WorldWideScience

Sample records for identify specific aspects

  1. Leprosy Specific Orofacial Aspects

    Directory of Open Access Journals (Sweden)

    Vathsala Naik

    2011-01-01

    Full Text Available Leprosy is a chronic infection caused by Mycobactenum leprae, GHA- Hansen first identified the organism in 1873, so called Hansen disease. Mycobacterium leprae is a bacillus that presents a peculiar tropism for the skin and peripheral nerves. The upper airway has a great importance as a route of M. Leprae infection. The clinical spectrum of leprosy ranges from the tuberculoid form (TT to the disseminative and progressive lepromatous form (LL. Cell-mediated immunity is considered to be the crucial defence against the disease and the magnitude of this immunity defines the extent of the disease- Facial lesions in leprosy can occur in all form of the disease and also in lepra reaction, oral lesions are rare but, when present, occur in the lepromatous form

  2. Recent advances in cross-cultural measurement in psychiatric epidemiology: utilizing 'what matters most' to identify culture-specific aspects of stigma.

    Science.gov (United States)

    Yang, Lawrence Hsin; Thornicroft, Graham; Alvarado, Ruben; Vega, Eduardo; Link, Bruce George

    2014-04-01

    While stigma measurement across cultures has assumed growing importance in psychiatric epidemiology, it is unknown to what extent concepts arising from culture have been incorporated. We utilize a formulation of culture-as the everyday interactions that 'matter most' to individuals within a cultural group-to identify culturally-specific stigma dynamics relevant to measurement. A systematic literature review from January 1990 to September 2012 was conducted using PsycINFO, Medline and Google Scholar to identify articles studying: (i) mental health stigma-related concepts; (ii) ≥ 1 non-Western European cultural group. From 5292 abstracts, 196 empirical articles were located. The vast majority of studies (77%) utilized adaptations of existing Western-developed stigma measures to new cultural groups. Extremely few studies (2.0%) featured quantitative stigma measures derived within a non-Western European cultural group. A sizeable amount (16.8%) of studies employed qualitative methods to identify culture-specific stigma processes. The 'what matters most' perspective identified cultural ideals of the everyday activities that comprise 'personhood' of 'preserving lineage' among specific Asian groups, 'fighting hard to overcome problems and taking advantage of immigration opportunities' among specific Latino-American groups, and 'establishing trust among religious institutions due to institutional discrimination' among African-American groups. These essential cultural interactions shaped culture-specific stigma manifestations. Mixed method studies (3.6%) corroborated these qualitative results. Quantitatively-derived, culturally-specific stigma measures were lacking. Further, the vast majority of qualitative studies on stigma were conducted without using stigma-specific frameworks. We propose the 'what matters most' approach to address this key issue in future research.

  3. ASPECTS REGARDING NEUROMARKETING SPECIFIC RESEARCH METHODS

    Directory of Open Access Journals (Sweden)

    MIRELA-CRISTINA VOICU

    2012-05-01

    Full Text Available Information is one of the most important resources that a company must posses. Some informations are hidden deep in the black box - the mind of the consumer. Neuromarketing helps us find what is inside of the black box without troubling the consumer with questions that he doesn’t want to answer or that he can’t answer. Today because of an extensive research in mapping cortical and subcortical activity in association with behaviors and thoughts, the confidence in neurological data is growing. Thanks to discoveries in perceptual sciences we can identify the parts of the brain that are responsible for the phenomena that we experience daily. For all those interested in information obtained through neuromarketing techniques it becomes evident that there are corresponding neural substrates of consumer decision making process and these substrates can be observed, measured, and possibly manipulated. The following paper reveals some important aspects of the use of neuromarketing in studying consumer behavior by presenting the concepts, methods and techniques used under this sophisticated name, the limitations and advantages of using neuromarketing techniques and the importance of this type of information in decision making process at a company level.

  4. Lung transplantation in children. Specific aspects.

    Science.gov (United States)

    Moreno Galdó, Antonio; Solé Montserrat, Juan; Roman Broto, Antonio

    2013-12-01

    Lung transplantation has become in recent years a therapeutic option for infantswith terminal lung disease with similar results to transplantation in adults.In Spain, since 1996 114 children lung transplants have been performed; this corresponds to3.9% of the total transplant number.The most common indication in children is cystic fibrosis, which represents between 70-80% of the transplants performed in adolescents. In infants common indications areinterstitial lung disease and pulmonary hypertension.In most children a sequential double lung transplant is performed, generally with the help ofextracorporeal circulation. Lung transplantation in children presents special challenges in monitoring and follow-up, especially in infants, given the difficulty in assessing lung function and performing transbronchial biopsies.There are some more specific complications in children like postransplant lymphoproliferative syndrome or a greater severity of respiratory virus infections .After lung transplantation children usually experiment a very important improvement in their quality of life. Eighty eight per cent of children have no limitations in their activity after 3 years of transplantation.According to the registry of the International Society for Heart & Lung Transplantation (ISHLT) survival at 5 years of transplantation is 54% and at 10 years is around 35%. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

  5. Identifying specific interstellar polycyclic aromatic hydrocarbons

    International Nuclear Information System (INIS)

    Mulas, Giacomo; Malloci, Giuliano; Porceddu, Ignazio

    2005-01-01

    Interstellar Polycyclic Aromatic Hydrocarbons (PAHs) have been thought to be ubiquitous for more than twenty years, yet no single species in this class has been identified in the Interstellar Medium (ISM) to date. The unprecedented sensitivity and resolution of present Infrared Space Observatory (ISO) and forthcoming Herschel observations in the far infrared spectral range will offer a unique way out of this embarrassing impasse

  6. Specific aspects of radiotherapy of malignant tumors in childhood

    International Nuclear Information System (INIS)

    Bek, V.; Abrahamova, J.

    1987-01-01

    Based on the experience with radiotherapy of malignant tumors in 1839 children treated at the Oncological Clinic in Prague from 1946 to 1985, the conclusion is arrived at that some specific aspects of radiotherapy of tumors in children, such as kinetics and biological features are so important that it can be considered a special sub-discipline of clinical radiotherapy. An opinion is expressed about the application of irradiation in non-malignant affections in children. (author). 2 figs., 4 tabs., 25 refs

  7. Foreign language teaching for specific purposes: basic aspects

    Directory of Open Access Journals (Sweden)

    Svitlana Grynyuk

    2016-03-01

    Full Text Available The present article is an attempt to understand, analyse and provide an overall picture on basic aspects of English for Specific Purposes: its definition, scope, historical background, characteristics, types and aims. It also discusses the ESP teaching objectives, the role of ESP teacher and the training process to become an ESP teacher, the purpose of an ESP course and an ESP program.We see a clear rationale, amongst the variety of contradicting views on ESP policy, in coming to an agreement finally that ESP is the teaching of English to the learners who have specific goals and purposes: professional, academic or scientific.The article analyses the main roles and functions of teachers of foreign languages for specific purposes. It outlines the general tasks and responsibilities of higher education teachers whose professional activity is multispectral and multifunctiona; it also analyses the ESP courses and their specific features

  8. ASPECTS OF SEASONALITY TOURISTIC ACTIVITY SPECIFIC TO MAMAIA STATION

    Directory of Open Access Journals (Sweden)

    Mariana C. JUGANARU

    2017-05-01

    Full Text Available The study of phenomena and social-economic processes under the aspect of their evolution in time, mainly on a short term or intra-annual represents a preoccupation at a micro and macroeconomic level. For the tourism operators, this process includes knowing the touristic market and the anticipations of its evolution, as an important condition for taking decisions in their activity. The aim of this work is to analyze the touristic activity according to seasonality in Mamaia station, using qualitative and quantitative research methods. The study is important through the aspects that emphasize the specific evolution of the touristic activity from this station. For this aim, a database was formed by the monthly values of three indicators of the touristic activity (number of arrivals, number of overnights and the average duration of the stay from the period 2010-2016, using a series of statistic and econometric instruments. The results of the research can be proved by the units that maintain or are connected to the touristic activity, but also to the local administration, in making up the attenuation strategy of the touristic activity concerning the seasonality of Mamaia. Also, the work is a case study for the work with the students (especially, for tourism economy, applied statistics in tourism and marketing.

  9. Specific aspects for Cernavoda - Unit 1 NPP life assurance

    International Nuclear Information System (INIS)

    Rucareanu, R.

    2002-01-01

    Full text: The main scope of a Plant Life Management Program is to operate the NPP in a safe manner and at a competitive cost during the reactor life. To achieve this goal, it is important to continuously evaluate the degradation of the main structures and components of the NPP. Background -Cernavoda NPP design life is 30 years. Compared with this target, the operation history is not long (Unit 1 is in commercial operation since 1997). It is still important to begin a plant life management program early to identify the critical components and structures, to establish the data needed for their monitoring and to find methods to mitigate their degradation. A specific aspect for Cernavoda NPP - Unit 1 is the long delay between the fabrication of the main components and the start-up. Most components were procured 10-15 years before start-up. First criticality was achieved in 1996, but the containment perimeter wall sliding was complete in 1983, the Calandria vessel was installed in 1985, the Steam Generators were in position in 1987, the fuel channels were installed in 1989. In evaluating the history of these components, the preservation period must be observed. For Unit 2, which will be in service around 2005, the delay will be longer. For this reason, CNCAN (the Romanian Regulatory Authority) imposed, as a condition to resume the work, to evaluate the ageing of the existing components and structures in order to establish their acceptability for use in the plant. The results of this evaluation can be used as references for subsequent evaluations. Plant Life Assurance Programme - The first step of a PLIM programme is to identify the components and structures that are important for the plant life management. Critical components and structures selection is done using the following criteria: safety criteria - components and structures whose failure can cause a release of radioactivity or which have to mitigate the release of radioactivity in case of a failure of other

  10. Combinatorial Drug Screening Identifies Ewing Sarcoma-specific Sensitivities

    DEFF Research Database (Denmark)

    Radic-Sarikas, Branka; Tsafou, Kalliopi P; Emdal, Kristina B.

    2017-01-01

    Improvements in survival for Ewing sarcoma pediatric and adolescent patients have been modest over the past 20 years. Combinations of anticancer agents endure as an option to overcome resistance to single treatments caused by compensatory pathways. Moreover, combinations are thought to lessen any...... associated adverse side effects through reduced dosing, which is particularly important in childhood tumors. Using a parallel phenotypic combinatorial screening approach of cells derived from three pediatric tumor types, we identified Ewing sarcoma-specific interactions of a diverse set of targeted agents...... including approved drugs. We were able to retrieve highly synergistic drug combinations specific for Ewing sarcoma and identified signaling processes important for Ewing sarcoma cell proliferation determined by EWS-FLI1 We generated a molecular target profile of PKC412, a multikinase inhibitor with strong...

  11. Combinatorial Drug Screening Identifies Ewing Sarcoma-specific Sensitivities.

    Science.gov (United States)

    Radic-Sarikas, Branka; Tsafou, Kalliopi P; Emdal, Kristina B; Papamarkou, Theodore; Huber, Kilian V M; Mutz, Cornelia; Toretsky, Jeffrey A; Bennett, Keiryn L; Olsen, Jesper V; Brunak, Søren; Kovar, Heinrich; Superti-Furga, Giulio

    2017-01-01

    Improvements in survival for Ewing sarcoma pediatric and adolescent patients have been modest over the past 20 years. Combinations of anticancer agents endure as an option to overcome resistance to single treatments caused by compensatory pathways. Moreover, combinations are thought to lessen any associated adverse side effects through reduced dosing, which is particularly important in childhood tumors. Using a parallel phenotypic combinatorial screening approach of cells derived from three pediatric tumor types, we identified Ewing sarcoma-specific interactions of a diverse set of targeted agents including approved drugs. We were able to retrieve highly synergistic drug combinations specific for Ewing sarcoma and identified signaling processes important for Ewing sarcoma cell proliferation determined by EWS-FLI1 We generated a molecular target profile of PKC412, a multikinase inhibitor with strong synergistic propensity in Ewing sarcoma, revealing its targets in critical Ewing sarcoma signaling routes. Using a multilevel experimental approach including quantitative phosphoproteomics, we analyzed the molecular rationale behind the disease-specific synergistic effect of simultaneous application of PKC412 and IGF1R inhibitors. The mechanism of the drug synergy between these inhibitors is different from the sum of the mechanisms of the single agents. The combination effectively inhibited pathway crosstalk and averted feedback loop repression, in EWS-FLI1-dependent manner. Mol Cancer Ther; 16(1); 88-101. ©2016 AACR. ©2016 American Association for Cancer Research.

  12. Identifying plant traits: a key aspect for suitable species selection in ecological restoration of semiarid slopes

    Science.gov (United States)

    Bochet, Esther; García-Fayos, Patricio

    2017-04-01

    In the context of ecological restoration, one of the greatest challenges for practitioners and scientists is to select suitable species for revegetation purposes. In semiarid environments where restoration projects often fail, little attention has been paid so far to the contribution of plant traits to species success. The objective of this study was to (1) identify plant traits associated with species success on four roadside situations along an erosion-productivity gradient, and (2) to provide an ecological framework for selecting suitable species on the basis of their morphological and functional traits, applied to semiarid environments. We analyzed the association of 10 different plant traits with species success of 296 species surveyed on the four roadside situations in a semiarid region (Valencia, Spain). Plant traits included general plant traits (longevity, woodiness) and more specific root-, seed- and leaf-related traits (root type, sprouting ability, seed mucilage, seed mass, seed susceptibility to removal, specific leaf area and leaf dry matter content). All of them were selected according to the prevailing limiting ecogeomorphological processes acting along the erosion-productivity gradient. We observed strong shifts along the erosion-productivity gradient in the traits associated to species success. At the harshest end of the gradient, the most intensely eroded and driest one, species success was mainly associated to seed resistance to removal by runoff and to resistance to drought. At the opposite end of the gradient, the most productive one, species success was associated to a competitive-ruderal plant strategy (herbaceous successful species with high specific leaf area and low leaf dry matter content). Our study provides an ecologically-based approach for selecting suitable native species on the basis or their morphological and functional traits and supports a differential trait-based selection of species as regards roadslope type and aspect. In

  13. Combinatorial Drug Screening Identifies Ewing Sarcoma-specific Sensitivities

    DEFF Research Database (Denmark)

    Radic-Sarikas, Branka; Tsafou, Kalliopi P; Emdal, Kristina B.

    2017-01-01

    Improvements in survival for Ewing sarcoma pediatric and adolescent patients have been modest over the past 20 years. Combinations of anticancer agents endure as an option to overcome resistance to single treatments caused by compensatory pathways. Moreover, combinations are thought to lessen any...... including approved drugs. We were able to retrieve highly synergistic drug combinations specific for Ewing sarcoma and identified signaling processes important for Ewing sarcoma cell proliferation determined by EWS-FLI1 We generated a molecular target profile of PKC412, a multikinase inhibitor with strong...

  14. The specific aspects for the ASSET methodology implementation in Romania

    Energy Technology Data Exchange (ETDEWEB)

    Serbanescu, D [National Commission for Nuclear Activities Control of Romania (Romania)

    1997-10-01

    The main aspects of the implementation of a root cause analysis methodology are as follows: The Test Operating Licence requires that a systematical root cause analysis method for the event analysis to clarify the three questions from the ASSET methodology has to be implemented; A Training seminar on the ASSET methodology for the plant staff was performed at Cernavoda 1 NPP in April 1997, with the IAEA support; The self assessment process for the events which occurred during commissioning phases has to be performed by the plant up to the end of this year; An ASSET Peer Review of the Plant Self Assessment is planned in 1998; The Regulatory Authority has the task to evaluated independently the plant conclusions on various events. The tool used by CNCAN is the ASSET methodology.

  15. Specific aspects of turbulent flow in rectangular ducts

    Directory of Open Access Journals (Sweden)

    Stanković Branislav D.

    2017-01-01

    Full Text Available The essential ideas of investigations of turbulent flow in a straight rectangular duct are chronologically presented. Fundamentally significant experimental and theoretical studies for mathematical modeling and numerical computations of this flow configuration are analyzed. An important physical aspect of this type of flow is presence of secondary motion in the plane perpendicular to the streamwise direction, which is of interest from both the engineering and the scientific viewpoints. The key facts for a task of turbulence modeling and optimal choice of the turbulence model are obtained through careful examination of physical mechanisms that generate secondary flows. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no.TR-33018: Increase in Energy and Ecology Efficiency of Processes in Pulverized Coal-Fired Furnace and Optimization of Utility Steam Boiler Air Pre-heater by Using In-House Developed Software Tools

  16. [Immigration in the countries of the Gulf: some specific aspects].

    Science.gov (United States)

    Labib, A

    1987-06-01

    "This essay analyses some aspects of the in-migration flows to the Gulf countries, coming from other Arab countries as well as developing nations. Since the 80's, the Gulf countries have endorsed a restrictive policy concerning manpower import, even though they still need foreign workers. The Gulf countries pursue this policy as they fear that the presence of millions of foreign labourers will create social tension. The situation of the foreign labour force is uncertain and is bound to the role of the middleman, the local kafil, and that of the recruiting agencies. Rotation of foreign workers is very high. It has reached the 10 million mark in ten years." (SUMMARY IN ENG) excerpt

  17. The specific aspects for the ASSET methodology implementation in Romania

    International Nuclear Information System (INIS)

    Serbanescu, D.

    1997-01-01

    The main aspects of the implementation of a root cause analysis methodology are as follows: The Test Operating Licence requires that a systematical root cause analysis method for the event analysis to clarify the three questions from the ASSET methodology has to be implemented; A Training seminar on the ASSET methodology for the plant staff was performed at Cernavoda 1 NPP in April 1997, with the IAEA support; The self assessment process for the events which occurred during commissioning phases has to be performed by the plant up to the end of this year; An ASSET Peer Review of the Plant Self Assessment is planned in 1998; The Regulatory Authority has the task to evaluated independently the plant conclusions on various events. The tool used by CNCAN is the ASSET methodology

  18. Identifying the sociological implications of the main aspects affecting the optimal sporting career development

    OpenAIRE

    2014-01-01

    M.Phil. (Sport Management) This study is strengthened by several studies that have indicated that the dualist nature of student-athletes is problematic, as well as the management thereof. The study aimed to identify the sociological implications of the main aspects affecting the optimal sporting career development in athletics (throwers) at University of Johannesburg Sport, and offers recommendations for managing student-athletes. The methods utilized for this study included: i) self-desig...

  19. SEVERAL ASPECTS REGARDING THE SPECIFIC ACTIVITIES FROM MUREŞ DEFILE

    Directory of Open Access Journals (Sweden)

    George-Bogdan TOFAN

    2013-12-01

    Full Text Available The geographical location, as well as the natural conditions (the relief’s morphometry, less than favourable climatic conditions, as well as the presence of shallow soils played a deciding role in developing some activities characteristic to mountain areas, mainly represented by forestry and animal husbandry, with peaks and lows caused by social and historical factors that also affected the population of the area. Agriculture became one of the most important components of the defile’s economy, and still remains the main source of nourishment and income for a rather significant part of the population. When it comes to industry, it developed based on the extraction and exploitation of the area’s natural riches (construction rocks, mineral waters, timber, which are then incorporated into the economic circuit. The tertiary activities, in a strong correlation with the territory’s specificity, are less representative, trade being the one activity that stands out (timber, mineral water, construction rocks.

  20. Sex-specific aspects of endogenous retroviral insertion and deletion.

    Science.gov (United States)

    Gemmell, Patrick; Hein, Jotun; Katzourakis, Aris

    2013-11-07

    We wish to understand how sex and recombination affect endogenous retroviral insertion and deletion. While theory suggests that the risk of ectopic recombination will limit the accumulation of repetitive DNA in areas of high meiotic recombination, the experimental evidence so far has been inconsistent. Under the assumption of neutrality, we examine the genomes of eighteen species of animal in order to compute the ratio of solo-LTRs that derive from insertions occurring down the male germ line as opposed to the female one (male bias). We also extend the simple idea of comparing autosome to allosome in order to predict the ratio of full-length proviruses we would expect to see under conditions of recombination linked deletion or otherwise. Using our model, we predict the ratio of allosomal to autosomal full-length proviruses to lie between32 and 23 under increasing male bias in mammals and between 1 and 2 under increasing male bias in birds. In contrast to our expectations, we find that a pattern of male bias is not universal across species and that there is a frequent overabundance of full-length proviruses on the allosome beyond the ratios predicted by our model. We use our data as a whole to argue that full-length proviruses should be treated as deleterious mutations or as effectively neutral mutations whose persistence in a full-length state is linked to the rate of meiotic recombination and whose origin is not universally male biased. These conclusions suggest that retroviral insertions on the allosome may be more prolific and that it might be possible to identify mechanisms of replication that are enhanced in the female sex.

  1. Tissue-type-specific transcriptome analysis identifies developing xylem-specific promoters in poplar.

    Science.gov (United States)

    Ko, Jae-Heung; Kim, Hyun-Tae; Hwang, Ildoo; Han, Kyung-Hwan

    2012-06-01

    Plant biotechnology offers a means to create novel phenotypes. However, commercial application of biotechnology in crop improvement programmes is severely hindered by the lack of utility promoters (or freedom to operate the existing ones) that can drive gene expression in a tissue-specific or temporally controlled manner. Woody biomass is gaining popularity as a source of fermentable sugars for liquid fuel production. To improve the quantity and quality of woody biomass, developing xylem (DX)-specific modification of the feedstock is highly desirable. To develop utility promoters that can drive transgene expression in a DX-specific manner, we used the Affymetrix Poplar Genome Arrays to obtain tissue-type-specific transcriptomes from poplar stems. Subsequent bioinformatics analysis identified 37 transcripts that are specifically or strongly expressed in DX cells of poplar. After further confirmation of their DX-specific expression using semi-quantitative PCR, we selected four genes (DX5, DX8, DX11 and DX15) for in vivo confirmation of their tissue-specific expression in transgenic poplars. The promoter regions of the selected DX genes were isolated and fused to a β-glucuronidase (GUS)-reported gene in a binary vector. This construct was used to produce transgenic poplars via Agrobacterium-mediated transformation. The GUS expression patterns of the resulting transgenic plants showed that these promoters were active in the xylem cells at early seedling growth and had strongest expression in the developing xylem cells at later growth stages of poplar. We conclude that these DX promoters can be used as a utility promoter for DX-specific biomass engineering. © 2012 The Authors. Plant Biotechnology Journal © 2012 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

  2. A qualitative analysis of aspects of treatment that adolescents with anorexia identify as helpful.

    Science.gov (United States)

    Zaitsoff, Shannon; Pullmer, Rachelle; Menna, Rosanne; Geller, Josie

    2016-04-30

    This study aimed to identify aspects of treatment that adolescents with anorexia nervosa (AN) believe are helpful or unhelpful. Adolescent females receiving treatment for AN or subthreshold AN (n=21) were prompted during semi-structured interviews to generate responses to open-ended questions on what they felt would be most helpful or unhelpful in treating adolescents with eating disorders. Eight codes were developed and the two most frequently endorsed categories were (1) Alliance, where the therapist demonstrates clinical expertise and also expresses interest in the patient (n=21, 100.0%), and (2) Client Involvement in treatment (n=16, 76.2%). These top two categories were shared by participants with AN versus subthreshold AN and participants with high versus low readiness to change their dietary restriction behaviours. Development of the coding scheme and sample participant responses will be discussed. The integration of identified factors into empirically supported treatments for adolescent AN, such as Family-based Treatment, will be considered. This study provides initial information regarding aspects of treatment that adolescents identify as most helpful or unhelpful in their treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Identifying aspects of neighbourhood deprivation associated with increased incidence of schizophrenia.

    Science.gov (United States)

    Bhavsar, Vishal; Boydell, Jane; Murray, Robin; Power, Paddy

    2014-06-01

    Several studies have found an association between area deprivation and incidence of schizophrenia. However, not all studies have concurred and definitions of deprivation have varied between studies. Relative deprivation and inequality seem to be particularly important, but which aspects of deprivation or how this effect might operate is not known. The Lambeth Early Onset case register is a database of all cases of first episode psychosis aged 16 to 35years from the London Borough of Lambeth, a highly urban area. We identified 405 people with first onset schizophrenia who presented between 2000 and 2007. We calculated the overall incidence of first onset schizophrenia and tested for an association with area-level deprivation, using a multi-domain index of deprivation (IMD 2004). Specific analyses into associations with individual sub-domains of deprivation were then undertaken. Incidence rates, directly standardized for age and gender, were calculated for Lambeth at two geographical levels (small and large neighbourhood level). The Poisson regression model predicting incidence rate ratios for schizophrenia using overall deprivation score was statistically significant at both levels after adjusting for ethnicity, ethnic density, population density and population turnover. The incidence rate ratio for electoral ward deprivation was 1.03 (95% CI=1.004-1.04) and for the super output area deprivation was 1.04 (95% CI=1.02-1.06). The individual domains of crime, employment deprivation and educational deprivation were statistically significant predictors of incidence but, after adjusting for the other domains as well as age, gender, ethnicity and population density, only crime and educational deprivation, remained statistically significant. Low income, poor housing and deprived living environment did not predict incidence. In a highly urban area, an association was found between area-level deprivation and incidence of schizophrenia, after controlling for age, gender

  4. Graph-based specification and verification for aspect-oriented languages

    NARCIS (Netherlands)

    Staijen, T.

    2010-01-01

    Aspect-oriented software development aims at improving separation of concerns at all levels in the software development life-cycle, from architecture to code implementation. In this thesis we strive to develop verification methods specifically for aspect-oriented programming languages. For this

  5. Utilization of genomic signatures to identify phenotype-specific drugs.

    Directory of Open Access Journals (Sweden)

    Seiichi Mori

    2009-08-01

    Full Text Available Genetic and genomic studies highlight the substantial complexity and heterogeneity of human cancers and emphasize the general lack of therapeutics that can match this complexity. With the goal of expanding opportunities for drug discovery, we describe an approach that makes use of a phenotype-based screen combined with the use of multiple cancer cell lines. In particular, we have used the NCI-60 cancer cell line panel that includes drug sensitivity measures for over 40,000 compounds assayed on 59 independent cells lines. Targets are cancer-relevant phenotypes represented as gene expression signatures that are used to identify cells within the NCI-60 panel reflecting the signature phenotype and then connect to compounds that are selectively active against those cells. As a proof-of-concept, we show that this strategy effectively identifies compounds with selectivity to the RAS or PI3K pathways. We have then extended this strategy to identify compounds that have activity towards cells exhibiting the basal phenotype of breast cancer, a clinically-important breast cancer characterized as ER-, PR-, and Her2- that lacks viable therapeutic options. One of these compounds, Simvastatin, has previously been shown to inhibit breast cancer cell growth in vitro and importantly, has been associated with a reduction in ER-, PR- breast cancer in a clinical study. We suggest that this approach provides a novel strategy towards identification of therapeutic agents based on clinically relevant phenotypes that can augment the conventional strategies of target-based screens.

  6. Simplified LCA and matrix methods in identifying the environmental aspects of a product system.

    Science.gov (United States)

    Hur, Tak; Lee, Jiyong; Ryu, Jiyeon; Kwon, Eunsun

    2005-05-01

    In order to effectively integrate environmental attributes into the product design and development processes, it is crucial to identify the significant environmental aspects related to a product system within a relatively short period of time. In this study, the usefulness of life cycle assessment (LCA) and a matrix method as tools for identifying the key environmental issues of a product system were examined. For this, a simplified LCA (SLCA) method that can be applied to Electrical and Electronic Equipment (EEE) was developed to efficiently identify their significant environmental aspects for eco-design, since a full scale LCA study is usually very detailed, expensive and time-consuming. The environmentally responsible product assessment (ERPA) method, which is one of the matrix methods, was also analyzed. Then, the usefulness of each method in eco-design processes was evaluated and compared using the case studies of the cellular phone and vacuum cleaner systems. It was found that the SLCA and the ERPA methods provided different information but they complemented each other to some extent. The SLCA method generated more information on the inherent environmental characteristics of a product system so that it might be useful for new design/eco-innovation when developing a completely new product or method where environmental considerations play a major role from the beginning. On the other hand, the ERPA method gave more information on the potential for improving a product so that it could be effectively used in eco-redesign which intends to alleviate environmental impacts of an existing product or process.

  7. Comparative transcriptional profiling of the axolotl limb identifies a tripartite regeneration-specific gene program.

    Directory of Open Access Journals (Sweden)

    Dunja Knapp

    Full Text Available Understanding how the limb blastema is established after the initial wound healing response is an important aspect of regeneration research. Here we performed parallel expression profile time courses of healing lateral wounds versus amputated limbs in axolotl. This comparison between wound healing and regeneration allowed us to identify amputation-specific genes. By clustering the expression profiles of these samples, we could detect three distinguishable phases of gene expression - early wound healing followed by a transition-phase leading to establishment of the limb development program, which correspond to the three phases of limb regeneration that had been defined by morphological criteria. By focusing on the transition-phase, we identified 93 strictly amputation-associated genes many of which are implicated in oxidative-stress response, chromatin modification, epithelial development or limb development. We further classified the genes based on whether they were or were not significantly expressed in the developing limb bud. The specific localization of 53 selected candidates within the blastema was investigated by in situ hybridization. In summary, we identified a set of genes that are expressed specifically during regeneration and are therefore, likely candidates for the regulation of blastema formation.

  8. Process framework for identifying sustainability aspects in university curricula and integrating education for sustainable development

    DEFF Research Database (Denmark)

    Holm, Tove; Sammalisto, Kaisu; Grindsted, Thomas Skou

    2015-01-01

    Sustainability aspects in higher education must be enhanced with more concrete actions. Universities are globally required to have quality assurance to secure and improve teaching and learning, and they use management systems to this aim. Integrating education for sustainable development...... and management systems are alike in that they are based on continuous improvement and systematic thinking; for both processes all stakeholders need to be involved. Although quality assurance is compulsory for higher education, education for sustainable development has barely been examined or integrated...... in this context. This article examines how voluntary integration of education for sustainable development into management systems at universities could facilitate a scheme to overcome the challenges to integrating education for sustainable development that were identified in previous research. For this, a process...

  9. Identifying and addressing specific student difficulties in advanced thermal physics

    Science.gov (United States)

    Smith, Trevor I.

    As part of an ongoing multi-university research study on student understanding of concepts in thermal physics at the upper division, I identified several student difficulties with topics related to heat engines (especially the Carnot cycle), as well as difficulties related to the Boltzmann factor. In an effort to address these difficulties, I developed two guided-inquiry worksheet activities (a.k.a. tutorials) for use in advanced undergraduate thermal physics courses. Both tutorials seek to improve student understanding of the utility and physical background of a particular mathematical expression. One tutorial focuses on a derivation of Carnot's theorem regarding the limit on thermodynamic efficiency, starting from the Second Law of Thermodynamics. The other tutorial helps students gain an appreciation for the origin of the Boltzmann factor and when it is applicable; focusing on the physical justification of its mathematical derivation, with emphasis on the connections between probability, multiplicity, entropy, and energy. Student understanding of the use and physical implications of Carnot's theorem and the Boltzmann factor was assessed using written surveys both before and after tutorial instruction within the advanced thermal physics courses at the University of Maine and at other institutions. Classroom tutorial sessions at the University of Maine were videotaped to allow in-depth scrutiny of student successes and failures following tutorial prompts. I also interviewed students on various topics related to the Boltzmann factor to gain a more complete picture of their understanding and inform tutorial revisions. Results from several implementations of my tutorials at the University of Maine indicate that students did not have a robust understanding of these physical principles after lectures alone, and that they gain a better understanding of relevant topics after tutorial instruction; Fisher's exact tests yield statistically significant improvement at the

  10. Aspects regarding the use of the INFREP network for identifying possible seismic precursors

    Science.gov (United States)

    Dolea, Paul; Cristea, Octavian; Dascal, Paul Vladut; Moldovan, Iren-Adelina; Biagi, Pier Francesco

    even global causes generated by high-intensity solar flares. As a consequence, classifying these perturbations and minimizing them (when possible) would represent an important step towards identifying significant pattern deviations caused by seismic activities. Taken into consideration some of the issues mentioned above, this paper intends to present some aspects meant to improve the overall performance of the existing INFREP network. The signal-to-noise ratio improvement of the monitoring receiver may be achieved by relocating the antenna (or even the entire monitoring system if possible) in areas with less electromagnetic pollution within the VLF and LF bands. Other solution may involve replacing the existing electric ;whip; antennas with magnetic loop antennas. Regarding the measuring method, long-term averaging of the received signal to reduce the electromagnetic noise should be carefully applied. If the averaging time is too long, there is a risk that, during a seismic event, the details of the received signal envelope would be lost. Moreover, this may reduce the possibility of making correlations between the monitored stations and INFREP receivers in case of sudden ERP (Effective Radiated Power) variations of the VLF/LF stations. For the same reason, the time synchronization of the recorded data using (for instance) GPS technology is highly recommended. Other aspects related to the overall performance improvement of the INFREP network consist of monitoring other VLF/LF stations such as the Krasnodar station (south of Russia), part of the ALPHA/RSDN-20 VLF navigation system, or the 77.5 kHz DCF77 time signal transmitter (near Frankfurt am Main, Germany). Moreover, the installation of a new reception point in Romania (near Cluj-Napoca) for monitoring the Vrancea area (within the Carpathians Mountains) and the Adriatic region will provide complementary scientific data within the network.

  11. Electronic Health Record in Occupational Medicine: Specific Aspects and Requirements of Data Structuring and Standardization

    Directory of Open Access Journals (Sweden)

    Dorin TRIFF

    2009-07-01

    Full Text Available The service of occupational medicine of a specific economic agent, as integrated part of the System of Labor Health and Safety, requires efficient, well-organized information management through standardized and computerized data processing and exploitation. Legal requirements and practical aspects of information management in occupational medicine trigger necessary operational modifications in the Electronic Health File. The goal of the paper is to present basic requirements of structuring the electronic health file and the necessary standards in recording specific data.

  12. Domain Specific Aspects of Locus of Control: Implications for Modifying Locus of Control Orientation

    Science.gov (United States)

    Bradley, Robert H.; Gaa, John P.

    1977-01-01

    Goal-setting conferences were employed to improve LOC orientation for academic achievement situations among junior high school students (N=36). Results were interpreted as supporting domain-specific aspects of LOC. Results implied that educators can design programs to modify LOC orientation. (Author)

  13. Specific Aspects of Forecasting and Perception of the Norm by Juniour Schoolchildren with Developmental Disorders

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    Anna I. Akhmetzyanova

    2017-09-01

    Full Text Available Introduction: juniour schoolchildren with special needs should take into account the existing system of norms and rules in the school space. They should understand both their own inner world and that of surrounding people, but in conditions of deficiency dysontogenesis, the inability to forecast the outcome of any situation and the use of irrational behavioural strategies reduce the opportunities for successful social adaptation. The purpose of this study is to identify the specifics of forecasting and understanding normative situations by juniour schoolchildren with musculoskeletal system disorder, as well as with vision, hearing and speech impairment. Materials and Methods: to study the forecasting specifics of juniour schoolchildren, we used the guessing game methodology by L. I. Peresleni. We studied the specific character of normative behaviour using a set of methodologies: Perception of the normative situation by A. K. Pashchenko, Anticipation of the outcome with violation of the norm by V. P. Ulyanova, and Identification of the cultural congruity of juniour schoolchildren by L. F. Bayanova. Results: the study made it possible to identify the forecasting characteristics of juniour schoolchildren with normative development and with vision, hearing, speech impairments and musculoskeletal disorder. Students with developmental disabilities experienced forecasting difficulties, associated with decreasing sustainability of voluntary attention and its distribution in the course of the activity. The perception of norms by schoolchildren with developmental disorders often depended on random, brightly coloured emotional events or objects. The norms were differentiated more successfully in a situation of communication, than in educational activity. Discussion and Conclusions: the obtained data are consistent with the results of the studies by national and foreign scientists, who note that children with health limitations lack understanding of the

  14. Development of Specific Aspects of Spirituality during a 6-Month Intensive Yoga Practice

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    Arndt Büssing

    2012-01-01

    Full Text Available The majority of research on yoga focuses on its psychophysiological and therapeutic benefits, while the spiritual aspects are rarely addressed. Changes of specific aspects of spirituality were thus investigated among 160 individuals (91% women, mean age 40.9±8.3 years; 57% Christians starting a 2-year yoga teacher training. We used standardized questionnaires to measure aspects of spirituality (ASP, mindfulness (FMI—Freiburg Mindfulness Inventory, life satisfaction (BMLSS—Brief Multidimensional Life Satisfaction Scale, and positive mood (lightheartedness/relief. At the start of the course, scores of the respective ASP subscales for search for insight/wisdom, transcendence conviction, and conscious interactions/compassion were high, while those for religious orientation were low. Within the 6 month observation period, both conscious interactions/compassion (effect size, Cohen’s =.33, Religious orientation (=.21, Lightheartedness/Relief (=.75 and mindfulness (=.53 increased significantly. Particularly non-religious/non-spiritual individuals showed moderate effects for an increase of conscious interactions/compassion. The results from this study suggest that an intensive yoga practice (1 may significantly increase specific aspects of practitioners’ spirituality, mindfulness, and mood, (2 that these changes are dependent in part on their original spiritual/religious self-perception, and (3 that there are strong correlations amongst these constructs (i.e., conscious interactions/compassion, and mindfulness.

