General Atomics, San Diego, CA (United States)

    2016-09-23

    The fabrication of the modules for the ITER Central Solenoid (CS) has started in a dedicated production facility located in Poway, California, USA. The necessary tools have been designed, built, installed, and tested in the facility to enable the start of production. The current schedule has first module fabrication completed in 2017, followed by testing and subsequent shipment to ITER. The Central Solenoid is a key component of the ITER tokamak providing the inductive voltage to initiate and sustain the plasma current and to position and shape the plasma. The design of the CS has been a collaborative effort between the US ITER Project Office (US ITER), the international ITER Organization (IO) and General Atomics (GA). GA’s responsibility includes: completing the fabrication design, developing and qualifying the fabrication processes and tools, and then completing the fabrication of the seven 110 tonne CS modules. The modules will be shipped separately to the ITER site, and then stacked and aligned in the Assembly Hall prior to insertion in the core of the ITER tokamak. A dedicated facility in Poway, California, USA has been established by GA to complete the fabrication of the seven modules. Infrastructure improvements included thick reinforced concrete floors, a diesel generator for backup power, along with, cranes for moving the tooling within the facility. The fabrication process for a single module requires approximately 22 months followed by five months of testing, which includes preliminary electrical testing followed by high current (48.5 kA) tests at 4.7K. The production of the seven modules is completed in a parallel fashion through ten process stations. The process stations have been designed and built with most stations having completed testing and qualification for carrying out the required fabrication processes. The final qualification step for each process station is achieved by the successful production of a prototype coil. Fabrication of the first

  8. Central neural pathways for thermoregulation

    Science.gov (United States)

    Morrison, Shaun F.; Nakamura, Kazuhiro

    2010-01-01

    Central neural circuits orchestrate a homeostatic repertoire to maintain body temperature during environmental temperature challenges and to alter body temperature during the inflammatory response. This review summarizes the functional organization of the neural pathways through which cutaneous thermal receptors alter thermoregulatory effectors: the cutaneous circulation for heat loss, the brown adipose tissue, skeletal muscle and heart for thermogenesis and species-dependent mechanisms (sweating, panting and saliva spreading) for evaporative heat loss. These effectors are regulated by parallel but distinct, effector-specific neural pathways that share a common peripheral thermal sensory input. The thermal afferent circuits include cutaneous thermal receptors, spinal dorsal horn neurons and lateral parabrachial nucleus neurons projecting to the preoptic area to influence warm-sensitive, inhibitory output neurons which control thermogenesis-promoting neurons in the dorsomedial hypothalamus that project to premotor neurons in the rostral ventromedial medulla, including the raphe pallidus, that descend to provide the excitation necessary to drive thermogenic thermal effectors. A distinct population of warm-sensitive preoptic neurons controls heat loss through an inhibitory input to raphe pallidus neurons controlling cutaneous vasoconstriction. PMID:21196160

  9. Towards a centralized Grid Speedometer

    International Nuclear Information System (INIS)

    Dzhunov, I; Andreeva, J; Saiz, P; Fajardo, E; Gutsche, O; Luyckx, S

    2014-01-01

    Given the distributed nature of the Worldwide LHC Computing Grid and the way CPU resources are pledged and shared around the globe, Virtual Organizations (VOs) face the challenge of monitoring the use of these resources. For CMS and the operation of centralized workflows, the monitoring of how many production jobs are running and pending in the Glidein WMS production pools is very important. The Dashboard Site Status Board (SSB) provides a very flexible framework to collect, aggregate and visualize data. The CMS production monitoring team uses the SSB to define the metrics that have to be monitored and the alarms that have to be raised. During the integration of CMS production monitoring into the SSB, several enhancements to the core functionality of the SSB were required; They were implemented in a generic way, so that other VOs using the SSB can exploit them. Alongside these enhancements, there were a number of changes to the core of the SSB framework. This paper presents the details of the implementation and the advantages for current and future usage of the new features in SSB.

  10. The Centrality of Organization Design

    Directory of Open Access Journals (Sweden)

    Raymond E. Miles

    2012-05-01

    Full Text Available I am excited about this new journal focused on the subject of organization design. In my view, organization design is a central issue in the field of management. Designing an organization requires an understanding of strategy, as we pointed out some time ago (Miles & Snow, 1978. For example, if you want to be a prospector (a first-mover strategy, you have to design your firm to move quickly in new directions, which is likely to require that it be arranged so that various kinds of teams can interact across organizational units and levels. Designing an organization to follow a first-mover strategy also requires both an understanding of leadership and a commitment to the free flow of information throughout the organization. Leaders must understand how cross-functional teams pursue ideas and opportunities, and they must facilitate collaborative knowledge sharing to drive innovations that help the firm operate entrepreneurially. Because an organization is a complex, dynamic system, perhaps no other single topic is so deeply implanted at the core of management, organization theory, and organizational behavior as organization design. Moreover, organization design once was, and could be again, the topic of an ongoing dialogue between managers and academics focused on business organizations.

  11. Radioresistance in Central Asian tortoise

    Energy Technology Data Exchange (ETDEWEB)

    Turdyev, A.A.; Bogdanova-Berezovskaya, I.G.; Dvornikova, L.I.

    Season-related studies were conducted on the phenomenal radioresistance of the Central Asian tortoise (Testudo horsfieldii), in order to obtain greater understanding of the factors that determine this physiological uniqueness. Test animals were exposed to gamma radiation from a Co-60 source with dosages ranging from 12.9 to 25.8 Cl/kg in the spring, summer, fall, and winter. Using Pearson's ..gamma..-distribution coefficient calculations of the mean lethal dose for the season yielded 16.33 Cl/kg for winter, 10.94 Cl/kg for spring, 7.1 Cl/kg for summer, and 19.71 Cl/kg for fall. The animals were thus seen to be most susceptible to radiation damage in the spring and summer. Correlation with histological and hematological studies showed that animals irradiated in spring and summer succumbed as a result of damage to the GI and the hematopoietic systems, whereas animals that died as a result of irradiation during the fall and winter season did so because of depletion of hepatic glycogen stores. 5 references, 1 figure.