  15. Is Seeing Believing? Identifying Aspects of Informative Videos that Indicate Objectivity

    NARCIS (Netherlands)

    H.M. Boots-Blankers (Helen)

    2017-01-01

    textabstractInformation in online videos can be misleading and unreliable. Video users tend to select videos with misleading information (Butler, 2013). To facilitate video users in their selection of videos they need an objectivity measure (Palumbo, 2012). We propose thirteen aspects of video that

  16. Aspects

    Directory of Open Access Journals (Sweden)

    Fatma A. Abdel Razek

    2014-01-01

    Full Text Available The reproductive cycle of the eared horse mussel, Modiolus auriculatus, was followed for one year from February, 2011 to January, 2012 based on 240 individuals collected from Hurghada, north coast of Red Sea, Egypt. The gonadal maturation of M. auriculatus was examined by means of macroscopic and histological preparations of the mantle. Annual cycle with periods of growth, maturity and discharge of gonadic products occurs simultaneously in both sexes. Ripe individuals were observed throughout the year. The largest number of spawning for the individuals occurred from March to June and July for the population. So, it was clear to identify one heavy spawning period for this species. Sexation of M. auriculatus did not differ significantly from 1:1. Sexes were distinguishable in all individuals at the ripe stage with a shell length greater than 3.00 cm. A direct positive correlation was observed between gonad index and water temperature.

  17. Enhanced Assessment Technology and Neurocognitive Aspects of Specific Learning Disorder with Impairment in Mathematics.

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    Marios A. Pappas

    2018-02-01

    Full Text Available Specific Learning Disorder with impairment in Mathematics (Developmental Dyscalculia is a complex learning disorder which affects arithmetic skills, symbolic magnitude processing, alertness, flexibility in problem solving and maintained attention. Neuro-cognitive studies revealed that such difficulties in children with DD could be related to poor Working Memory and attention deficits. Furthermore, neuroimaging studies indicate that brain structure differences in children with DD compared to typically developing children could affect mathematical performance. In this study we present the cognitive profile of Dyscalculia, as well as the neuropsychological aspects of the deficit, with special reference to the utilization of enhanced assessment technology such as computerized neuropsychological tools and neuroimaging techniques.

  18. Clinical Microbiological Aspects of Epileptic Seizures in the Tropical Countries with Specific Focus on Nigeria

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    Ijeoma Kanu

    2005-01-01

    Full Text Available Epilepsy is a common neurological disorder; however, in Nigeria and other tropical regions, the causes of epileptic seizures differ greatly in etiology. This paper is an attempt to highlight some possible microbiological aspects of epileptic seizures. A literature review was carried out to identify the extent to which microbial infections were involved in the elicitation of epileptic seizures. Data were collected from several clinics in the community and hospitals in Nigeria and correlated with the evidence from the literature review. It was found that different microbial agents including viral, bacterial, protozoa, and fungal agents were involved in several aspects of epileptic seizures. Malaria was found to cause more than 88% of childhood epileptic seizures and 12% of adult seizures. Generalized tonic-clonic seizures occurred in more than 40% of adult patients. Partial seizures were uncommon. Cases of epileptic seizures associated with bacteria (e.g., brucellosis, viral, fungal, and protozoa infections were frequently reported. Malaria, tapeworm, and cysticercosis were some of the common infectious causes of epilepsy; however, in some cases, the cause remained unknown. From these findings, it was evident that microbiological aspects of epilepsies are possible research areas that might be developed. It is believed that the unraveling of the various microbiological factors in epileptic seizures would have important implications for understanding the underlying neurobiology, evaluating treatment strategies, and perhaps planning health-care resources for the affected. It will also help to improve the prognostic factors in initial seizure symptomatic etiology and presence of any structural cerebral abnormalities.

  19. Specific Preschool Executive Functions Predict Unique Aspects of Mathematics Development: A 3-Year Longitudinal Study.

    Science.gov (United States)

    Simanowski, Stefanie; Krajewski, Kristin

    2017-08-10

    This study assessed the extent to which executive functions (EF), according to their factor structure in 5-year-olds (N = 244), influenced early quantity-number competencies, arithmetic fluency, and mathematics school achievement throughout first and second grades. A confirmatory factor analysis resulted in updating as a first, and inhibition and shifting as a combined second factor. In the structural equation model, updating significantly affected knowledge of the number word sequence, suggesting a facilitatory effect on basic encoding processes in numerical materials that can be learnt purely by rote. Shifting and inhibition significantly influenced quantity to number word linkages, indicating that these processes promote developing a profound understanding of numbers. These results show the supportive role of specific EF for specific aspects of a numerical foundation. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

  20. Analysis of a Caenorhabditis elegans Twist homolog identifies conserved and divergent aspects of mesodermal patterning

    OpenAIRE

    Harfe, Brian D.; Gomes, Ana Vaz; Kenyon, Cynthia; Liu, Jun; Krause, Michael; Fire, Andrew

    1998-01-01

    Mesodermal development is a multistep process in which cells become increasingly specialized to form specific tissue types. In Drosophila and mammals, proper segregation and patterning of the mesoderm involves the bHLH factor Twist. We investigated the activity of a Twist-related factor, CeTwist, during Caenorhabditis elegans mesoderm development. Embryonic mesoderm in C. elegans derives from a number of distinct founder cells that are specified during the early lineages; in contrast, a singl...

  1. Aspects of signaling hazards and of identifying opportunities in crisis situations

    Directory of Open Access Journals (Sweden)

    Ion IMBRESCU

    2012-12-01

    Full Text Available This present research attempts to highlight some causes that have led to the current crisis, the role and importance of signals in anticipating events that characterize a situation of crisis, the need for interpreting these signals not only based on the economic theory but also on interdisciplinary methods and theories. The threats that may occur in situations of crisis should be identified properly, as well as opportunities, in order that the measures that are to be taken at macroeconomic level could be imbedded in the economic policies so as to contribute to improving the macroeconomic decisions and to successfully achieve the objectives already set.

  2. [Rehabilitation after occupational accidents in professional dancers: advice with due regard to dance specific aspects].

    Science.gov (United States)

    Wanke, E M; Quarcoo, D; Uibel, S; Groneberg, D A

    2012-08-01

    The highly specialized occupation of professional dancers is a combination of sport and artistic expression. The exertion is only possible with a fully operative body. Although professional dancers may be compared with elite athletes and acute injuries frequently happen, dancers do not seem to be granted an appropriate therapy after accidents as compared with athletes. Although even minor injuries may potentially endanger the career of a professional dancer, physiotherapeutic or physical treatment methods are applied in every tenth case only. Alternative and holistic concepts such as Pilates or dance-specific re-integration that proved successful in professional dancers, are used in even fewer instances. The aim of this study is to develop a rehabilitation concept for professional dancers focusing on dance-medicine aspects. It has been taken into account that the best physical outcomes are reflected in an optimized, holistic, dance-specific therapy and rehabilitation. Intensifying and exploiting dance-specific methods of treatment can not only reduce costs in the end but can even contribute to reducing the duration of rehabilitation after injuries of dancers. Preconditions for realization of the rehabilitative model are a high qualification of all persons working in the rehabilitative field as well as a marked willingness to cooperate in the various dance fields. Both gender-specific and dance-style particularities are to be taken into account to ensure a successful rehabilitation. © Georg Thieme Verlag KG Stuttgart · New York.

  3. Energy-Extended CES Aggregate Production: Current Aspects of Their Specification and Econometric Estimation

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    Paul E. Brockway

    2017-02-01

    Full Text Available Capital–labour–energy Constant Elasticity of Substitution (CES production functions and their estimated parameters now form a key part of energy–economy models which inform energy and emissions policy. However, the collation and guidance as to the specification and estimation choices involved with such energy-extended CES functions is disparate. This risks poorly specified and estimated CES functions, with knock-on implications for downstream energy–economic models and climate policy. In response, as a first step, this paper assembles in one place the major considerations involved in the empirical estimation of these CES functions. Discussions of the choices and their implications lead to recommendations for CES empiricists. The extensive bibliography allows those interested to dig deeper into any aspect of the CES parameter estimation process.

  4. Identifying States along the Hematopoietic Stem Cell Differentiation Hierarchy with Single Cell Specificity via Raman Spectroscopy.

    Science.gov (United States)

    Ilin, Yelena; Choi, Ji Sun; Harley, Brendan A C; Kraft, Mary L

    2015-11-17

    A major challenge for expanding specific types of hematopoietic cells ex vivo for the treatment of blood cell pathologies is identifying the combinations of cellular and matrix cues that direct hematopoietic stem cells (HSC) to self-renew or differentiate into cell populations ex vivo. Microscale screening platforms enable minimizing the number of rare HSCs required to screen the effects of numerous cues on HSC fate decisions. These platforms create a strong demand for label-free methods that accurately identify the fate decisions of individual hematopoietic cells at specific locations on the platform. We demonstrate the capacity to identify discrete cells along the HSC differentiation hierarchy via multivariate analysis of Raman spectra. Notably, cell state identification is accurate for individual cells and independent of the biophysical properties of the functionalized polyacrylamide gels upon which these cells are cultured. We report partial least-squares discriminant analysis (PLS-DA) models of single cell Raman spectra enable identifying four dissimilar hematopoietic cell populations across the HSC lineage specification. Successful discrimination was obtained for a population enriched for long-term repopulating HSCs (LT-HSCs) versus their more differentiated progeny, including closely related short-term repopulating HSCs (ST-HSCs) and fully differentiated lymphoid (B cells) and myeloid (granulocytes) cells. The lineage-specific differentiation states of cells from these four subpopulations were accurately identified independent of the stiffness of the underlying biomaterial substrate, indicating subtle spectral variations that discriminated these populations were not masked by features from the culture substrate. This approach enables identifying the lineage-specific differentiation stages of hematopoietic cells on biomaterial substrates of differing composition and may facilitate correlating hematopoietic cell fate decisions with the extrinsic cues that

  5. SMM-system: A mining tool to identify specific markers in Salmonella enterica.

    Science.gov (United States)

    Yu, Shuijing; Liu, Weibing; Shi, Chunlei; Wang, Dapeng; Dan, Xianlong; Li, Xiao; Shi, Xianming

    2011-03-01

    This report presents SMM-system, a software package that implements various personalized pre- and post-BLASTN tasks for mining specific markers of microbial pathogens. The main functionalities of SMM-system are summarized as follows: (i) converting multi-FASTA file, (ii) cutting interesting genomic sequence, (iii) automatic high-throughput BLASTN searches, and (iv) screening target sequences. The utility of SMM-system was demonstrated by using it to identify 214 Salmonella enterica-specific protein-coding sequences (CDSs). Eighteen primer pairs were designed based on eighteen S. enterica-specific CDSs, respectively. Seven of these primer pairs were validated with PCR assay, which showed 100% inclusivity for the 101 S. enterica genomes and 100% exclusivity of 30 non-S. enterica genomes. Three specific primer pairs were chosen to develop a multiplex PCR assay, which generated specific amplicons with a size of 180bp (SC1286), 238bp (SC1598) and 405bp (SC4361), respectively. This study demonstrates that SMM-system is a high-throughput specific marker generation tool that can be used to identify genus-, species-, serogroup- and even serovar-specific DNA sequences of microbial pathogens, which has a potential to be applied in food industries, diagnostics and taxonomic studies. SMM-system is freely available and can be downloaded from http://foodsafety.sjtu.edu.cn/SMM-system.html. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Homophilic and Heterophilic Interactions of Type II Cadherins Identify Specificity Groups Underlying Cell-Adhesive Behavior

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    Julia Brasch

    2018-05-01

    Full Text Available Summary: Type II cadherins are cell-cell adhesion proteins critical for tissue patterning and neuronal targeting but whose molecular binding code remains poorly understood. Here, we delineate binding preferences for type II cadherin cell-adhesive regions, revealing extensive heterophilic interactions between specific pairs, in addition to homophilic interactions. Three distinct specificity groups emerge from our analysis with members that share highly similar heterophilic binding patterns and favor binding to one another. Structures of adhesive fragments from each specificity group confirm near-identical dimer topology conserved throughout the family, allowing interface residues whose conservation corresponds to specificity preferences to be identified. We show that targeted mutation of these residues converts binding preferences between specificity groups in biophysical and co-culture assays. Our results provide a detailed understanding of the type II cadherin interaction map and a basis for defining their role in tissue patterning and for the emerging importance of their heterophilic interactions in neural connectivity. : Type II cadherins are a family of vertebrate cell adhesion proteins expressed primarily in the CNS. Brasch et al. measure binding between adhesive fragments, revealing homophilic and extensive selective heterophilic binding with specificities that define groups of similar cadherins. Structures reveal common adhesive dimers, with residues governing cell-adhesive specificity. Keywords: cell adhesion, crystal structure, hemophilic specificity, heterophilic specificity, neural patterning, synaptic targeting, cadherin

  7. MUCOLYTIC AGENTS IN PEDIATRICS: RATIONAL SELECTION, THERAPEUTIC EFFECTS AND SPECIFIC ASPECTS OF TREATMENT

    Directory of Open Access Journals (Sweden)

    O. I. Simonova

    2013-01-01

    Full Text Available The article deals with the cough treatment options with mucolytic agents administration at the first several days of acute respiratory tract infections in children. Efficacy of treatment with secretolytic and secretomotoric drugs significantly depends on certain factors. The article contains the criteria of therapeutic efficacy of expectorants. A special attention is given to N-acetylcysteine — a direct acting mucolytic agent, which effect is caused by presence of free sulfhydryl groups, disrupting disulfide bonds between molecules of acid mucopolysaccharides and glycoproteins therefore changing the structure of sputum. Acetylcysteine is active against every type of sputum (mucous, muco-purulent, purulent, that is especially important in treatment of bacterial infections, when it is necessary to quickly decrease sputum thickness, eliminate it from the respiratory tract and prevent dissemination of the infection. High efficacy of acetylcysteine is caused by its unique triple action: mucolytic, antioxidant and antitoxic. Mechanism of action of acetylcysteine is discussed in detail. Timely administered treatment will improve sputum discharge and therefore eliminate one of the main factors of bronchial obstruction and decrease the risk of microbial colonization of the respiratory tract. The article also includes indications, contraindications and dosage regimens of acetylcysteine in children. The most common mistakes and specific aspects of mucolytic drugs in pediatrics are listed in the conclusion. 

  8. COMPETITIVE METAGENOMIC DNA HYBRIDIZATION IDENTIFIES HOST-SPECIFIC MICROBIAL GENETIC MARKERS IN COW FECAL SAMPLES

    Science.gov (United States)

    Several PCR methods have recently been developed to identify fecal contamination in surface waters. In all cases, researchers have relied on one gene or one microorganism for selection of host specific markers. Here, we describe the application of a genome fragment enrichment met...

  9. Saporin-conjugated tetramers identify efficacious anti-HIV CD8+ T-cell specificities

    DEFF Research Database (Denmark)

    Leitman, Ellen M.; Palmer, Christine D.; Buus, Søren

    2017-01-01

    Antigen-specific T-cells are highly variable, spanning potent antiviral efficacy and damaging auto-reactivity. In virus infections, identifying the most efficacious responses is critical to vaccine design. However, current methods depend on indirect measures or on ex vivo expanded CTL clones. We...

  10. Deep sequencing identifies ethnicity-specific bacterial signatures in the oral microbiome.

    Directory of Open Access Journals (Sweden)

    Matthew R Mason

    Full Text Available Oral infections have a strong ethnic predilection; suggesting that ethnicity is a critical determinant of oral microbial colonization. Dental plaque and saliva samples from 192 subjects belonging to four major ethnicities in the United States were analyzed using terminal restriction fragment length polymorphism (t-RFLP and 16S pyrosequencing. Ethnicity-specific clustering of microbial communities was apparent in saliva and subgingival biofilms, and a machine-learning classifier was capable of identifying an individual's ethnicity from subgingival microbial signatures. The classifier identified African Americans with a 100% sensitivity and 74% specificity and Caucasians with a 50% sensitivity and 91% specificity. The data demonstrates a significant association between ethnic affiliation and the composition of the oral microbiome; to the extent that these microbial signatures appear to be capable of discriminating between ethnicities.

  11. Allele-specific deletions in mouse tumors identify Fbxw7 as germline modifier of tumor susceptibility.

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    Jesus Perez-Losada

    Full Text Available Genome-wide association studies (GWAS have been successful in finding associations between specific genetic variants and cancer susceptibility in human populations. These studies have identified a range of highly statistically significant associations between single nucleotide polymorphisms (SNPs and susceptibility to development of a range of human tumors. However, the effect of each SNP in isolation is very small, and all of the SNPs combined only account for a relatively minor proportion of the total genetic risk (5-10%. There is therefore a major requirement for alternative routes to the discovery of genetic risk factors for cancer. We have previously shown using mouse models that chromosomal regions harboring susceptibility genes identified by linkage analysis frequently exhibit allele-specific genetic alterations in tumors. We demonstrate here that the Fbxw7 gene, a commonly mutated gene in a wide range of mouse and human cancers, shows allele-specific deletions in mouse lymphomas and skin tumors. Lymphomas from three different F1 hybrids show 100% allele-specificity in the patterns of allelic loss. Parental alleles from 129/Sv or Spretus/Gla mice are lost in tumors from F1 hybrids with C57BL/6 animals, due to the presence of a specific non-synonymous coding sequence polymorphism at the N-terminal portion of the gene. A specific genetic test of association between this SNP and lymphoma susceptibility in interspecific backcross mice showed a significant linkage (p = 0.001, but only in animals with a functional p53 gene. These data therefore identify Fbxw7 as a p53-dependent tumor susceptibility gene. Increased p53-dependent tumor susceptibility and allele-specific losses were also seen in a mouse skin model of skin tumor development. We propose that analysis of preferential allelic imbalances in tumors may provide an efficient means of uncovering genetic variants that affect mouse and human tumor susceptibility.

  12. Transcriptional Profiling Identifies Location-Specific and Breed-Specific Differentially Expressed Genes in Embryonic Myogenesis in Anas Platyrhynchos.

    Directory of Open Access Journals (Sweden)

    Rong-Ping Zhang

    Full Text Available Skeletal muscle growth and development are highly orchestrated processes involving significant changes in gene expressions. Differences in the location-specific and breed-specific genes and pathways involved have important implications for meat productions and meat quality. Here, RNA-Seq was performed to identify differences in the muscle deposition between two muscle locations and two duck breeds for functional genomics studies. To achieve those goals, skeletal muscle samples were collected from the leg muscle (LM and the pectoral muscle (PM of two genetically different duck breeds, Heiwu duck (H and Peking duck (P, at embryonic 15 days. Functional genomics studies were performed in two experiments: Experiment 1 directly compared the location-specific genes between PM and LM, and Experiment 2 compared the two breeds (H and P at the same developmental stage (embryonic 15 days. Almost 13 million clean reads were generated using Illumina technology (Novogene, Beijing, China on each library, and more than 70% of the reads mapped to the Peking duck (Anas platyrhynchos genome. A total of 168 genes were differentially expressed between the two locations analyzed in Experiment 1, whereas only 8 genes were differentially expressed when comparing the same location between two breeds in Experiment 2. Gene Ontology (GO and the Kyoto Encyclopedia of Genes and Genomes pathways (KEGG were used to functionally annotate DEGs (differentially expression genes. The DEGs identified in Experiment 1 were mainly involved in focal adhesion, the PI3K-Akt signaling pathway and ECM-receptor interaction pathways (corrected P-value<0.05. In Experiment 2, the DEGs were associated with only the ribosome signaling pathway (corrected P-value<0.05. In addition, quantitative real-time PCR was used to confirm 15 of the differentially expressed genes originally detected by RNA-Seq. A comparative transcript analysis of the leg and pectoral muscles of two duck breeds not only

  13. Graph-based Specification and Verification for Aspect-Oriented Languages

    NARCIS (Netherlands)

    Staijen, T.

    2010-01-01

    Aspect-oriented software development aims at improving separation of concerns at all levels in the software development life-cycle, from architecture to code implementation. In particular, aspect-oriented programming addresses separation of concerns at the implementation level, by allowing the

  14. Appraisal of Specific Aspects of Self, Salience, and Spontaneous Self-Esteem.

    Science.gov (United States)

    Reeder, Glenn D.; Mangiarcina, Janet

    Although self-concept is traditionally viewed as being fairly stable over time and situations, a more recent position takes note of the variability or inconsistency characteristic of certain aspects of the self-concept. To determine whether spontaneous self-esteem (SSE) increases when a valued aspect of self is made salient, college students…

  15. Overlapping and disease specific aspects of impulsivity in children and adolescents with schizophrenia spectrum disorders or Attention-Deficit/Hyperactivity Disorder

    DEFF Research Database (Denmark)

    Jepsen, Jens Richardt Møllegaard; Rydkjær, Jacob; Fagerlund, Birgitte

    Objectives: To identify disease specific and overlapping aspects of impulsivity in children and adolescents with early-onset schizophrenia spectrum disorders or ADHD. Methods: Motor impulsivity (Stop Signal Task), reflection impulsivity (Information Sampling Task), and trait impulsivity (Barratt ...... their decision making to gather more information in a condition with a conflict between reward and certainty. The reduced information sampling may also reflect an increased conviction in the decision at a point of relative uncertainty....

  16. A novel data mining method to identify assay-specific signatures in functional genomic studies

    Directory of Open Access Journals (Sweden)

    Guidarelli Jack W

    2006-08-01

    Full Text Available Abstract Background: The highly dimensional data produced by functional genomic (FG studies makes it difficult to visualize relationships between gene products and experimental conditions (i.e., assays. Although dimensionality reduction methods such as principal component analysis (PCA have been very useful, their application to identify assay-specific signatures has been limited by the lack of appropriate methodologies. This article proposes a new and powerful PCA-based method for the identification of assay-specific gene signatures in FG studies. Results: The proposed method (PM is unique for several reasons. First, it is the only one, to our knowledge, that uses gene contribution, a product of the loading and expression level, to obtain assay signatures. The PM develops and exploits two types of assay-specific contribution plots, which are new to the application of PCA in the FG area. The first type plots the assay-specific gene contribution against the given order of the genes and reveals variations in distribution between assay-specific gene signatures as well as outliers within assay groups indicating the degree of importance of the most dominant genes. The second type plots the contribution of each gene in ascending or descending order against a constantly increasing index. This type of plots reveals assay-specific gene signatures defined by the inflection points in the curve. In addition, sharp regions within the signature define the genes that contribute the most to the signature. We proposed and used the curvature as an appropriate metric to characterize these sharp regions, thus identifying the subset of genes contributing the most to the signature. Finally, the PM uses the full dataset to determine the final gene signature, thus eliminating the chance of gene exclusion by poor screening in earlier steps. The strengths of the PM are demonstrated using a simulation study, and two studies of real DNA microarray data – a study of

  17. Specific aspects of contemporary triathlon: implications for physiological analysis and performance.

    Science.gov (United States)

    Bentley, David J; Millet, Grégoire P; Vleck, Verónica E; McNaughton, Lars R

    2002-01-01

    Triathlon competitions are performed over markedly different distances and under a variety of technical constraints. In 'standard-distance' triathlons involving 1.5km swim, 40km cycling and 10km running, a World Cup series as well as a World Championship race is available for 'elite' competitors. In contrast, 'age-group' triathletes may compete in 5-year age categories at a World Championship level, but not against the elite competitors. The difference between elite and age-group races is that during the cycle stage elite competitors may 'draft' or cycle in a sheltered position; age-group athletes complete the cycle stage as an individual time trial. Within triathlons there are a number of specific aspects that make the physiological demands different from the individual sports of swimming, cycling and running. The physiological demands of the cycle stage in elite races may also differ compared with the age-group format. This in turn may influence performance during the cycle leg and subsequent running stage. Wetsuit use and drafting during swimming (in both elite and age-group races) result in improved buoyancy and a reduction in frontal resistance, respectively. Both of these factors will result in improved performance and efficiency relative to normal pool-based swimming efforts. Overall cycling performance after swimming in a triathlon is not typically affected. However, it is possible that during the initial stages of the cycle leg the ability of an athlete to generate the high power outputs necessary for tactical position changes may be impeded. Drafting during cycling results in a reduction in frontal resistance and reduced energy cost at a given submaximal intensity. The reduced energy expenditure during the cycle stage results in an improvement in running, so an athlete may exercise at a higher percentage of maximal oxygen uptake. In elite triathlon races, the cycle courses offer specific physiological demands that may result in different fatigue responses

  18. Selected aspects and specifics of the economic development in sub-Saharan Africa

    Directory of Open Access Journals (Sweden)

    Karel Tomššík

    2013-01-01

    Full Text Available The paper examines the development of economies in the sub-Saharan region. It aims to identify particular development trends specific to the region. That means identifying changes which have occurred in the past five decades in following areas: development of the GDP value ​​and structure, growth in the value of foreign trade, demographic growth, and changes in the value of GDP per capita. The results of the analysis show very constrained economic power of sub-Saharan region. Not only weak economy of the region but also a significant population growth is a problem. Increasing production and trade does not contribute effectively to elimination of high level of poverty and malnutrition which remains a long-term problem of the sub-Saharan region. In real terms, the GDP per capita was growing by less than 1 % in the period 1961–2010. Sub-Saharan region is highly dependent on cooperation with other world regions in its effort to increase economic growth and to improve the economic situation of own population. The GDP growth is thus very sensitive to GDP development in Europe and North America. Concerning the foreign trade, development of sub-Saharan trade is dependent on regions of the Southern and Eastern Asia, and Europe.

  19. Evaluation of Antigen-Conjugated Fluorescent Beads to Identify Antigen-Specific B Cells.

    Science.gov (United States)

    Correa, Isabel; Ilieva, Kristina M; Crescioli, Silvia; Lombardi, Sara; Figini, Mariangela; Cheung, Anthony; Spicer, James F; Tutt, Andrew N J; Nestle, Frank O; Karagiannis, Panagiotis; Lacy, Katie E; Karagiannis, Sophia N

    2018-01-01

    Selection of single antigen-specific B cells to identify their expressed antibodies is of considerable interest for evaluating human immune responses. Here, we present a method to identify single antibody-expressing cells using antigen-conjugated fluorescent beads. To establish this, we selected Folate Receptor alpha (FRα) as a model antigen and a mouse B cell line, expressing both the soluble and the membrane-bound forms of a human/mouse chimeric antibody (MOv18 IgG1) specific for FRα, as test antibody-expressing cells. Beads were conjugated to FRα using streptavidin/avidin-biotin bridges and used to select single cells expressing the membrane-bound form of anti-FRα. Bead-bound cells were single cell-sorted and processed for single cell RNA retrotranscription and PCR to isolate antibody heavy and light chain variable regions. Variable regions were then cloned and expressed as human IgG1/k antibodies. Like the original clone, engineered antibodies from single cells recognized native FRα. To evaluate whether antigen-coated beads could identify specific antibody-expressing cells in mixed immune cell populations, human peripheral blood mononuclear cells (PBMCs) were spiked with test antibody-expressing cells. Antigen-specific cells could comprise up to 75% of cells selected with antigen-conjugated beads when the frequency of the antigen-positive cells was 1:100 or higher. In PBMC pools, beads conjugated to recombinant antigens FRα and HER2 bound antigen-specific anti-FRα MOv18 and anti-HER2 Trastuzumab antibody-expressing cells, respectively. From melanoma patient-derived B cells selected with melanoma cell line-derived protein-coated fluorescent beads, we generated a monoclonal antibody that recognized melanoma antigen-coated beads. This approach may be further developed to facilitate analysis of B cells and their antibody profiles at the single cell level and to help unravel humoral immune repertoires.

  20. Evaluation of Antigen-Conjugated Fluorescent Beads to Identify Antigen-Specific B Cells

    Directory of Open Access Journals (Sweden)

    Isabel Correa

    2018-03-01

    Full Text Available Selection of single antigen-specific B cells to identify their expressed antibodies is of considerable interest for evaluating human immune responses. Here, we present a method to identify single antibody-expressing cells using antigen-conjugated fluorescent beads. To establish this, we selected Folate Receptor alpha (FRα as a model antigen and a mouse B cell line, expressing both the soluble and the membrane-bound forms of a human/mouse chimeric antibody (MOv18 IgG1 specific for FRα, as test antibody-expressing cells. Beads were conjugated to FRα using streptavidin/avidin-biotin bridges and used to select single cells expressing the membrane-bound form of anti-FRα. Bead-bound cells were single cell-sorted and processed for single cell RNA retrotranscription and PCR to isolate antibody heavy and light chain variable regions. Variable regions were then cloned and expressed as human IgG1/k antibodies. Like the original clone, engineered antibodies from single cells recognized native FRα. To evaluate whether antigen-coated beads could identify specific antibody-expressing cells in mixed immune cell populations, human peripheral blood mononuclear cells (PBMCs were spiked with test antibody-expressing cells. Antigen-specific cells could comprise up to 75% of cells selected with antigen-conjugated beads when the frequency of the antigen-positive cells was 1:100 or higher. In PBMC pools, beads conjugated to recombinant antigens FRα and HER2 bound antigen-specific anti-FRα MOv18 and anti-HER2 Trastuzumab antibody-expressing cells, respectively. From melanoma patient-derived B cells selected with melanoma cell line-derived protein-coated fluorescent beads, we generated a monoclonal antibody that recognized melanoma antigen-coated beads. This approach may be further developed to facilitate analysis of B cells and their antibody profiles at the single cell level and to help unravel humoral immune repertoires.

  1. Evaluation of Antigen-Conjugated Fluorescent Beads to Identify Antigen-Specific B Cells

    Science.gov (United States)

    Correa, Isabel; Ilieva, Kristina M.; Crescioli, Silvia; Lombardi, Sara; Figini, Mariangela; Cheung, Anthony; Spicer, James F.; Tutt, Andrew N. J.; Nestle, Frank O.; Karagiannis, Panagiotis; Lacy, Katie E.; Karagiannis, Sophia N.

    2018-01-01

    Selection of single antigen-specific B cells to identify their expressed antibodies is of considerable interest for evaluating human immune responses. Here, we present a method to identify single antibody-expressing cells using antigen-conjugated fluorescent beads. To establish this, we selected Folate Receptor alpha (FRα) as a model antigen and a mouse B cell line, expressing both the soluble and the membrane-bound forms of a human/mouse chimeric antibody (MOv18 IgG1) specific for FRα, as test antibody-expressing cells. Beads were conjugated to FRα using streptavidin/avidin-biotin bridges and used to select single cells expressing the membrane-bound form of anti-FRα. Bead-bound cells were single cell-sorted and processed for single cell RNA retrotranscription and PCR to isolate antibody heavy and light chain variable regions. Variable regions were then cloned and expressed as human IgG1/k antibodies. Like the original clone, engineered antibodies from single cells recognized native FRα. To evaluate whether antigen-coated beads could identify specific antibody-expressing cells in mixed immune cell populations, human peripheral blood mononuclear cells (PBMCs) were spiked with test antibody-expressing cells. Antigen-specific cells could comprise up to 75% of cells selected with antigen-conjugated beads when the frequency of the antigen-positive cells was 1:100 or higher. In PBMC pools, beads conjugated to recombinant antigens FRα and HER2 bound antigen-specific anti-FRα MOv18 and anti-HER2 Trastuzumab antibody-expressing cells, respectively. From melanoma patient-derived B cells selected with melanoma cell line-derived protein-coated fluorescent beads, we generated a monoclonal antibody that recognized melanoma antigen-coated beads. This approach may be further developed to facilitate analysis of B cells and their antibody profiles at the single cell level and to help unravel humoral immune repertoires. PMID:29628923

  2. High-Throughput Screening to Identify Regulators of Meiosis-Specific Gene Expression in Saccharomyces cerevisiae.

    Science.gov (United States)

    Kassir, Yona

    2017-01-01

    Meiosis and gamete formation are processes that are essential for sexual reproduction in all eukaryotic organisms. Multiple intracellular and extracellular signals feed into pathways that converge on transcription factors that induce the expression of meiosis-specific genes. Once triggered the meiosis-specific gene expression program proceeds in a cascade that drives progress through the events of meiosis and gamete formation. Meiosis-specific gene expression is tightly controlled by a balance of positive and negative regulatory factors that respond to a plethora of signaling pathways. The budding yeast Saccharomyces cerevisiae has proven to be an outstanding model for the dissection of gametogenesis owing to the sophisticated genetic manipulations that can be performed with the cells. It is possible to use a variety selection and screening methods to identify genes and their functions. High-throughput screening technology has been developed to allow an array of all viable yeast gene deletion mutants to be screened for phenotypes and for regulators of gene expression. This chapter describes a protocol that has been used to screen a library of homozygous diploid yeast deletion strains to identify regulators of the meiosis-specific IME1 gene.

  3. Hypocretin neuron-specific transcriptome profiling identifies the sleep modulator Kcnh4a.

    Science.gov (United States)

    Yelin-Bekerman, Laura; Elbaz, Idan; Diber, Alex; Dahary, Dvir; Gibbs-Bar, Liron; Alon, Shahar; Lerer-Goldshtein, Tali; Appelbaum, Lior

    2015-10-01

    Sleep has been conserved throughout evolution; however, the molecular and neuronal mechanisms of sleep are largely unknown. The hypothalamic hypocretin/orexin (Hcrt) neurons regulate sleep\\wake states, feeding, stress, and reward. To elucidate the mechanism that enables these various functions and to identify sleep regulators, we combined fluorescence cell sorting and RNA-seq in hcrt:EGFP zebrafish. Dozens of Hcrt-neuron-specific transcripts were identified and comprehensive high-resolution imaging revealed gene-specific localization in all or subsets of Hcrt neurons. Clusters of Hcrt-neuron-specific genes are predicted to be regulated by shared transcription factors. These findings show that Hcrt neurons are heterogeneous and that integrative molecular mechanisms orchestrate their diverse functions. The voltage-gated potassium channel Kcnh4a, which is expressed in all Hcrt neurons, was silenced by the CRISPR-mediated gene inactivation system. The mutant kcnh4a (kcnh4a(-/-)) larvae showed reduced sleep time and consolidation, specifically during the night, suggesting that Kcnh4a regulates sleep.

  4. Recommendations for equipment requirements and specifications for digital and interventional radiology: Dosimetric aspects

    International Nuclear Information System (INIS)

    Suliman, I.I.; Zoetelief, J.

    2002-01-01

    The recognition of radiation induced injuries from fluoroscopically guided interventional procedures has resulted in the current demand for development of recommendations and standards to limit dose to both patients and staff. This paper outlines the recommendations drafted within the framework of European Project DIMOND III. The actual work involves survey and review of national and international documents as well as scientific publications in areas relevant to the digital and/or interventional radiology with an aim of developing recommendations for equipment requirements and specifications for digital and interventional radiology. A pilot study of experimental investigations in at least three hospitals will be conducted to test the requirements and the specifications, the result of which will be presented. The recommendations are expected to provide an effective means of dose reduction to both patients and staff while maintaining image quality adequate for the specific diagnosis or interventional procedure. Different components of x-ray systems that have direct impact on patient and staff doses have been considered. Where necessary a compromise between patient dose and image quality has been made. The dosimetric aspects of the recommendations propose detailed descriptions and limits to dosimetric information relevant to patient and staff doses. International recommendations on maximum patient entrance surface dose rate vary in the range from 25 to 65 mGy.min -1 for normal mode fluoroscopy. Maximum image intensifier or image receptor input dose rate around 0.1 Gy min -1 at a distance 30 cm from the image intensifier input surface has been generally recommended. Maximum fluoroscopic dose rate in air must not exceed 50 mGy.min -1 at a location depending on the configuration e.g. for undertable x-ray tube at 10 mm from the patient support on the patient side of the support. The use of pulsed fluoroscopy or low dose fluoroscopy is proposed as good options to minimize

  5. Novel HTS strategy identifies TRAIL-sensitizing compounds acting specifically through the caspase-8 apoptotic axis.

    Directory of Open Access Journals (Sweden)

    Darren Finlay

    Full Text Available Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL is potentially a very important therapeutic as it shows selectivity for inducing apoptosis in cancer cells whilst normal cells are refractory. TRAIL binding to its cognate receptors, Death Receptors-4 and -5, leads to recruitment of caspase-8 and classical activation of downstream effector caspases, leading to apoptosis. As with many drugs however, TRAIL's usefulness is limited by resistance, either innate or acquired. We describe here the development of a novel 384-well high-throughput screening (HTS strategy for identifying potential TRAIL-sensitizing agents that act solely in a caspase-8 dependent manner. By utilizing a TRAIL resistant cell line lacking caspase-8 (NB7 compared to the same cells reconstituted with the wild-type protein, or with a catalytically inactive point mutant of caspase-8, we are able to identify compounds that act specifically through the caspase-8 axis, rather than through general toxicity. In addition, false positive hits can easily be "weeded out" in this assay due to their activity in cells lacking caspase-8-inducible activity. Screening of the library of pharmacologically active compounds (LOPAC was performed as both proof-of-concept and to discover potential unknown TRAIL sensitizers whose mechanism is caspase-8 mediated. We identified known TRAIL sensitizers from the library and identified new compounds that appear to sensitize specifically through caspase-8. In sum, we demonstrate proof-of-concept and discovery of novel compounds with a screening strategy optimized for the detection of caspase-8 pathway-specific TRAIL sensitizers. This screen was performed in the 384-well format, but could easily be further miniaturized, allows easy identification of artifactual false positives, and is highly scalable to accommodate diverse libraries.

  6. Identify alternative splicing events based on position-specific evolutionary conservation.

    Directory of Open Access Journals (Sweden)

    Liang Chen

    Full Text Available The evolution of eukaryotes is accompanied by the increased complexity of alternative splicing which greatly expands genome information. One of the greatest challenges in the post-genome era is a complete revelation of human transcriptome with consideration of alternative splicing. Here, we introduce a comparative genomics approach to systemically identify alternative splicing events based on the differential evolutionary conservation between exons and introns and the high-quality annotation of the ENCODE regions. Specifically, we focus on exons that are included in some transcripts but are completely spliced out for others and we call them conditional exons. First, we characterize distinguishing features among conditional exons, constitutive exons and introns. One of the most important features is the position-specific conservation score. There are dramatic differences in conservation scores between conditional exons and constitutive exons. More importantly, the differences are position-specific. For flanking intronic regions, the differences between conditional exons and constitutive exons are also position-specific. Using the Random Forests algorithm, we can classify conditional exons with high specificities (97% for the identification of conditional exons from intron regions and 95% for the classification of known exons and fair sensitivities (64% and 32% respectively. We applied the method to the human genome and identified 39,640 introns that actually contain conditional exons and classified 8,813 conditional exons from the current RefSeq exon list. Among those, 31,673 introns containing conditional exons and 5,294 conditional exons classified from known exons cannot be inferred from RefSeq, UCSC or Ensembl annotations. Some of these de novo predictions were experimentally verified.

  7. Identifying protein phosphorylation sites with kinase substrate specificity on human viruses.

    Directory of Open Access Journals (Sweden)

    Neil Arvin Bretaña

    Full Text Available Viruses infect humans and progress inside the body leading to various diseases and complications. The phosphorylation of viral proteins catalyzed by host kinases plays crucial regulatory roles in enhancing replication and inhibition of normal host-cell functions. Due to its biological importance, there is a desire to identify the protein phosphorylation sites on human viruses. However, the use of mass spectrometry-based experiments is proven to be expensive and labor-intensive. Furthermore, previous studies which have identified phosphorylation sites in human viruses do not include the investigation of the responsible kinases. Thus, we are motivated to propose a new method to identify protein phosphorylation sites with its kinase substrate specificity on human viruses. The experimentally verified phosphorylation data were extracted from virPTM--a database containing 301 experimentally verified phosphorylation data on 104 human kinase-phosphorylated virus proteins. In an attempt to investigate kinase substrate specificities in viral protein phosphorylation sites, maximal dependence decomposition (MDD is employed to cluster a large set of phosphorylation data into subgroups containing significantly conserved motifs. The experimental human phosphorylation sites are collected from Phospho.ELM, grouped according to its kinase annotation, and compared with the virus MDD clusters. This investigation identifies human kinases such as CK2, PKB, CDK, and MAPK as potential kinases for catalyzing virus protein substrates as confirmed by published literature. Profile hidden Markov model is then applied to learn a predictive model for each subgroup. A five-fold cross validation evaluation on the MDD-clustered HMMs yields an average accuracy of 84.93% for Serine, and 78.05% for Threonine. Furthermore, an independent testing data collected from UniProtKB and Phospho.ELM is used to make a comparison of predictive performance on three popular kinase-specific

  8. Identifying protein phosphorylation sites with kinase substrate specificity on human viruses.

    Science.gov (United States)

    Bretaña, Neil Arvin; Lu, Cheng-Tsung; Chiang, Chiu-Yun; Su, Min-Gang; Huang, Kai-Yao; Lee, Tzong-Yi; Weng, Shun-Long

    2012-01-01

    Viruses infect humans and progress inside the body leading to various diseases and complications. The phosphorylation of viral proteins catalyzed by host kinases plays crucial regulatory roles in enhancing replication and inhibition of normal host-cell functions. Due to its biological importance, there is a desire to identify the protein phosphorylation sites on human viruses. However, the use of mass spectrometry-based experiments is proven to be expensive and labor-intensive. Furthermore, previous studies which have identified phosphorylation sites in human viruses do not include the investigation of the responsible kinases. Thus, we are motivated to propose a new method to identify protein phosphorylation sites with its kinase substrate specificity on human viruses. The experimentally verified phosphorylation data were extracted from virPTM--a database containing 301 experimentally verified phosphorylation data on 104 human kinase-phosphorylated virus proteins. In an attempt to investigate kinase substrate specificities in viral protein phosphorylation sites, maximal dependence decomposition (MDD) is employed to cluster a large set of phosphorylation data into subgroups containing significantly conserved motifs. The experimental human phosphorylation sites are collected from Phospho.ELM, grouped according to its kinase annotation, and compared with the virus MDD clusters. This investigation identifies human kinases such as CK2, PKB, CDK, and MAPK as potential kinases for catalyzing virus protein substrates as confirmed by published literature. Profile hidden Markov model is then applied to learn a predictive model for each subgroup. A five-fold cross validation evaluation on the MDD-clustered HMMs yields an average accuracy of 84.93% for Serine, and 78.05% for Threonine. Furthermore, an independent testing data collected from UniProtKB and Phospho.ELM is used to make a comparison of predictive performance on three popular kinase-specific phosphorylation site

  9. Identifying tagging SNPs for African specific genetic variation from the African Diaspora Genome.

    Science.gov (United States)

    Johnston, Henry Richard; Hu, Yi-Juan; Gao, Jingjing; O'Connor, Timothy D; Abecasis, Gonçalo R; Wojcik, Genevieve L; Gignoux, Christopher R; Gourraud, Pierre-Antoine; Lizee, Antoine; Hansen, Mark; Genuario, Rob; Bullis, Dave; Lawley, Cindy; Kenny, Eimear E; Bustamante, Carlos; Beaty, Terri H; Mathias, Rasika A; Barnes, Kathleen C; Qin, Zhaohui S

    2017-04-21

    A primary goal of The Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to develop an 'African Diaspora Power Chip' (ADPC), a genotyping array consisting of tagging SNPs, useful in comprehensively identifying African specific genetic variation. This array is designed based on the novel variation identified in 642 CAAPA samples of African ancestry with high coverage whole genome sequence data (~30× depth). This novel variation extends the pattern of variation catalogued in the 1000 Genomes and Exome Sequencing Projects to a spectrum of populations representing the wide range of West African genomic diversity. These individuals from CAAPA also comprise a large swath of the African Diaspora population and incorporate historical genetic diversity covering nearly the entire Atlantic coast of the Americas. Here we show the results of designing and producing such a microchip array. This novel array covers African specific variation far better than other commercially available arrays, and will enable better GWAS analyses for researchers with individuals of African descent in their study populations. A recent study cataloging variation in continental African populations suggests this type of African-specific genotyping array is both necessary and valuable for facilitating large-scale GWAS in populations of African ancestry.

  10. Investigations regarding the lowering of specific intellectual property risks identified in the production process

    Directory of Open Access Journals (Sweden)

    Pakocs Ramona

    2017-01-01

    Full Text Available The main purpose of this research is to decrease the emergence of specific intellectual property risks within the production process as well as increasing risk management performance of IP by preventing them. In order to achieve this, previous studies regarding the main specific intellectual property risks from industrial companies were analyzed together with their managerial methods as well as the possibility of reducing their emergence. As a result of the research conducted were identified five types of intellectual property risks that have a high potential of emergence in the production process, namely: the risk of production of goods in violation of IP rights; the know-how, production knowledge and trade secret disclosure risk; the technological risk of unprotected utility models; the technological risk of unprotected integrated circuits topographies and finally the risk of product counterfeit. In order to achieve the main purpose of our investigation, we have proposed new formulas for estimating the specific intellectual property risks identified in the production process. Their purpose was to minimalize the risk’s negative effects on industrial companies and to increase the managerial performance from the intellectual property domain through a new type of management appropriately named: intellectual property management. The research is finalized with a case study regarding the lapse of rights of a patented invention. Based on a case analysis, it was proved that the exploitation of an invention without a contract represents a counterfeit.

  11. [Specific aspects of thrombocyte system of serotonin in patients with different manifestations of schizoaffective psychosis].

    Science.gov (United States)

    Brusov, O S; Dikaia, V I; Zlobina, G P; Faktor, M I; Pavlova, O A; Bologov, P V; Korenev, A N

    2000-01-01

    45 women with different manifestations of schizoaffective psychosis (SAP) were examined. The diagnosis corresponded to ICD-10 (F25). According to the classification elaborated in Mental Health Research Centre of Russian Academy of Medical Sciences, groups of patients were identified with different variants of the psychoses course: a nuclear SAP type; a borderline SAP variation with phasic-recurrent course; SAP with progredient variation (schizoaffective variation of schizophrenia). The patients were examined both during the attack and remission. A rate of serotonine uptake (Vmax) in blood platelets, a specific imipramine binding (Bmax) and the level of serotonin in blood platelets were evaluated. It was found that dynamics of both Vmax and the level of serotonin in different SAP types were different, that was related to clinical and biological SAP heterogeneity. A tendency to decreasing of serotonin system functional activity was found in progredient SAP variations, especially during the remission, which was of low quality in these cases. On the contrary, in the borderline variations the indices of the decreased function of serotonin system corresponded well to those of acute psychosis. In nuclear type--a type with the most favourable course of psychosis--any significant changes weren't revealed as compared with the normal parameters.

  12. Cuprolinic Blue: a specific dye for single-stranded RNA in the presence of magnesium chloride. I. Fundamental aspects

    NARCIS (Netherlands)

    Tas, J.; MENDELSON, D.; NOORDEN, C. J. F.

    1983-01-01

    Qualitative and quantitative aspects of the cationic dye Cuprolinic Blue were investigated with model films of polyacrylamide gel in which RNA, DNA and other biological polyanionic compounds had been incorporated. In the presence of 1 M MgCl2, Curpolinic Blue was found to bind specifically to

  13. WMAXC: a weighted maximum clique method for identifying condition-specific sub-network.

    Directory of Open Access Journals (Sweden)

    Bayarbaatar Amgalan

    Full Text Available Sub-networks can expose complex patterns in an entire bio-molecular network by extracting interactions that depend on temporal or condition-specific contexts. When genes interact with each other during cellular processes, they may form differential co-expression patterns with other genes across different cell states. The identification of condition-specific sub-networks is of great importance in investigating how a living cell adapts to environmental changes. In this work, we propose the weighted MAXimum clique (WMAXC method to identify a condition-specific sub-network. WMAXC first proposes scoring functions that jointly measure condition-specific changes to both individual genes and gene-gene co-expressions. It then employs a weaker formula of a general maximum clique problem and relates the maximum scored clique of a weighted graph to the optimization of a quadratic objective function under sparsity constraints. We combine a continuous genetic algorithm and a projection procedure to obtain a single optimal sub-network that maximizes the objective function (scoring function over the standard simplex (sparsity constraints. We applied the WMAXC method to both simulated data and real data sets of ovarian and prostate cancer. Compared with previous methods, WMAXC selected a large fraction of cancer-related genes, which were enriched in cancer-related pathways. The results demonstrated that our method efficiently captured a subset of genes relevant under the investigated condition.

  14. Compendium of Immune Signatures Identifies Conserved and Species-Specific Biology in Response to Inflammation.

    Science.gov (United States)

    Godec, Jernej; Tan, Yan; Liberzon, Arthur; Tamayo, Pablo; Bhattacharya, Sanchita; Butte, Atul J; Mesirov, Jill P; Haining, W Nicholas

    2016-01-19

    Gene-expression profiling has become a mainstay in immunology, but subtle changes in gene networks related to biological processes are hard to discern when comparing various datasets. For instance, conservation of the transcriptional response to sepsis in mouse models and human disease remains controversial. To improve transcriptional analysis in immunology, we created ImmuneSigDB: a manually annotated compendium of ∼5,000 gene-sets from diverse cell states, experimental manipulations, and genetic perturbations in immunology. Analysis using ImmuneSigDB identified signatures induced in activated myeloid cells and differentiating lymphocytes that were highly conserved between humans and mice. Sepsis triggered conserved patterns of gene expression in humans and mouse models. However, we also identified species-specific biological processes in the sepsis transcriptional response: although both species upregulated phagocytosis-related genes, a mitosis signature was specific to humans. ImmuneSigDB enables granular analysis of transcriptomic data to improve biological understanding of immune processes of the human and mouse immune systems. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Measuring the Electronic Properties of DNA-Specific Schottky Diodes Towards Detecting and Identifying Basidiomycetes DNA

    Science.gov (United States)

    Periasamy, Vengadesh; Rizan, Nastaran; Al-Ta’ii, Hassan Maktuff Jaber; Tan, Yee Shin; Tajuddin, Hairul Annuar; Iwamoto, Mitsumasa

    2016-01-01

    The discovery of semiconducting behavior of deoxyribonucleic acid (DNA) has resulted in a large number of literatures in the study of DNA electronics. Sequence-specific electronic response provides a platform towards understanding charge transfer mechanism and therefore the electronic properties of DNA. It is possible to utilize these characteristic properties to identify/detect DNA. In this current work, we demonstrate a novel method of DNA-based identification of basidiomycetes using current-voltage (I-V) profiles obtained from DNA-specific Schottky barrier diodes. Electronic properties such as ideality factor, barrier height, shunt resistance, series resistance, turn-on voltage, knee-voltage, breakdown voltage and breakdown current were calculated and used to quantify the identification process as compared to morphological and molecular characterization techniques. The use of these techniques is necessary in order to study biodiversity, but sometimes it can be misleading and unreliable and is not sufficiently useful for the identification of fungi genera. Many of these methods have failed when it comes to identification of closely related species of certain genus like Pleurotus. Our electronics profiles, both in the negative and positive bias regions were however found to be highly characteristic according to the base-pair sequences. We believe that this simple, low-cost and practical method could be useful towards identifying and detecting DNA in biotechnology and pathology. PMID:27435636

  16. An HTS-compatible 3D colony formation assay to identify tumor-specific chemotherapeutics.

    Science.gov (United States)

    Horman, Shane R; To, Jeremy; Orth, Anthony P

    2013-12-01

    There has been increasing interest in the development of cellular behavior models that take advantage of three-dimensional (3D) cell culture. To enable assessment of differential perturbagen impacts on cell growth in 2D and 3D, we have miniaturized and adapted for high-throughput screening (HTS) the soft agar colony formation assay, employing a laser-scanning cytometer to image and quantify multiple cell types simultaneously. The assay is HTS compatible, providing high-quality, image-based, replicable data for multiple, co-cultured cell types. As proof of concept, we subjected colorectal carcinoma colonies in 3D soft agar to a mini screen of 1528 natural product compounds. Hit compounds from the primary screen were rescreened in an HTS 3D co-culture matrix containing colon stromal cells and cancer cells. By combining tumor cells and normal, nontransformed colon epithelial cells in one primary screening assay, we were able to obtain differential IC50 data, thereby distinguishing tumor-specific compounds from general cytotoxic compounds. Moreover, we were able to identify compounds that antagonized tumor colony formation in 3D only, highlighting the importance of this assay in identifying agents that interfere with 3D tumor structural growth. This screening platform provides a fast, simple, and robust method for identification of tumor-specific agents in a biologically relevant microenvironment.

  17. Regulatory aspects of the use of PSA to evaluate technical specifications

    International Nuclear Information System (INIS)

    Rumpf, J.

    1991-01-01

    Based on experiences gained in PSA activities the regulatory body of the GDR initiated a programme to investigate the feasibility of using PSA for the evaluation of technical specifications. This programme is just under work. In addition, to improve PSA, the GDR takes part in a programme which is aimed at performing plant specific level 1, PSA as well as and which enables operating organizations to carry out PSA on their own. The most important of some preliminary general findings presented in this paper are: - Technical specifications form a well established envelope of operational conditions and procedures. A total re-evaluation is not considered necessary; Probabilistic evaluation of technical specifications should be an integrated part of PSA activities (at least level 1). Single assessment is not considered reasonable; Probabilistic evaluation of technical specifications has to be based on plant specific information and realistic accident sequence calculations; Up to now no quantitative probabilistic criteria for technical specifications have been established. (author)

  18. Identifying functional cancer-specific miRNA-mRNA interactions in testicular germ cell tumor.

    Science.gov (United States)

    Sedaghat, Nafiseh; Fathy, Mahmood; Modarressi, Mohammad Hossein; Shojaie, Ali

    2016-09-07

    Testicular cancer is the most common cancer in men aged between 15 and 35 and more than 90% of testicular neoplasms are originated at germ cells. Recent research has shown the impact of microRNAs (miRNAs) in different types of cancer, including testicular germ cell tumor (TGCT). MicroRNAs are small non-coding RNAs which affect the development and progression of cancer cells by binding to mRNAs and regulating their expressions. The identification of functional miRNA-mRNA interactions in cancers, i.e. those that alter the expression of genes in cancer cells, can help delineate post-regulatory mechanisms and may lead to new treatments to control the progression of cancer. A number of sequence-based methods have been developed to predict miRNA-mRNA interactions based on the complementarity of sequences. While necessary, sequence complementarity is, however, not sufficient for presence of functional interactions. Alternative methods have thus been developed to refine the sequence-based interactions using concurrent expression profiles of miRNAs and mRNAs. This study aims to find functional cancer-specific miRNA-mRNA interactions in TGCT. To this end, the sequence-based predicted interactions are first refined using an ensemble learning method, based on two well-known methods of learning miRNA-mRNA interactions, namely, TaLasso and GenMiR++. Additional functional analyses were then used to identify a subset of interactions to be most likely functional and specific to TGCT. The final list of 13 miRNA-mRNA interactions can be potential targets for identifying TGCT-specific interactions and future laboratory experiments to develop new therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Identifying specific protein interaction partners using quantitative mass spectrometry and bead proteomes

    Science.gov (United States)

    Trinkle-Mulcahy, Laura; Boulon, Séverine; Lam, Yun Wah; Urcia, Roby; Boisvert, François-Michel; Vandermoere, Franck; Morrice, Nick A.; Swift, Sam; Rothbauer, Ulrich; Leonhardt, Heinrich; Lamond, Angus

    2008-01-01

    The identification of interaction partners in protein complexes is a major goal in cell biology. Here we present a reliable affinity purification strategy to identify specific interactors that combines quantitative SILAC-based mass spectrometry with characterization of common contaminants binding to affinity matrices (bead proteomes). This strategy can be applied to affinity purification of either tagged fusion protein complexes or endogenous protein complexes, illustrated here using the well-characterized SMN complex as a model. GFP is used as the tag of choice because it shows minimal nonspecific binding to mammalian cell proteins, can be quantitatively depleted from cell extracts, and allows the integration of biochemical protein interaction data with in vivo measurements using fluorescence microscopy. Proteins binding nonspecifically to the most commonly used affinity matrices were determined using quantitative mass spectrometry, revealing important differences that affect experimental design. These data provide a specificity filter to distinguish specific protein binding partners in both quantitative and nonquantitative pull-down and immunoprecipitation experiments. PMID:18936248

  20. Linguistic and pragmatic aspects of narration in Finnish typically developing children and children with specific language impairment.

    Science.gov (United States)

    Mäkinen, Leena; Loukusa, Soile; Laukkanen, Päivi; Leinonen, Eeva; Kunnari, Sari

    2014-06-01

    This study investigates narratives of Finnish children with specific language impairment (SLI) from linguistic and pragmatic perspectives, in order to get a comprehensive overview of these children's narrative abilities. Nineteen children with SLI (mean age 6;1 years) and 19 typically developing age-matched children participated in the study. Their picture-elicited narrations were analysed for linguistic productivity and complexity, grammatical and referential accuracy, event content, the use of mental state expressions and narrative comprehension. Children with SLI showed difficulties in every aspect of narration in comparison to their peers. Only one measure of productivity, the number of communication units, did not reach statistical significance. Not only was linguistic structure fragile but also pragmatic aspects of storytelling (referencing, event content, mental state expressions and inferencing) were demanding for children with SLI. Results suggest that pragmatic aspects of narration should be taken into account more often when assessing narrative abilities of children with SLI.

  1. Genome-wide association studies identify four ER negative-specific breast cancer risk loci

    DEFF Research Database (Denmark)

    Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara

    2013-01-01

    differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls......), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER...

  2. Identifying Gender-Specific Developmental Trajectories of Nonviolent and Violent Delinquency from Adolescence to Young Adulthood

    Science.gov (United States)

    Zheng, Yao; Cleveland, H. Harrington

    2013-01-01

    Most research examining gender differences in developmental trajectories of antisocial behavior does not consider subtypes of antisocial behavior and is difficult to generalize due to small nonrepresentative samples. The current study investigated gender difference in developmental trajectories from adolescence to young adulthood while addressing those limitations. Analyses were limited to respondents ages 15 and 16 in wave 1 (16–17 in wave 2, and 21–22 in wave 3) of the National Longitudinal Study of Adolescent Health (n = 6244, 49.5% males). Self-report nonviolent and violent delinquencies were simultaneously entered into latent class analysis. Four latent classes were identified: low, desister, decliner, and chronic (male-only). In addition to finding a male-specific chronic class, gender differences included differences in levels of nonviolent and violent delinquency between synonymous classes of males and females, and differences in prevalence of classes across genders. Neighborhood disadvantage and family support predicted trajectories. PMID:23375843

  3. CloudNeo: a cloud pipeline for identifying patient-specific tumor neoantigens.

    Science.gov (United States)

    Bais, Preeti; Namburi, Sandeep; Gatti, Daniel M; Zhang, Xinyu; Chuang, Jeffrey H

    2017-10-01

    We present CloudNeo, a cloud-based computational workflow for identifying patient-specific tumor neoantigens from next generation sequencing data. Tumor-specific mutant peptides can be detected by the immune system through their interactions with the human leukocyte antigen complex, and neoantigen presence has recently been shown to correlate with anti T-cell immunity and efficacy of checkpoint inhibitor therapy. However computing capabilities to identify neoantigens from genomic sequencing data are a limiting factor for understanding their role. This challenge has grown as cancer datasets become increasingly abundant, making them cumbersome to store and analyze on local servers. Our cloud-based pipeline provides scalable computation capabilities for neoantigen identification while eliminating the need to invest in local infrastructure for data transfer, storage or compute. The pipeline is a Common Workflow Language (CWL) implementation of human leukocyte antigen (HLA) typing using Polysolver or HLAminer combined with custom scripts for mutant peptide identification and NetMHCpan for neoantigen prediction. We have demonstrated the efficacy of these pipelines on Amazon cloud instances through the Seven Bridges Genomics implementation of the NCI Cancer Genomics Cloud, which provides graphical interfaces for running and editing, infrastructure for workflow sharing and version tracking, and access to TCGA data. The CWL implementation is at: https://github.com/TheJacksonLaboratory/CloudNeo. For users who have obtained licenses for all internal software, integrated versions in CWL and on the Seven Bridges Cancer Genomics Cloud platform (https://cgc.sbgenomics.com/, recommended version) can be obtained by contacting the authors. jeff.chuang@jax.org. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

  4. Multifactor dimensionality reduction analysis identifies specific nucleotide patterns promoting genetic polymorphisms

    Directory of Open Access Journals (Sweden)

    Arehart Eric

    2009-03-01

    Full Text Available Abstract Background The fidelity of DNA replication serves as the nidus for both genetic evolution and genomic instability fostering disease. Single nucleotide polymorphisms (SNPs constitute greater than 80% of the genetic variation between individuals. A new theory regarding DNA replication fidelity has emerged in which selectivity is governed by base-pair geometry through interactions between the selected nucleotide, the complementary strand, and the polymerase active site. We hypothesize that specific nucleotide combinations in the flanking regions of SNP fragments are associated with mutation. Results We modeled the relationship between DNA sequence and observed polymorphisms using the novel multifactor dimensionality reduction (MDR approach. MDR was originally developed to detect synergistic interactions between multiple SNPs that are predictive of disease susceptibility. We initially assembled data from the Broad Institute as a pilot test for the hypothesis that flanking region patterns associate with mutagenesis (n = 2194. We then confirmed and expanded our inquiry with human SNPs within coding regions and their flanking sequences collected from the National Center for Biotechnology Information (NCBI database (n = 29967 and a control set of sequences (coding region not associated with SNP sites randomly selected from the NCBI database (n = 29967. We discovered seven flanking region pattern associations in the Broad dataset which reached a minimum significance level of p ≤ 0.05. Significant models (p Conclusion The present study represents the first use of this computational methodology for modeling nonlinear patterns in molecular genetics. MDR was able to identify distinct nucleotide patterning around sites of mutations dependent upon the observed nucleotide change. We discovered one flanking region set that included five nucleotides clustered around a specific type of SNP site. Based on the strongly associated patterns identified in

  5. Identifying Industry-Specific Components of Product Liability Response System Using Delphi-AHP Method

    Directory of Open Access Journals (Sweden)

    Seo JunHyeok

    2016-12-01

    Full Text Available PL (product liability response system is an enterprise-wide system that prevents company’s financial loss due to PL-related accidents. Existing researches on PL response system are mainly focused on preventive and/or defense strategies for the companies. Also, it is obvious that each industry has their original characteristics related on PL issues. It means industry-specific characteristics should be considered to adopt PL response strategies. Thus, this paper aims to discuss industry-specific PL response system and their components. Based on prior researches, we tried to reveal the possibility of its application to manufacturing companies of existing PL response strategies using Delphi method with PL experts. Based on first round results, we tried to classify existing PL strategies of manufacturing companies into several categories. To validate our suggestion for essential components of PL response system, second round Delphi method are applied. Analytic hierarchy process (AHP technique will be applied to identify a prioritized list of each components and strategies. Existing PL response strategies could be categorized with six components – strategy, technology, investment, training, awareness, and organization. Among six components, Technology – it represents the technology needed for improving the safety of all products – is the most important components to prepare PL accidents. The limitation of this paper is on the size of survey and variety of examples. However, the future study will enhance the potential of the proposed method. Regardless of rich research efforts to identify PL response strategies, there is no effort to categorize these strategies and prioritized them. Well-coordinated and actionable PL response strategies and their priorities could help small-and-medium sized enterprise (SME to develop their own PL response system with their limited resources.

  6. GSHSite: exploiting an iteratively statistical method to identify s-glutathionylation sites with substrate specificity.

    Directory of Open Access Journals (Sweden)

    Yi-Ju Chen

    Full Text Available S-glutathionylation, the covalent attachment of a glutathione (GSH to the sulfur atom of cysteine, is a selective and reversible protein post-translational modification (PTM that regulates protein activity, localization, and stability. Despite its implication in the regulation of protein functions and cell signaling, the substrate specificity of cysteine S-glutathionylation remains unknown. Based on a total of 1783 experimentally identified S-glutathionylation sites from mouse macrophages, this work presents an informatics investigation on S-glutathionylation sites including structural factors such as the flanking amino acids composition and the accessible surface area (ASA. TwoSampleLogo presents that positively charged amino acids flanking the S-glutathionylated cysteine may influence the formation of S-glutathionylation in closed three-dimensional environment. A statistical method is further applied to iteratively detect the conserved substrate motifs with statistical significance. Support vector machine (SVM is then applied to generate predictive model considering the substrate motifs. According to five-fold cross-validation, the SVMs trained with substrate motifs could achieve an enhanced sensitivity, specificity, and accuracy, and provides a promising performance in an independent test set. The effectiveness of the proposed method is demonstrated by the correct identification of previously reported S-glutathionylation sites of mouse thioredoxin (TXN and human protein tyrosine phosphatase 1b (PTP1B. Finally, the constructed models are adopted to implement an effective web-based tool, named GSHSite (http://csb.cse.yzu.edu.tw/GSHSite/, for identifying uncharacterized GSH substrate sites on the protein sequences.

  7. Global Transcriptome Sequencing Identifies Chlamydospore Specific Markers in Candida albicans and Candida dubliniensis

    LENUS (Irish Health Repository)

    Palige, Katja

    2013-04-15

    Candida albicans and Candida dubliniensis are pathogenic fungi that are highly related but differ in virulence and in some phenotypic traits. During in vitro growth on certain nutrient-poor media, C. albicans and C. dubliniensis are the only yeast species which are able to produce chlamydospores, large thick-walled cells of unknown function. Interestingly, only C. dubliniensis forms pseudohyphae with abundant chlamydospores when grown on Staib medium, while C. albicans grows exclusively as a budding yeast. In order to further our understanding of chlamydospore development and assembly, we compared the global transcriptional profile of both species during growth in liquid Staib medium by RNA sequencing. We also included a C. albicans mutant in our study which lacks the morphogenetic transcriptional repressor Nrg1. This strain, which is characterized by its constitutive pseudohyphal growth, specifically produces masses of chlamydospores in Staib medium, similar to C. dubliniensis. This comparative approach identified a set of putatively chlamydospore-related genes. Two of the homologous C. albicans and C. dubliniensis genes (CSP1 and CSP2) which were most strongly upregulated during chlamydospore development were analysed in more detail. By use of the green fluorescent protein as a reporter, the encoded putative cell wall related proteins were found to exclusively localize to C. albicans and C. dubliniensis chlamydospores. Our findings uncover the first chlamydospore specific markers in Candida species and provide novel insights in the complex morphogenetic development of these important fungal pathogens.

  8. Machine-learning identifies substance-specific behavioral markers for opiate and stimulant dependence.

    Science.gov (United States)

    Ahn, Woo-Young; Vassileva, Jasmin

    2016-04-01

    Recent animal and human studies reveal distinct cognitive and neurobiological differences between opiate and stimulant addictions; however, our understanding of the common and specific effects of these two classes of drugs remains limited due to the high rates of polysubstance-dependence among drug users. The goal of the current study was to identify multivariate substance-specific markers classifying heroin dependence (HD) and amphetamine dependence (AD), by using machine-learning approaches. Participants included 39 amphetamine mono-dependent, 44 heroin mono-dependent, 58 polysubstance dependent, and 81 non-substance dependent individuals. The majority of substance dependent participants were in protracted abstinence. We used demographic, personality (trait impulsivity, trait psychopathy, aggression, sensation seeking), psychiatric (attention deficit hyperactivity disorder, conduct disorder, antisocial personality disorder, psychopathy, anxiety, depression), and neurocognitive impulsivity measures (Delay Discounting, Go/No-Go, Stop Signal, Immediate Memory, Balloon Analogue Risk, Cambridge Gambling, and Iowa Gambling tasks) as predictors in a machine-learning algorithm. The machine-learning approach revealed substance-specific multivariate profiles that classified HD and AD in new samples with high degree of accuracy. Out of 54 predictors, psychopathy was the only classifier common to both types of addiction. Important dissociations emerged between factors classifying HD and AD, which often showed opposite patterns among individuals with HD and AD. These results suggest that different mechanisms may underlie HD and AD, challenging the unitary account of drug addiction. This line of work may shed light on the development of standardized and cost-efficient clinical diagnostic tests and facilitate the development of individualized prevention and intervention programs for HD and AD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. The effectiveness of front fork systems at damping accelerations during isolated aspects specific to cross-country mountain biking.

    Science.gov (United States)

    Macdermid, Paul W; Miller, Matthew C; Fink, Philip W; Stannard, Stephen R

    2017-11-01

    Cross-country mountain bike suspension reportedly enhances comfort and performance through reduced vibration and impact exposure. This study analysed the effectiveness of three different front fork systems at damping accelerations during the crossing of three isolated obstacles (stairs, drop, and root). One participant completed three trials on six separate occasions in a randomised order using rigid, air-sprung, and carbon leaf-sprung forks. Performance was determined by time to cross obstacles, while triaxial accelerometers quantified impact exposure and damping response. Results identified significant main effect of fork type for performance time (p < 0.05). The air-sprung and leaf-sprung forks were significantly slower than the rigid forks for the stairs (p < 0.05), while air-sprung suspension was slower than the rigid for the root protocol (p < 0.05). There were no differences for the drop protocol (p < 0.05). Rigid forks reduced overall exposure (p < 0.05), specifically at the handlebars for the stairs and drop trials. More detailed analysis presented smaller vertical accelerations at the handlebar for air-sprung and leaf-sprung forks on the stairs (p < 0.05), and drop (p < 0.05) but not the root. As such, it appears that the suspension systems tested were ineffective at reducing overall impact exposure at the handlebar during isolated aspects of cross-country terrain features which may be influenced to a larger extent by rider technique.

  10. Functional genomics identifies specific vulnerabilities in PTEN-deficient breast cancer.

    Science.gov (United States)

    Tang, Yew Chung; Ho, Szu-Chi; Tan, Elisabeth; Ng, Alvin Wei Tian; McPherson, John R; Goh, Germaine Yen Lin; Teh, Bin Tean; Bard, Frederic; Rozen, Steven G

    2018-03-22

    -SSL patterns of activity in a large proportion of PTEN-deficient breast cancer cell lines and are potential specific vulnerabilities in PTEN-deficient breast cancer. Furthermore, the NUAK1 PTEN-SSL vulnerability identified by RNA interference techniques can be recapitulated and exploited using the small molecule kinase inhibitor HTH-01-015. Thus, NUAK1 inhibition may be an effective strategy for precision treatment of PTEN-deficient breast tumors.