  12. Central Au on Au collisions

    Energy Technology Data Exchange (ETDEWEB)

    Alard, J.P.; Amouroux, V. [Labo de Phys. Corp., IN2P3-CRNS, Univ. Blaise Pascal, Clermont-Fd. (France); Basrak, Z. [Rudjer Boskovic Institute, Zagreb (Croatia)] [and others; FOPI-Collaboration

    1995-02-06

    In nucleus-nucleus collisions the initial relative kinetic energy of target and projectile is available for internal excitation of the interacting system; it is however still not well established to what extent local equilibrium and thermalisation occur. Local equilibrium is of interest to derive, within the formalism of transport equations and of the equation of state, (EOS), general properties of compressed and excited nuclear matter. Such approach describes in relatively simple terms the complex many body interactions occuring within extended baryonic and hadronic (or quark) matter. For a basic microscopic understanding it is highly desirable to investigate the elementary in-medium interactions in relation to the free elementary processes. Excitation function measurements of central collisions between the heaviest available nuclei (like Au on Au), supply the best ground for such studies: the highest degree of thermalisation and compression is expected for such reactions. The consideration presented here of energy thermalisation and of an expanding system clusterizing at freeze-out in a situation close to the liquid gas phase transition can be of interest to astrophysics as well as to the quark gluon plasma deconfinement studied in nucleus-nucleus collisions at the higher energy regime of CERN and Brookhaven. (orig.).

  13. Towards a centralized Grid Speedometer

    CERN Document Server

    Gutsche, Oliver

    2013-01-01

    Given the distributed nature of the grid and the way CPU resources are pledged and scared around the globe, VOs are facing the challenge to monitor the use of these resources. For CMS and the operation of centralized workflows the monitoring of how many production jobs are running and pending in the Glidein WMS production pools is very important. The Dashboard SSB (Site Status Board) provides a very flexible framework to collect, aggregate and visualize data. The CMS production monitoring team uses the SSB to define the metrics that have to be monitored and the alarms that have to be set. During the integration of the CMS production monitoring into the SSB, several enhancements to the core functionality of the SSB were implemented; all in a generic way, so that other VOs using the SSB can use them as well. Alongside these enhancements, there were a few changes to the core of the SSB framework from which the CMS production team was able to benefit. We will present the details of the implementation and the adva...

  14. Central nervous system tuberculosis: MRI

    Energy Technology Data Exchange (ETDEWEB)

    Kioumehr, F.; Dadsetan, M.R.; Rooholamini, S.A.; Au, A.

    1994-02-01

    The MRI findings of 18 proven cases of central nervous system (CNS) tuberculosis were reviewed; 10 patients were seropositive for HIV. All had medical, laboratory, or surgical proof of CNS tuberculosis. Eleven patients had meningitis, of whom two also had arachnoiditis. Five patients had focal intra-axial tuberculomas: four brain masses and one an intramedullary spinal lesion. Two patients had focal extra-axial tuberculomas: one in the pontine cistern, and one in the spine. In all 11 patients with meningitis MRI showed diffuse, thick, meningeal enhancement. All intraparenchymal tuberculomas showed low signal intensity on T2-weighted images and ring or nodular enhancement. The extra-axial tuberculomas had areas isointense or hypointense relative to normal brain and spinal cord on T2-weighted images. Although tuberculous meningitis cannot be differentiated from other meningitides on the basis of MR findings, intraparenchymal tuberculomas show characteristic T2 shortening, not found in most other space-occupying lesions. In the appropriate clinical setting, tuberculoma should be considered. (orig.)

  15. Central Nervous System Infections in Denmark

    Science.gov (United States)

    2018-02-04

    Central Nervous System Infections; Bacterial Meningitis; Viral Meningitis; Aseptic Meningitis; Encephalitis; Brain Abscess; Neuroborreliosis; Neurosyphilis; Lyme Disease; Tertiary Syphilis; Cerebral Abscess; Meningitis

  16. Central blood pressure and chronic kidney disease

    Science.gov (United States)

    Ohno, Yoichi; Kanno, Yoshihiko; Takenaka, Tsuneo

    2016-01-01

    In this review, we focused on the relationship between central blood pressure and chronic kidney diseases (CKD). Wave reflection is a major mechanism that determines central blood pressure in patients with CKD. Recent medical technology advances have enabled non-invasive central blood pressure measurements. Clinical trials have demonstrated that compared with brachial blood pressure, central blood pressure is a stronger risk factor for cardiovascular (CV) and renal diseases. CKD is characterized by a diminished renal autoregulatory ability, an augmented direct transmission of systemic blood pressure to glomeruli, and an increase in proteinuria. Any elevation in central blood pressure accelerates CKD progression. In the kidney, interstitial inflammation induces oxidative stress to handle proteinuria. Oxidative stress facilitates atherogenesis, increases arterial stiffness and central blood pressure, and worsens the CV prognosis in patients with CKD. A vicious cycle exists between CKD and central blood pressure. To stop this cycle, vasodilator antihypertensive drugs and statins can reduce central blood pressure and oxidative stress. Even in early-stage CKD, mineral and bone disorders (MBD) may develop. MBD promotes oxidative stress, arteriosclerosis, and elevated central blood pressure in patients with CKD. Early intervention or prevention seems necessary to maintain vascular health in patients with CKD. PMID:26788468

  17. Current status of laparoscopic central pancreatectomy

    Directory of Open Access Journals (Sweden)

    CAO Yang

    2017-04-01

    Full Text Available Central pancreatectomy is an ideal surgical procedure for the treatment of benign or low-grade malignant tumors in the pancreatic neck or the proximal body of the pancreas, and it can preserve more normal pancreatic tissue in order to reduce the incidence of endocrine and exocrine insufficiency after surgery. Although some clinical studies have demonstrated the feasibility and safety of this procedure, laparoscopic central pancreatectomy was technically challenging with a few number of cases. This article reviews the current status of laparoscopic central pancreatectomy and introduces our clinical experience of laparoscopic central pancreatectomy and pancreaticojejunostomy.

  18. Central cell confinement in MFTF-B

    International Nuclear Information System (INIS)

    Jong, R.A.

    1981-01-01

    The point code TANDEM has been used to survey the range of plasma parameters which can be attained in MFTF-B. The code solves for the electron and ion densities and temperatures in the central cell, yin-yang, barrier, and A-cell regions as well as the plasma potential in each region. In these studies, the A-cell sloshing ion beams were fixed while the neutral beams in the yin-yang and central cell, the gas feed in the central cell, and the applied ECRH power β, central cell ion density and temperature, and the confining potential are discussed

  19. Risk Premium and Central Bank Intervention

    OpenAIRE

    Pinar Ozlu

    2006-01-01

    This study examines the relation between the risk premium and central bank intervention. Forward rates are calculated for the Turkish Lira-USD exchange market and then the effect of central bank intervention on the risk premium is estimated. Using high quality daily intervention data from the Central Bank of Turkey as well as implied forward rates, an MA (21)-GARCH (1,1) model is estimated. Both purchases and sales of US dollars by the Central Bank of Turkey appear to have no effect on the si...

  20. Indonesia: population central to development.

    Science.gov (United States)

    1994-05-01

    The Indonesian representative to the 50th session of the Economic and Social Commission for Asia and the Pacific (ESCAP) reiterated the issue of population as being central to sustainable development. Indonesia recognizes that quality of life, which can be improved with education, health, skills, productivity, self reliance, and resiliency, has an impact on the process of development. Without quality improvements, large numbers of people become a burden. Population programs must aim to reduce population growth rates simultaneously with enhancing the quality of life. Women's improvement in education, health, and employment opportunities must be accomplished because of women's important role in national development. The goals of sustainable development are to maintain a balance between human needs and desires of the population and available resources and the environment. Sustainable development is necessary for present and future generations. The Fourth Asian and Pacific Population Conference was held in Bali in August 1992, at which time the Bali Declaration was affirmed. At the January 1994 meeting of officials regarding the implementation of the Bali Declaration held in Bangkok, Thailand, the Indonesian representative stressed the importance of the vigorous involvement of the ESCAP secretariat in planning and implementing population programs in the region. Recommendations included in the Bali Declaration are related to the issues being addressed at the International Conference on Population and Development to be held in Cairo in September 1994. The secretariat was also asked by the Indonesian representative to disseminate information on the implementation of the Bali Declaration through regular publications and other appropriate venues. Comprehensive data collection and information systems were needed on the links between population, development, and resources.

  1. Centralized consolidation/recycling center

    International Nuclear Information System (INIS)

    St. Georges, L.T.; Poor, A.D.

    1995-05-01

    There are approximately 175 separate locations on the Hanford Site where dangerous waste is accumulated in hundreds of containers according to compatibility. Materials that are designated as waste could be kept from entering the waste stream by establishing collection points for these materials and wastes and then transporting them to a centralized consolidation/recycling center (hereinafter referred to as the consolidation center). Once there the materials would be prepared for offsite recycling. This document discusses the removal of batteries, partially full aerosol cans, and DOP light ballasts from the traditional waste management approach, which eliminates 89 satellite accumulation areas from the Hanford Site (43 for batteries, 33 for aerosols, and 13 for DOP ballasts). Eliminating these 89 satellite accumulation areas would reduce by hundreds the total number of containers shipped offsite as hazardous waste (due to the increase in containers when the wastes that are accumulated are segregated according to compatibility for final shipment). This new approach is in line with the U.S. Environmental Protection Agency's (EPA) draft Universal Waste Rules for these open-quotes nuisanceclose quotes and common waste streams. Additionally, future reviews of other types of wastes that can be handled in this less restrictive and more cost-effective manner will occur as part of daily operations at the consolidation center. The Hanford Site has been identified as a laboratory for reinventing government by the Secretary of the U.S. Department of Energy (DOE), Hazel O'Leary, and as a demonstration zone where open-quotes innovative ideas, processes and technologies can be created, tested and demonstrated.close quotes Additionally, DOE, EPA, and the Washington State Department of Ecology (Ecology) have agreed to cut Hanford cleanup costs by $1 billion over a 5-year period

  2. A global central banker competency model

    Directory of Open Access Journals (Sweden)

    David W. Brits

    2014-07-01

    Full Text Available Orientation: No comprehensive, integrated competency model exists for central bankers. Due to the importance of central banks in the context of the ongoing global financial crisis, it was deemed necessary to design and validate such a model. Research purpose: To craft and validate a comprehensive, integrated global central banker competency model (GCBCM and to assess whether central banks using the GCBCM for training have a higher global influence. Motivation for the study: Limited consensus exists globally about what constitutes a ‘competent’ central banker. A quantitatively validated GCBCM would make a significant contribution to enhancing central banker effectiveness, and also provide a solid foundation for effective people management. Research approach, design and method: A blended quantitative and qualitative research approach was taken. Two sets of hypotheses were tested regarding the relationships between the GCBCM and the training offered, using the model on the one hand, and a central bank’s global influence on the other. Main findings: The GCBCM was generally accepted across all participating central banks globally, although some differences were found between central banks with higher and lower global influence. The actual training offered by central banks in terms of the model, however, is generally limited to technical-functional skills. The GCBCM is therefore at present predominantly aspirational. Significant differences were found regarding the training offered. Practical/managerial implications: By adopting the GCBCM, central banks would be able to develop organisation-specific competency models in order to enhance their organisational capabilities and play their increasingly important global role more effectively. Contribution: A generic conceptual framework for the crafting of a competency model with evaluation criteria was developed. A GCBCM was quantitatively validated.

  3. Connecting Students, Creating Futures at Central Campus

    Science.gov (United States)

    Rosin, Julie; Erbes, Elizabeth; Britt, James; Good, Bill

    2012-01-01

    Des Moines is an urban community located in the heart of Iowa. Des Moines Public Schools serves 32,000 students in a system with 62 buildings, including Central Campus--a Regional Academy. Central Campus is housed in four buildings, including the main campus at 1800 Grand located on the western edge of downtown Des Moines. As a regional academy,…

  4. International Regulation of Central Arctic Ocean Fisheries

    NARCIS (Netherlands)

    Molenaar, E.J.

    Due in particular to the impacts of climate change, the adequacy of the international regulation of Central Arctic Ocean fisheries has come under increasing scrutiny in recent years. As shown in this article, however, international regulation of Central Arctic Ocean fisheries is by no means entirely

  5. Centralized rehabilitation after servere traumatic brain injury

    DEFF Research Database (Denmark)

    Engberg, Aase Worså; Liebach, Annette; Nordenbo, Annette Mosbæk

    2006-01-01

    OBJECTIVES: To present results from the first 3 years of centralized subacute rehabilitation after very severe traumatic brain injury (TBI), and to compare results of centralized versus decentralized rehabilitation. MATERIAL AND METHODS: Prospectively, the most severely injured group of adults fr...

  6. An overview of CMS central hadron calorimeter

    CERN Document Server

    Katta, S

    2002-01-01

    The central hadron calorimeter for CMS detector is a sampling calorimeter with active medium as scintillator plates interleaved with brass absorber plates. It covers the central pseudorapidity region (¿ eta ¿<3.0). The design and construction aspects are reported. The status of construction and assembly of various subdetectors of HCAL are presented. (5 refs).