  11. Methods for Identifying Specific Language Impairment in Bilingual Populations in Germany

    Directory of Open Access Journals (Sweden)

    Cornelia Hamann

    2017-10-01

    Full Text Available This study investigates the performance of 22 monolingual and 54 bilingual children with and without specific language impairment (SLI, in a non-word repetition task (NWRT and a sentence repetition task (SRT. Both tasks were constructed according to the principles for LITMUS tools (Language Impairment Testing in Multilingual Settings developed within COST Action IS0804 and incorporated phonological or syntactic structures that are linguistically complex and have been shown to be difficult for children with SLI across languages. For phonology these are in particular (nonwords containing consonant clusters. In morphosyntax, complexity has been attributed to factors such as embedding and/or syntactic movement. Tasks focusing on such structures are expected to identify SLI in bilinguals across language combinations. This is notoriously difficult because structures that are problematic for typically developing bilinguals (BiTDs and monolingual children with SLI (MoSLI often overlap. We show that the NWRT and the SRT are reliable tools for identification of SLI in bilingual contexts. However, interpretation of the performance of bilingual children depends on background information as provided by parental questionnaires. To evaluate the accuracy of our tasks, we recruited children in ordinary kindergartens or schools and in speech language therapy centers and verified their status with a battery of standardized language tests, assessing bilingual children in both their languages. We consider a bilingual child language impaired if she shows impairments in two language domains in both her languages. For assessment, we used tests normed for monolinguals (with one exception and adjusted the norms for bilingualism and for language dominance. This procedure established the following groups: 10 typical monolinguals (MoTD, 12 MoSLI, 46 BiTD, and 8 bilingual children with SLI (BiSLI. Our results show that both tasks target relevant structures: monolingual

  12. Phospho-specific flow cytometry identifies aberrant signaling in indolent B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Blix Egil S

    2012-10-01

    Full Text Available Abstract Background Knowledge about signaling pathways in malignant cells may provide prognostic and diagnostic information in addition to identify potential molecular targets for therapy. B-cell receptor (BCR and co-receptor CD40 signaling is essential for normal B cells, and there is increasing evidence that signaling via BCR and CD40 plays an important role in the pathogenesis of B-cell lymphoma. The aim of this study was to investigate basal and induced signaling in lymphoma B cells and infiltrating T cells in single-cell suspensions of biopsies from small cell lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL and marginal zone lymphoma (MZL patients. Methods Samples from untreated SLL/CLL and MZL patients were examined for basal and activation induced signaling by phospho-specific flow cytometry. A panel of 9 stimulation conditions targeting B and T cells, including crosslinking of the B cell receptor (BCR, CD40 ligand and interleukins in combination with 12 matching phospho-protein readouts was used to study signaling. Results Malignant B cells from SLL/CLL patients had higher basal levels of phosphorylated (p-SFKs, p-PLCγ, p-ERK, p-p38, p-p65 (NF-κB, p-STAT5 and p-STAT6, compared to healthy donor B cells. In contrast, anti-BCR induced signaling was highly impaired in SLL/CLL and MZL B cells as determined by low p-SFK, p-SYK and p-PLCγ levels. Impaired anti-BCR-induced p-PLCγ was associated with reduced surface expression of IgM and CD79b. Similarly, CD40L-induced p-ERK and p-p38 were also significantly reduced in lymphoma B cells, whereas p-p65 (NF-κB was equal to that of normal B cells. In contrast, IL-2, IL-7 and IL-15 induced p-STAT5 in tumor-infiltrating T cells were not different from normal T cells. Conclusions BCR signaling and CD40L-induced p-p38 was suppressed in malignant B cells from SLL/CLL and MZL patients. Single-cell phospho-specific flow cytometry for detection of basal as well as activation

  13. Identifying context-specific competencies required by community Australian Football sports trainers.

    Science.gov (United States)

    Donaldson, Alex; Finch, Caroline F

    2012-08-01

    First-aid is a recommended injury prevention and risk management strategy in community sport; however, little is known about the sport-specific competencies required by first-aid providers. To achieve expert consensus on the competencies required by community Australian Football (community-AF) sports trainers. A three-round online Delphi process. Community-AF. 16 Australian sports first-aid and community-AF experts. Rating of competencies as either 'essential', 'expected', 'ideal' or 'not required'. Results After Round 3, 47 of the 77 (61%) competencies were endorsed as 'essential' or 'expected' for a sports trainer to effectively perform the activities required to the standards expected at a community-AF club by ≥75% of experts. These competencies covered: the role of the sports trainer; the responsibilities of the sports trainer; emergency management; injury and illness assessment and immediate management; taping; and injury prevention and risk management. Four competencies (5%) were endorsed as 'ideal' or 'not required' by ≥85% of experts and were excluded from further consideration. The 26 competencies where consensus was not reached were retained as second-tier, optional competencies. Sports trainers are important members of on-field first-aid teams, providing support to both injured players and other sports medicine professionals. The competencies identified in this study provide the basis of a proposed two-tiered community-AF-specific sports trainer education structure that can be implemented by the peak sports body. This includes six mandatory modules, relating to the 'required' competencies, and a further six optional modules covering competencies on which consensus was not reached.

  14. Theoretical and Numerical Modeling of Transport of Land Use-Specific Fecal Source Identifiers

    Science.gov (United States)

    Bombardelli, F. A.; Sirikanchana, K. J.; Bae, S.; Wuertz, S.

    2008-12-01

    Microbial contamination in coastal and estuarine waters is of particular concern to public health officials. In this work, we advocate that well-formulated and developed mathematical and numerical transport models can be combined with modern molecular techniques in order to predict continuous concentrations of microbial indicators under diverse scenarios of interest, and that they can help in source identification of fecal pollution. As a proof of concept, we present initially the theory, numerical implementation and validation of one- and two-dimensional numerical models aimed at computing the distribution of fecal source identifiers in water bodies (based on Bacteroidales marker DNA sequences) coming from different land uses such as wildlife, livestock, humans, dogs or cats. These models have been developed to allow for source identification of fecal contamination in large bodies of water. We test the model predictions using diverse velocity fields and boundary conditions. Then, we present some preliminary results of an application of a three-dimensional water quality model to address the source of fecal contamination in the San Pablo Bay (SPB), United States, which constitutes an important sub-embayment of the San Francisco Bay. The transport equations for Bacteroidales include the processes of advection, diffusion, and decay of Bacteroidales. We discuss the validation of the developed models through comparisons of numerical results with field campaigns developed in the SPB. We determine the extent and importance of the contamination in the bay for two decay rates obtained from field observations, corresponding to total host-specific Bacteroidales DNA and host-specific viable Bacteroidales cells, respectively. Finally, we infer transport conditions in the SPB based on the numerical results, characterizing the fate of outflows coming from the Napa, Petaluma and Sonoma rivers.

  15. SNOSite: exploiting maximal dependence decomposition to identify cysteine S-nitrosylation with substrate site specificity.

    Directory of Open Access Journals (Sweden)

    Tzong-Yi Lee

    Full Text Available S-nitrosylation, the covalent attachment of a nitric oxide to (NO the sulfur atom of cysteine, is a selective and reversible protein post-translational modification (PTM that regulates protein activity, localization, and stability. Despite its implication in the regulation of protein functions and cell signaling, the substrate specificity of cysteine S-nitrosylation remains unknown. Based on a total of 586 experimentally identified S-nitrosylation sites from SNAP/L-cysteine-stimulated mouse endothelial cells, this work presents an informatics investigation on S-nitrosylation sites including structural factors such as the flanking amino acids composition, the accessible surface area (ASA and physicochemical properties, i.e. positive charge and side chain interaction parameter. Due to the difficulty to obtain the conserved motifs by conventional motif analysis, maximal dependence decomposition (MDD has been applied to obtain statistically significant conserved motifs. Support vector machine (SVM is applied to generate predictive model for each MDD-clustered motif. According to five-fold cross-validation, the MDD-clustered SVMs could achieve an accuracy of 0.902, and provides a promising performance in an independent test set. The effectiveness of the model was demonstrated on the correct identification of previously reported S-nitrosylation sites of Bos taurus dimethylarginine dimethylaminohydrolase 1 (DDAH1 and human hemoglobin subunit beta (HBB. Finally, the MDD-clustered model was adopted to construct an effective web-based tool, named SNOSite (http://csb.cse.yzu.edu.tw/SNOSite/, for identifying S-nitrosylation sites on the uncharacterized protein sequences.

  16. Psychological aspects of idiopathic scoliosis: the specificity of the mother-daughter relationship

    Directory of Open Access Journals (Sweden)

    Galina V. Pyatakova

    2016-12-01

    Conclusion: General and specific characteristics of the mother-daughter relationship in families of adolescent girls with idiopathic scoliosis and families of healthy adolescent girls were revealed. In the context of complex surgical treatment, preventive measures are necessary to address psychological difficulties in adolescent patients with idiopathic scoliosis.

  17. Empathy in Children with Autism and Conduct Disorder: Group-Specific Profiles and Developmental Aspects

    Science.gov (United States)

    Schwenck, Christina; Mergenthaler, Julia; Keller, Katharina; Zech, Julie; Salehi, Sarah; Taurines, Regina; Romanos, Marcel; Schecklmann, Martin; Schneider, Wolfgang; Warnke, Andreas; Freitag, Christine M.

    2012-01-01

    Background: A deficit in empathy is discussed to underlie difficulties in social interaction of children with autism spectrum disorder (ASD) and conduct disorder (CD). To date, no study has compared children with ASD and different subtypes of CD to describe disorder-specific empathy profiles in clinical samples. Furthermore, little is known about…

  18. Developmental Change and Time-Specific Variation in Global and Specific Aspects of Self-Concept in Adolescence and Association with Depressive Symptoms

    Science.gov (United States)

    Kuzucu, Yasar; Bontempo, Daniel E.; Hofer, Scott M.; Stallings, Michael C.; Piccinin, Andrea M.

    2014-01-01

    Previous research has demonstrated that adolescents make differential self-evaluations in multiple domains that include physical appearance, academic competence, and peer acceptance. We report growth curve analyses over a seven year period from age 9 to age 16 on the six domains of the Harter Self-Perception Profile for Children. In general, we find little change in self-concept, on average, but do find substantial individual differences in level, rate of change, and time-specific variation in these self- evaluations. The results suggest that sex differences and adoptive status were related to only certain aspects of the participants’ self-concept. Depressive symptoms were found to have significant effects on individual differences in rate of change and on time-specific variation in general self-concept, as well as on some of the specific domains of self-concept. PMID:25143664

  19. Teacher's opinions about learning continuum based on the student's level of competence and specific pedagogical materials on anatomical aspects

    Science.gov (United States)

    Astuti, Laili Dwi; Subali, Bambang

    2017-08-01

    This research deals with designing learning continuum for developing a curriculum. The objective of this study is to gather the opinion of public junior and high school teachers about Learning Continuum based on Student's Level of Competence and Specific Pedagogical Material on Anatomical Aspects. This is a survey research. The population of the research is natural science teachers at junior high school and biology teacher at senior high school in Yogyakarta Special Region. Data were collected using a questionnaire. Data were analyzed using a descriptive analysis technique. Based on the results of the survey, the teachers opinion are in accordance with the level of the students they teach. Junior high school teachers argued that anatomical aspects were taught in grade VII,VIII, IX and X on the level of C2 (understanding), the high school teacher argued that anatomical aspects were taught in grade VIII, X and XI on the level of C2 (understanding) and C3 (apply). While according to the opinions of primary school teachers about aspects of anatomy resulted from the research of Subali (2016), anatomy is mostly not taught at the elementary school level, only some of the materials that are taught in this school level. Therefore, the results of the survey can be inferred that the opinions of teachers is still based on the existing curriculum.

  20. SPECIFIC ASPECTS OF THE PROCESS OF BANKING CONCENTRATION AND CONSOLIDATION IN THE EUROPEAN UNION

    Directory of Open Access Journals (Sweden)

    COPIL CRINA ANGELA

    2015-04-01

    Full Text Available In this paper I proposed to anaylze the main aspect that characterized the process of bank concentration and consolidation in the European union, knowing their evolutions and particularities on the European and world bank sector and the effects that they have on the banks and the economy altogether. I presented the evolution of the number of banks, evolution that reflects the degree of consolidation of the bank system. Based on the financial crisis begun in 2008 the number of credit institutions decreased continuously as a consequence of the processes of bank mergers and acquisitions generated by the uncertainties of the economic perspectives. Also I analyzed the evolution of the degree of bank concentration in the European countries, process that underlines the degree of domination of the banking market accomplished by some great banks. We consider essential the knowing of this process because the increase of the bank concentration leads to the creating of some bank entities with very large dimensions, that in the periods of crisis can generate macro economic imbalances by involving the state in their subventioning. The research is based mainly on compiled statistic data offered by the European Central Bank (BCE, data that are published annualy and that were processed to be able to offer an overview on the most important modifications that took place in the European union and in its representative countries.

  1. Genome-wide association studies identify four ER negative–specific breast cancer risk loci

    Science.gov (United States)

    Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K; Brook, Mark N; orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather s; Le Marchand, Loic; Buring, Julie E; Eccles, Diana; Miron, Penelope; Fasching, Peter A; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K; Nevanlinna, Heli; Giles, Graham G; Cox, Angela; Hopper, John L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J; Schoof, Nils; Bojesen, Stig E; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C; Park, Daniel J; Hammet, Fleur; Stone, Jennifer; Veer, Laura J Van’t; Rutgers, Emiel J; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Silva, Isabel dos Santos; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Balleine, Rosemary; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; Mclean, Catriona; Coetzee, Gerhard A; Feng, Ye; Henderson, Brian E; Schumacher, Fredrick; Bogdanova, Natalia V; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A E M; Seynaeve, Caroline M; Kriege, Mieke; Hooning, Maartje J; Van den Ouweland, Ans M W; Van Deurzen, Carolien H M; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P; Cross, Simon S; Reed, Malcolm W R; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B; Bandera, Elisa V; John, Esther M; Chen, Gary K; Hu, Jennifer J; Rodriguez-gil, Jorge L; Bernstein, Leslie; Press, Michael F; Ziegler, Regina G; Millikan, Robert M; Deming-Halverson, Sandra L; Nyante, Sarah; Ingles, Sue A; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G; Montgomery, Grant W; Slamon, Dennis J; Rauh, Claudia; Lux, Michael P; Jud, Sebastian M; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N; Chen, Constance; Beck, Andy; Hankinson, Susan E; Berg, Christine D; Hoover, Robert N; Lissowska, Jolanta; Figueroa, Jonine D; Chasman, Daniel I; Gaudet, Mia M; Diver, W Ryan; Willett, Walter C; Hunter, David J; Simard, Jacques; Benitez, Javier; Dunning, Alison M; Sherman, Mark E; Chenevix-Trench, Georgia; Chanock, Stephen J; Hall, Per; Pharoah, Paul D P; Vachon, Celine; Easton, Douglas F; Haiman, Christopher A; Kraft, Peter

    2013-01-01

    Estrogen receptor (ER)-negative tumors represent 20–30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry1. The etiology2 and clinical behavior3 of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition4. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10−12 and LGR6, P = 1.4 × 10−8), 2p24.1 (P = 4.6 × 10−8) and 16q12.2 (FTO, P = 4.0 × 10−8), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers. PMID:23535733

  2. Genome-wide association studies identify four ER negative-specific breast cancer risk loci.

    Science.gov (United States)

    Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K; Brook, Mark N; Orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather S; Le Marchand, Loic; Buring, Julie E; Eccles, Diana; Miron, Penelope; Fasching, Peter A; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K; Nevanlinna, Heli; Giles, Graham G; Cox, Angela; Hopper, John L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J; Schoof, Nils; Bojesen, Stig E; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C; Park, Daniel J; Hammet, Fleur; Stone, Jennifer; Veer, Laura J Van't; Rutgers, Emiel J; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Dos Santos Silva, Isabel; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Balleine, Rosemary; Tseng, Chiu-Chen; Berg, David Van Den; Stram, Daniel O; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; McLean, Catriona; Coetzee, Gerhard A; Feng, Ye; Henderson, Brian E; Schumacher, Fredrick; Bogdanova, Natalia V; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A E M; Seynaeve, Caroline M; Kriege, Mieke; Hooning, Maartje J; van den Ouweland, Ans M W; van Deurzen, Carolien H M; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P; Cross, Simon S; Reed, Malcolm W R; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B; Bandera, Elisa V; John, Esther M; Chen, Gary K; Hu, Jennifer J; Rodriguez-Gil, Jorge L; Bernstein, Leslie; Press, Michael F; Ziegler, Regina G; Millikan, Robert M; Deming-Halverson, Sandra L; Nyante, Sarah; Ingles, Sue A; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G; Montgomery, Grant W; Slamon, Dennis J; Rauh, Claudia; Lux, Michael P; Jud, Sebastian M; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N; Chen, Constance; Beck, Andy; Hankinson, Susan E; Berg, Christine D; Hoover, Robert N; Lissowska, Jolanta; Figueroa, Jonine D; Chasman, Daniel I; Gaudet, Mia M; Diver, W Ryan; Willett, Walter C; Hunter, David J; Simard, Jacques; Benitez, Javier; Dunning, Alison M; Sherman, Mark E; Chenevix-Trench, Georgia; Chanock, Stephen J; Hall, Per; Pharoah, Paul D P; Vachon, Celine; Easton, Douglas F; Haiman, Christopher A; Kraft, Peter

    2013-04-01

    Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

  3. SPECIFIC ASPECTS OF THE OFFENSE OF LEAVING THE PLACE OF THE ACCIDENT

    Directory of Open Access Journals (Sweden)

    Alin-Sorin NICOLESCU

    2018-05-01

    Full Text Available The legislator has adopted the respective texts of law to the new social realities once with the repeal of the criminal segment of GEO no. 195/2002 relating to the circulation on public roads, republished and the introduction of this one in the content of the New Criminal Code. The offence of leaving the place of the accident, actually found in the content of the provisions of art. 338 of Criminal Code is one of the eight offences against the safety on public roads. Knowing important modifications, the legal text may appear relatively ambiguous if we refer to the old indictment, meaning that certain factual situations remained outside the criminal law. We will analyse in this regard the obligations that arise to the driver in case of a traffic accident, bringing into question even the decriminalization of the prohibition of the consumption of alcohol after the road event. Furthermore, we will treat even aspects related to the causes of special no imputation that, on a closer analysis, can create problems of interpretation. Through the phrase “it does not constitute the offence of leaving the place of the accident when only material damages occurred after the accident”, the legislator has chosen to indict this offence even if the victim has evaluable lesions within 1-2 days of medical care, on condition that for the same fact, in the old regulation, 10 days were required or it was an oversight of the legislator that it is to be resolved at some point?

  4. Specificity of SPC Procedures Application in Foundry in Aspect of Data Acquisition and Data Exploration

    Directory of Open Access Journals (Sweden)

    Ignaszak Z.

    2012-12-01

    Full Text Available The paper presents an analysis of SPC (Statistical Process Control procedures usability in foundry engineering. The authors pay particular attention to the processes complexity and necessity of correct preparation of data acquisition procedures. Integration of SPC systems with existing IT solutions in area of aiding and assistance during the manufacturing process is important. For each particular foundry, methodology of selective SPC application needs to prepare for supervision and control of stability of manufacturing conditions, regarding specificity of data in particular “branches” of foundry production (Sands, Pouring, Metallurgy, Quality.

  5. Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

    NARCIS (Netherlands)

    van Leeuwen, E.M.; Karssen, L.C.; Deelen, J.; Isaacs, A.; Medina-Gomez, C.; Mbarek, H.; Kanterakis, A.; Trompet, S.; Postmus, I.; Verweij, N.; van Enckevort, D.; Huffman, J.E.; White, C.C.; Feitosa, M.F.; Bartz, T.M.; Manichaikul, A.; Joshi, P.K.; Peloso, G.M.; Deelen, P.; Dijk, F.; Willemsen, G.; de Geus, E.J.C.; Milaneschi, Y.; Penninx, B.W.J.H.; Francioli, L.C.; Menelaou, A.; Pulit, S.L.; Rivadeneira, F.; Hofman, A.; Oostra, B.A.; Franco, O.H.; Mateo Leach, I.; Beekman, M.; de Craen, A.J.; Uh, H.W.; Trochet, H.; Hocking, L.J.; Porteous, D.J.; Sattar, N.; Packard, C.J.; Buckley, B.M.; Brody, J.A.; Bis, J.C.; Rotter, J.I.; Mychaleckyj, J.C.; Campbell, H.; Duan, Q.; Lange, L.A.; Wilson, J.F.; Hayward, C.; Polasek, O.; Vitart, V.; Rudan, I.; Wright, A.F.; Rich, S.S.; Psaty, B.M.; Borecki, I.B.; Kearney, P.M.; Stott, D.J.; Cupples, L.A.; Jukema, J.W.; van der Harst, P.; Sijbrands, E.J.; Hottenga, J.J.; Uitterlinden, A.G.; Swertz, M.A.; van Ommen, G.J.B; Bakker, P.I.W.; Slagboom, P.E.; Boomsma, D.I.; Wijmenga, C.; van Duijn, C.M.

    2015-01-01

    Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (∼35,000 samples) with the population-specific reference panel created

  6. Identifying Country-Specific Cultures of Physics Education: A differential item functioning approach

    Science.gov (United States)

    Mesic, Vanes

    2012-11-01

    In international large-scale assessments of educational outcomes, student achievement is often represented by unidimensional constructs. This approach allows for drawing general conclusions about country rankings with respect to the given achievement measure, but it typically does not provide specific diagnostic information which is necessary for systematic comparisons and improvements of educational systems. Useful information could be obtained by exploring the differences in national profiles of student achievement between low-achieving and high-achieving countries. In this study, we aimed to identify the relative weaknesses and strengths of eighth graders' physics achievement in Bosnia and Herzegovina in comparison to the achievement of their peers from Slovenia. For this purpose, we ran a secondary analysis of Trends in International Mathematics and Science Study (TIMSS) 2007 data. The student sample consisted of 4,220 students from Bosnia and Herzegovina and 4,043 students from Slovenia. After analysing the cognitive demands of TIMSS 2007 physics items, the correspondent differential item functioning (DIF)/differential group functioning contrasts were estimated. Approximately 40% of items exhibited large DIF contrasts, indicating significant differences between cultures of physics education in Bosnia and Herzegovina and Slovenia. The relative strength of students from Bosnia and Herzegovina showed to be mainly associated with the topic area 'Electricity and magnetism'. Classes of items which required the knowledge of experimental method, counterintuitive thinking, proportional reasoning and/or the use of complex knowledge structures proved to be differentially easier for students from Slovenia. In the light of the presented results, the common practice of ranking countries with respect to universally established cognitive categories seems to be potentially misleading.

  7. Empathy in children with autism and conduct disorder: group-specific profiles and developmental aspects.

    Science.gov (United States)

    Schwenck, Christina; Mergenthaler, Julia; Keller, Katharina; Zech, Julie; Salehi, Sarah; Taurines, Regina; Romanos, Marcel; Schecklmann, Martin; Schneider, Wolfgang; Warnke, Andreas; Freitag, Christine M

    2012-06-01

      A deficit in empathy is discussed to underlie difficulties in social interaction of children with autism spectrum disorder (ASD) and conduct disorder (CD). To date, no study has compared children with ASD and different subtypes of CD to describe disorder-specific empathy profiles in clinical samples. Furthermore, little is known about age influences on the development of empathic skills. The aim of the current study was to compare cognitive and emotional empathy in different age groups of children with ASD, CD with elevated or low callous-unemotional-traits (CU+ vs. CU-) and a matched control group (CG).   Fifty-five boys with ASD, 36 boys with CD-CU+, 34 boys with CD-CU- and 67 controls were included. The study implemented three tasks on emotion recognition, perspective taking and emotional affection induced by another person's situation. Multivariate Analysis of variance with the factors group and age (median split) including their interaction term was performed to describe disorder-specific profiles.   Empathy profiles showed differential impairment in children with ASD and CD-CU+. Boys with ASD were impaired in cognitive empathy while participants with CD-CU+ were impaired in emotional empathy. Children with CD-CU- did not differ from the CG. However, boys with CD-CU- were less emotionally reactive in response to film stimuli than children with ASD. Furthermore, we found strong age effects indicating an increase in cognitive and affective empathic skills beyond early infancy in all groups.   In this study, distinct empathic profiles in children with ASD and CD-CU+ were found. Furthermore, the work demonstrates improvement of empathic skills throughout childhood and adolescence, which is comparable for individuals with psychiatric disorders and control children. These results yield implications for further research as well as for therapeutic interventions. © 2011 The Authors. Journal of Child Psychology and Psychiatry © 2011 Association for Child and

  8. Goal specific social capital and job satisfaction Effects of different types of networks on instrumental and social aspects of work

    OpenAIRE

    Flap, Henk; Völker, Beate

    2001-01-01

    This paper addresses the question “To what extent can job satisfaction be explained as the revenue of social capital?” By conceiving someone’s social network as social capital we specify conditions under which social ties do lead to job satisfaction. We inquire into the idea of goal specificity of social capital, which implies that a network with a given structure and content will have different impacts on various aspects of job satisfaction. If the content of the ties and the structure of th...

  9. Animal Health Challenges and Veterinary Aspects of Organic Livestock Farming Identified Through a 3 Year EU Network Project

    DEFF Research Database (Denmark)

    Vaarst, Mette; Padel, Susanne; Younie, David

    2008-01-01

    From 2003-2006, an EU network project ‘Sustaining Animal Health and Food Safety in Organic Farming‘ (SAFO), was carried out with 26 partners from 20 EU-countries and 4 related partners from 4 candidate or new member states. The focus was the integration of animal health and welfare issues...... in organic farming with food safety aspects. Four very consistent conclusions became apparent: 1) The climatic, physical and socio-economic conditions vary considerably throughout Europe, leading to different livestock farming systems. This limits the possibility for technology transfer between regions...

  10. Specification Search for Identifying the Correct Mean Trajectory in Polynomial Latent Growth Models

    Science.gov (United States)

    Kim, Minjung; Kwok, Oi-Man; Yoon, Myeongsun; Willson, Victor; Lai, Mark H. C.

    2016-01-01

    This study investigated the optimal strategy for model specification search under the latent growth modeling (LGM) framework, specifically on searching for the correct polynomial mean or average growth model when there is no a priori hypothesized model in the absence of theory. In this simulation study, the effectiveness of different starting…

  11. The Yin and Yang aspects of IL-27 in induction of cancer-specific T-cell responses and immunotherapy.

    Science.gov (United States)

    Li, Ming-Song; Liu, Zhenzhen; Liu, Jin-Qing; Zhu, Xiaotong; Liu, Zhihao; Bai, Xue-Feng

    2015-01-01

    Accumulating evidences from animal studies have indicated that both endogenous and exogenous IL-27, an IL-12 family of cytokine, can increase antitumor T-cell activities and inhibit tumor growth. IL-27 can modulate Treg responses, and program effector T cells into a unique T-effector stem cell (TSEC) phenotype, which enhances T-cell survival in the tumor microenvironment. However, animal studies also suggest that IL-27 induces molecular pathways such as IL-10, PD-L1 and CD39, which may downregulate tumor-specific T-cell responses. In this review paper, we will discuss the Yin and Yang aspects of IL-27 in the induction of tumor-specific T-cell responses, and the potential impacts of these functions of IL-27 in the design of cancer immunotherapy.

  12. Diagnosed, identified, current and complete depression among patients attending primary care in southern Catalonia: different aspects of the same concept.

    Science.gov (United States)

    Montesó-Curto, Pilar; Ferré-Grau, Carme; Lleixà-Fortuño, Mar; Albacar-Riobóo, Nuria; Lejeune, Marylene

    2014-02-01

    The aims of this study were to explore the prevalence and the conceptualizations of depression detected by the healthcare system, identified by the patient or classified/identified in the validated Goldberg's questionnaire in a community. We conducted a cross-sectional evaluation of 317 patients. The different types of depression diagnosed, identified, current or total were stratified by age and gender groups. The difference in the conceptualization of depression from the medical or ordinary people point of view indicate that depression care requires the understanding of the lifestyle, beliefs, attitudes, family and social networks of the people the physicians and nurses care for. © 2014.

  13. The learning continuum based on student's level of competence and specific pedagogical learning material on physiological aspects from teachers's opinions

    Science.gov (United States)

    Hadi, Ria Fitriyani; Subali, Bambang

    2017-08-01

    The scope of learning continuum at the conceptual knowledge is formulated based on the student's level of competence and specific pedagogical learning material. The purpose of this study is to develop a learning continuum of specific pedagogical material aspects of physiology targeted for students in primary and secondary education. This research was conducted in Province of Yogyakarta Special Region from October 2016 to January 2017. The method used in this study was survey method. The data were collected using questionnaire that had been validated from the aspects of construct validity and experts judgements. Respondents in this study consist of 281 Science/Biology teachers at Public Junior and Senior High Schools in the Province of Yogyakarta Special Region which spread in Yogyakarta city and 4 regencies namely Sleman, Bantul, Kulonprogo, and Gunungkidul. The data were taken using a census. Data were analyzed using a descriptive analysis technique. The results show the learning continuum of physiology based on teachers's opinion from grade VII, VIII, and IX are taught in grade VII, VIII, IX and X on level of C2 (understanding) and the learning continuum of physiology based on teachers's opinion from grade X, XI and XII are taught in grade X and XI on level of C2 (understanding), C3 (applying), and C4 (analyzing) based on teachers's opinions. The conclusion is that many teachers refer to the existing curriculum rather than their own original idea for developing learning continuum.

  14. VOCATIONAL EDUCATION AND TRAINING FOR TOURISM. SPECIFIC ASPECTS WHICH INFLUENCE THE STUDENTS’ PERCEPTION OF THE QUALITY OF THEIR LEARNING EXPERIENCE

    Directory of Open Access Journals (Sweden)

    SILVIA IRIMIEA

    2014-06-01

    Full Text Available Vocational Education and Training for Tourism. Specific Aspects which Influence the Students’ Perception of the Quality of Their Learning Experience. Quality in education has been defined in various ways, each definition representing a different approach. Karl Popper defines human rationality by the adequacy of one’s action to a specific situation. Furthermore, the French sociologist Pierre Bourdieu argues that the actions that people undertake are based on their previous life experiences and on their social and professional status. Vocational Education and Training (VET addresses young people and adults whose social status can influence their level of satisfaction with the quality of the educational process. The present article seeks to present the results of a questionnaire-based survey applied to the students who have attended the travel agent and tourism manager courses at the Centre for Tourism Training of the Babeş-Bolyai University, Cluj-Napoca. The data illustrate the strong influence of the variable age and previous educational experience on the subjects' satisfaction regarding some aspects of the training activities.

  15. A sex-specific metabolite identified in a marine invertebrate utilizing phosphorus-31 nuclear magnetic resonance.

    Directory of Open Access Journals (Sweden)

    Robert A Kleps

    Full Text Available Hormone level differences are generally accepted as the primary cause for sexual dimorphism in animal and human development. Levels of low molecular weight metabolites also differ between men and women in circulating amino acids, lipids and carbohydrates and within brain tissue. While investigating the metabolism of blue crab tissues using Phosphorus-31 Nuclear Magnetic Resonance, we discovered that only the male blue crab (Callinectes sapidus contained a phosphorus compound with a chemical shift well separated from the expected phosphate compounds. Spectra obtained from male gills were readily differentiated from female gill spectra. Analysis from six years of data from male and female crabs documented that the sex-specificity of this metabolite was normal for this species. Microscopic analysis of male and female gills found no differences in their gill anatomy or the presence of parasites or bacteria that might produce this phosphorus compound. Analysis of a rare gynandromorph blue crab (laterally, half male and half female proved that this sex-specificity was an intrinsic biochemical process and was not caused by any variations in the diet or habitat of male versus female crabs. The existence of a sex-specific metabolite is a previously unrecognized, but potentially significant biochemical phenomenon. An entire enzyme system has been synthesized and activated only in one sex. Unless blue crabs are a unique species, sex-specific metabolites are likely to be present in other animals. Would the presence or absence of a sex-specific metabolite affect an animal's development, anatomy and biochemistry?

  16. Variation of the anterior aspect of the femoral head-neck junction in a modern human identified skeletal collection

    DEFF Research Database (Denmark)

    Radi, Nico; Mariotti, Valentina; Riga, Alessandro

    2013-01-01

    behaviors and specific activities (e.g., squatting, horseback riding, etc.). However, disagreement on terminology and descriptions, the absence of standardized scoring methods and poor knowledge of the variability and distribution of these features make it difficult to interpret their meaning. The aim...

  17. Electronic problem lists: a thematic analysis of a systematic literature review to identify aspects critical to success.

    Science.gov (United States)

    Hodge, Chad M; Narus, Scott P

    2018-05-01

    Problem list data is a driving force for many beneficial clinical tools, yet these data remain underutilized. We performed a systematic literature review, pulling insights from previous research, aggregating insights into themes, and distilling themes into actionable advice. We sought to learn what changes we could make to existing applications, to the clinical workflow, and to clinicians' perceptions that would improve problem list utilization and increase the prevalence of problems data in the electronic medical record. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to systematically curate a corpus of pertinent articles. We performed a thematic analysis, looking for interesting excerpts and ideas. By aggregating excerpts from many authors, we gained broader, more inclusive insights into what makes a good problem list and what factors are conducive to its success. Analysis led to a list of 7 benefits of using the problem list, 15 aspects critical to problem list success, and knowledge to help inform policy development, such as consensus on what belongs on the problem list, who should maintain the problem list, and when. A list of suggestions is made on ways in which the problem list can be improved to increase utilization by clinicians. There is also a need for standard measurements of the problem list, so that lists can be measured, compared, and discussed with rigor and a common vocabulary.

  18. Defining the Undefinable: Operationalization of Methods to Identify Specific Learning Disabilities among Practicing School Psychologists

    Science.gov (United States)

    Cottrell, Joseph M.; Barrett, Courtenay A.

    2016-01-01

    Accurate and consistent identification of students with specific learning disabilities (SLDs) is crucial; however, state and district guidelines regarding identification methods lack operationalization and are inconsistent throughout the United States. In the current study, the authors surveyed 471 school psychologists about "school" SLD…

  19. Identifying Facial Emotions: Valence Specific Effects and an Exploration of the Effects of Viewer Gender

    Science.gov (United States)

    Jansari, Ashok; Rodway, Paul; Goncalves, Salvador

    2011-01-01

    The valence hypothesis suggests that the right hemisphere is specialised for negative emotions and the left hemisphere is specialised for positive emotions (Silberman & Weingartner, 1986). It is unclear to what extent valence-specific effects in facial emotion perception depend upon the gender of the perceiver. To explore this question 46…

  20. Training School Psychologists to Identify Specific Learning Disabilities: A Content Analysis of Syllabi

    Science.gov (United States)

    Barrett, Courtenay A.; Cottrell, Joseph M.; Newman, Daniel S.; Pierce, Benjamin G.; Anderson, Alisha

    2015-01-01

    Approximately 2.4 million children receive special education services for specific learning disabilities (SLDs), and school psychologists are key contributors to the SLD eligibility decision-making process. The Individuals with Disabilities Education Act (2004) enabled local education agencies to use response to intervention (RTI) instead of the…

  1. Using the Domain Specific Innovativeness Scale To Identify Innovative Internet Consumers.

    Science.gov (United States)

    Goldsmith, Ronald E.

    2001-01-01

    The Domain Specific Innovativeness Scale was included in a survey of student consumers to measure how innovative participants were with regard to buying online. Data analyses confirmed hypotheses that an innovative predisposition toward online buying would be associated positively with more hours of Internet use, greater Internet purchasing,…

  2. Identifying Learning Patterns of Children at Risk for Specific Reading Disability

    Science.gov (United States)

    Barbot, Baptiste; Krivulskaya, Suzanna; Hein, Sascha; Reich, Jodi; Thuma, Philip E.; Grigorenko, Elena L.

    2016-01-01

    Differences in learning patterns of vocabulary acquisition in children at risk (+SRD) and not at risk (-SRD) for Specific Reading Disability (SRD) were examined using a microdevelopmental paradigm applied to the multi-trial Foreign Language Learning Task (FLLT; Baddeley et al., 1995). The FLLT was administered to 905 children from rural…

  3. Using Discrete Trial Training to Identify Specific Learning Impairments in Boys with Fragile X Syndrome

    Science.gov (United States)

    Hall, Scott S.; Hustyi, Kristin M.; Hammond, Jennifer L.; Hirt, Melissa; Reiss, Allan L.

    2014-01-01

    We examined whether "discrete trial training" (DTT) could be used to identify learning impairments in mathematical reasoning in boys with fragile X syndrome (FXS). Boys with FXS, aged 10-23 years, and age and IQ-matched controls, were trained to match fractions to pie-charts and pie-charts to decimals either on a computer or with a…

  4. Preoccupied Attachment and Emotional Dysregulation: Specific Aspects of Borderline Personality Disorder or General Dimensions of Personality Pathology?

    Science.gov (United States)

    Scott, Lori N.; Kim, Yookyung; Nolf, Kimberly A.; Hallquist, Michael N.; Wright, Aidan G.C.; Stepp, Stephanie D.; Morse, Jennifer Q.; Pilkonis, Paul A.

    2013-01-01

    Emotional dysregulation and impaired attachment are seen by many clinical researchers as central aspects of borderline personality disorder (BPD). Alternatively, these constructs may represent general impairments in personality that are nonspecific to BPD. Using multitrait-multimethod models, we examined the strength of associations among preoccupied attachment, difficulties with emotion regulation, BPD features, and features of two other personality disorders (i.e., antisocial and avoidant) in a combined psychiatric outpatient and community sample of adults. Results suggested that preoccupied attachment and difficulties with emotion regulation shared strong positive associations with each other and with each of the selected personality disorders. However, preoccupied attachment and emotional dysregulation were more strongly related to BPD features than to features of other personality disorders. Our findings suggest that although impairments in relational and emotional domains may underlie personality pathology in general, preoccupied attachment and emotional dysregulation also have specificity for understanding core difficulties in those with BPD. PMID:23586934

  5. Preoccupied attachment and emotional dysregulation: specific aspects of borderline personality disorder or general dimensions of personality pathology?

    Science.gov (United States)

    Scott, Lori N; Kim, Yookyung; Nolf, Kimberly A; Hallquist, Michael N; Wright, Aidan G C; Stepp, Stephanie D; Morse, Jennifer Q; Pilkonis, Paul A

    2013-08-01

    Emotional dysregulation and impaired attachment are seen by many clinical researchers as central aspects of borderline personality disorder (BPD). Alternatively, these constructs may represent general impairments in personality that are nonspecific to BPD. Using multitraitmultimethod models, the authors examined the strength of associations among preoccupied attachment, difficulties with emotion regulation, BPD features, and features of two other personality disorders (i.e., antisocial and avoidant) in a combined psychiatric outpatient and community sample of adults. Results suggested that preoccupied attachment and difficulties with emotion regulation shared strong positive associations with each other and with each of the selected personality disorders. However, preoccupied attachment and emotional dysregulation were more strongly related to BPD features than to features of other personality disorders. Findings suggest that although impairments in relational and emotional domains may underlie personality pathology in general, preoccupied attachment and emotional dysregulation also have specificity for understanding core difficulties in those with BPD.

  6. Culture, threat, and mental illness stigma: identifying culture-specific threat among Chinese-American groups.

    Science.gov (United States)

    Yang, Lawrence H; Purdie-Vaughns, Valerie; Kotabe, Hiroki; Link, Bruce G; Saw, Anne; Wong, Gloria; Phelan, Jo C

    2013-07-01

    We incorporate anthropological insights into a stigma framework to elucidate the role of culture in threat perception and stigma among Chinese groups. Prior work suggests that genetic contamination that jeopardizes the extension of one's family lineage may comprise a culture-specific threat among Chinese groups. In Study 1, a national survey conducted from 2002 to 2003 assessed cultural differences in mental illness stigma and perceptions of threat in 56 Chinese-Americans and 589 European-Americans. Study 2 sought to empirically test this culture-specific threat of genetic contamination to lineage via a memory paradigm. Conducted from June to August 2010, 48 Chinese-American and 37 European-American university students in New York City read vignettes containing content referring to lineage or non-lineage concerns. Half the participants in each ethnic group were assigned to a condition in which the illness was likely to be inherited (genetic condition) and the rest read that the illness was unlikely to be inherited (non-genetic condition). Findings from Study 1 and 2 were convergent. In Study 1, culture-specific threat to lineage predicted cultural variation in stigma independently and after accounting for other forms of threat. In Study 2, Chinese-Americans in the genetic condition were more likely to accurately recall and recognize lineage content than the Chinese-Americans in the non-genetic condition, but that memorial pattern was not found for non-lineage content. The identification of this culture-specific threat among Chinese groups has direct implications for culturally-tailored anti-stigma interventions. Further, this framework might be implemented across other conditions and cultural groups to reduce stigma across cultures. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Evolutionary inference across eukaryotes identifies specific pressures favoring mitochondrial gene retention

    OpenAIRE

    Williams, Ben; Johnston, Iain

    2016-01-01

    Since their endosymbiotic origin, mitochondria have lost most of their genes. Although many selective mechanisms underlying the evolution of mitochondrial genomes have been proposed, a data-driven exploration of these hypotheses is lacking, and a quantitatively supported consensus remains absent. We developed HyperTraPS, a methodology coupling stochastic modelling with Bayesian inference, to identify the ordering of evolutionary events and suggest their causes. Using 2015 complete mitochondri...

  8. Comparative analyses identified species-specific functional roles in oral microbial genomes

    Science.gov (United States)

    Chen, Tsute; Gajare, Prasad; Olsen, Ingar; Dewhirst, Floyd E.

    2017-01-01

    ABSTRACT The advent of next generation sequencing is producing more genomic sequences for various strains of many human oral microbial species and allows for insightful functional comparisons at both intra- and inter-species levels. This study performed in-silico functional comparisons for currently available genomic sequences of major species associated with periodontitis including Aggregatibacter actinomycetemcomitans (AA), Porphyromonas gingivalis (PG), Treponema denticola (TD), and Tannerella forsythia (TF), as well as several cariogenic and commensal streptococcal species. Complete or draft sequences were annotated with the RAST to infer structured functional subsystems for each genome. The subsystems profiles were clustered to groups of functions with similar patterns. Functional enrichment and depletion were evaluated based on hypergeometric distribution to identify subsystems that are unique or missing between two groups of genomes. Unique or missing metabolic pathways and biological functions were identified in different species. For example, components involved in flagellar motility were found only in the motile species TD, as expected, with few exceptions scattered in several streptococcal species, likely associated with chemotaxis. Transposable elements were only found in the two Bacteroidales species PG and TF, and half of the AA genomes. Genes involved in CRISPR were prevalent in most oral species. Furthermore, prophage related subsystems were also commonly found in most species except for PG and Streptococcus mutans, in which very few genomes contain prophage components. Comparisons between pathogenic (P) and nonpathogenic (NP) genomes also identified genes potentially important for virulence. Two such comparisons were performed between AA (P) and several A. aphrophilus (NP) strains, and between S. mutans + S. sobrinus (P) and other oral streptococcal species (NP). This comparative genomics approach can be readily used to identify functions unique to

  9. Amygdala-enriched genes identified by microarray technology are restricted to specific amygdaloid subnuclei

    OpenAIRE

    Zirlinger, M.; Kreiman, Gabriel; Anderson, D. J.

    2001-01-01

    Microarray technology represents a potentially powerful method for identifying cell type- and regionally restricted genes expressed in the brain. Here we have combined a microarray analysis of differential gene expression among five selected brain regions, including the amygdala, cerebellum, hippocampus, olfactory bulb, and periaqueductal gray, with in situ hybridization. On average, 0.3% of the 34,000 genes interrogated were highly enriched in each of the five regions...

  10. BISQUE: locus- and variant-specific conversion of genomic, transcriptomic and proteomic database identifiers.

    Science.gov (United States)

    Meyer, Michael J; Geske, Philip; Yu, Haiyuan

    2016-05-15

    Biological sequence databases are integral to efforts to characterize and understand biological molecules and share biological data. However, when analyzing these data, scientists are often left holding disparate biological currency-molecular identifiers from different databases. For downstream applications that require converting the identifiers themselves, there are many resources available, but analyzing associated loci and variants can be cumbersome if data is not given in a form amenable to particular analyses. Here we present BISQUE, a web server and customizable command-line tool for converting molecular identifiers and their contained loci and variants between different database conventions. BISQUE uses a graph traversal algorithm to generalize the conversion process for residues in the human genome, genes, transcripts and proteins, allowing for conversion across classes of molecules and in all directions through an intuitive web interface and a URL-based web service. BISQUE is freely available via the web using any major web browser (http://bisque.yulab.org/). Source code is available in a public GitHub repository (https://github.com/hyulab/BISQUE). haiyuan.yu@cornell.edu 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.

  11. Specific biases for identifying facial expression of emotion in children and adolescents with conversion disorders.

    Science.gov (United States)

    Kozlowska, Kasia; Brown, Kerri J; Palmer, Donna M; Williams, Lea M

    2013-04-01

    This study aimed to assess how children and adolescents with conversion disorders identify universal facial expressions of emotion and to determine whether identification of emotion in faces relates to subjective emotional distress. Fifty-seven participants (41 girls and 16 boys) aged 8.5 to 18 years with conversion disorders and 57 age- and sex-matched healthy controls completed a computerized task in which their accuracy and reaction times for identifying facial expressions were recorded. To isolate the effect of individual emotional expressions, participants' reaction times for each emotion (fear, anger, sadness, disgust, and happiness) were subtracted from their reaction times for the neutral control face. Participants also completed self-report measures of subjective emotional distress. Children/Adolescents with conversion disorders showed faster reaction times for identifying expressions of sadness (t(112) = -2.2, p = .03; 444 [609] versus 713 [695], p = .03) and slower reactions times for happy expressions (t(99.3) = 2.28, p ≤ .024; -33 [35] versus 174 [51], p = .024), compared with controls (F(33.75, 419.81) = 3.76, p .018). There were also no differences in identification accuracy for any emotion (p > .82). The observation of faster reaction times to sad faces in children and adolescents with conversion disorders suggests increased vigilance and motor readiness to emotional signals that are potential threats to self or to close others. These effects may occur before conscious processing.

  12. ApoE4-specific Misfolded Intermediate Identified by Molecular Dynamics Simulations.

    Directory of Open Access Journals (Sweden)

    Benfeard Williams

    2015-10-01

    Full Text Available The increased risk of developing Alzheimer's disease (AD is associated with the APOE gene, which encodes for three variants of Apolipoprotein E, namely E2, E3, E4, differing only by two amino acids at positions 112 and 158. ApoE4 is known to be the strongest risk factor for AD onset, while ApoE3 and ApoE2 are considered to be the AD-neutral and AD-protective isoforms, respectively. It has been hypothesized that the ApoE isoforms may contribute to the development of AD by modifying the homeostasis of ApoE physiological partners and AD-related proteins in an isoform-specific fashion. Here we find that, despite the high sequence similarity among the three ApoE variants, only ApoE4 exhibits a misfolded intermediate state characterized by isoform-specific domain-domain interactions in molecular dynamics simulations. The existence of an ApoE4-specific intermediate state can contribute to the onset of AD by altering multiple cellular pathways involved in ApoE-dependent lipid transport efficiency or in AD-related protein aggregation and clearance. We present what we believe to be the first structural model of an ApoE4 misfolded intermediate state, which may serve to elucidate the molecular mechanism underlying the role of ApoE4 in AD pathogenesis. The knowledge of the structure for the ApoE4 folding intermediate provides a new platform for the rational design of alternative therapeutic strategies to fight AD.

  13. An organelle-specific protein landscape identifies novel diseases and molecular mechanisms.

    Science.gov (United States)

    Boldt, Karsten; van Reeuwijk, Jeroen; Lu, Qianhao; Koutroumpas, Konstantinos; Nguyen, Thanh-Minh T; Texier, Yves; van Beersum, Sylvia E C; Horn, Nicola; Willer, Jason R; Mans, Dorus A; Dougherty, Gerard; Lamers, Ideke J C; Coene, Karlien L M; Arts, Heleen H; Betts, Matthew J; Beyer, Tina; Bolat, Emine; Gloeckner, Christian Johannes; Haidari, Khatera; Hetterschijt, Lisette; Iaconis, Daniela; Jenkins, Dagan; Klose, Franziska; Knapp, Barbara; Latour, Brooke; Letteboer, Stef J F; Marcelis, Carlo L; Mitic, Dragana; Morleo, Manuela; Oud, Machteld M; Riemersma, Moniek; Rix, Susan; Terhal, Paulien A; Toedt, Grischa; van Dam, Teunis J P; de Vrieze, Erik; Wissinger, Yasmin; Wu, Ka Man; Apic, Gordana; Beales, Philip L; Blacque, Oliver E; Gibson, Toby J; Huynen, Martijn A; Katsanis, Nicholas; Kremer, Hannie; Omran, Heymut; van Wijk, Erwin; Wolfrum, Uwe; Kepes, François; Davis, Erica E; Franco, Brunella; Giles, Rachel H; Ueffing, Marius; Russell, Robert B; Roepman, Ronald

    2016-05-13

    Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub-complexes in exocyst and intraflagellar transport complexes, which we validate biochemically, and by probing structurally predicted, disruptive, genetic variants from ciliary disease patients. The landscape suggests other genetic diseases could be ciliary including 3M syndrome. We show that 3M genes are involved in ciliogenesis, and that patient fibroblasts lack cilia. Overall, this organelle-specific targeting strategy shows considerable promise for Systems Medicine.

  14. Overlapping and disease specific aspects of impulsivety in children and adolescents with schiozphrenia spectrum disorders or Attention-Deficit/Hyperactivity Disorder

    DEFF Research Database (Denmark)

    Jepsen, Jens Richardt Møllegaard; Rydkjær, Jacob; Fagerlund, Birgitte

    making to gather more information in a condition with a conflict between reward and certainty. The reduced information sampling may also reflect an increased risk-taking or conviction in the decision at a point of relative uncertainty. Children and adolescents with schizophrenia spectrum disorder......Background and aim: Dimensions of impulsivity have been observed in Attention-Deficit/Hyperactivity Disorder (ADHD) and schizophrenia patients. The purpose is to identify disease specific and overlapping aspects of impulsivity in children and adolescents with ADHD or early-onset schizophrenia......-onset schizophrenia spectrum disorder patients appear to perform differently from the healthy controls and the schizphrenia spectrum disorder patients, although not signivicantly (p = .163). Conclusion: Reduced information sampling in children and adolescents with ADHD may reflect an inability to delay their decision...

  15. Evolutionary Inference across Eukaryotes Identifies Specific Pressures Favoring Mitochondrial Gene Retention.

    Science.gov (United States)

    Johnston, Iain G; Williams, Ben P

    2016-02-24

    Since their endosymbiotic origin, mitochondria have lost most of their genes. Although many selective mechanisms underlying the evolution of mitochondrial genomes have been proposed, a data-driven exploration of these hypotheses is lacking, and a quantitatively supported consensus remains absent. We developed HyperTraPS, a methodology coupling stochastic modeling with Bayesian inference, to identify the ordering of evolutionary events and suggest their causes. Using 2015 complete mitochondrial genomes, we inferred evolutionary trajectories of mtDNA gene loss across the eukaryotic tree of life. We find that proteins comprising the structural cores of the electron transport chain are preferentially encoded within mitochondrial genomes across eukaryotes. A combination of high GC content and high protein hydrophobicity is required to explain patterns of mtDNA gene retention; a model that accounts for these selective pressures can also predict the success of artificial gene transfer experiments in vivo. This work provides a general method for data-driven inference of the ordering of evolutionary and progressive events, here identifying the distinct features shaping mitochondrial genomes of present-day species. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Citation searches are more sensitive than keyword searches to identify studies using specific measurement instruments.

    Science.gov (United States)

    Linder, Suzanne K; Kamath, Geetanjali R; Pratt, Gregory F; Saraykar, Smita S; Volk, Robert J

    2015-04-01

    To compare the effectiveness of two search methods in identifying studies that used the Control Preferences Scale (CPS), a health care decision-making instrument commonly used in clinical settings. We searched the literature using two methods: (1) keyword searching using variations of "Control Preferences Scale" and (2) cited reference searching using two seminal CPS publications. We searched three bibliographic databases [PubMed, Scopus, and Web of Science (WOS)] and one full-text database (Google Scholar). We report precision and sensitivity as measures of effectiveness. Keyword searches in bibliographic databases yielded high average precision (90%) but low average sensitivity (16%). PubMed was the most precise, followed closely by Scopus and WOS. The Google Scholar keyword search had low precision (54%) but provided the highest sensitivity (70%). Cited reference searches in all databases yielded moderate sensitivity (45-54%), but precision ranged from 35% to 75% with Scopus being the most precise. Cited reference searches were more sensitive than keyword searches, making it a more comprehensive strategy to identify all studies that use a particular instrument. Keyword searches provide a quick way of finding some but not all relevant articles. Goals, time, and resources should dictate the combination of which methods and databases are used. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. CXCR6, a newly defined biomarker of tissue-specific stem cell asymmetric self-renewal, identifies more aggressive human melanoma cancer stem cells.

    Directory of Open Access Journals (Sweden)

    Rouzbeh Taghizadeh

    2010-12-01

    Full Text Available A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells. Recent investigations of a variety of tumor types have shown that phenotypically identifiable and isolable subfractions of cells possess the tumor-forming ability. In the present paper, using two lineage-related human melanoma cell lines, primary melanoma line IGR39 and its metastatic derivative line IGR37, two main observations are reported. The first one is the first phenotypic evidence to support the origin of melanoma cancer stem cells (CSCs from mutated tissue-specific stem cells; and the second one is the identification of a more aggressive subpopulation of CSCs in melanoma that are CXCR6+.We defined CXCR6 as a new biomarker for tissue-specific stem cell asymmetric self-renewal. Thus, the relationship between melanoma formation and ABCG2 and CXCR6 expression was investigated. Consistent with their non-metastatic character, unsorted IGR39 cells formed significantly smaller tumors than unsorted IGR37 cells. In addition, ABCG2+ cells produced tumors that had a 2-fold greater mass than tumors produced by unsorted cells or ABCG2- cells. CXCR6+ cells produced more aggressive tumors. CXCR6 identifies a more discrete subpopulation of cultured human melanoma cells with a more aggressive MCSC phenotype than cells selected on the basis of the ABCG2+ phenotype alone.The association of a more aggressive tumor phenotype with asymmetric self-renewal phenotype reveals a previously unrecognized aspect of tumor cell physiology. Namely, the retention of some tissue-specific stem cell attributes, like the ability to asymmetrically self-renew, impacts the natural history of human tumor development. Knowledge of this new aspect of tumor development and progression may provide new targets for cancer prevention and treatment.

  18. Identifying specific prefrontal neurons that contribute to autism-associated abnormalities in physiology and social behavior

    DEFF Research Database (Denmark)

    Brumback, A C; Ellwood, I T; Kjaerby, C

    2017-01-01

    Functional imaging and gene expression studies both implicate the medial prefrontal cortex (mPFC), particularly deep-layer projection neurons, as a potential locus for autism pathology. Here, we explored how specific deep-layer prefrontal neurons contribute to abnormal physiology and behavior...... in mouse models of autism. First, we find that across three etiologically distinct models-in utero valproic acid (VPA) exposure, CNTNAP2 knockout and FMR1 knockout-layer 5 subcortically projecting (SC) neurons consistently exhibit reduced input resistance and action potential firing. To explore how altered...... SC neuron physiology might impact behavior, we took advantage of the fact that in deep layers of the mPFC, dopamine D2 receptors (D2Rs) are mainly expressed by SC neurons, and used D2-Cre mice to label D2R+ neurons for calcium imaging or optogenetics. We found that social exploration preferentially...

  19. Specific olfactory receptor populations projecting to identified glomeruli in the rat olfactory bulb.

    Science.gov (United States)

    Jastreboff, P J; Pedersen, P E; Greer, C A; Stewart, W B; Kauer, J S; Benson, T E; Shepherd, G M

    1984-08-01

    A critical gap exists in our knowledge of the topographical relationship between the olfactory epithelium and olfactory bulb. The present report describes the application to this problem of a method involving horseradish peroxidase conjugated to wheat germ agglutinin. This material was iontophoretically delivered to circumscribed glomeruli in the olfactory bulb and the characteristics and distribution of retrogradely labeled receptor cells were assessed. After discrete injections into small glomerular groups in the caudomedial bulb, topographically defined populations of receptor cells were labeled. Labeled receptor cell somata appeared at several levels within the epithelium. The receptor cell apical dendrites followed a tight helical course towards the surface of the epithelium. The data thus far demonstrate that functional units within the olfactory system may include not only glomeruli as previously suggested but, in addition, a corresponding matrix of receptor cells possessing functional and topographical specificity.

  20. In Vivo RNA Interference Screening Identifies a Leukemia-Specific Dependence on Integrin Beta 3 Signaling

    Science.gov (United States)

    Miller, Peter G.; Al-Shahrour, Fatima; Hartwell, Kimberly A.; Chu, Lisa P.; Järås, Marcus; Puram, Rishi V.; Puissant, Alexandre; Callahan, Kevin P.; Ashton, John; McConkey, Marie E.; Poveromo, Luke P.; Cowley, Glenn S.; Kharas, Michael G.; Labelle, Myriam; Shterental, Sebastian; Fujisaki, Joji; Silberstein, Lev; Alexe, Gabriela; Al-Hajj, Muhammad A.; Shelton, Christopher A.; Armstrong, Scott A.; Root, David E.; Scadden, David T.; Hynes, Richard O.; Mukherjee, Siddhartha; Stegmaier, Kimberly; Jordan, Craig T.; Ebert, Benjamin L.

    2013-01-01

    SUMMARY We used an in vivo short hairpin RNA (shRNA) screening approach to identify genes that are essential for MLL-AF9 acute myeloid leukemia (AML). We found that Integrin Beta 3 (Itgb3) is essential for murine leukemia cells in vivo, and for human leukemia cells in xenotransplantation studies. In leukemia cells, Itgb3 knockdown impaired homing, downregulated LSC transcriptional programs, and induced differentiation via the intracellular kinase, Syk. In contrast, loss of Itgb3 in normal HSPCs did not affect engraftment, reconstitution, or differentiation. Finally, we confirmed that Itgb3 is dispensable for normal hematopoiesis and required for leukemogenesis using an Itgb3 knockout mouse model. Our results establish the significance of the Itgb3 signaling pathway as a potential therapeutic target in AML. PMID:23770013

  1. Identifying Aspects of the Post-Transcriptional Program Governing the Proteome of the Green Alga Micromonas pusilla

    Energy Technology Data Exchange (ETDEWEB)

    Waltman, Peter H.; Guo, Jian; Reistetter, Emily Nahas; Purvine, Samuel; Ansong, Charles K.; van Baren, Marijke J.; Wong, Chee-Hong; Wei, Chia-Lin; Smith, Richard D.; Callister, Stephen J.; Stuart, Joshua M.; Worden, Alexandra Z.; Mills, Ken

    2016-07-19

    Micromonas is a unicellular green alga that belongs to the prasinophytes, a sister lineage to land plants. This picoeukaryotic (<2 μm diameter) alga is widespread in the marine environment but still not understood at the cellular level. Here, we examine the mRNA and protein level changes that take place over the course of the day-night cycle using mid-exponential nutrient replete cultures of Micromonas pusilla CCMP1545 grown and analyzed in biological triplicate. During the experiment, samples were collected at key transition points during the diel for evaluation using high-throughput LC-MS proteomics. We also sequenced matched mRNA samples from the same time points, using pair-ended directional Illumina RNA-Seq to investigate the dynamics and relationship between the mRNA and protein expression programs of M. pusilla. Similar to a prior study of the marine cyanobacterium Prochlorococcus, we found significant divergence in the mRNA and proteomics expression dynamics in response to the light:dark cycle. Additionally, expressional responses of genes and the proteins they encoded could also be variable within the same metabolic pathway, such as the oxygenic photosynthesis pathway. A regression framework was used to predict protein levels using both mRNA expression and gene-specific sequence-based features. Several features in the genome sequence were found to influence protein abundance including the codon usage and the length of the 3’ UTR. Collectively, our studies provide insights into the regulation of the proteome over a diel as relationships between the transcriptional and translational programs in the widespread marine green alga Micromonas.

  2. Identifying Aspects of the Post-Transcriptional Program Governing the Proteome of the Green Alga Micromonas pusilla.

    Directory of Open Access Journals (Sweden)

    Peter H Waltman

    Full Text Available Micromonas is a unicellular motile alga within the Prasinophyceae, a green algal group that is related to land plants. This picoeukaryote (<2 μm diameter is widespread in the marine environment but is not well understood at the cellular level. Here, we examine shifts in mRNA and protein expression over the course of the day-night cycle using triplicated mid-exponential, nutrient replete cultures of Micromonas pusilla CCMP1545. Samples were collected at key transition points during the diel cycle for evaluation using high-throughput LC-MS proteomics. In conjunction, matched mRNA samples from the same time points were sequenced using pair-ended directional Illumina RNA-Seq to investigate the dynamics and relationship between the mRNA and protein expression programs of M. pusilla. Similar to a prior study of the marine cyanobacterium Prochlorococcus, we found significant divergence in the mRNA and proteomics expression dynamics in response to the light:dark cycle. Additionally, expressional responses of genes and the proteins they encoded could also be variable within the same metabolic pathway, such as we observed in the oxygenic photosynthesis pathway. A regression framework was used to predict protein levels from both mRNA expression and gene-specific sequence-based features. Several features in the genome sequence were found to influence protein abundance including codon usage as well as 3' UTR length and structure. Collectively, our studies provide insights into the regulation of the proteome over a diel cycle as well as the relationships between transcriptional and translational programs in the widespread marine green alga Micromonas.

  3. New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background

    Directory of Open Access Journals (Sweden)

    Marocchi Alessandro

    2008-05-01

    Full Text Available Abstract Background Few genetic factors predisposing to the sporadic form of amyotrophic lateral sclerosis (ALS have been identified, but the pathology itself seems to be a true multifactorial disease in which complex interactions between environmental and genetic susceptibility factors take place. The purpose of this study was to approach genetic data with an innovative statistical method such as artificial neural networks to identify a possible genetic background predisposing to the disease. A DNA multiarray panel was applied to genotype more than 60 polymorphisms within 35 genes selected from pathways of lipid and homocysteine metabolism, regulation of blood pressure, coagulation, inflammation, cellular adhesion and matrix integrity, in 54 sporadic ALS patients and 208 controls. Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis Results Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis. An unexpected discovery of a strong genetic background in sporadic ALS using a DNA multiarray panel and analytical processing of the data with advanced artificial neural networks was found. The predictive accuracy obtained with Linear Discriminant Analysis and Standard Artificial Neural Networks ranged from 70% to 79% (average 75.31% and from 69.1 to 86.2% (average 76.6% respectively. The corresponding value obtained with Advanced Intelligent Systems reached an average of 96.0% (range 94.4 to 97.6%. This latter approach allowed the identification of seven genetic variants essential to differentiate cases from controls: apolipoprotein E arg

  4. New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background.

    Science.gov (United States)

    Penco, Silvana; Buscema, Massimo; Patrosso, Maria Cristina; Marocchi, Alessandro; Grossi, Enzo

    2008-05-30

    Few genetic factors predisposing to the sporadic form of amyotrophic lateral sclerosis (ALS) have been identified, but the pathology itself seems to be a true multifactorial disease in which complex interactions between environmental and genetic susceptibility factors take place. The purpose of this study was to approach genetic data with an innovative statistical method such as artificial neural networks to identify a possible genetic background predisposing to the disease. A DNA multiarray panel was applied to genotype more than 60 polymorphisms within 35 genes selected from pathways of lipid and homocysteine metabolism, regulation of blood pressure, coagulation, inflammation, cellular adhesion and matrix integrity, in 54 sporadic ALS patients and 208 controls. Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis. An unexpected discovery of a strong genetic background in sporadic ALS using a DNA multiarray panel and analytical processing of the data with advanced artificial neural networks was found. The predictive accuracy obtained with Linear Discriminant Analysis and Standard Artificial Neural Networks ranged from 70% to 79% (average 75.31%) and from 69.1 to 86.2% (average 76.6%) respectively. The corresponding value obtained with Advanced Intelligent Systems reached an average of 96.0% (range 94.4 to 97.6%). This latter approach allowed the identification of seven genetic variants essential to differentiate cases from controls: apolipoprotein E arg158cys; hepatic lipase -480 C/T; endothelial

  5. A novel CpG island set identifies tissue-specific methylation at developmental gene loci.

    Directory of Open Access Journals (Sweden)

    Robert Illingworth

    2008-01-01

    Full Text Available CpG islands (CGIs are dense clusters of CpG sequences that punctuate the CpG-deficient human genome and associate with many gene promoters. As CGIs also differ from bulk chromosomal DNA by their frequent lack of cytosine methylation, we devised a CGI enrichment method based on nonmethylated CpG affinity chromatography. The resulting library was sequenced to define a novel human blood CGI set that includes many that are not detected by current algorithms. Approximately half of CGIs were associated with annotated gene transcription start sites, the remainder being intra- or intergenic. Using an array representing over 17,000 CGIs, we established that 6%-8% of CGIs are methylated in genomic DNA of human blood, brain, muscle, and spleen. Inter- and intragenic CGIs are preferentially susceptible to methylation. CGIs showing tissue-specific methylation were overrepresented at numerous genetic loci that are essential for development, including HOX and PAX family members. The findings enable a comprehensive analysis of the roles played by CGI methylation in normal and diseased human tissues.

  6. A specific DNA probe which identifies Babesia bovis in whole blood.

    Science.gov (United States)

    Petchpoo, W; Tan-ariya, P; Boonsaeng, V; Brockelman, C R; Wilairat, P; Panyim, S

    1992-05-01

    A genomic library of Babesia bovis DNA from the Mexican strain M was constructed in plasmid pUN121 and cloned in Escherichia coli. Several recombinants which hybridized strongly to radioactively labeled B. bovis genomic DNA in an in situ screening were selected and further analyzed for those which specifically hybridized to B. bovis DNA. It was found that pMU-B1 had the highest sensitivity, detecting 25 pg of purified B. bovis DNA, and 300 parasites in 10 microliters of whole infected blood, or 0.00025% parasitemia. pMU-B1 contained a 6.0 kb B. bovis DNA insert which did not cross-hybridize to Babesia bigemina, Trypanosoma evansi, Plasmodium falciparum, Anaplasma marginale, Boophilus microplus and cow DNA. In the Southern blot analysis of genomic DNA, pMU-B1 could differentiate between two B. bovis geographic isolates, Mexican strain M and Thai isolate TS4. Thus, the pMU-B1 probe will be useful in the diagnosis of Babesia infection in cattle and ticks, and in the differentiation of B. bovis strains.

  7. CSF Proteomics Identifies Specific and Shared Pathways for Multiple Sclerosis Clinical Subtypes.

    Directory of Open Access Journals (Sweden)

    Timucin Avsar

    Full Text Available Multiple sclerosis (MS is an immune-mediated, neuro-inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS with a heterogeneous clinical presentation and course. There is a remarkable phenotypic heterogeneity in MS, and the molecular mechanisms underlying it remain unknown. We aimed to investigate further the etiopathogenesis related molecular pathways in subclinical types of MS using proteomic and bioinformatics approaches in cerebrospinal fluids of patients with clinically isolated syndrome, relapsing remitting MS and progressive MS (n=179. Comparison of disease groups with controls revealed a total of 151 proteins that are differentially expressed in clinically different MS subtypes. KEGG analysis using PANOGA tool revealed the disease related pathways including aldosterone-regulated sodium reabsorption (p=8.02x10-5 which is important in the immune cell migration, renin-angiotensin (p=6.88x10-5 system that induces Th17 dependent immunity, notch signaling (p=1.83x10-10 pathway indicating the activated remyelination and vitamin digestion and absorption pathways (p=1.73x10-5. An emerging theme from our studies is that whilst all MS clinical forms share common biological pathways, there are also clinical subtypes specific and pathophysiology related pathways which may have further therapeutic implications.

  8. Bat Accelerated Regions Identify a Bat Forelimb Specific Enhancer in the HoxD Locus.

    Directory of Open Access Journals (Sweden)

    Betty M Booker

    2016-03-01

    Full Text Available The molecular events leading to the development of the bat wing remain largely unknown, and are thought to be caused, in part, by changes in gene expression during limb development. These expression changes could be instigated by variations in gene regulatory enhancers. Here, we used a comparative genomics approach to identify regions that evolved rapidly in the bat ancestor, but are highly conserved in other vertebrates. We discovered 166 bat accelerated regions (BARs that overlap H3K27ac and p300 ChIP-seq peaks in developing mouse limbs. Using a mouse enhancer assay, we show that five Myotis lucifugus BARs drive gene expression in the developing mouse limb, with the majority showing differential enhancer activity compared to the mouse orthologous BAR sequences. These include BAR116, which is located telomeric to the HoxD cluster and had robust forelimb expression for the M. lucifugus sequence and no activity for the mouse sequence at embryonic day 12.5. Developing limb expression analysis of Hoxd10-Hoxd13 in Miniopterus natalensis bats showed a high-forelimb weak-hindlimb expression for Hoxd10-Hoxd11, similar to the expression trend observed for M. lucifugus BAR116 in mice, suggesting that it could be involved in the regulation of the bat HoxD complex. Combined, our results highlight novel regulatory regions that could be instrumental for the morphological differences leading to the development of the bat wing.

  9. An All-Recombinant Protein-Based Culture System Specifically Identifies Hematopoietic Stem Cell Maintenance Factors

    Directory of Open Access Journals (Sweden)

    Aki Ieyasu

    2017-03-01

    Full Text Available Hematopoietic stem cells (HSCs are considered one of the most promising therapeutic targets for the treatment of various blood disorders. However, due to difficulties in establishing stable maintenance and expansion of HSCs in vitro, their insufficient supply is a major constraint to transplantation studies. To solve these problems we have developed a fully defined, all-recombinant protein-based culture system. Through this system, we have identified hemopexin (HPX and interleukin-1α as responsible for HSC maintenance in vitro. Subsequent molecular analysis revealed that HPX reduces intracellular reactive oxygen species levels within cultured HSCs. Furthermore, bone marrow immunostaining and 3D immunohistochemistry revealed that HPX is expressed in non-myelinating Schwann cells, known HSC niche constituents. These results highlight the utility of this fully defined all-recombinant protein-based culture system for reproducible in vitro HSC culture and its potential to contribute to the identification of factors responsible for in vitro maintenance, expansion, and differentiation of stem cell populations.

  10. Unique aspects of impulsive traits in substance use and overeating: specific contributions of common assessments of impulsivity.

    Science.gov (United States)

    Beaton, Derek; Abdi, Hervé; Filbey, Francesca M

    2014-11-01

    Abstract Background: Impulsivity is a complex trait often studied in substance abuse and overeating disorders, but the exact nature of impulsivity traits and their contribution to these disorders are still debated. Thus, understanding how to measure impulsivity is essential for comprehending addictive behaviors. Identify unique impulsivity traits specific to substance use and overeating. Impulsive Sensation Seeking (ImpSS) and Barratt's Impulsivity scales (BIS) Scales were analyzed with a non-parametric factor analytic technique (discriminant correspondence analysis) to identify group-specific traits on 297 individuals from five groups: Marijuana (n = 88), Nicotine (n = 82), Overeaters (n = 27), Marijuauna + Nicotine (n = 63), and CONTROLs (n = 37). A significant overall factor structure revealed three components of impulsivity that explained respectively 50.19% (pperm Overeating: lacks focus, but plans (short and long term). Our results reveal impulsivity traits specific to each group. This may provide better criteria to define spectrums and trajectories - instead of categories - of symptoms for substance use and eating disorders. Defining symptomatic spectrums could be an important step forward in diagnostic strategies.