  7. CENTRAL BANKING IN THE NEW ERA

    Directory of Open Access Journals (Sweden)

    Bilal Bagis

    2017-12-01

    Full Text Available This paper analyzes the evolution of central banking, and in particular the American experience of central banking. It provides projections for the future of central banking in the new era of post 2008. The paper initially demonstrates recent improvements in the financial and banking sectors, regulations and different measures of monetary and financial rules both in the USA and the rest of the advanced economies. Then, it claims institutions, such as central banks, will gain new objectives and more significance in this new era and thus will be given new roles, over time and along with the improvements and deepening in the financial system. The paper argues centuries long central bank evolution is not complete yet and that more objectives should be expected to come forward. In that line, there is need for a shift in the conventional policy measures. New trends in central banking such as the helicopter money, popular nominal GDP targeting regime and the retro developmental central banking are all critically analyzed. The paper provides a breakdown of financial development and central banking activities in a historical context and provides a rationale and a new basis for possible future innovations.

  8. African Journals Online: Central African Republic

    African Journals Online (AJOL)

    African Journals Online: Central African Republic. Home > African Journals Online: Central African Republic. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register · Browse By Category · Browse Alphabetically · Browse By Country · List All Titles · Free to read Titles This ...

  9. Visualizing the Central Limit Theorem through Simulation

    Science.gov (United States)

    Ruggieri, Eric

    2016-01-01

    The Central Limit Theorem is one of the most important concepts taught in an introductory statistics course, however, it may be the least understood by students. Sure, students can plug numbers into a formula and solve problems, but conceptually, do they really understand what the Central Limit Theorem is saying? This paper describes a simulation…

  10. Central nervous system depressant activityof Leonurus sibiricus ...

    African Journals Online (AJOL)

    The methanol extract of aerial parts of Leonurus sibiricus was shown to possess central nervous system depressant action by significantly decreased the time of onset of sleep and potentiated the pentobarbital induced sleeping time in mice. Keywords: Leonurus sibiricus, labiatae, central nervous depressant, sedation

  11. Genetics Home Reference: congenital central hypoventilation syndrome

    Science.gov (United States)

    ... Kravis EM, Zhou L, Rand CM, Weese-Mayer DE. Congenital central hypoventilation syndrome: PHOX2B mutations and phenotype. Am J Respir Crit ... BA, Leurgans SE, Berry-Kravis EM, Weese-Mayer DE. Congenital central hypoventilation syndrome: PHOX2B genotype determines risk for sudden death. Pediatr ...

  12. Switchings, extensions, and reductions in central digraphs

    DEFF Research Database (Denmark)

    Kündgen, André; Leander, Gregor; Thomassen, Carsten

    2011-01-01

    A directed graph is called central if its adjacency matrix A satisfies the equation A2=J, where J is the matrix with a 1 in each entry. It has been conjectured that every central directed graph can be obtained from a standard example by a sequence of simple operations called switchings, and also ...

  13. Nuclear Energy in Central Europe 98, Proceedings

    International Nuclear Information System (INIS)

    Ravnik, M.; Jencic, I.; Zagar, T.

    1998-01-01

    Regional Meeting for Nuclear Energy in Central Europe is an annual meeting of the Nuclear Society of Slovenia. The proceedings contain 63 articles from Slovenia, sorounding countries and countries of the Central and Eastern European Region. Topics are: Research Reactors, Nuclear Methods, Reactor Physics, Thermal Hydraulics, Structural Analysis, Probabilistic Safety Assessment, Severe Accidents, NPP Operation and Nuclear Waste disposal

  14. Computing betweenness centrality in external memory

    DEFF Research Database (Denmark)

    Arge, Lars; Goodrich, Michael T.; Walderveen, Freek van

    2013-01-01

    Betweenness centrality is one of the most well-known measures of the importance of nodes in a social-network graph. In this paper we describe the first known external-memory and cache-oblivious algorithms for computing betweenness centrality. We present four different external-memory algorithms...

  15. Central control system for the EAST tokamak

    International Nuclear Information System (INIS)

    Sun Xiaoyang; Ji Zhenshan; Wu Yicun; Luo Jiarong

    2008-01-01

    The architecture, the main function and the design scheme of the central control system and the collaboration system of EAST tokamak are described. The main functions of the central control system are to supply a union control interface for all the control, diagnoses, and data acquisition (DAQ) subsystem and it is also designed to synchronize all those subsystem. (authors)

  16. The Cartan Matrix of a Centralizer Algebra

    Indian Academy of Sciences (India)

    2010-12-20

    Dec 20, 2010 ... The centralizer algebra of a matrix consists of those matrices that commute with it. We investigate the basic representation-theoretic invariants of centralizer algebras, namely their radicals, projective indecomposable modules, injective indecomposable modules, simple modules and Cartan matrices.

  17. Centralization and Decentralization in American Education Policy

    Science.gov (United States)

    DeBoer, Jennifer

    2012-01-01

    This article examines the trend toward centralization in American education policy over the last century through a variety of lenses. The overall picture that emerges is one of a continuous tug-of-war, with national and local policymakers stumbling together toward incrementally more standardized and centralized policies. There is a center of power…

  18. Decentralization or centralization: striking a balance.

    Science.gov (United States)

    Dirschel, K M

    1994-09-01

    An Executive Vice President for Nursing can provide the necessary link to meet diverse clinical demands when encountering centralization--decentralization decisions. Centralized communication links hospital departments giving nurses a unified voice. Decentralization acknowledges the need for diversity and achieves the right balance of uniformity through a responsive communications network.

  19. Central bank independence and financial instability

    NARCIS (Netherlands)

    Klomp, J.G.; de Haan, J.

    2009-01-01

    It has been argued that central bank independence (CBI) may not only be beneficial for reaching the objective of price stability, but also for maintaining financial stability. Greater independence from external pressure implies that central banks are less politically constrained in acting to prevent

  20. Junk DNA and the long non-coding RNA twist in cancer genetics

    NARCIS (Netherlands)

    H. Ling (Hui); K. Vincent; M. Pichler; R. Fodde (Riccardo); I. Berindan-Neagoe (Ioana); F.J. Slack (Frank); G.A. Calin (George)

    2015-01-01

    textabstractThe central dogma of molecular biology states that the flow of genetic information moves from DNA to RNA to protein. However, in the last decade this dogma has been challenged by new findings on non-coding RNAs (ncRNAs) such as microRNAs (miRNAs). More recently, long non-coding RNAs

  1. Fulltext PDF

    Indian Academy of Sciences (India)

    Madhu urs

    dogma is something which a true believer cannot doubt”. (Judson 1996) ... with no experimental support (Crick 1988; Judson 1996). During his whole life, Crick ... helping to eliminate lines of research leading to dead ends. The choice of the .... As in the previous example, it is easy to show that it was not the Central. Dogma ...