  11. Computational Biology Tools for Identifying Specific Ligand Binding Residues for Novel Agrochemical and Drug Design.

    Science.gov (United States)

    Neshich, Izabella Agostinho Pena; Nishimura, Leticia; de Moraes, Fabio Rogerio; Salim, Jose Augusto; Villalta-Romero, Fabian; Borro, Luiz; Yano, Inacio Henrique; Mazoni, Ivan; Tasic, Ljubica; Jardine, Jose Gilberto; Neshich, Goran

    2015-01-01

    The term "agrochemicals" is used in its generic form to represent a spectrum of pesticides, such as insecticides, fungicides or bactericides. They contain active components designed for optimized pest management and control, therefore allowing for economically sound and labor efficient agricultural production. A "drug" on the other side is a term that is used for compounds designed for controlling human diseases. Although drugs are subjected to much more severe testing and regulation procedures before reaching the market, they might contain exactly the same active ingredient as certain agrochemicals, what is the case described in present work, showing how a small chemical compound might be used to control pathogenicity of Gram negative bacteria Xylella fastidiosa which devastates citrus plantations, as well as for control of, for example, meningitis in humans. It is also clear that so far the production of new agrochemicals is not benefiting as much from the in silico new chemical compound identification/discovery as pharmaceutical production. Rational drug design crucially depends on detailed knowledge of structural information about the receptor (target protein) and the ligand (drug/agrochemical). The interaction between the two molecules is the subject of analysis that aims to understand relationship between structure and function, mainly deciphering some fundamental elements of the nanoenvironment where the interaction occurs. In this work we will emphasize the role of understanding nanoenvironmental factors that guide recognition and interaction of target protein and its function modifier, an agrochemical or a drug. The repertoire of nanoenvironment descriptors is used for two selected and specific cases we have approached in order to offer a technological solution for some very important problems that needs special attention in agriculture: elimination of pathogenicity of a bacterium which is attacking citrus plants and formulation of a new fungicide. Finally

  12. Use of stream water pH and specific conductance measurements to identify ground water discharges of fly ash leachate

    International Nuclear Information System (INIS)

    Price, R.M.

    1992-01-01

    Low pH and high specific conductance are typical chemical characteristics of coal fly ash leachate. Measurements of these parameters in streams adjacent to a fly ash facility were used to identify areas of ground water discharge into the streams. In-situ specific conductance and pH were determined at approximately 50 surface water stations from on-site and off-site streams. The results of the in-situ determinations were used to select twelve surface water stations for more detailed chemical analyses. The chemical character of the stream water affected by ground water discharges was similar to the water quality of sedimentation ponds which received drainage from the fly ash embankment. The results indicated that in-situ measurements of indicator parameters such as pH and specific conductance can be used as a screening method for identifying surface water quality impacts at fly ash facilities

  13. CT-guided Bipolar and Multipolar Radiofrequency Ablation (RF Ablation) of Renal Cell Carcinoma: Specific Technical Aspects and Clinical Results

    International Nuclear Information System (INIS)

    Sommer, C. M.; Lemm, G.; Hohenstein, E.; Bellemann, N.; Stampfl, U.; Goezen, A. S.; Rassweiler, J.; Kauczor, H. U.; Radeleff, B. A.; Pereira, P. L.

    2013-01-01

    Purpose. This study was designed to evaluate the clinical efficacy of CT-guided bipolar and multipolar radiofrequency ablation (RF ablation) of renal cell carcinoma (RCC) and to analyze specific technical aspects between both technologies. Methods. We included 22 consecutive patients (3 women; age 74.2 ± 8.6 years) after 28 CT-guided bipolar or multipolar RF ablations of 28 RCCs (diameter 2.5 ± 0.8 cm). Procedures were performed with a commercially available RF system (Celon AG Olympus, Berlin, Germany). Technical aspects of RF ablation procedures (ablation mode [bipolar or multipolar], number of applicators and ablation cycles, overall ablation time and deployed energy, and technical success rate) were analyzed. Clinical results (local recurrence-free survival and local tumor control rate, renal function [glomerular filtration rate (GFR)]) and complication rates were evaluated. Results. Bipolar RF ablation was performed in 12 procedures and multipolar RF ablation in 16 procedures (2 applicators in 14 procedures and 3 applicators in 2 procedures). One ablation cycle was performed in 15 procedures and two ablation cycles in 13 procedures. Overall ablation time and deployed energy were 35.0 ± 13.6 min and 43.7 ± 17.9 kJ. Technical success rate was 100 %. Major and minor complication rates were 4 and 14 %. At an imaging follow-up of 15.2 ± 8.8 months, local recurrence-free survival was 14.4 ± 8.8 months and local tumor control rate was 93 %. GFR did not deteriorate after RF ablation (50.8 ± 16.6 ml/min/1.73 m 2 before RF ablation vs. 47.2 ± 11.9 ml/min/1.73 m 2 after RF ablation; not significant). Conclusions. CT-guided bipolar and multipolar RF ablation of RCC has a high rate of clinical success and low complication rates. At short-term follow-up, clinical efficacy is high without deterioration of the renal function.

  14. CT-guided Bipolar and Multipolar Radiofrequency Ablation (RF Ablation) of Renal Cell Carcinoma: Specific Technical Aspects and Clinical Results

    Energy Technology Data Exchange (ETDEWEB)

    Sommer, C. M., E-mail: christof.sommer@med.uni-heidelberg.de [University Hospital Heidelberg, INF 110, Department of Diagnostic and Interventional Radiology (Germany); Lemm, G.; Hohenstein, E. [Minimally Invasive Therapies and Nuclear Medicine, SLK Kliniken Heilbronn GmbH, Clinic for Radiology (Germany); Bellemann, N.; Stampfl, U. [University Hospital Heidelberg, INF 110, Department of Diagnostic and Interventional Radiology (Germany); Goezen, A. S.; Rassweiler, J. [Clinic for Urology, SLK Kliniken Heilbronn GmbH (Germany); Kauczor, H. U.; Radeleff, B. A. [University Hospital Heidelberg, INF 110, Department of Diagnostic and Interventional Radiology (Germany); Pereira, P. L. [Minimally Invasive Therapies and Nuclear Medicine, SLK Kliniken Heilbronn GmbH, Clinic for Radiology (Germany)

    2013-06-15

    Purpose. This study was designed to evaluate the clinical efficacy of CT-guided bipolar and multipolar radiofrequency ablation (RF ablation) of renal cell carcinoma (RCC) and to analyze specific technical aspects between both technologies. Methods. We included 22 consecutive patients (3 women; age 74.2 {+-} 8.6 years) after 28 CT-guided bipolar or multipolar RF ablations of 28 RCCs (diameter 2.5 {+-} 0.8 cm). Procedures were performed with a commercially available RF system (Celon AG Olympus, Berlin, Germany). Technical aspects of RF ablation procedures (ablation mode [bipolar or multipolar], number of applicators and ablation cycles, overall ablation time and deployed energy, and technical success rate) were analyzed. Clinical results (local recurrence-free survival and local tumor control rate, renal function [glomerular filtration rate (GFR)]) and complication rates were evaluated. Results. Bipolar RF ablation was performed in 12 procedures and multipolar RF ablation in 16 procedures (2 applicators in 14 procedures and 3 applicators in 2 procedures). One ablation cycle was performed in 15 procedures and two ablation cycles in 13 procedures. Overall ablation time and deployed energy were 35.0 {+-} 13.6 min and 43.7 {+-} 17.9 kJ. Technical success rate was 100 %. Major and minor complication rates were 4 and 14 %. At an imaging follow-up of 15.2 {+-} 8.8 months, local recurrence-free survival was 14.4 {+-} 8.8 months and local tumor control rate was 93 %. GFR did not deteriorate after RF ablation (50.8 {+-} 16.6 ml/min/1.73 m{sup 2} before RF ablation vs. 47.2 {+-} 11.9 ml/min/1.73 m{sup 2} after RF ablation; not significant). Conclusions. CT-guided bipolar and multipolar RF ablation of RCC has a high rate of clinical success and low complication rates. At short-term follow-up, clinical efficacy is high without deterioration of the renal function.

  15. Transcriptome Analysis of Mycobacteria-Specific CD4+ T Cells Identified by Activation-Induced Expression of CD154.

    Science.gov (United States)

    Kunnath-Velayudhan, Shajo; Goldberg, Michael F; Saini, Neeraj K; Johndrow, Christopher T; Ng, Tony W; Johnson, Alison J; Xu, Jiayong; Chan, John; Jacobs, William R; Porcelli, Steven A

    2017-10-01

    Analysis of Ag-specific CD4 + T cells in mycobacterial infections at the transcriptome level is informative but technically challenging. Although several methods exist for identifying Ag-specific T cells, including intracellular cytokine staining, cell surface cytokine-capture assays, and staining with peptide:MHC class II multimers, all of these have significant technical constraints that limit their usefulness. Measurement of activation-induced expression of CD154 has been reported to detect live Ag-specific CD4 + T cells, but this approach remains underexplored and, to our knowledge, has not previously been applied in mycobacteria-infected animals. In this article, we show that CD154 expression identifies adoptively transferred or endogenous Ag-specific CD4 + T cells induced by Mycobacterium bovis bacillus Calmette-Guérin vaccination. We confirmed that Ag-specific cytokine production was positively correlated with CD154 expression by CD4 + T cells from bacillus Calmette-Guérin-vaccinated mice and show that high-quality microarrays can be performed from RNA isolated from CD154 + cells purified by cell sorting. Analysis of microarray data demonstrated that the transcriptome of CD4 + CD154 + cells was distinct from that of CD154 - cells and showed major enrichment of transcripts encoding multiple cytokines and pathways of cellular activation. One notable finding was the identification of a previously unrecognized subset of mycobacteria-specific CD4 + T cells that is characterized by the production of IL-3. Our results support the use of CD154 expression as a practical and reliable method to isolate live Ag-specific CD4 + T cells for transcriptomic analysis and potentially for a range of other studies in infected or previously immunized hosts. Copyright © 2017 by The American Association of Immunologists, Inc.

  16. An integrated chemical biology approach identifies specific vulnerability of Ewing's sarcoma to combined inhibition of Aurora kinases A and B.

    Science.gov (United States)

    Winter, Georg E; Rix, Uwe; Lissat, Andrej; Stukalov, Alexey; Müllner, Markus K; Bennett, Keiryn L; Colinge, Jacques; Nijman, Sebastian M; Kubicek, Stefan; Kovar, Heinrich; Kontny, Udo; Superti-Furga, Giulio

    2011-10-01

    Ewing's sarcoma is a pediatric cancer of the bone that is characterized by the expression of the chimeric transcription factor EWS-FLI1 that confers a highly malignant phenotype and results from the chromosomal translocation t(11;22)(q24;q12). Poor overall survival and pronounced long-term side effects associated with traditional chemotherapy necessitate the development of novel, targeted, therapeutic strategies. We therefore conducted a focused viability screen with 200 small molecule kinase inhibitors in 2 different Ewing's sarcoma cell lines. This resulted in the identification of several potential molecular intervention points. Most notably, tozasertib (VX-680, MK-0457) displayed unique nanomolar efficacy, which extended to other cell lines, but was specific for Ewing's sarcoma. Furthermore, tozasertib showed strong synergies with the chemotherapeutic drugs etoposide and doxorubicin, the current standard agents for Ewing's sarcoma. To identify the relevant targets underlying the specific vulnerability toward tozasertib, we determined its cellular target profile by chemical proteomics. We identified 20 known and unknown serine/threonine and tyrosine protein kinase targets. Additional target deconvolution and functional validation by RNAi showed simultaneous inhibition of Aurora kinases A and B to be responsible for the observed tozasertib sensitivity, thereby revealing a new mechanism for targeting Ewing's sarcoma. We further corroborated our cellular observations with xenograft mouse models. In summary, the multilayered chemical biology approach presented here identified a specific vulnerability of Ewing's sarcoma to concomitant inhibition of Aurora kinases A and B by tozasertib and danusertib, which has the potential to become a new therapeutic option.

  17. Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

    Science.gov (United States)

    van Leeuwen, Elisabeth M.; Karssen, Lennart C.; Deelen, Joris; Isaacs, Aaron; Medina-Gomez, Carolina; Mbarek, Hamdi; Kanterakis, Alexandros; Trompet, Stella; Postmus, Iris; Verweij, Niek; van Enckevort, David J.; Huffman, Jennifer E.; White, Charles C.; Feitosa, Mary F.; Bartz, Traci M.; Manichaikul, Ani; Joshi, Peter K.; Peloso, Gina M.; Deelen, Patrick; van Dijk, Freerk; Willemsen, Gonneke; de Geus, Eco J.; Milaneschi, Yuri; Penninx, Brenda W.J.H.; Francioli, Laurent C.; Menelaou, Androniki; Pulit, Sara L.; Rivadeneira, Fernando; Hofman, Albert; Oostra, Ben A.; Franco, Oscar H.; Leach, Irene Mateo; Beekman, Marian; de Craen, Anton J.M.; Uh, Hae-Won; Trochet, Holly; Hocking, Lynne J.; Porteous, David J.; Sattar, Naveed; Packard, Chris J.; Buckley, Brendan M.; Brody, Jennifer A.; Bis, Joshua C.; Rotter, Jerome I.; Mychaleckyj, Josyf C.; Campbell, Harry; Duan, Qing; Lange, Leslie A.; Wilson, James F.; Hayward, Caroline; Polasek, Ozren; Vitart, Veronique; Rudan, Igor; Wright, Alan F.; Rich, Stephen S.; Psaty, Bruce M.; Borecki, Ingrid B.; Kearney, Patricia M.; Stott, David J.; Adrienne Cupples, L.; Neerincx, Pieter B.T.; Elbers, Clara C.; Francesco Palamara, Pier; Pe'er, Itsik; Abdellaoui, Abdel; Kloosterman, Wigard P.; van Oven, Mannis; Vermaat, Martijn; Li, Mingkun; Laros, Jeroen F.J.; Stoneking, Mark; de Knijff, Peter; Kayser, Manfred; Veldink, Jan H.; van den Berg, Leonard H.; Byelas, Heorhiy; den Dunnen, Johan T.; Dijkstra, Martijn; Amin, Najaf; Joeri van der Velde, K.; van Setten, Jessica; Kattenberg, Mathijs; van Schaik, Barbera D.C.; Bot, Jan; Nijman, Isaäc J.; Mei, Hailiang; Koval, Vyacheslav; Ye, Kai; Lameijer, Eric-Wubbo; Moed, Matthijs H.; Hehir-Kwa, Jayne Y.; Handsaker, Robert E.; Sunyaev, Shamil R.; Sohail, Mashaal; Hormozdiari, Fereydoun; Marschall, Tobias; Schönhuth, Alexander; Guryev, Victor; Suchiman, H. Eka D.; Wolffenbuttel, Bruce H.; Platteel, Mathieu; Pitts, Steven J.; Potluri, Shobha; Cox, David R.; Li, Qibin; Li, Yingrui; Du, Yuanping; Chen, Ruoyan; Cao, Hongzhi; Li, Ning; Cao, Sujie; Wang, Jun; Bovenberg, Jasper A.; Jukema, J. Wouter; van der Harst, Pim; Sijbrands, Eric J.; Hottenga, Jouke-Jan; Uitterlinden, Andre G.; Swertz, Morris A.; van Ommen, Gert-Jan B.; de Bakker, Paul I.W.; Eline Slagboom, P.; Boomsma, Dorret I.; Wijmenga, Cisca; van Duijn, Cornelia M.

    2015-01-01

    Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (~35,000 samples) with the population-specific reference panel created by the Genome of the Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (P value <6.61 × 10−4), including a rare missense variant in ABCA6 (rs77542162, p.Cys1359Arg, frequency 0.034), which is predicted to be deleterious. The frequency of this ABCA6 variant is 3.65-fold increased in the Dutch and its effect (βLDL-C=0.135, βTC=0.140) is estimated to be very similar to those observed for single variants in well-known lipid genes, such as LDLR. PMID:25751400

  18. Coupling genetics and proteomics to identify aphid proteins associated with vector-specific transmission of polerovirus (luteoviridae).

    Science.gov (United States)

    Yang, Xiaolong; Thannhauser, T W; Burrows, Mary; Cox-Foster, Diana; Gildow, Fred E; Gray, Stewart M

    2008-01-01

    Cereal yellow dwarf virus-RPV (CYDV-RPV) is transmitted specifically by the aphids Rhopalosiphum padi and Schizaphis graminum in a circulative nonpropagative manner. The high level of vector specificity results from the vector aphids having the functional components of the receptor-mediated endocytotic pathways to allow virus to transverse the gut and salivary tissues. Studies of F(2) progeny from crosses of vector and nonvector genotypes of S. graminum showed that virus transmission efficiency is a heritable trait regulated by multiple genes acting in an additive fashion and that gut- and salivary gland-associated factors are not genetically linked. Utilizing two-dimensional difference gel electrophoresis to compare the proteomes of vector and nonvector parental and F(2) genotypes, four aphid proteins (S4, S8, S29, and S405) were specifically associated with the ability of S. graminum to transmit CYDV-RPV. The four proteins were coimmunoprecipitated with purified RPV, indicating that the aphid proteins are capable of binding to virus. Analysis by mass spectrometry identified S4 as a luciferase and S29 as a cyclophilin, both of which have been implicated in macromolecular transport. Proteins S8 and S405 were not identified from available databases. Study of this unique genetic system coupled with proteomic analysis indicated that these four virus-binding aphid proteins were specifically inherited and conserved in different generations of vector genotypes and suggests that they play a major role in regulating polerovirus transmission.

  19. Coupling Genetics and Proteomics To Identify Aphid Proteins Associated with Vector-Specific Transmission of Polerovirus (Luteoviridae)▿

    Science.gov (United States)

    Yang, Xiaolong; Thannhauser, T. W.; Burrows, Mary; Cox-Foster, Diana; Gildow, Fred E.; Gray, Stewart M.

    2008-01-01

    Cereal yellow dwarf virus-RPV (CYDV-RPV) is transmitted specifically by the aphids Rhopalosiphum padi and Schizaphis graminum in a circulative nonpropagative manner. The high level of vector specificity results from the vector aphids having the functional components of the receptor-mediated endocytotic pathways to allow virus to transverse the gut and salivary tissues. Studies of F2 progeny from crosses of vector and nonvector genotypes of S. graminum showed that virus transmission efficiency is a heritable trait regulated by multiple genes acting in an additive fashion and that gut- and salivary gland-associated factors are not genetically linked. Utilizing two-dimensional difference gel electrophoresis to compare the proteomes of vector and nonvector parental and F2 genotypes, four aphid proteins (S4, S8, S29, and S405) were specifically associated with the ability of S. graminum to transmit CYDV-RPV. The four proteins were coimmunoprecipitated with purified RPV, indicating that the aphid proteins are capable of binding to virus. Analysis by mass spectrometry identified S4 as a luciferase and S29 as a cyclophilin, both of which have been implicated in macromolecular transport. Proteins S8 and S405 were not identified from available databases. Study of this unique genetic system coupled with proteomic analysis indicated that these four virus-binding aphid proteins were specifically inherited and conserved in different generations of vector genotypes and suggests that they play a major role in regulating polerovirus transmission. PMID:17959668

  20. Candidate gene resequencing to identify rare, pedigree-specific variants influencing healthy aging phenotypes in the long life family study

    DEFF Research Database (Denmark)

    Druley, Todd E; Wang, Lihua; Lin, Shiow J

    2016-01-01

    from six pedigrees. OBFC1 (chromosome 10) is involved in telomere maintenance, and falls within a linkage peak recently reported from an analysis of telomere length in LLFS families. Two different algorithms for single gene associations identified three genes with an enrichment of variation......BACKGROUND: The Long Life Family Study (LLFS) is an international study to identify the genetic components of various healthy aging phenotypes. We hypothesized that pedigree-specific rare variants at longevity-associated genes could have a similar functional impact on healthy phenotypes. METHODS......: We performed custom hybridization capture sequencing to identify the functional variants in 464 candidate genes for longevity or the major diseases of aging in 615 pedigrees (4,953 individuals) from the LLFS, using a multiplexed, custom hybridization capture. Variants were analyzed individually...

  1. [Voice and vibration sensations in the speech forming organs: clinical and theoretical aspects of rare symptoms specific for schizophrenia].

    Science.gov (United States)

    Vilela, W; Lolas, F; Wolpert, E

    1978-01-01

    When studying 750 psychiatric in-patients with psychoses of various diagnostic groups, the symptoms of voice sensations and vibration feelings could only be found among patients with paranoid schizophrenia. In addition, these symptoms were located exclusively in body areas that are involved in the peripheral motor production of voice and speech (areas of head, throat, thorax). In 11 of 15 such cases that could be identified, the sensations of voices and vibrations occurred simultaneously and in identical body parts; in the remaining 4 cases only voices without vibration sensations were reported. Therefore these symptoms can be considered as highly specific for schizophrenia. According to the terminology of Bleuler these two symptoms are because of their rareness to be taken as accessoric symptoms; according to the terminology of Kurt Schneider they have the value of first rank symptoms because of their highly diagnostic specifity for schizophrenia. The pathogenesis of these symptoms is on the one hand discussed under the perspective of language development and the changing function of language for behaviour control; on the other hand, the pathogenesis of these symptoms is discussed from the viewpoint of cybernetic, or neurophysiological-neuroanatomical foundation of speech production and speech control. Both models of explanation have in common that the ideational component of speech is noticed as acustic halluzinations and the motor proprioceptive part of speech is noticed as sensation of vibrations, both in a typically schiphrenic manner, i.e. dissociated and ego-alienated.

  2. Incorporating deep learning with convolutional neural networks and position specific scoring matrices for identifying electron transport proteins.

    Science.gov (United States)

    Le, Nguyen-Quoc-Khanh; Ho, Quang-Thai; Ou, Yu-Yen

    2017-09-05

    In several years, deep learning is a modern machine learning technique using in a variety of fields with state-of-the-art performance. Therefore, utilization of deep learning to enhance performance is also an important solution for current bioinformatics field. In this study, we try to use deep learning via convolutional neural networks and position specific scoring matrices to identify electron transport proteins, which is an important molecular function in transmembrane proteins. Our deep learning method can approach a precise model for identifying of electron transport proteins with achieved sensitivity of 80.3%, specificity of 94.4%, and accuracy of 92.3%, with MCC of 0.71 for independent dataset. The proposed technique can serve as a powerful tool for identifying electron transport proteins and can help biologists understand the function of the electron transport proteins. Moreover, this study provides a basis for further research that can enrich a field of applying deep learning in bioinformatics. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  3. Degradation of sulfamethoxazole using ozone and chlorine dioxide - Compound-specific stable isotope analysis, transformation product analysis and mechanistic aspects.

    Science.gov (United States)

    Willach, Sarah; Lutze, Holger V; Eckey, Kevin; Löppenberg, Katja; Lüling, Michelle; Terhalle, Jens; Wolbert, Jens-Benjamin; Jochmann, Maik A; Karst, Uwe; Schmidt, Torsten C

    2017-10-01

    The sulfonamide antibiotic sulfamethoxazole (SMX) is a widely detected micropollutant in surface and groundwaters. Oxidative treatment with e.g. ozone or chlorine dioxide is regularly applied for disinfection purposes at the same time exhibiting a high potential for removal of micropollutants. Especially for nitrogen containing compounds such as SMX, the related reaction mechanisms are largely unknown. In this study, we systematically investigated reaction stoichiometry, product formation and reaction mechanisms in reactions of SMX with ozone and chlorine dioxide. To this end, the neutral and anionic SMX species, which may occur at typical pH-values of water treatment were studied. Two moles of chlorine dioxide and approximately three moles of ozone were consumed per mole SMX degraded. Oxidation of SMX with ozone and chlorine dioxide leads in both cases to six major transformation products (TPs) as revealed by high-resolution mass spectrometry (HRMS). Tentatively formulated TP structures from other studies could partly be confirmed by compound-specific stable isotope analysis (CSIA). However, for one TP, a hydroxylated SMX, it was not possible by HRMS alone to identify whether hydroxylation occurred at the aromatic ring, as suggested in literature before, or at the anilinic nitrogen. By means of CSIA and an analytical standard it was possible to identify sulfamethoxazole hydroxylamine unequivocally as one of the TPs of the reaction of SMX with ozone as well as with chlorine dioxide. H-abstraction and electron transfer at the anilinic nitrogen are suggested as likely initial reactions of ozone and chlorine dioxide, respectively, leading to its formation. Oxidation of anionic SMX with ozone did not show any significant isotopic fractionation whereas the other reactions studied resulted in a significant carbon isotope fractionation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. CRISPRseek: a bioconductor package to identify target-specific guide RNAs for CRISPR-Cas9 genome-editing systems.

    Directory of Open Access Journals (Sweden)

    Lihua J Zhu

    Full Text Available CRISPR-Cas systems are a diverse family of RNA-protein complexes in bacteria that target foreign DNA sequences for cleavage. Derivatives of these complexes have been engineered to cleave specific target sequences depending on the sequence of a CRISPR-derived guide RNA (gRNA and the source of the Cas9 protein. Important considerations for the design of gRNAs are to maximize aimed activity at the desired target site while minimizing off-target cleavage. Because of the rapid advances in the understanding of existing CRISPR-Cas9-derived RNA-guided nucleases and the development of novel RNA-guided nuclease systems, it is critical to have computational tools that can accommodate a wide range of different parameters for the design of target-specific RNA-guided nuclease systems. We have developed CRISPRseek, a highly flexible, open source software package to identify gRNAs that target a given input sequence while minimizing off-target cleavage at other sites within any selected genome. CRISPRseek will identify potential gRNAs that target a sequence of interest for CRISPR-Cas9 systems from different bacterial species and generate a cleavage score for potential off-target sequences utilizing published or user-supplied weight matrices with position-specific mismatch penalty scores. Identified gRNAs may be further filtered to only include those that occur in paired orientations for increased specificity and/or those that overlap restriction enzyme sites. For applications where gRNAs are desired to discriminate between two related sequences, CRISPRseek can rank gRNAs based on the difference between predicted cleavage scores in each input sequence. CRISPRseek is implemented as a Bioconductor package within the R statistical programming environment, allowing it to be incorporated into computational pipelines to automate the design of gRNAs for target sequences identified in a wide variety of genome-wide analyses. CRISPRseek is available under the GNU General

  5. Use of epitope libraries to identify exon-specific monoclonal antibodies for characterization of altered dystrophins in muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen thi Man; Morris, G.E. (North East Wales Inst., Clwyd (United Kingdom))

    1993-06-01

    The majority of mutations in Xp21-linked muscular dystrophy (MD) can be identified by PCR or Southern blotting, as deletions or duplications of groups of exons in the dystrophin gene, but it is not always possible to predict how much altered dystrophin, if any, will be produced. Use of exon-specific monoclonal antibodies (mAbs) on muscle biopsies from MD patients can, in principle, provide information on both the amount of altered dystrophin produced and, when dystrophin is present, the nature of the genetic deletion or point mutation. For this purpose, mAbs which recognize regions of dystrophin encoded by known exons and whose binding is unaffected by the absence of adjacent exons are required. To map mAbs to specific exons, random [open quotes]libraries[close quotes] of expressed dystrophin fragments were created by cloning DNAseI digestion fragments of a 4.3-kb dystrophin cDNA into a pTEX expression vector. The libraries were then used to locate the epitopes recognized by 48 mAbs to fragments of 25--60 amino acids within the 1,434-amino-acid dystrophin fragment used to produce the antibodies. This is sufficiently detailed to allow further refinement by using synthetic peptides and, in many cases, to identify the exon in the DMD (Duchenne MD) gene which encodes the epitope. To illustrate their use in dystrophin analysis, a Duchenne patient with a frameshift deletion of exons 42 and 43 makes a truncated dystrophin encoded by exons 1--41, and the authors now show that this can be detected in the sarcolemma by mAbs up to and including those specific for exon 41 epitopes but not by mAbs specific for exon 43 or later epitopes. 38 refs., 2 figs., 4 tabs.

  6. An Investigation to Validate the Grammar and Phonology Screening (GAPS) Test to Identify Children with Specific Language Impairment

    Science.gov (United States)

    van der Lely, Heather K. J.; Payne, Elisabeth; McClelland, Alastair

    2011-01-01

    Background The extraordinarily high incidence of grammatical language impairments in developmental disorders suggests that this uniquely human cognitive function is “fragile”. Yet our understanding of the neurobiology of grammatical impairments is limited. Furthermore, there is no “gold-standard” to identify grammatical impairments and routine screening is not undertaken. An accurate screening test to identify grammatical abilities would serve the research, health and education communities, further our understanding of developmental disorders, and identify children who need remediation, many of whom are currently un-diagnosed. A potential realistic screening tool that could be widely administered is the Grammar and Phonology Screening (GAPS) test – a 10 minute test that can be administered by professionals and non-professionals alike. Here we provide a further step in evaluating the validity and accuracy (sensitivity and specificity) of the GAPS test in identifying children who have Specific Language Impairment (SLI). Methods and Findings We tested three groups of children; two groups aged 3;6–6:6, a typically developing (n = 30) group, and a group diagnosed with SLI: (n = 11) (Young (Y)-SLI), and a further group aged 6;9–8;11 with SLI (Older (O)-SLI) (n = 10) who were above the test age norms. We employed a battery of language assessments including the GAPS test to assess the children's language abilities. For Y-SLI children, analyses revealed a sensitivity and specificity at the 5th and 10th percentile of 1.00 and 0.98, respectively, and for O-SLI children at the 10th and 15th percentile .83 and .90, respectively. Conclusions The findings reveal that the GAPS is highly accurate in identifying impaired vs. non-impaired children up to 6;8 years, and has moderate-to-high accuracy up to 9 years. The results indicate that GAPS is a realistic tool for the early identification of grammatical abilities and impairment in young children. A larger

  7. Identifying Domain-General and Domain-Specific Predictors of Low Mathematics Performance: A Classification and Regression Tree Analysis

    Directory of Open Access Journals (Sweden)

    David J. Purpura

    2017-12-01

    Full Text Available Many children struggle to successfully acquire early mathematics skills. Theoretical and empirical evidence has pointed to deficits in domain-specific skills (e.g., non-symbolic mathematics skills or domain-general skills (e.g., executive functioning and language as underlying low mathematical performance. In the current study, we assessed a sample of 113 three- to five-year old preschool children on a battery of domain-specific and domain-general factors in the fall and spring of their preschool year to identify Time 1 (fall factors associated with low performance in mathematics knowledge at Time 2 (spring. We used the exploratory approach of classification and regression tree analyses, a strategy that uses step-wise partitioning to create subgroups from a larger sample using multiple predictors, to identify the factors that were the strongest classifiers of low performance for younger and older preschool children. Results indicated that the most consistent classifier of low mathematics performance at Time 2 was children’s Time 1 mathematical language skills. Further, other distinct classifiers of low performance emerged for younger and older children. These findings suggest that risk classification for low mathematics performance may differ depending on children’s age.

  8. A data-driven modeling approach to identify disease-specific multi-organ networks driving physiological dysregulation.

    Directory of Open Access Journals (Sweden)

    Warren D Anderson

    2017-07-01

    Full Text Available Multiple physiological systems interact throughout the development of a complex disease. Knowledge of the dynamics and connectivity of interactions across physiological systems could facilitate the prevention or mitigation of organ damage underlying complex diseases, many of which are currently refractory to available therapeutics (e.g., hypertension. We studied the regulatory interactions operating within and across organs throughout disease development by integrating in vivo analysis of gene expression dynamics with a reverse engineering approach to infer data-driven dynamic network models of multi-organ gene regulatory influences. We obtained experimental data on the expression of 22 genes across five organs, over a time span that encompassed the development of autonomic nervous system dysfunction and hypertension. We pursued a unique approach for identification of continuous-time models that jointly described the dynamics and structure of multi-organ networks by estimating a sparse subset of ∼12,000 possible gene regulatory interactions. Our analyses revealed that an autonomic dysfunction-specific multi-organ sequence of gene expression activation patterns was associated with a distinct gene regulatory network. We analyzed the model structures for adaptation motifs, and identified disease-specific network motifs involving genes that exhibited aberrant temporal dynamics. Bioinformatic analyses identified disease-specific single nucleotide variants within or near transcription factor binding sites upstream of key genes implicated in maintaining physiological homeostasis. Our approach illustrates a novel framework for investigating the pathogenesis through model-based analysis of multi-organ system dynamics and network properties. Our results yielded novel candidate molecular targets driving the development of cardiovascular disease, metabolic syndrome, and immune dysfunction.

  9. Cancer in silico drug discovery: a systems biology tool for identifying candidate drugs to target specific molecular tumor subtypes.

    Science.gov (United States)

    San Lucas, F Anthony; Fowler, Jerry; Chang, Kyle; Kopetz, Scott; Vilar, Eduardo; Scheet, Paul

    2014-12-01

    Large-scale cancer datasets such as The Cancer Genome Atlas (TCGA) allow researchers to profile tumors based on a wide range of clinical and molecular characteristics. Subsequently, TCGA-derived gene expression profiles can be analyzed with the Connectivity Map (CMap) to find candidate drugs to target tumors with specific clinical phenotypes or molecular characteristics. This represents a powerful computational approach for candidate drug identification, but due to the complexity of TCGA and technology differences between CMap and TCGA experiments, such analyses are challenging to conduct and reproduce. We present Cancer in silico Drug Discovery (CiDD; scheet.org/software), a computational drug discovery platform that addresses these challenges. CiDD integrates data from TCGA, CMap, and Cancer Cell Line Encyclopedia (CCLE) to perform computational drug discovery experiments, generating hypotheses for the following three general problems: (i) determining whether specific clinical phenotypes or molecular characteristics are associated with unique gene expression signatures; (ii) finding candidate drugs to repress these expression signatures; and (iii) identifying cell lines that resemble the tumors being studied for subsequent in vitro experiments. The primary input to CiDD is a clinical or molecular characteristic. The output is a biologically annotated list of candidate drugs and a list of cell lines for in vitro experimentation. We applied CiDD to identify candidate drugs to treat colorectal cancers harboring mutations in BRAF. CiDD identified EGFR and proteasome inhibitors, while proposing five cell lines for in vitro testing. CiDD facilitates phenotype-driven, systematic drug discovery based on clinical and molecular data from TCGA. ©2014 American Association for Cancer Research.

  10. Using the Textpresso Site-Specific Recombinases Web server to identify Cre expressing mouse strains and floxed alleles.

    Science.gov (United States)

    Condie, Brian G; Urbanski, William M

    2014-01-01

    Effective tools for searching the biomedical literature are essential for identifying reagents or mouse strains as well as for effective experimental design and informed interpretation of experimental results. We have built the Textpresso Site Specific Recombinases (Textpresso SSR) Web server to enable researchers who use mice to perform in-depth searches of a rapidly growing and complex part of the mouse literature. Our Textpresso Web server provides an interface for searching the full text of most of the peer-reviewed publications that report the characterization or use of mouse strains that express Cre or Flp recombinase. The database also contains most of the publications that describe the characterization or analysis of strains carrying conditional alleles or transgenes that can be inactivated or activated by site-specific recombinases such as Cre or Flp. Textpresso SSR complements the existing online databases that catalog Cre and Flp expression patterns by providing a unique online interface for the in-depth text mining of the site specific recombinase literature.

  11. Fluorescently labeled dengue viruses as probes to identify antigen-specific memory B cells by multiparametric flow cytometry.

    Science.gov (United States)

    Woda, Marcia; Mathew, Anuja

    2015-01-01

    Low frequencies of memory B cells in the peripheral blood make it challenging to measure the functional and phenotypic characteristics of this antigen experienced subset of B cells without in vitro culture. To date, reagents are lacking to measure ex vivo frequencies of dengue virus (DENV)-specific memory B cells. We wanted to explore the possibility of using fluorescently labeled DENV as probes to detect antigen-specific memory B cells in the peripheral blood of DENV immune individuals. Alexa Fluor dye-labeled DENV yielded viable virus that could be stored at -80°C for long periods of time. Using a careful gating strategy and methods to decrease non-specific binding, we were able to identify a small frequency of B cells from dengue immune individuals that bound labeled DENV. Sorted DENV(+) B cells from immune, but not naïve donors secreted antibodies that bound DENV after in vitro stimulation. Overall, Alexa Fluor dye-labeled DENVs are useful reagents to enable the detection and characterization of memory B cells in DENV immune individuals. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. An Efficient Stepwise Statistical Test to Identify Multiple Linked Human Genetic Variants Associated with Specific Phenotypic Traits.

    Directory of Open Access Journals (Sweden)

    Iksoo Huh

    Full Text Available Recent advances in genotyping methodologies have allowed genome-wide association studies (GWAS to accurately identify genetic variants that associate with common or pathological complex traits. Although most GWAS have focused on associations with single genetic variants, joint identification of multiple genetic variants, and how they interact, is essential for understanding the genetic architecture of complex phenotypic traits. Here, we propose an efficient stepwise method based on the Cochran-Mantel-Haenszel test (for stratified categorical data to identify causal joint multiple genetic variants in GWAS. This method combines the CMH statistic with a stepwise procedure to detect multiple genetic variants associated with specific categorical traits, using a series of associated I × J contingency tables and a null hypothesis of no phenotype association. Through a new stratification scheme based on the sum of minor allele count criteria, we make the method more feasible for GWAS data having sample sizes of several thousands. We also examine the properties of the proposed stepwise method via simulation studies, and show that the stepwise CMH test performs better than other existing methods (e.g., logistic regression and detection of associations by Markov blanket for identifying multiple genetic variants. Finally, we apply the proposed approach to two genomic sequencing datasets to detect linked genetic variants associated with bipolar disorder and obesity, respectively.

  13. Identifying risk factors for exposure to culturable allergenic moulds in energy efficient homes by using highly specific monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Sharpe, Richard A. [European Centre for Environment and Human Health, University of Exeter Medical School, Truro TR1 3HD (United Kingdom); Cocq, Kate Le [Rothamsted Research, North Wyke, Okehampton EX20 2SB (United Kingdom); Nikolaou, Vasilis [University of Exeter Medical School, The Veysey Building, Salmon Pool Lane, Exeter EX2 4SG (United Kingdom); Osborne, Nicholas J. [European Centre for Environment and Human Health, University of Exeter Medical School, Truro TR1 3HD (United Kingdom); Clinical Pharmacology and Toxicology Research Group, Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW (Australia); Thornton, Christopher R., E-mail: c.r.thornton@exeter.ac.uk [Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter EX4 4QD (United Kingdom)

    2016-01-15

    The aim of this study was to determine the accuracy of monoclonal antibodies (mAbs) in identifying culturable allergenic fungi present in visible mould growth in energy efficient homes, and to identify risk factors for exposure to these known allergenic fungi. Swabs were taken from fungal contaminated surfaces and culturable yeasts and moulds isolated by using mycological culture. Soluble antigens from cultures were tested by ELISA using mAbs specific to the culturable allergenic fungi Aspergillus and Penicillium spp., Ulocladium, Alternaria, and Epicoccum spp., Cladosporium spp., Fusarium spp., and Trichoderma spp. Diagnostic accuracies of the ELISA tests were determined by sequencing of the internally transcribed spacer 1 (ITS1)-5.8S-ITS2-encoding regions of recovered fungi following ELISA. There was 100% concordance between the two methods, with ELISAs providing genus-level identity and ITS sequencing providing species-level identities (210 out of 210 tested). Species of Aspergillus/Penicillium, Cladosporium, Ulocladium/Alternaria/Epicoccum, Fusarium and Trichoderma were detected in 82% of the samples. The presence of condensation was associated with an increased risk of surfaces being contaminated by Aspergillus/Penicillium spp. and Cladosporium spp., whereas moisture within the building fabric (water ingress/rising damp) was only associated with increased risk of Aspergillus/Penicillium spp. Property type and energy efficiency levels were found to moderate the risk of indoor surfaces becoming contaminated with Aspergillus/Penicillium and Cladosporium which in turn was modified by the presence of condensation, water ingress and rising damp, consistent with previous literature. - Highlights: • Monoclonal antibodies were used to track culturable allergenic moulds in homes. • Allergenic moulds were recovered from 82% of swabs from contaminated surfaces. • The mAbs were highly specific with 100% agreement to PCR of recovered fungi. • Improvements to energy

  14. Identifying risk factors for exposure to culturable allergenic moulds in energy efficient homes by using highly specific monoclonal antibodies

    International Nuclear Information System (INIS)

    Sharpe, Richard A.; Cocq, Kate Le; Nikolaou, Vasilis; Osborne, Nicholas J.; Thornton, Christopher R.

    2016-01-01

    The aim of this study was to determine the accuracy of monoclonal antibodies (mAbs) in identifying culturable allergenic fungi present in visible mould growth in energy efficient homes, and to identify risk factors for exposure to these known allergenic fungi. Swabs were taken from fungal contaminated surfaces and culturable yeasts and moulds isolated by using mycological culture. Soluble antigens from cultures were tested by ELISA using mAbs specific to the culturable allergenic fungi Aspergillus and Penicillium spp., Ulocladium, Alternaria, and Epicoccum spp., Cladosporium spp., Fusarium spp., and Trichoderma spp. Diagnostic accuracies of the ELISA tests were determined by sequencing of the internally transcribed spacer 1 (ITS1)-5.8S-ITS2-encoding regions of recovered fungi following ELISA. There was 100% concordance between the two methods, with ELISAs providing genus-level identity and ITS sequencing providing species-level identities (210 out of 210 tested). Species of Aspergillus/Penicillium, Cladosporium, Ulocladium/Alternaria/Epicoccum, Fusarium and Trichoderma were detected in 82% of the samples. The presence of condensation was associated with an increased risk of surfaces being contaminated by Aspergillus/Penicillium spp. and Cladosporium spp., whereas moisture within the building fabric (water ingress/rising damp) was only associated with increased risk of Aspergillus/Penicillium spp. Property type and energy efficiency levels were found to moderate the risk of indoor surfaces becoming contaminated with Aspergillus/Penicillium and Cladosporium which in turn was modified by the presence of condensation, water ingress and rising damp, consistent with previous literature. - Highlights: • Monoclonal antibodies were used to track culturable allergenic moulds in homes. • Allergenic moulds were recovered from 82% of swabs from contaminated surfaces. • The mAbs were highly specific with 100% agreement to PCR of recovered fungi. • Improvements to energy

  15. Frequency and predictors of stroke after acute myocardial infarction: specific aspects of in-hospital and postdischarge events.

    Science.gov (United States)

    Hachet, Olivier; Guenancia, Charles; Stamboul, Karim; Daubail, Benoit; Richard, Carole; Béjot, Yannick; Yameogo, Valentin; Gudjoncik, Aurélie; Cottin, Yves; Giroud, Maurice; Lorgis, Luc

    2014-12-01

    Stroke is a serious complication after acute myocardial infarction (AMI) and is closely associated with decreased survival. This study aimed to investigate the frequency, characteristics, and factors associated with in-hospital and postdischarge stroke in patients with AMI. Eight thousand four hundred eighty-five consecutive patients admitted to a cardiology intensive care unit for AMI, between January 2001 and July 2010. Stroke/transient ischemic attack were collected during 1-year follow-up. One hundred twenty-three in-hospital strokes were recorded: 65 (52.8%) occurred on the first day after admission for AMI, and 108 (87%) within the first 5 days. One hundred six patients (86.2%-incidence rate 1.25%) experienced in-hospital ischemic stroke, and 14 patients (11.4%-incidence rate 0.16%) were diagnosed with an in-hospital hemorrhagic stroke. In-hospital ischemic stroke subtypes according to the Trial of Org 10 172 in Acute Stroke Treatment (TOAST) classification showed that only 2 types of stroke were identified more frequently. As expected, the leading subtype of in-hospital ischemic stroke was cardioembolic stroke (n=64, 60%), the second was stroke of undetermined pathogenesis (n=38, 36%). After multivariable backward regression analysis, female sex, previous transient ischemic attack (TIA)/stroke, new-onset atrial fibrillation, left ventricular ejection fraction (odds ratio per point of left ventricular ejection fraction), and C-reactive protein were independently associated with in-hospital ischemic stroke. When antiplatelet and anticoagulation therapy within the first 48 hours was introduced into the multivariable model, we found that implementing these treatments (≥1) was an independent protective factor of in-hospital stroke. In-hospital hemorrhagic stroke was dramatically increased (5-fold) when thrombolysis was prescribed as the reperfusion treatment. However, the different parenteral anticoagulants were not predictors of risk in univariable analysis

  16. Serum Metabolomics to Identify the Liver Disease-Specific Biomarkers for the Progression of Hepatitis to Hepatocellular Carcinoma

    Science.gov (United States)

    Gao, Rong; Cheng, Jianhua; Fan, Chunlei; Shi, Xiaofeng; Cao, Yuan; Sun, Bo; Ding, Huiguo; Hu, Chengjin; Dong, Fangting; Yan, Xianzhong

    2015-12-01

    Hepatocellular carcinoma (HCC) is a common malignancy that has region specific etiologies. Unfortunately, 85% of cases of HCC are diagnosed at an advanced stage. Reliable biomarkers for the early diagnosis of HCC are urgently required to reduced mortality and therapeutic expenditure. We established a non-targeted gas chromatography-time of flight-mass spectrometry (GC-TOFMS) metabolomics method in conjunction with Random Forests (RF) analysis based on 201 serum samples from healthy controls (NC), hepatitis B virus (HBV), liver cirrhosis (LC) and HCC patients to explore the metabolic characteristics in the progression of hepatocellular carcinogenesis. Ultimately, 15 metabolites were identified intimately associated with the process. Phenylalanine, malic acid and 5-methoxytryptamine for HBV vs. NC, palmitic acid for LC vs. HBV, and asparagine and β-glutamate for HCC vs. LC were screened as the liver disease-specific potential biomarkers with an excellent discriminant performance. All the metabolic perturbations in these liver diseases are associated with pathways for energy metabolism, macromolecular synthesis, and maintaining the redox balance to protect tumor cells from oxidative stress.

  17. Multiplexed screening of natural humoral immunity identifies antibodies at fine specificity for complex and dynamic viral targets.

    Science.gov (United States)

    McCutcheon, Krista M; Gray, Julia; Chen, Natalie Y; Liu, Keyi; Park, Minha; Ellsworth, Stote; Tripp, Ralph A; Tompkins, S Mark; Johnson, Scott K; Samet, Shelly; Pereira, Lenore; Kauvar, Lawrence M

    2014-01-01

    Viral entry targets with therapeutic neutralizing potential are subject to multiple escape mechanisms, including antigenic drift, immune dominance of functionally irrelevant epitopes, and subtle variations in host cell mechanisms. A surprising finding of recent years is that potent neutralizing antibodies to viral epitopes independent of strain exist, but are poorly represented across the diverse human population. Identifying these antibodies and understanding the biology mediating the specific immune response is thus difficult. An effective strategy for meeting this challenge is to incorporate multiplexed antigen screening into a high throughput survey of the memory B cell repertoire from immune individuals. We used this approach to discover suites of cross-clade antibodies directed to conformational epitopes in the stalk region of the influenza A hemagglutinin (HA) protein and to select high-affinity anti-peptide antibodies to the glycoprotein B (gB) of human cytomegalovirus. In each case, our screens revealed a restricted VH and VL germline usage, including published and previously unidentified gene families. The in vivo evolution of paratope specificity with optimal neutralizing activity was understandable after correlating biological activities with kinetic binding and epitope recognition. Iterative feedback between antigen probe design based on structure and function information with high throughput multiplexed screening demonstrated a generally applicable strategy for efficient identification of safe, native, finely tuned antibodies with the potential for high genetic barriers to viral escape.

  18. Systematic screening of isogenic cancer cells identifies DUSP6 as context-specific synthetic lethal target in melanoma

    DEFF Research Database (Denmark)

    Wittig-Blaich, Stephanie; Wittig, Rainer; Schmidt, Steffen

    2017-01-01

    Next-generation sequencing has dramatically increased genome-wide profiling options and conceptually initiates the possibility for personalized cancer therapy. State-of-the-art sequencing studies yield large candidate gene sets comprising dozens or hundreds of mutated genes. However, few technolo......Next-generation sequencing has dramatically increased genome-wide profiling options and conceptually initiates the possibility for personalized cancer therapy. State-of-the-art sequencing studies yield large candidate gene sets comprising dozens or hundreds of mutated genes. However, few...... technologies are available for the systematic downstream evaluation of these results to identify novel starting points of future cancer therapies. We improved and extended a site-specific recombination-based system for systematic analysis of the individual functions of a large number of candidate genes......, a library of 108 isogenic melanoma cell lines was constructed and 8 genes were identified that significantly reduced viability in a discovery screen and in an independent validation screen. Here, we demonstrate the broad applicability of this recombination-based method and we proved its potential...

  19. Technical aspects of typing for HLA-DP alleles using allele-specific DNA in vitro amplification and sequence-specific oligonucleotide probes. Detection of single base mismatches

    DEFF Research Database (Denmark)

    Fugger, L; Morling, N; Ryder, L P

    1990-01-01

    The polymerase chain reaction (PCR) is an effective method for in vitro DNA amplification which combined with probing with synthetic oligonucleotides can be used for, e.g., HLA-typing. We have studied the technical aspects of HLA-DP typing with the technique. DNA from mononuclear nucleated cells...... was extracted with either a simple salting out method or phenol/chloroform. Both DNAs could be readily used for PCR. The MgC2 concentration of the PCR buffer and the annealing temperature of the thermal cycle of the PCR were the two most important variables. The MgCl2 concentration and the temperature must...... be carefully titrated for each primer pair in the PCR. The influence of mismatches between the primer and the DNA template were studied and we found that, by using primers differing only from each other at the 3' end, cross-amplification of closely homologous alleles could be avoided. Thus, single base...

  20. Combined gene expression analysis of whole-tissue and microdissected pancreatic ductal adenocarcinoma identifies genes specifically overexpressed in tumor epithelia.

    Science.gov (United States)

    Badea, Liviu; Herlea, Vlad; Dima, Simona Olimpia; Dumitrascu, Traian; Popescu, Irinel

    2008-01-01

    The precise details of pancreatic ductal adenocarcinoma (PDAC) pathogenesis are still insufficiently known, requiring the use of high-throughput methods. However, PDAC is especially difficult to study using microarrays due to its strong desmoplastic reaction, which involves a hyperproliferating stroma that effectively "masks" the contribution of the minoritary neoplastic epithelial cells. Thus it is not clear which of the genes that have been found differentially expressed between normal and whole tumor tissues are due to the tumor epithelia and which simply reflect the differences in cellular composition. To address this problem, laser microdissection studies have been performed, but these have to deal with much smaller tissue sample quantities and therefore have significantly higher experimental noise. In this paper we combine our own large sample whole-tissue study with a previously published smaller sample microdissection study by Grützmann et al. to identify the genes that are specifically overexpressed in PDAC tumor epithelia. The overlap of this list of genes with other microarray studies of pancreatic cancer as well as with the published literature is impressive. Moreover, we find a number of genes whose over-expression appears to be inversely correlated with patient survival: keratin 7, laminin gamma 2, stratifin, platelet phosphofructokinase, annexin A2, MAP4K4 and OACT2 (MBOAT2), which are all specifically upregulated in the neoplastic epithelia, rather than the tumor stroma. We improve on other microarray studies of PDAC by putting together the higher statistical power due to a larger number of samples with information about cell-type specific expression and patient survival.

  1. An Integrated Metabolomic and Microbiome Analysis Identified Specific Gut Microbiota Associated with Fecal Cholesterol and Coprostanol in Clostridium difficile Infection.

    Directory of Open Access Journals (Sweden)

    Vijay C Antharam

    Full Text Available Clostridium difficile infection (CDI is characterized by dysbiosis of the intestinal microbiota and a profound derangement in the fecal metabolome. However, the contribution of specific gut microbes to fecal metabolites in C. difficile-associated gut microbiome remains poorly understood. Using gas-chromatography mass spectrometry (GC-MS and 16S rRNA deep sequencing, we analyzed the metabolome and microbiome of fecal samples obtained longitudinally from subjects with Clostridium difficile infection (n = 7 and healthy controls (n = 6. From 155 fecal metabolites, we identified two sterol metabolites at >95% match to cholesterol and coprostanol that significantly discriminated C. difficile-associated gut microbiome from healthy microbiota. By correlating the levels of cholesterol and coprostanol in fecal extracts with 2,395 bacterial operational taxonomic units (OTUs determined by 16S rRNA sequencing, we identified 63 OTUs associated with high levels of coprostanol and 2 OTUs correlated with low coprostanol levels. Using indicator species analysis (ISA, 31 of the 63 coprostanol-associated bacteria correlated with health, and two Veillonella species were associated with low coprostanol levels that correlated strongly with CDI. These 65 bacterial taxa could be clustered into 12 sub-communities, with each community containing a consortium of organisms that co-occurred with one another. Our studies identified 63 human gut microbes associated with cholesterol-reducing activities. Given the importance of gut bacteria in reducing and eliminating cholesterol from the GI tract, these results support the recent finding that gut microbiome may play an important role in host lipid metabolism.

  2. Integrated genetic and epigenetic analysis identifies haplotype-specific methylation in the FTO type 2 diabetes and obesity susceptibility locus.

    Directory of Open Access Journals (Sweden)

    Christopher G Bell

    2010-11-01

    Full Text Available Recent multi-dimensional approaches to the study of complex disease have revealed powerful insights into how genetic and epigenetic factors may underlie their aetiopathogenesis. We examined genotype-epigenotype interactions in the context of Type 2 Diabetes (T2D, focussing on known regions of genomic susceptibility. We assayed DNA methylation in 60 females, stratified according to disease susceptibility haplotype using previously identified association loci. CpG methylation was assessed using methylated DNA immunoprecipitation on a targeted array (MeDIP-chip and absolute methylation values were estimated using a Bayesian algorithm (BATMAN. Absolute methylation levels were quantified across LD blocks, and we identified increased DNA methylation on the FTO obesity susceptibility haplotype, tagged by the rs8050136 risk allele A (p = 9.40×10(-4, permutation p = 1.0×10(-3. Further analysis across the 46 kb LD block using sliding windows localised the most significant difference to be within a 7.7 kb region (p = 1.13×10(-7. Sequence level analysis, followed by pyrosequencing validation, revealed that the methylation difference was driven by the co-ordinated phase of CpG-creating SNPs across the risk haplotype. This 7.7 kb region of haplotype-specific methylation (HSM, encapsulates a Highly Conserved Non-Coding Element (HCNE that has previously been validated as a long-range enhancer, supported by the histone H3K4me1 enhancer signature. This study demonstrates that integration of Genome-Wide Association (GWA SNP and epigenomic DNA methylation data can identify potential novel genotype-epigenotype interactions within disease-associated loci, thus providing a novel route to aid unravelling common complex diseases.

  3. An extended data mining method for identifying differentially expressed assay-specific signatures in functional genomic studies

    Directory of Open Access Journals (Sweden)

    Rollins Derrick K

    2010-12-01

    Full Text Available Abstract Background Microarray data sets provide relative expression levels for thousands of genes for a small number, in comparison, of different experimental conditions called assays. Data mining techniques are used to extract specific information of genes as they relate to the assays. The multivariate statistical technique of principal component analysis (PCA has proven useful in providing effective data mining methods. This article extends the PCA approach of Rollins et al. to the development of ranking genes of microarray data sets that express most differently between two biologically different grouping of assays. This method is evaluated on real and simulated data and compared to a current approach on the basis of false discovery rate (FDR and statistical power (SP which is the ability to correctly identify important genes. Results This work developed and evaluated two new test statistics based on PCA and compared them to a popular method that is not PCA based. Both test statistics were found to be effective as evaluated in three case studies: (i exposing E. coli cells to two different ethanol levels; (ii application of myostatin to two groups of mice; and (iii a simulated data study derived from the properties of (ii. The proposed method (PM effectively identified critical genes in these studies based on comparison with the current method (CM. The simulation study supports higher identification accuracy for PM over CM for both proposed test statistics when the gene variance is constant and for one of the test statistics when the gene variance is non-constant. Conclusions PM compares quite favorably to CM in terms of lower FDR and much higher SP. Thus, PM can be quite effective in producing accurate signatures from large microarray data sets for differential expression between assays groups identified in a preliminary step of the PCA procedure and is, therefore, recommended for use in these applications.

  4. An Integrated Metabolomic and Microbiome Analysis Identified Specific Gut Microbiota Associated with Fecal Cholesterol and Coprostanol in Clostridium difficile Infection.

    Science.gov (United States)

    Antharam, Vijay C; McEwen, Daniel C; Garrett, Timothy J; Dossey, Aaron T; Li, Eric C; Kozlov, Andrew N; Mesbah, Zhubene; Wang, Gary P

    2016-01-01

    Clostridium difficile infection (CDI) is characterized by dysbiosis of the intestinal microbiota and a profound derangement in the fecal metabolome. However, the contribution of specific gut microbes to fecal metabolites in C. difficile-associated gut microbiome remains poorly understood. Using gas-chromatography mass spectrometry (GC-MS) and 16S rRNA deep sequencing, we analyzed the metabolome and microbiome of fecal samples obtained longitudinally from subjects with Clostridium difficile infection (n = 7) and healthy controls (n = 6). From 155 fecal metabolites, we identified two sterol metabolites at >95% match to cholesterol and coprostanol that significantly discriminated C. difficile-associated gut microbiome from healthy microbiota. By correlating the levels of cholesterol and coprostanol in fecal extracts with 2,395 bacterial operational taxonomic units (OTUs) determined by 16S rRNA sequencing, we identified 63 OTUs associated with high levels of coprostanol and 2 OTUs correlated with low coprostanol levels. Using indicator species analysis (ISA), 31 of the 63 coprostanol-associated bacteria correlated with health, and two Veillonella species were associated with low coprostanol levels that correlated strongly with CDI. These 65 bacterial taxa could be clustered into 12 sub-communities, with each community containing a consortium of organisms that co-occurred with one another. Our studies identified 63 human gut microbes associated with cholesterol-reducing activities. Given the importance of gut bacteria in reducing and eliminating cholesterol from the GI tract, these results support the recent finding that gut microbiome may play an important role in host lipid metabolism.

  5. Specificity of the Acute Tryptophan and Tyrosine Plus Phenylalanine Depletion and Loading Tests I. Review of Biochemical Aspects and Poor Specificity of Current Amino Acid Formulations

    Directory of Open Access Journals (Sweden)

    Abdulla A.-B. Badawy

    2010-06-01

    Full Text Available The acute tryptophan or tyrosine plus phenylalanine depletion and loading tests are powerful tools for studying the roles of serotonin, dopamine and noradrenaline in normal subjects and those with behavioural disorders. The current amino acid formulations for these tests, however, are associated with undesirable decreases in ratios of tryptophan or tyrosine plus phenylalanine to competing amino acids resulting in loss of specificity. This could confound biochemical and behavioural findings. Compositions of current formulations are reviewed, the biochemical principles underpinning the tests are revisited and examples of unintended changes in the above ratios and their impact on monoamine function and behaviour will be demonstrated from data in the literature. The presence of excessive amounts of the 3 branched-chain amino acids Leu, Ile and Val is responsible for these unintended decreases and the consequent loss of specificity. Strategies for enhancing the specificity of the different formulations are proposed.

  6. Specificity of the Acute Tryptophan and Tyrosine plus Phenylalanine Depletion and Loading Tests I. Review of Biochemical Aspects and Poor Specificity of Current Amino Acid Formulations

    Directory of Open Access Journals (Sweden)

    Abdulla A.-B. Badawy

    2010-01-01

    Full Text Available The acute tryptophan or tyrosine plus phenylalanine depletion and loading tests are powerful tools for studying the roles of serotonin, dopamine and noradrenaline in normal subjects and those with behavioural disorders. The current amino acid formulations for these tests, however, are associated with undesirable decreases in ratios of tryptophan or tyrosine plus phenylalanine to competing amino acids resulting in loss of specificity. This could confound biochemical and behavioural findings. Compositions of current formulations are reviewed, the biochemical principles underpinning the tests are revisited and examples of unintended changes in the above ratios and their impact on monoamine function and behaviour will be demonstrated from data in the literature. The presence of excessive amounts of the 3 branched-chain amino acids Leu, Ile and Val is responsible for these unintended decreases and the consequent loss of specificity. Strategies for enhancing the specificity of the different formulations are proposed.

  7. BAC CGH-array identified specific small-scale genomic imbalances in diploid DMBA-induced rat mammary tumors

    International Nuclear Information System (INIS)

    Samuelson, Emma; Karlsson, Sara; Partheen, Karolina; Nilsson, Staffan; Szpirer, Claude; Behboudi, Afrouz

    2012-01-01

    Development of breast cancer is a multistage process influenced by hormonal and environmental factors as well as by genetic background. The search for genes underlying this malignancy has recently been highly productive, but the etiology behind this complex disease is still not understood. In studies using animal cancer models, heterogeneity of the genetic background and environmental factors is reduced and thus analysis and identification of genetic aberrations in tumors may become easier. To identify chromosomal regions potentially involved in the initiation and progression of mammary cancer, in the present work we subjected a subset of experimental mammary tumors to cytogenetic and molecular genetic analysis. Mammary tumors were induced with DMBA (7,12-dimethylbenz[a]anthrazene) in female rats from the susceptible SPRD-Cu3 strain and from crosses and backcrosses between this strain and the resistant WKY strain. We first produced a general overview of chromosomal aberrations in the tumors using conventional kartyotyping (G-banding) and Comparative Genome Hybridization (CGH) analyses. Particular chromosomal changes were then analyzed in more details using an in-house developed BAC (bacterial artificial chromosome) CGH-array platform. Tumors appeared to be diploid by conventional karyotyping, however several sub-microscopic chromosome gains or losses in the tumor material were identified by BAC CGH-array analysis. An oncogenetic tree analysis based on the BAC CGH-array data suggested gain of rat chromosome (RNO) band 12q11, loss of RNO5q32 or RNO6q21 as the earliest events in the development of these mammary tumors. Some of the identified changes appear to be more specific for DMBA-induced mammary tumors and some are similar to those previously reported in ACI rat model for estradiol-induced mammary tumors. The later group of changes is more interesting, since they may represent anomalies that involve genes with a critical role in mammary tumor development. Genetic

  8. An in vivo cis-regulatory screen at the type 2 diabetes associated TCF7L2 locus identifies multiple tissue-specific enhancers.

    Directory of Open Access Journals (Sweden)

    Daniel Savic

    Full Text Available Genome-wide association studies (GWAS have repeatedly shown an association between non-coding variants in the TCF7L2 locus and risk for type 2 diabetes (T2D, implicating a role for cis-regulatory variation within this locus in disease etiology. Supporting this hypothesis, we previously localized complex regulatory activity to the TCF7L2 T2D-associated interval using an in vivo bacterial artificial chromosome (BAC enhancer-trapping reporter strategy. To follow-up on this broad initial survey of the TCF7L2 regulatory landscape, we performed a fine-mapping enhancer scan using in vivo mouse transgenic reporter assays. We functionally interrogated approximately 50% of the sequences within the T2D-associated interval, utilizing sequence conservation within this 92-kb interval to determine the regulatory potential of all evolutionary conserved sequences that exhibited conservation to the non-eutherian mammal opossum. Included in this study was a detailed functional interrogation of sequences spanning both protective and risk alleles of single nucleotide polymorphism (SNP rs7903146, which has exhibited allele-specific enhancer function in pancreatic beta cells. Using these assays, we identified nine segments regulating various aspects of the TCF7L2 expression profile and that constitute nearly 70% of the sequences tested. These results highlight the regulatory complexity of this interval and support the notion that a TCF7L2 cis-regulatory disruption leads to T2D predisposition.

  9. The sensitivity and specificity of four questions (HARK to identify intimate partner violence: a diagnostic accuracy study in general practice

    Directory of Open Access Journals (Sweden)

    Feder Gene

    2007-08-01

    Full Text Available Abstract Background Intimate partner violence (IPV including physical, sexual and emotional violence, causes short and long term ill-health. Brief questions that reliably identify women experiencing IPV who present in clinical settings are a pre-requisite for an appropriate response from health services to this substantial public health problem. We estimated the sensitivity and specificity of four questions (HARK developed from the Abuse Assessment screen, compared to a 30-item abuse questionnaire, the Composite Abuse Scale (CAS. Methods We administered the four HARK questions and the CAS to women approached by two researchers in general practice waiting rooms in Newham, east London. Inclusions: women aged more than 17 years waiting to see a doctor or nurse, who had been in an intimate relationship in the last year. Exclusions: women who were accompanied by children over four years of age or another adult, too unwell to complete the questionnaires, unable to understand English or unable to give informed consent. Results Two hundred and thirty two women were recruited. The response rate was 54%. The prevalence of current intimate partner violence, within the last 12 months, using the CAS cut off score of ≥3, was 23% (95% C.I. 17% to 28% with pre-test odds of 0.3 (95% C.I. 0.2 to 0.4. The receiver operator characteristic curve demonstrated that a HARK cut off score of ≥1 maximises the true positives whilst minimising the false positives. The sensitivity of the optimal HARK cut-off score of ≥1 was 81% (95% C.I. 69% to 90%, specificity 95% (95% C.I. 91% to 98%, positive predictive value 83% (95% C.I. 70% to 91%, negative predictive value 94% (95% C.I. 90% to 97%, likelihood ratio 16 (95% C.I. 8 to 31 and post-test odds 5. Conclusion The four HARK questions accurately identify women experiencing IPV in the past year and may help women disclose abuse in general practice. The HARK questions could be incorporated into the electronic medical record

  10. Zebrafish transgenic constructs label specific neurons in Xenopus laevis spinal cord and identify frog V0v spinal neurons.

    Science.gov (United States)

    Juárez-Morales, José L; Martinez-De Luna, Reyna I; Zuber, Michael E; Roberts, Alan; Lewis, Katharine E

    2017-09-01

    A correctly functioning spinal cord is crucial for locomotion and communication between body and brain but there are fundamental gaps in our knowledge of how spinal neuronal circuitry is established and functions. To understand the genetic program that regulates specification and functions of this circuitry, we need to connect neuronal molecular phenotypes with physiological analyses. Studies using Xenopus laevis tadpoles have increased our understanding of spinal cord neuronal physiology and function, particularly in locomotor circuitry. However, the X. laevis tetraploid genome and long generation time make it difficult to investigate how neurons are specified. The opacity of X. laevis embryos also makes it hard to connect functional classes of neurons and the genes that they express. We demonstrate here that Tol2 transgenic constructs using zebrafish enhancers that drive expression in specific zebrafish spinal neurons label equivalent neurons in X. laevis and that the incorporation of a Gal4:UAS amplification cassette enables cells to be observed in live X. laevis tadpoles. This technique should enable the molecular phenotypes, morphologies and physiologies of distinct X. laevis spinal neurons to be examined together in vivo. We have used an islet1 enhancer to label Rohon-Beard sensory neurons and evx enhancers to identify V0v neurons, for the first time, in X. laevis spinal cord. Our work demonstrates the homology of spinal cord circuitry in zebrafish and X. laevis, suggesting that future work could combine their relative strengths to elucidate a more complete picture of how vertebrate spinal cord neurons are specified, and function to generate behavior. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1007-1020, 2017. © 2017 Wiley Periodicals, Inc.

  11. Identifying risk factors for exposure to culturable allergenic moulds in energy efficient homes by using highly specific monoclonal antibodies.

    Science.gov (United States)

    Sharpe, Richard A; Cocq, Kate Le; Nikolaou, Vasilis; Osborne, Nicholas J; Thornton, Christopher R

    2016-01-01

    The aim of this study was to determine the accuracy of monoclonal antibodies (mAbs) in identifying culturable allergenic fungi present in visible mould growth in energy efficient homes, and to identify risk factors for exposure to these known allergenic fungi. Swabs were taken from fungal contaminated surfaces and culturable yeasts and moulds isolated by using mycological culture. Soluble antigens from cultures were tested by ELISA using mAbs specific to the culturable allergenic fungi Aspergillus and Penicillium spp., Ulocladium, Alternaria, and Epicoccum spp., Cladosporium spp., Fusarium spp., and Trichoderma spp. Diagnostic accuracies of the ELISA tests were determined by sequencing of the internally transcribed spacer 1 (ITS1)-5.8S-ITS2-encoding regions of recovered fungi following ELISA. There was 100% concordance between the two methods, with ELISAs providing genus-level identity and ITS sequencing providing species-level identities (210 out of 210 tested). Species of Aspergillus/Penicillium, Cladosporium, Ulocladium/Alternaria/Epicoccum, Fusarium and Trichoderma were detected in 82% of the samples. The presence of condensation was associated with an increased risk of surfaces being contaminated by Aspergillus/Penicillium spp. and Cladosporium spp., whereas moisture within the building fabric (water ingress/rising damp) was only associated with increased risk of Aspergillus/Penicillium spp. Property type and energy efficiency levels were found to moderate the risk of indoor surfaces becoming contaminated with Aspergillus/Penicillium and Cladosporium which in turn was modified by the presence of condensation, water ingress and rising damp, consistent with previous literature. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Gametogenesis in the Pacific oyster Crassostrea gigas: a microarrays-based analysis identifies sex and stage specific genes.

    Directory of Open Access Journals (Sweden)

    Nolwenn M Dheilly

    . CONCLUSIONS/SIGNIFICANCE: This study allowed us to identify potential markers of early sex differentiation in the oyster C. gigas, an alternative hermaphrodite mollusk. We also provided new highly valuable information on genes specifically expressed by mature spermatozoids and mature oocytes.

  13. Goal specific social capital and job satisfaction Effects of different types of networks on instrumental and social aspects of work

    NARCIS (Netherlands)

    Flap, Henk; Völker, Beate

    2001-01-01

    This paper addresses the question “To what extent can job satisfaction be explained as the revenue of social capital?” By conceiving someone’s social network as social capital we specify conditions under which social ties do lead to job satisfaction. We inquire into the idea of goal specificity of

  14. Genetic Counselling for Predictive Testing in Huntington's Disease in One Centre since 1993. Gender-Specific Aspects of Decision-Making.

    Science.gov (United States)

    Arning, Larissa; Witt, Constantin N; Epplen, Jörg T; Stemmler, Susanne

    2015-01-01

    The discovery of the mutation causing Huntington's disease (HD) in 1993 allowed direct mutation analysis and predictive testing to identify currently unaffected carriers with a sensitivity and specificity of virtually 100%. The present study was designed to comprehensively profile the participants who sought predictive testing for HD between 1993 and 2009 in our Huntington centre. Using a retrospective design, we analysed the written documentation of the counselling sessions for all referrals for predictive mutation testing in this time span. Six hundred sixty-three individuals at risk for HD requested predictive testing. Roughly half (n = 333) completed the protocol and received their test result. In general our findings are in accordance with other reports: most participants share an a priori risk of 50% (91.1%); more females request testing (58.5%); and those who ask for the result are mostly in their 30 s (mean = 35.1 years). Of those at 50% or 25% prior risks, 47.4% and 22.7%, respectively, tested positive in accordance with the respective risk of inheriting HD. Generally, more participants with an affected mother than father sought genetic testing (52.5% versus 47.5%). Interestingly, this difference was especially evident in the group of females who finally withdrew from testing (59.1%, p = 0.040). Men, in particular those who decided in favour of the test, were more often accompanied by their partner in the pre-test counselling session than vice versa (67.9% versus 44.7%, p = 0.003). On the other hand, significantly more men who were being tested did not have a companion in the pre-test session as compared with men who decided against the test (40.0% versus 25.7%, p = 0.012). During the first four years of predictive testing (1993–1996) more participants completed the protocol and received their test result as in later years. Yet, in this early time span significantly fewer females finally decided in favour of the test (48.4%, p = 0.005). These findings

  15. Organization aspect

    NARCIS (Netherlands)

    Grefen, P.W.P.J.; Mehandjiev, N.; Mehandjiev, N.; Grefen, P.W.P.J.

    2010-01-01

    Following the BOAT framework discussed in Chapter 1, this chapter describes the organization aspect of the CrossWork approach. It shows how the business requirements identified in the previous chapter can be fulfilled by dynamic organization structures and business processes in Networks of

  16. Cross-cultural generality and specificity in self-regulation: avoidance personal goals and multiple aspects of well-being in the United States and Japan.

    Science.gov (United States)

    Elliot, Andrew J; Sedikides, Constantine; Murayama, Kou; Tanaka, Ayumi; Thrash, Todd M; Mapes, Rachel R

    2012-10-01

    The authors examined avoidance personal goals as concurrent (Study 1) and longitudinal (Study 2) predictors of multiple aspects of well-being in the United States and Japan. In both studies, participants adopted more avoidance personal goals in Japan relative to the United States. Both studies also demonstrated that avoidance personal goals were significant negative predictors of the most relevant aspects of well-being in each culture. Specifically, avoidance personal goals were negative predictors of intrapersonal and eudaimonic well-being in the United States and were negative predictors of interpersonal and eudaimonic well-being in Japan. The findings clarify and extend puzzling findings from prior empirical work in this area, and raise provocative possibilities about the nature of avoidance goal pursuit.