  2. A new paradigm of modern central banking

    Directory of Open Access Journals (Sweden)

    Aleksandra Szunke

    2013-05-01

    Full Text Available The changes in the modern monetary policy, which took place at the beginning of the twenty-first century, in response to the global financial crisis led to the transformation of the place and the role of central banks. The strategic aim of the central monetary institutions has become preventing financial instability. So far, central banks have defined financial stability as a public good, which took care independently of other monetary purposes (Pyka, 2010. Unconventional monetary policy resulted in changes the global central banking. The aim of the study is to identify a new paradigm of the role and place of the central bank in the financial system and its new responsibilities, aimed at countering financial instability.

  3. Central station market development strategies for photovoltaics

    Science.gov (United States)

    1980-01-01

    Federal market development strategies designed to accelerate the market penetration of central station applications of photovoltaic energy system are analyzed. Since no specific goals were set for the commercialization of central station applications, strategic principles are explored which, when coupled with specific objectives for central stations, can produce a market development implementation plan. The study includes (1) background information on the National Photovoltaic Program, photovoltaic technology, and central stations; (2) a brief market assessment; (3) a discussion of the viewpoints of the electric utility industry with respect to solar energy; (4) a discussion of commercialization issues; and (5) strategy principles. It is recommended that a set of specific goals and objectives be defined for the photovoltaic central station program, and that these goals and objectives evolve into an implementation plan that identifies the appropriate federal role.

  4. Actual versus Perceived Central Bank Transparency : The Case of the European Central Bank

    NARCIS (Netherlands)

    van der Cruijsen, C.A.B.; Eijffinger, S.C.W.

    2007-01-01

    Central banks have become more and more transparent about their monetary policy making process. In the central bank transparency lit- erature the distinction between actual and perceived central bank trans- parency is often lacking. However, as perceptions are crucial for the ac- tions of economic

  5. Central hypothyroidism - a neglected thyroid disorder.

    Science.gov (United States)

    Beck-Peccoz, Paolo; Rodari, Giulia; Giavoli, Claudia; Lania, Andrea

    2017-10-01

    Central hypothyroidism is a rare and heterogeneous disorder that is characterized by a defect in thyroid hormone secretion in an otherwise normal thyroid gland due to insufficient stimulation by TSH. The disease results from the abnormal function of the pituitary gland, the hypothalamus, or both. Moreover, central hypothyroidism can be isolated or combined with other pituitary hormone deficiencies, which are mostly acquired and are rarely congenital. The clinical manifestations of central hypothyroidism are usually milder than those observed in primary hypothyroidism. Obtaining a positive diagnosis for central hypothyroidism can be difficult from both a clinical and a biochemical perspective. The diagnosis of central hypothyroidism is based on low circulating levels of free T 4 in the presence of low to normal TSH concentrations. The correct diagnosis of both acquired (also termed sporadic) and congenital (also termed genetic) central hypothyroidism can be hindered by methodological interference in free T 4 or TSH measurements; routine utilization of total T 4 or T 3 measurements; concurrent systemic illness that is characterized by low levels of free T 4 and normal TSH concentrations; the use of the sole TSH-reflex strategy, which is the measurement of the sole level of TSH, without free T 4 , if levels of TSH are in the normal range; and the diagnosis of congenital hypothyroidism based on TSH analysis without the concomitant measurement of serum levels of T 4 . In this Review, we discuss current knowledge of the causes of central hypothyroidism, emphasizing possible pitfalls in the diagnosis and treatment of this disorder.

  6. Report of the Central Tracking Group

    International Nuclear Information System (INIS)

    Cassel, D.G.; Hanson, G.G.

    1986-10-01

    Issues involved in building a realistic central tracking system for a general-purpose 4π detector for the SSC are addressed. Such a central tracking system must be capable of running at the full design luminosity of 10 33 cm -2 s -1 . Momentum measurement was required in a general-purpose 4π detector. Limitations on charged particle tracking detectors at the SSC imposed by rates and radiation damage are reviewed. Cell occupancy is the dominant constraint, which led us to the conclusion that only small cells, either wires or straw tubes, are suitable for a central tracking system at the SSC. Mechanical problems involved in building a central tracking system of either wires or straw tubes were studied, and our conclusion was that it is possible to build such a large central tracking system. Of course, a great deal of research and development is required. We also considered central tracking systems made of scintillating fibers or silicon microstrips, but our conclusion was that neither is a realistic candidate given the current state of technology. We began to work on computer simulation of a realistic central tracking system. Events from interesting physics processes at the SSC will be complex and will be further complicated by hits from out-of-time bunch crossings and multiple interactions within the same bunch crossing. Detailed computer simulations are needed to demonstrate that the pattern recognition and tracking problems can be solved

  7. Centralized rehabilitation after servere traumatic brain injury

    DEFF Research Database (Denmark)

    Engberg, Aase Worså; Liebach, Annette; Nordenbo, Annette Mosbæk

    2006-01-01

    OBJECTIVES: To present results from the first 3 years of centralized subacute rehabilitation after very severe traumatic brain injury (TBI), and to compare results of centralized versus decentralized rehabilitation. MATERIAL AND METHODS: Prospectively, the most severely injured group of adults from...... post-trauma was 0.29, and at 1 year 0.055 per 100,000 population. By comparison of 39 patients from the centralized unit injured in 2000-2003 with 21 patients injured in 1982, 1987 or 1992 and with similar PTA- and age distributions and male/female ratio, Glasgow Outcome Scale score at discharge...

  8. Centralized vs. decentralized child mental health services.

    Science.gov (United States)

    Adams, M S

    1977-09-01

    One of the basic tenets of the Community Mental Health Center movement is that services should be provided in the consumers' community. Various centers across the country have attempted to do this in either a centralized or decentralized fashion. Historically, most health services have been provided centrally, a good example being the traditional general hospital with its centralized medical services. Over the years, some of these services have become decentralized to take the form of local health centers, health maintenance organizations, community clinics, etc, and now various large mental health centers are also being broken down into smaller community units. An example of each type of mental health facility is delineated here.

  9. Environmental Protection Agency - EPA Pub Central

    Data.gov (United States)

    U.S. Environmental Protection Agency — PubMed Central (PMC) is a full-text, online archive of journal literature operated by the National Library of Medicine. The EPA is using PMC to permanently preserve...

  10. Central venous obstruction in the thorax

    International Nuclear Information System (INIS)

    Collin, G.; Jones, R.G.; Willis, A.P.

    2015-01-01

    Central venous stenosis and occlusion can occur secondary to a spectrum of conditions ranging from aggressive malignancy to benign extrinsic anatomical compression in otherwise healthy individuals. Irrespective of aetiology, significant morbidity in the acute setting and long term can occur unless prompt accurate diagnosis and appropriate management is initiated, the radiologist being central to both. The present review will provide radiologists with a thorough illustration and explanation of the range of central venous conditions in the thorax (including deep vein thrombosis, thoracic outlet syndrome, haemodialysis, and malignancy related causes), the salient imaging findings and interventional management using case examples from the authors' practice. - Highlights: • We show a range of causes of central venous disease in the thorax. • We provide information about different imaging and management strategies. • We show several cases with successes and complications of endovascular management

  11. Centrality measures for immunization of weighted networks

    Directory of Open Access Journals (Sweden)

    Mohammad Khansari

    2016-03-01

    Full Text Available Effective immunization of individual communities with minimal cost in vaccination has made great discussion surrounding the realm of complex networks. Meanwhile, proper realization of relationship among people in society and applying it to social networks brings about substantial improvements in immunization. Accordingly, weighted graph in which link weights represent the intensity and intimacy of relationships is an acceptable approach. In this work we employ weighted graphs and a wide variety of weighted centrality measures to distinguish important individuals in contagion of diseases. Furthermore, we propose new centrality measures for weighted networks. Our experimental results show that Radiality-Degree centrality is satisfying for weighted BA networks. Additionally, PageRank-Degree and Radiality-Degree centralities showmoreacceptable performance in targeted immunization of weighted networks.

  12. Central Oregon 6 arc-second DEM

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The 6-second Central Coastal Oregon Elevation Grid provides bathymetric data in ASCII raster format of 6-second resolution in geographic coordinates. This grid is...

  13. On the centrality of some graphs

    Directory of Open Access Journals (Sweden)

    Vecdi Aytac

    2017-10-01

    Full Text Available A central issue in the analysis of complex networks is the assessment of their stability and vulnerability. A variety of measures have been proposed in the literature to quantify the stability of networks and a number of graph-theoretic parameters have been used to derive formulas for calculating network reliability. Different measures for graph vulnerability have been introduced so far to study different aspects of the graph behavior after removal of vertices or links such as connectivity, toughness, scattering number, binding number, residual closeness and integrity. In this paper, we consider betweenness centrality of a graph. Betweenness centrality of a vertex of a graph is portion of the shortest paths all pairs of vertices passing through a given vertex. In this paper, we obtain exact values for betweenness centrality for some wheel related graphs namely gear, helm, sunflower and friendship graphs.

  14. Early macroseismic maps in Central Europe

    Czech Academy of Sciences Publication Activity Database

    Kozák, Jan; Vaněk, Jiří

    2013-01-01

    Roč. 1, č. 2 (2013), s. 43-53 ISSN 2330-1740 Institutional support: RVO:67985530 Keywords : macroseismic maps * intensity scales * Central Europe * 19th century Subject RIV: DC - Siesmology, Volcanology, Earth Structure

  15. Psychosocial Factors and Central Sensitivity Syndromes

    OpenAIRE

    Adams, Leah M.; Turk, Dennis C.

    2015-01-01

    Central sensitivity syndromes (CSSs) represent a heterogeneous group of disorders (e.g., fibromyalgia [FM], irritable bowel syndrome [IBS], chronic headache, temporomandibular disorders [TMDs], pelvic pain syndromes) that share common symptoms, with persistent pain being the most prominent feature.

  16. NCPC Central Files Information System (CFIS)

    Data.gov (United States)

    National Capital Planning Commission — This dataset contains records from NCPC's Central Files Information System (CFIS), which is a comprehensive database of projects submitted to NCPC for design review...

  17. Magnetic anomalies in Central Bengal fan

    Digital Repository Service at National Institute of Oceanography (India)

    Rao, T.C.S.; Lakshminarayana, S.; Sarma, K.V.L.N.S.

    Total magnetic field anomalies recorded over the Central Bengal Fan are analysed and the depths to the magnetic basement are computed using the analytical signal and the Werner deconvolution methods. To the west and east of 85 degrees E...

  18. BWR plant advanced central control panel PODIA

    International Nuclear Information System (INIS)

    Fujii, K.; Hayakawa, H.; Ikeda, Y.; Neda, T.; Suto, O.; Takamiya, S.

    1983-01-01

    BWR plant central control panels have become more and more enlarged and complicated recently due to the magnification of the scale of a plant and the requirement to reinforce safety. So, it is important to make communication between men and the complicated central control panel smooth. Toshiba has developed an advanced central control panel, named PODIA, which uses many computers and color CRTs, and PODIA is now in the stage of application to practical plants. In this article, the writers first touch upon control functions transition in the central control room, the PODIA position concerning the world-wide trend in this technology phase and the human engineering on the design. Then they present concrete design concepts for the control board and computer system which constitute PODIA

  19. Central corneal thickness among glaucoma patients attending ...

    African Journals Online (AJOL)

    AAU_CHS

    ocular pressure measurement and is different among different ethnic population and subtypes of glaucoma. The central corneal thickness of different subtypes of glaucoma at Menelik II Hospital ... Intraocular pressure is a key element in the.

  20. Initial TMX central-cell ICRH experiments

    International Nuclear Information System (INIS)

    Molvik, A.W.; Coffield, F.E.; Falabella, S.; Griffin, D.; McVey, B.; Pickles, W.; P.

    1980-01-01

    Four topics are discussed in this report: the feasibility of applying ion cyclotron resonance heating (ICRH) in the TMX central cell, some applications of heating, the results of preliminary experiments, and plans for further ICRH experiments

  1. Central Asian Snow Cover from Hydrometeorological Surveys

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Central Asian Snow Cover from Hydrometeorological Surveys data are based on observations made by personnel for three river basins: Amu Darya, Sir Darya, and...

  2. Veterans Affairs Central Cancer Registry (VACCR)

    Data.gov (United States)

    Department of Veterans Affairs — The Veterans Affairs Central Cancer Registry (VACCR) receives and stores information on cancer diagnosis and treatment constraints compiled and sent in by the local...

  3. Central Gulf of Alaska Rockfish Permit Program

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The North Pacific Fishery Management Council adopted the Central Gulf of Alaska Rockfish Program (Rockfish Program) on June 14, 2010, to replace the expiring Pilot...

  4. Nutrient Limitation in Central Red Sea Mangroves

    KAUST Repository

    Almahasheer, Hanan; Duarte, Carlos M.; Irigoien, Xabier

    2016-01-01

    Red Sea have characteristic heights of ~2 m, suggesting nutrient limitation. We assessed the nutrient status of mangrove stands in the Central Red Sea and conducted a fertilization experiment (N, P and Fe and various combinations thereof) on 4-week

  5. Development of the ZEUS central tracking detector

    Science.gov (United States)

    Brooks, C. B.; Bullock, F. W.; Cashmore, R. J.; Devenish, R. C.; Foster, B.; Fraser, T. J.; Gibson, M. D.; Gilmore, R. S.; Gingrich, D.; Harnew, N.; Hart, J. C.; Heath, G. P.; Hiddleston, J.; Holmes, A. R.; Jamdagni, A. K.; Jones, T. W.; Llewellyn, T. J.; Long, K. R.; Lush, G. J.; Malos, J.; Martin, N. C.; McArthur, I.; McCubbin, N. A.; McQuillan, D.; Miller, D. B.; Mobayyen, M. M.; Morgado, C.; Nash, J.; Nixon, G.; Parham, A. G.; Payne, B. T.; Roberts, J. H. C.; Salmon, G.; Saxon, D. H.; Sephton, A. J.; Shaw, D.; Shaw, T. B.; Shield, P. D.; Shulman, J.; Silvester, I.; Smith, S.; Strachan, D. E.; Tapper, R. J.; Tkaczyk, S. M.; Toudup, L. W.; Wallis, E. W.; Wastie, R.; Wells, J.; White, D. J.; Wilson, F. F.; Yeo, K. L.; ZEUS-UK Collaboration

    1989-11-01

    The design concept and development of the ZEUS central tracking detector is described. This is a cylindrical drift chamber designed for track reconstruction, electron identification and event triggering in a high-crossing-rate, high-magnetic-field environment.

  6. Development of the ZEUS central tracking detector

    International Nuclear Information System (INIS)

    Brooks, C.B.; Cashmore, R.J.; Gingrich, D.; Harnew, N.; Heath, G.P.; Holmes, A.R.; Martin, N.C.; McArthur, I.; Nash, J.; Salmon, G.; Shield, P.D.; Silvester, I.; Smith, S.; Wastie, R.; Wells, J.; Jamdagni, A.K.; McQuillan, D.; Miller, D.B.; Mobayyen, M.M.; Shulman, J.; Toudup, L.W.

    1989-01-01

    The design concept and development of the ZEUS central tracking detector is described. This is a cylindrical drift chamber designed for track reconstruction, electron identification and event triggering in a high-crossing-rate, high-magnetic-field environment. (orig.)

  7. The CDF central and endwall hadron calorimeter

    International Nuclear Information System (INIS)

    Bertolucci, S.; Cordelli, M.; Eposito, B.; Curatolo, M.; Giromini, P.; Miscetti, S.; Sansoni, A.; Barnes, V.E.; Di Virgilio, A.; Garfinkel, A.F.; Kuhlmann, S.E.; Laasanen, A.T.

    1988-01-01

    The CDF central and endwall hadron calorimeter covers the polar region between 30 0 and 150 0 and a full 2π in azimuth. It consists of 48 steel-scintillator central modules with 2.5 cm sampling and 48 steel-scintillator endwall modules with 5.0 cm sampling. A general description of the detector is given. Calibration techniques and performance are discussed. Some results of the test beam studies are shown. (orig.)

  8. Central Institute for Nuclear Research (1956 - 1979)

    International Nuclear Information System (INIS)

    Flach, G.; Bonitz, M.

    1979-12-01

    The Central Institute for Nuclear Research (ZfK) of the Academy of Sciences of the GDR is presented. This first overall survey covers the development of the ZfK since 1956, the main research activities and results, a description of the departments responsible for the complex implementation of nuclear research, the social services for staff and the activities of different organizations in the largest central institute of the Academy of Sciences of the GDR. (author)

  9. Transient central diabetes insipidus following ischemic stroke

    Directory of Open Access Journals (Sweden)

    Muthukrishnan Jayaraman

    2013-01-01

    Full Text Available Central Diabetes Insipidus (CDI following ischemic infarction of the brain has been described as a rare presentation. Posterior pituitary ischemia has also been postulated as a possible cause of idiopathic CDI. We encountered a young male with bilateral extensive ischemic infarction sustained at high altitude, who had transient polyuria due to central diabetes insipidus, requiring desmopressin therapy. DI completely resolved during the course of his neurological recovery.

  10. Cancer Control in Central and Eastern Europe

    OpenAIRE

    La Vecchia, Carlo; Conte, Pierfranco

    2016-01-01

    In Central and Western Europe, cancer mortality is declining at slower rates as compared with rates in the rest of the world. More than a generation has now passed since the end of nonmarket economies in Central and Eastern Europe. It is time for this area of the continent to close the gap in cancer incidence and mortality rates between it and Western Europe and other high-income areas of the world.

  11. Focal lesions in the central nervous system

    International Nuclear Information System (INIS)

    Fabrikant, J.I.; Budinger, T.F.; Tobias, C.A.; Born, J.L.

    1980-01-01

    This report reviews the animal and human studies currently in progress at LBL with heavy-ion beams to induce focal lesions in the central nervous system, and discusses the potential future prospects of fundamental and applied brain research with heavy-ion beams. Methods are being developed for producing discrete focal lesions in the central nervous system using the Bragg ionization peak to investigate nerve pathways and neuroendocrine responses, and for treating pathological disorders of the brain

  12. Central structure preservation of the reversal sign

    International Nuclear Information System (INIS)

    Chen, C.J.

    1999-01-01

    We report serial changes of central structure preservation of the reversal sign in a case of child abuse. The serial CT images show that the relatively spared attenuation at the basal ganglia, thalami, and posterior fossa develops before the occurrence of transtentorial herniation. This finding makes the theory that central preservation of the reversal sign is due to pressure relief after transtentorial herniation less convincible. (orig.)

  13. Centralized, Decentralized, and Hybrid Purchasing Organizations

    DEFF Research Database (Denmark)

    Bals, Lydia; Turkulainen, Virpi

    This paper addresses one of the focal issues in purchasing and supply management – global sourcing – from an organizational design perspective. In particular, we elaborate the traditional classification of global sourcing organization designs into centralized, decentralized, and hybrid models. We...... organization we can identify organization designs beyond the classical centralization-decentralization continuum. We also provide explanations for the observed organization design at GCC. The study contributes to research on purchasing and supply management as well as research on organization design....

  14. Central structure preservation of the reversal sign

    Energy Technology Data Exchange (ETDEWEB)

    Chen, C.J. [Dept. of Diagnostic Radiology, Chang Gung Memorial Hospital, Taipei (Taiwan)

    1999-12-01

    We report serial changes of central structure preservation of the reversal sign in a case of child abuse. The serial CT images show that the relatively spared attenuation at the basal ganglia, thalami, and posterior fossa develops before the occurrence of transtentorial herniation. This finding makes the theory that central preservation of the reversal sign is due to pressure relief after transtentorial herniation less convincible. (orig.)

  15. Midwifery education in Central-Eastern Europe.

    Science.gov (United States)

    Mivšek, Polona; Baškova, Martina; Wilhelmova, Radka

    2016-02-01

    Problems in midwifery in many Central-Eastern European countries are very similar; it is possible to speak about the evolving Central-Eastern model of midwifery care. The educational models of this region have a relatively strong theoretical part; however, there is an insufficient practical dimension. Theoretical part of midwifery education in the universities is relatively autonomous and is slowly changing the professional identity of graduates. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Central Odontogenic Fibroma of Simple Type

    Directory of Open Access Journals (Sweden)

    Prasanth Thankappan

    2014-01-01

    Full Text Available Central odontogenic fibroma (COF is an extremely rare benign tumor that accounts for 0.1% of all odontogenic tumors. It is a lesion associated with the crown of an unerupted tooth resembling dentigerous cyst. In this report, a 10-year-old male patient is presented, who was diagnosed with central odontogenic fibroma of simple type from clinical, radiological, and histopathological findings.

  17. Dynamics-based centrality for directed networks.

    Science.gov (United States)

    Masuda, Naoki; Kori, Hiroshi

    2010-11-01

    Determining the relative importance of nodes in directed networks is important in, for example, ranking websites, publications, and sports teams, and for understanding signal flows in systems biology. A prevailing centrality measure in this respect is the PageRank. In this work, we focus on another class of centrality derived from the Laplacian of the network. We extend the Laplacian-based centrality, which has mainly been applied to strongly connected networks, to the case of general directed networks such that we can quantitatively compare arbitrary nodes. Toward this end, we adopt the idea used in the PageRank to introduce global connectivity between all the pairs of nodes with a certain strength. Numerical simulations are carried out on some networks. We also offer interpretations of the Laplacian-based centrality for general directed networks in terms of various dynamical and structural properties of networks. Importantly, the Laplacian-based centrality defined as the stationary density of the continuous-time random walk with random jumps is shown to be equivalent to the absorption probability of the random walk with sinks at each node but without random jumps. Similarly, the proposed centrality represents the importance of nodes in dynamics on the original network supplied with sinks but not with random jumps.

  18. Making Central Banks Serve The Real Economy

    Directory of Open Access Journals (Sweden)

    Suleika Reiners

    2013-10-01

    Full Text Available The challenge is to redirect central bank money into the real economy and to the needs of society. If new money is issued to expand the productive capacity, there is no reason for inflation. Long-term financing could become available at an affordable price. Central bank money must not replace a sound tax system and the distribution of income and wealth, but complement them. The remaining task, apart from the financing of real needs, is the prevention of speculative asset price inflation. For this, central banks and regulators should install debt brakes for the financial sector. Furthermore, independent monetary policy calls for capital account management. It enables national central banks to find space for the conduct of their own policies in an interdependent global economy. Coordination between central banks and governments might increase as policies combine monetary, fiscal and regulatory facets. The future role of central banks should particularly lie in their insights regarding capital flows and leverage cycles and in their ability to create and withdraw money, depend­ing on economic conditions.

  19. Central alarm system replacement in NPP Krsko

    International Nuclear Information System (INIS)

    Cicvaric, D.; Susnic, M.; Djetelic, N.

    2004-01-01

    Current NPP Krsko central alarm system consists of three main segments. Main Control Board alarm system (BETA 1000), Ventilation Control Board alarm system (BETA 1000) and Electrical Control Board alarm system (BETA 1100). All sections are equipped with specific BetaTone audible alarms and silence, acknowledge as well as test push buttons. The main reason for central alarm system replacement is system obsolescence and problems with maintenance, due to lack of spare parts. Other issue is lack of system redundancy, which could lead to loss of several Alarm Light Boxes in the event of particular power supply failure. Current central alarm system does not provide means of alarm optimization, grouping or prioritization. There are three main options for central alarm system replacement: Conventional annunciator system, hybrid annunciator system and advanced alarm system. Advanced alarm system implementation requires Main Control Board upgrade, integration of process instrumentation and plant process computer as well as long time for replacement. NPP Krsko has decided to implement hybrid alarm system with patchwork approach. The new central alarm system will be stand alone, digital, with advanced filtering and alarm grouping options. Sequence of event recorder will be linked with plant process computer and time synchronized with redundant GPS signal. Advanced functions such as link to plant procedures will be implemented with plant process computer upgrade in outage 2006. Central alarm system replacement is due in outage 2004.(author)

  20. Russian Language in the Central Asia Region

    Directory of Open Access Journals (Sweden)

    Ksenia Petrovna Borishpolets

    2014-01-01

    Full Text Available He article is devoted to the role of the Russian language in Central Asia and its development perspectives in the context of the Eurasian integration processes. Russian language has a long historical tradition in Central Asia and hasn't lost its importance even at the background of two waves of "derussification" that took place after 1991. Notwithstanding the decrease of the status, it keeps substantial public significance. During last two decades only in Turkmenistan we are witnessing the decrease in spreading of the Russian language among title population of the Central Asia region. Its positions as an active communication channel is secured not only by the social tradition, but also by the competitiveness of the Russian language education, advantages of the bilingual business, requirements of the labor migrants, HR interests and by some other pragmatic thoughts, which role within the context of Eurasian economic integration will increase. Despite the difficulties, it is too early to speak about the decrease of the Russian language in the Central Asia region. It is more likely that the institutes itself that maintain it and promoting it are at the low ebb. New scales and forms of practical work that is interested not only for Russia, but also Central Asia countries are required. Pressure on the resources of the Russian language increases the possibility of ethnic conflicts and strengthens the positions of political radicalism in Central Asia region.