  17. Methodological Aspects of Subjective Life Expectancy: Effects of Culture-Specific Reporting Heterogeneity Among Older Adults in the United States.

    Science.gov (United States)

    Lee, Sunghee; Smith, Jacqui

    2016-05-01

    Subjective life expectancy (SLE) has been suggested as a predictor of mortality and mortality-related behaviors. Although critical for culturally diverse societies, these findings do not consider cross-cultural methodological comparability. Culture-specific reporting heterogeneity is a well-known phenomenon introducing biases, and research on this issue with SLE is not established. Using data from the Health and Retirement Study, we examined reporting heterogeneity in SLE focusing on item nonresponse, focal points, and reports over time for five ethnic-cultural groups: non-Hispanic Whites, non-Hispanic Blacks, non-Hispanic other races, English-interviewed Hispanics, and Spanish-interviewed Hispanics. On item nonresponse, Spanish-interviewed Hispanics said, "I don't know," to SLE significantly more than any other groups. Nearly half of the respondents chose 0, 50, or 100, making them focal points. However, the focal points differed: 50 for Whites, 100 for Blacks, and 0 for Spanish-interviewed Hispanics. The relationship of SLE measured at two time points was higher for Whites than minorities. Moreover, those who said "I don't know" to SLE showed higher subsequent mortality than those who gave an answer. SLE was not a significant mortality predictor for Hispanics. Overall, SLE is not free from culture-specific reporting heterogeneity. This warrants further research about its culture-relevant measurement mechanisms. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. IgE to penicillins with different specificities can be identified by a multiepitope macromolecule: Bihaptenic penicillin structures and IgE specificities.

    Science.gov (United States)

    Ariza, A; Barrionuevo, E; Mayorga, C; Montañez, M I; Perez-Inestrosa, E; Ruiz-Sánchez, A; Rodríguez-Guéant, R M; Fernández, T D; Guéant, J L; Torres, M J; Blanca, M

    2014-04-01

    Quantitation of specific IgE by immunoassay is a recommended in vitro test for the diagnosis of immediate hypersensitivity reactions to betalactams (BLs), particularly when skin test results are negative. IgE antibodies that recognize the common nuclear structure of all BLs or the specific side chain structure can be mainly distinguished by immunoassays. The aim of this study was to develop an immunoassay system to detect IgE antibodies with different specificities. Cellulose discs conjugated with benzylpenicillin (BP), amoxicillin (AX) or both drugs, with poly-l-lysine (PLL) as carrier molecule, were used as solid phases in the radioallergosorbent test (RAST). Direct and inhibition radioimmunoassay studies were made to verify the structures recognized by serum IgE antibodies from penicillin-allergic patients. Our results indicated that the addition of both haptens did not decrease the capacity to capture IgE when serum specific to either BP or AX was used, at least in terms of sensitivity. In addition, the inclusion of two haptens improved significantly the levels of IgE detection in patients who recognized both BP and AX. Therefore, the use of a solid phase with a carrier molecule conjugated with two determinants (AX and BP) is helpful to recognize IgE antibodies against either of these determinants and is useful for screening sera with different specificities. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Practical aspects of treatment with target specific anticoagulants: initiation, payment and current market, transitions, and venous thromboembolism treatment.

    Science.gov (United States)

    Mahan, Charles E

    2015-04-01

    Target specific anticoagulants (TSOACs) have recently been introduced to the US market for multiple indications including venous thromboembolism (VTE) prevention in total hip and knee replacement surgeries, VTE treatment and reduction in the risk of stroke in patients with non-valvular atrial fibrillation (NVAF). Currently, three TSOACs are available including rivaroxaban, apixaban, and dabigatran with edoxaban currently under Food and Drug Administration review for VTE treatment and stroke prevention in NVAF. The introduction of these agents has created a paradigm shift in anticoagulation by considerably simplifying treatment and anticoagulant initiation for patients by giving clinicians the opportunity to use a rapid onset, rapid offset, oral agent. The availability of these rapid onset TSOACs is allowing for outpatient treatment of low risk pulmonary embolism and deep vein thrombosis which can greatly reduce healthcare costs by avoiding inpatient hospitalizations and treatment for the disease. Additionally with this practice, the complications of an inpatient hospitalization may also be avoided such as nosocomial infections. Single-agent approaches with TSOACs represent a paradigm shift in the treatment of VTE versus the complicated overlap of a parenteral agent with warfarin. Transitions between anticoagulants, including TSOACs, are a high-risk period for the patient, and clinicians must carefully consider patient characteristics such as renal function as well as the agents that are being transitioned. TSOAC use appears to be growing slowly with improved payment coverage throughout the US.

  20. Pre-steady-state kinetics of Escherichia coli aspartate aminotransferase catalyzed reactions and thermodynamic aspects of its substrate specificity

    International Nuclear Information System (INIS)

    Kuramitsu, Seiki; Hiromi, Keitaro; Hayashi, Hideyuki; Morino, Yoshimasa; Kagamiyama, Hiroyuki

    1990-01-01

    The four half-transamination reactions [the pyridoxal form of Escherichia coli aspartate aminotransferase (AspAT) with aspartate or glutamate and the pyridoxamine form of the enzyme with oxalacetate or 2-oxoglutarate] were followed in a stopped-flow spectrometer by monitoring the absorbance change at either 333 or 358 nm. The reaction progress curves in all cases gave fits to a monophasic exponential process. Kinetic analyses of these reactions showed that each half-reaction is composed of the following three processes: (1) the rapid binding of an amino acid substrate to the pyridoxal form of the enzyme; (2) the rapid binding of the corresponding keto acid to the pyridoxamine form of the enzyme; (3) the rate-determining interconversion between the two complexes. This mechanism was supported by the findings that the equilibrium constants for half- and overall-transamination reactions and the steady-state kinetic constants agreed well with the predicted values on the basis of the above mechanism using pre-steady-state kinetic parameters. The significant primary kinetic isotope effect observed in the reaction with deuterated amino acid suggests that the withdrawal of the α-proton of the substrates is rate determining. The pyridoxal form of E. coli AspAT reacted with a variety of amino acids as substrates. The substrate specificity of the E. coli enzyme was much broader than that of pig isoenzymes, reflecting some subtle but distinct difference in microenvironment accommodating the side chain of the substrate between e. coli and mammalian AspATs

  1. Energy storage technologies and hybrid architectures for specific diesel-driven rail duty cycles: Design and system integration aspects

    International Nuclear Information System (INIS)

    Meinert, M.; Prenleloup, P.; Schmid, S.; Palacin, R.

    2015-01-01

    Highlights: • We assessed integration of energy storage systems into hybrid system architectures. • We considered mechanical and electrical energy storage systems. • Potential of different combinations has been analyzed by standardized duty cycles. • Most promising are diesel-driven suburban, regional and shunting operations. • Double-layer capacitors and Lithium-ion batteries have the highest potential. - Abstract: The use of diesel-driven traction is an intrinsic part of the functioning of railway systems and it is expected to continue being so for the foreseeable future. The recent introduction of more restrictive greenhouse gas emission levels and other legislation aiming at the improvement of the environmental performance of railway systems has led to the need of exploring alternatives for cleaner diesel rolling stock. This paper focuses on assessing energy storage systems and the design of hybrid system architectures to determine their potential use in specific diesel-driven rail duty cycles. Hydrostatic accumulators, flywheels, Lithium-ion batteries and double-layer capacitors have been assessed and used to design hybrid system architectures. The potential of the different technology combinations has been analyzed using standardized duty cycles enhanced with gradient profiles related to suburban, regional and shunting operations. The results show that double-layer capacitors and Lithium-ion batteries have the highest potential to be successfully integrated into the system architecture of diesel-driven rail vehicles. Furthermore, the results also suggest that combining these two energy storage technologies into a single hybridisation package is a highly promising design that draws on their strengthens without any significant drawbacks.

  2. Functional interrogation of Plasmodium genus metabolism identifies species- and stage-specific differences in nutrient essentiality and drug targeting

    KAUST Repository

    Abdel-Haleem, Alyaa M.; Hefzi, Hooman; Mineta, Katsuhiko; Gao, Xin; Gojobori, Takashi; Palsson, Bernhard O.; Lewis, Nathan E.; Jamshidi, Neema

    2018-01-01

    and predicted potential targets that could affect several life cycle stages. The species-specific models further highlight differences between experimental animal models and the human-infecting species. Comparisons between human- and rodent-infecting species

  3. ATRX mutation in two adult brothers with non-specific moderate intellectual disability identified by exome sequencing

    OpenAIRE

    Moncini, S.; Bedeschi, M.F.; Castronovo, P.; Crippa, M.; Calvello, M.; Garghentino, R.R.; Scuvera, G.; Finelli, P.; Venturin, M.

    2013-01-01

    In this report, we describe two adult brothers affected by moderate non-specific intellectual disability (ID). They showed minor facial anomalies, not clearly ascribable to any specific syndromic patterns, microcephaly, brachydactyly and broad toes. Both brothers presented seizures. Karyotype, subtelomeric and FMR1 analysis were normal in both cases. We performed array-CGH analysis that revealed no copy-number variations potentially associated with ID. Subsequent exome sequence analysis allow...

  4. MUSI: an integrated system for identifying multiple specificity from very large peptide or nucleic acid data sets.

    Science.gov (United States)

    Kim, Taehyung; Tyndel, Marc S; Huang, Haiming; Sidhu, Sachdev S; Bader, Gary D; Gfeller, David; Kim, Philip M

    2012-03-01

    Peptide recognition domains and transcription factors play crucial roles in cellular signaling. They bind linear stretches of amino acids or nucleotides, respectively, with high specificity. Experimental techniques that assess the binding specificity of these domains, such as microarrays or phage display, can retrieve thousands of distinct ligands, providing detailed insight into binding specificity. In particular, the advent of next-generation sequencing has recently increased the throughput of such methods by several orders of magnitude. These advances have helped reveal the presence of distinct binding specificity classes that co-exist within a set of ligands interacting with the same target. Here, we introduce a software system called MUSI that can rapidly analyze very large data sets of binding sequences to determine the relevant binding specificity patterns. Our pipeline provides two major advances. First, it can detect previously unrecognized multiple specificity patterns in any data set. Second, it offers integrated processing of very large data sets from next-generation sequencing machines. The results are visualized as multiple sequence logos describing the different binding preferences of the protein under investigation. We demonstrate the performance of MUSI by analyzing recent phage display data for human SH3 domains as well as microarray data for mouse transcription factors.

  5. A robust approach to identifying tissue-specific gene expression regulatory variants using personalized human induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Je-Hyuk Lee

    2009-11-01

    Full Text Available Normal variation in gene expression due to regulatory polymorphisms is often masked by biological and experimental noise. In addition, some regulatory polymorphisms may become apparent only in specific tissues. We derived human induced pluripotent stem (iPS cells from adult skin primary fibroblasts and attempted to detect tissue-specific cis-regulatory variants using in vitro cell differentiation. We used padlock probes and high-throughput sequencing for digital RNA allelotyping and measured allele-specific gene expression in primary fibroblasts, lymphoblastoid cells, iPS cells, and their differentiated derivatives. We show that allele-specific expression is both cell type and genotype-dependent, but the majority of detectable allele-specific expression loci remains consistent despite large changes in the cell type or the experimental condition following iPS reprogramming, except on the X-chromosome. We show that our approach to mapping cis-regulatory variants reduces in vitro experimental noise and reveals additional tissue-specific variants using skin-derived human iPS cells.

  6. Unmasking the component-general and component-specific aspects of primary and secondary memory in the immediate free recall task.

    Science.gov (United States)

    Gibson, Bradley S; Gondoli, Dawn M

    2018-04-01

    The immediate free recall (IFR) task has been commonly used to estimate the capacities of the primary memory (PM) and secondary memory (SM) components of working memory (WM). Using this method, the correlation between estimates of the PM and SM components has hovered around zero, suggesting that PM and SM represent fully distinct and dissociable components of WM. However, this conclusion has conflicted with more recent studies that have observed moderately strong, positive correlations between PM and SM when separate attention and retrieval tasks are used to estimate these capacities, suggesting that PM and SM represent at least some related capacities. The present study attempted to resolve this empirical discrepancy by investigating the extent to which the relation between estimates of PM and SM might be suppressed by a third variable that operates during the recall portion of the IFR task. This third variable was termed "strength of recency" (SOR) in the present study as it reflected differences in the extent to which individuals used the same experimentally-induced recency recall initiation strategy. As predicted, the present findings showed that the positive correlation between estimates of PM and SM grew from small to medium when the indirect effect of SOR was controlled across two separate sets of studies. This finding is important because it provides stronger support for the distinction between "component-general" and "component-specific" aspects of PM and SM; furthermore, a proof is presented that demonstrates a limitation of using regression techniques to differentiate general and specific aspects of these components.

  7. Behavioural aspects of terrorism.

    Science.gov (United States)

    Leistedt, Samuel J

    2013-05-10

    Behavioural and social sciences are useful in collecting and analysing intelligence data, understanding terrorism, and developing strategies to combat terrorism. This article aims to examine the psychopathological concepts of terrorism and discusses the developing roles for behavioural scientists. A systematic review was conducted of studies investigating behavioural aspects of terrorism. These studies were identified by a systematic search of databases, textbooks, and a supplementary manual search of references. Several fundamental concepts were identified that continue to influence the motives and the majority of the behaviours of those who support or engage in this kind of specific violence. Regardless of the psychological aspects and new roles for psychiatrists, the behavioural sciences will continue to be called upon to assist in developing better methods to gather and analyse intelligence, to understand terrorism, and perhaps to stem the radicalisation process. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. A small interfering RNA screen of genes involved in DNA repair identifies tumor-specific radiosensitization by POLQ knockdown

    DEFF Research Database (Denmark)

    Higgins, Geoff S; Prevo, Remko; Lee, Yin-Fai

    2010-01-01

    The effectiveness of radiotherapy treatment could be significantly improved if tumor cells could be rendered more sensitive to ionizing radiation (IR) without altering the sensitivity of normal tissues. However, many of the key therapeutically exploitable mechanisms that determine intrinsic tumor...... radiosensitivity are largely unknown. We have conducted a small interfering RNA (siRNA) screen of 200 genes involved in DNA damage repair aimed at identifying genes whose knockdown increased tumor radiosensitivity. Parallel siRNA screens were conducted in irradiated and unirradiated tumor cells (SQ20B......) and irradiated normal tissue cells (MRC5). Using gammaH2AX foci at 24 hours after IR, we identified several genes, such as BRCA2, Lig IV, and XRCC5, whose knockdown is known to cause increased cell radiosensitivity, thereby validating the primary screening end point. In addition, we identified POLQ (DNA...

  9. Toward Greater Specificity in Identifying Associations among Interparental Aggression, Child Emotional Reactivity to Conflict, and Child Problems

    Science.gov (United States)

    Davies, Patrick T.; Cicchetti, Dante; Martin, Meredith J.

    2012-01-01

    This study examined specific forms of emotional reactivity to conflict and temperamental emotionality as explanatory mechanisms in pathways among interparental aggression and child psychological problems. Participants of the multimethod, longitudinal study included 201 two-year-old children and their mothers who had experienced elevated violence…

  10. Representational difference analysis of Neisseria meningitidis identifies sequences that are specific for the hyper-virulent lineage III clone

    NARCIS (Netherlands)

    Bart, A.; Dankert, J.; van der Ende, A.

    2000-01-01

    Neisseria meningitidis may cause meningitis and septicemia. Since the early 1980s, an increased incidence of meningococcal disease has been caused by the lineage III clone in many countries in Europe and in New Zealand. We hypothesized that lineage III meningococci have specific DNA sequences,

  11. Comparative proteomics as a tool for identifying specific alterations within interferon response pathways in human glioblastoma multiforme cells

    DEFF Research Database (Denmark)

    Tarasova, Irina A; Tereshkova, Alesya V; Lobas, Anna A

    2018-01-01

    An acquisition of increased sensitivity of cancer cells to viruses is a common outcome of malignant progression that justifies the development of oncolytic viruses as anticancer therapeutics. Studying molecular changes that underlie the sensitivity to viruses would help to identify cases where on...

  12. Development of a PubMed Based Search Tool for Identifying Sex and Gender Specific Health Literature.

    Science.gov (United States)

    Song, Michael M; Simonsen, Cheryl K; Wilson, Joanna D; Jenkins, Marjorie R

    2016-02-01

    An effective literature search strategy is critical to achieving the aims of Sex and Gender Specific Health (SGSH): to understand sex and gender differences through research and to effectively incorporate the new knowledge into the clinical decision making process to benefit both male and female patients. The goal of this project was to develop and validate an SGSH literature search tool that is readily and freely available to clinical researchers and practitioners. PubMed, a freely available search engine for the Medline database, was selected as the platform to build the SGSH literature search tool. Combinations of Medical Subject Heading terms, text words, and title words were evaluated for optimal specificity and sensitivity. The search tool was then validated against reference bases compiled for two disease states, diabetes and stroke. Key sex and gender terms and limits were bundled to create a search tool to facilitate PubMed SGSH literature searches. During validation, the search tool retrieved 50 of 94 (53.2%) stroke and 62 of 95 (65.3%) diabetes reference articles selected for validation. A general keyword search of stroke or diabetes combined with sex difference retrieved 33 of 94 (35.1%) stroke and 22 of 95 (23.2%) diabetes reference base articles, with lower sensitivity and specificity for SGSH content. The Texas Tech University Health Sciences Center SGSH PubMed Search Tool provides higher sensitivity and specificity to sex and gender specific health literature. The tool will facilitate research, clinical decision-making, and guideline development relevant to SGSH.

  13. Identifying long-term memory B-cells in vaccinated children despite waning antibody levels specific for Bordetella pertussis proteins.

    Science.gov (United States)

    Hendrikx, Lotte H; Oztürk, Kemal; de Rond, Lia G H; Veenhoven, Reinier H; Sanders, Elisabeth A M; Berbers, Guy A M; Buisman, Anne-Marie

    2011-02-04

    Whooping cough is a respiratory disease caused by Bordetella pertussis. Since the 1950s in developed countries pertussis vaccinations are included in the national immunization program. However, antibody levels rapidly wane after both whole cell and acellular pertussis vaccination. Therefore protection against pertussis may depend largely on long-term B- and T-cell immunities. We investigated long-term pertussis-specific memory B-cell responses in children who were primed at infant age with the Dutch wP-vaccine (ISRCTN65428640). Purified B-cells were characterized by FACS-analysis and after polyclonal stimulation memory B-cells were detected by ELISPOT-assays specific for pertussis toxin, filamentous haemagglutinin, pertactin and tetanus. In addition, plasma IgG levels directed to the same antigens were measured by a fluorescent bead-based multiplex immunoassay. Two and 3 years after wP priming as well as 2 and 5 years after the aP booster at the age of 4, low plasma IgG levels to the pertussis proteins were found. At the same time, however pertussis protein-specific memory B-cells could be detected and their number increased with age. The number of tetanus-specific memory B-cells was similar in all age groups, whereas IgG-tetanus levels were high 2 years after tetanus booster compared to pre- and 5 years post-booster levels. This study shows the presence of long-term pertussis protein-specific memory B-cells in children despite waning antibody levels after vaccination, which suggests that memory B-cells in addition to antibodies may contribute to protection against pertussis. Copyright © 2010 Elsevier Ltd. All rights reserved.

  14. ATRX mutation in two adult brothers with non-specific moderate intellectual disability identified by exome sequencing.

    Science.gov (United States)

    Moncini, S; Bedeschi, M F; Castronovo, P; Crippa, M; Calvello, M; Garghentino, R R; Scuvera, G; Finelli, P; Venturin, M

    2013-12-01

    In this report, we describe two adult brothers affected by moderate non-specific intellectual disability (ID). They showed minor facial anomalies, not clearly ascribable to any specific syndromic patterns, microcephaly, brachydactyly and broad toes. Both brothers presented seizures. Karyotype, subtelomeric and FMR1 analysis were normal in both cases. We performed array-CGH analysis that revealed no copy-number variations potentially associated with ID. Subsequent exome sequence analysis allowed the identification of the ATRX c.109C>T (p.R37X) mutation in both the affected brothers. Sanger sequencing confirmed the presence of the mutation in the brothers and showed that the mother is a healthy carrier. Mutations in the ATRX gene cause the X-linked alpha thalassemia/mental retardation (ATR-X) syndrome (MIM #301040), a severe clinical condition usually associated with profound ID, facial dysmorphism and alpha thalassemia. However, the syndrome is clinically heterogeneous and some mutations, including the c.109C>T, are associated with a broad phenotypic spectrum, with patients displaying a less severe phenotype with only mild-moderate ID. In the case presented here, exome sequencing provided an effective strategy to achieve the molecular diagnosis of ATR-X syndrome, which otherwise would have been difficult to consider due to the mild non-specific phenotype and the absence of a family history with typical severe cases.

  15. Comprehensive evaluation of disease- and trait-specific enrichment for eight functional elements among GWAS-identified variants.

    Science.gov (United States)

    Markunas, Christina A; Johnson, Eric O; Hancock, Dana B

    2017-07-01

    Genome-wide association study (GWAS)-identified variants are enriched for functional elements. However, we have limited knowledge of how functional enrichment may differ by disease/trait and tissue type. We tested a broad set of eight functional elements for enrichment among GWAS-identified SNPs (p Enrichment analyses were conducted using logistic regression, with Bonferroni correction. Overall, a significant enrichment was observed for all functional elements, except sequence motifs. Missense SNPs showed the strongest magnitude of enrichment. eQTLs were the only functional element significantly enriched across all diseases/traits. Magnitudes of enrichment were generally similar across diseases/traits, where enrichment was statistically significant. Blood vs. brain tissue effects on enrichment were dependent on disease/trait and functional element (e.g., cardiovascular disease: eQTLs P TissueDifference  = 1.28 × 10 -6 vs. enhancers P TissueDifference  = 0.94). Identifying disease/trait-relevant functional elements and tissue types could provide new insight into the underlying biology, by guiding a priori GWAS analyses (e.g., brain enhancer elements for psychiatric disease) or facilitating post hoc interpretation.

  16. Functional interrogation of Plasmodium genus metabolism identifies species- and stage-specific differences in nutrient essentiality and drug targeting.

    Directory of Open Access Journals (Sweden)

    Alyaa M Abdel-Haleem

    2018-01-01

    Full Text Available Several antimalarial drugs exist, but differences between life cycle stages among malaria species pose challenges for developing more effective therapies. To understand the diversity among stages and species, we reconstructed genome-scale metabolic models (GeMMs of metabolism for five life cycle stages and five species of Plasmodium spanning the blood, transmission, and mosquito stages. The stage-specific models of Plasmodium falciparum uncovered stage-dependent changes in central carbon metabolism and predicted potential targets that could affect several life cycle stages. The species-specific models further highlight differences between experimental animal models and the human-infecting species. Comparisons between human- and rodent-infecting species revealed differences in thiamine (vitamin B1, choline, and pantothenate (vitamin B5 metabolism. Thus, we show that genome-scale analysis of multiple stages and species of Plasmodium can prioritize potential drug targets that could be both anti-malarials and transmission blocking agents, in addition to guiding translation from non-human experimental disease models.

  17. Functional interrogation of Plasmodium genus metabolism identifies species- and stage-specific differences in nutrient essentiality and drug targeting

    KAUST Repository

    Abdel-Haleem, Alyaa M.

    2018-01-04

    Several antimalarial drugs exist, but differences between life cycle stages among malaria species pose challenges for developing more effective therapies. To understand the diversity among stages and species, we reconstructed genome-scale models (GEMs) of metabolism for five life cycle stages and five species of Plasmodium spanning the blood, transmission, and mosquito stages. The stage-specific models of Plasmodium falciparum uncovered stage-dependent changes in central carbon metabolism and predicted potential targets that could affect several life cycle stages. The species-specific models further highlight differences between experimental animal models and the human-infecting species. Comparisons between human- and rodent-infecting species revealed differences in thiamine (vitamin B1), choline, and pantothenate (vitamin B5) metabolism. Thus, we show that genome-scale analysis of multiple stages and species of Plasmodium can prioritize potential drug targets that could be both anti-malarials and transmission blocking agents, in addition to guiding translation from non-human experimental disease models.

  18. Identifying consumer preferences for specific beef flavor characteristics in relation to cattle production and postmortem processing parameters.

    Science.gov (United States)

    O'Quinn, T G; Woerner, D R; Engle, T E; Chapman, P L; Legako, J F; Brooks, J C; Belk, K E; Tatum, J D

    2016-02-01

    Sensory analysis of ground LL samples representing 12 beef product categories was conducted in 3 different regions of the U.S. to identify flavor preferences of beef consumers. Treatments characterized production-related flavor differences associated with USDA grade, cattle type, finishing diet, growth enhancement, and postmortem aging method. Consumers (N=307) rated cooked samples for 12 flavors and overall flavor desirability. Samples were analyzed to determine fatty acid content. Volatile compounds produced by cooking were extracted and quantified. Overall, consumers preferred beef that rated high for beefy/brothy, buttery/beef fat, and sweet flavors and disliked beef with fishy, livery, gamey, and sour flavors. Flavor attributes of samples higher in intramuscular fat with greater amounts of monounsaturated fatty acids and lesser proportions of saturated, odd-chain, omega-3, and trans fatty acids were preferred by consumers. Of the volatiles identified, diacetyl and acetoin were most closely correlated with desirable ratings for overall flavor and dimethyl sulfide was associated with an undesirable sour flavor. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Proteomic Analysis of Rhizoctonia solani Identifies Infection-specific, Redox Associated Proteins and Insight into Adaptation to Different Plant Hosts*

    Science.gov (United States)

    Anderson, Jonathan P.; Hane, James K.; Stoll, Thomas; Pain, Nicholas; Hastie, Marcus L.; Kaur, Parwinder; Hoogland, Christine; Gorman, Jeffrey J.; Singh, Karam B.

    2016-01-01

    Rhizoctonia solani is an important root infecting pathogen of a range of food staples worldwide including wheat, rice, maize, soybean, potato and others. Conventional resistance breeding strategies are hindered by the absence of tractable genetic resistance in any crop host. Understanding the biology and pathogenicity mechanisms of this fungus is important for addressing these disease issues, however, little is known about how R. solani causes disease. This study capitalizes on recent genomic studies by applying mass spectrometry based proteomics to identify soluble, membrane-bound and culture filtrate proteins produced under wheat infection and vegetative growth conditions. Many of the proteins found in the culture filtrate had predicted functions relating to modification of the plant cell wall, a major activity required for pathogenesis on the plant host, including a number found only under infection conditions. Other infection related proteins included a high proportion of proteins with redox associated functions and many novel proteins without functional classification. The majority of infection only proteins tested were confirmed to show transcript up-regulation during infection including a thaumatin which increased susceptibility to R. solani when expressed in Nicotiana benthamiana. In addition, analysis of expression during infection of different plant hosts highlighted how the infection strategy of this broad host range pathogen can be adapted to the particular host being encountered. Data are available via ProteomeXchange with identifier PXD002806. PMID:26811357

  20. Interactive cervical motion kinematics: sensitivity, specificity and clinically significant values for identifying kinematic impairments in patients with chronic neck pain.

    Science.gov (United States)

    Sarig Bahat, Hilla; Chen, Xiaoqi; Reznik, David; Kodesh, Einat; Treleaven, Julia

    2015-04-01

    Chronic neck pain has been consistently shown to be associated with impaired kinematic control including reduced range, velocity and smoothness of cervical motion, that seem relevant to daily function as in quick neck motion in response to surrounding stimuli. The objectives of this study were: to compare interactive cervical kinematics in patients with neck pain and controls; to explore the new measures of cervical motion accuracy; and to find the sensitivity, specificity, and optimal cutoff values for defining impaired kinematics in those with neck pain. In this cross-section study, 33 patients with chronic neck pain and 22 asymptomatic controls were assessed for their cervical kinematic control using interactive virtual reality hardware and customized software utilizing a head mounted display with built-in head tracking. Outcome measures included peak and mean velocity, smoothness (represented by number of velocity peaks (NVP)), symmetry (represented by time to peak velocity percentage (TTPP)), and accuracy of cervical motion. Results demonstrated significant and strong effect-size differences in peak and mean velocities, NVP and TTPP in all directions excluding TTPP in left rotation, and good effect-size group differences in 5/8 accuracy measures. Regression results emphasized the high clinical value of neck motion velocity, with very high sensitivity and specificity (85%-100%), followed by motion smoothness, symmetry and accuracy. These finding suggest cervical kinematics should be evaluated clinically, and screened by the provided cut off values for identification of relevant impairments in those with neck pain. Such identification of presence or absence of kinematic impairments may direct treatment strategies and additional evaluation when needed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Metaproteomics of saliva identifies human protein markers specific for individuals with periodontitis and dental caries compared to orally healthy controls

    DEFF Research Database (Denmark)

    Belstrøm, Daniel; Jersie-Christensen, Rosa R; Lyon, David

    2016-01-01

    BACKGROUND: The composition of the salivary microbiota has been reported to differentiate between patients with periodontitis, dental caries and orally healthy individuals. To identify characteristics of diseased and healthy saliva we thus wanted to compare saliva metaproteomes from patients...... with periodontitis and dental caries to healthy individuals. METHODS: Stimulated saliva samples were collected from 10 patients with periodontitis, 10 patients with dental caries and 10 orally healthy individuals. The proteins in the saliva samples were subjected to denaturing buffer and digested enzymatically...... and inflammatory markers in periodontitis and dental caries compared to healthy controls. Bacterial proteome profiles and functional annotation were very similar in health and disease. CONCLUSIONS: Overexpression of proteins related to the complement system and inflammation seems to correlate with oral disease...

  2. Systematic Expression Profiling Analysis Identifies Specific MicroRNA-Gene Interactions that May Differentiate between Active and Latent Tuberculosis Infection

    Directory of Open Access Journals (Sweden)

    Lawrence Shih-Hsin Wu

    2014-01-01

    Full Text Available Tuberculosis (TB is the second most common cause of death from infectious diseases. About 90% of those infected are asymptomatic—the so-called latent TB infections (LTBI, with a 10% lifetime chance of progressing to active TB. To further understand the molecular pathogenesis of TB, several molecular studies have attempted to compare the expression profiles between healthy controls and active TB or LTBI patients. However, the results vary due to diverse genetic backgrounds and study designs and the inherent complexity of the disease process. Thus, developing a sensitive and efficient method for the detection of LTBI is both crucial and challenging. For the present study, we performed a systematic analysis of the gene and microRNA profiles of healthy individuals versus those affected with TB or LTBI. Combined with a series of in silico analysis utilizing publicly available microRNA knowledge bases and published literature data, we have uncovered several microRNA-gene interactions that specifically target both the blood and lungs. Some of these molecular interactions are novel and may serve as potential biomarkers of TB and LTBI, facilitating the development for a more sensitive, efficient, and cost-effective diagnostic assay for TB and LTBI for the Taiwanese population.

  3. Systematic expression profiling analysis identifies specific microRNA-gene interactions that may differentiate between active and latent tuberculosis infection.

    Science.gov (United States)

    Wu, Lawrence Shih-Hsin; Lee, Shih-Wei; Huang, Kai-Yao; Lee, Tzong-Yi; Hsu, Paul Wei-Che; Weng, Julia Tzu-Ya

    2014-01-01

    Tuberculosis (TB) is the second most common cause of death from infectious diseases. About 90% of those infected are asymptomatic--the so-called latent TB infections (LTBI), with a 10% lifetime chance of progressing to active TB. To further understand the molecular pathogenesis of TB, several molecular studies have attempted to compare the expression profiles between healthy controls and active TB or LTBI patients. However, the results vary due to diverse genetic backgrounds and study designs and the inherent complexity of the disease process. Thus, developing a sensitive and efficient method for the detection of LTBI is both crucial and challenging. For the present study, we performed a systematic analysis of the gene and microRNA profiles of healthy individuals versus those affected with TB or LTBI. Combined with a series of in silico analysis utilizing publicly available microRNA knowledge bases and published literature data, we have uncovered several microRNA-gene interactions that specifically target both the blood and lungs. Some of these molecular interactions are novel and may serve as potential biomarkers of TB and LTBI, facilitating the development for a more sensitive, efficient, and cost-effective diagnostic assay for TB and LTBI for the Taiwanese population.

  4. Cyclic peptide inhibitors of lysine-specific demethylase 1 with improved potency identified by alanine scanning mutagenesis.

    Science.gov (United States)

    Kumarasinghe, Isuru R; Woster, Patrick M

    2018-03-25

    Lysine-specific demethylase 1 (LSD1) is a chromatin-remodeling enzyme that plays an important role in cancer. Over-expression of LSD1 decreases methylation at histone 3 lysine 4, and aberrantly silences tumor suppressor genes. Inhibitors of LSD1 have been designed as chemical probes and potential antitumor agents. We recently reported the cyclic peptide 9, which potently and reversibly inhibits LSD1 (IC 50 2.1 μM; K i 385 nM). Systematic alanine mutagenesis of 9 revealed residues that are critical for LSD1 inhibition, and these mutated peptides were evaluated as LSD1 inhibitors. Alanine substitution at positions 2, 3, 4, 6 and 11-17 preserved inhibition, while substitution of alanine at positions 8 and 9 resulted in complete loss of activity. Cyclic mutant peptides 11 and 16 produced the greatest LSD1 inhibition, and 11, 16, 27 and 28 increased global H3K4me2 in K562 cells. In addition, 16, 27 and 28 promoted significant increases in H3K4me2 levels at the promoter sites of the genes IGFBP2 and FEZ1. Data from these LSD1 inhibitors will aid in the design of peptidomimetics with improved stability and pharmacokinetics. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  5. Physician Rating Websites: What Aspects Are Important to Identify a Good Doctor, and Are Patients Capable of Assessing Them? A Mixed-Methods Approach Including Physicians' and Health Care Consumers' Perspectives.

    Science.gov (United States)

    Rothenfluh, Fabia; Schulz, Peter J

    2017-05-01

    Physician rating websites (PRWs) offer health care consumers the opportunity to evaluate their doctor anonymously. However, physicians' professional training and experience create a vast knowledge gap in medical matters between physicians and patients. This raises ethical concerns about the relevance and significance of health care consumers' evaluation of physicians' performance. To identify the aspects physician rating websites should offer for evaluation, this study investigated the aspects of physicians and their practice relevant for identifying a good doctor, and whether health care consumers are capable of evaluating these aspects. In a first step, a Delphi study with physicians from 4 specializations was conducted, testing various indicators to identify a good physician. These indicators were theoretically derived from Donabedian, who classifies quality in health care into pillars of structure, process, and outcome. In a second step, a cross-sectional survey with health care consumers in Switzerland (N=211) was launched based on the indicators developed in the Delphi study. Participants were asked to rate the importance of these indicators to identify a good physician and whether they would feel capable to evaluate those aspects after the first visit to a physician. All indicators were ordered into a 4×4 grid based on evaluation and importance, as judged by the physicians and health care consumers. Agreement between the physicians and health care consumers was calculated applying Holsti's method. In the majority of aspects, physicians and health care consumers agreed on what facets of care were important and not important to identify a good physician and whether patients were able to evaluate them, yielding a level of agreement of 74.3%. The two parties agreed that the infrastructure, staff, organization, and interpersonal skills are both important for a good physician and can be evaluated by health care consumers. Technical skills of a doctor and outcomes

  6. Core subjects at the end of primary school: identifying and explaining relative strengths of children with specific language impairment (SLI)

    Science.gov (United States)

    Durkin, Kevin; Mok, Pearl L H; Conti-Ramsden, Gina

    2015-01-01

    Background In general, children with specific language impairment (SLI) tend to fall behind their typically developing (TD) peers in educational attainment. Less is known about how children with SLI fare in particular areas of the curriculum and what predicts their levels of performance. Aims To compare the distributions of performance of children with SLI in three core school subjects (English, Mathematics and Science); to test the possibility that performance would vary across the core subjects; and to examine the extent to which language impairment predicts performance. Methods & Procedures This study was conducted in England and reports historical data on educational attainments. Teacher assessment and test scores of 176 eleven-year-old children with SLI were examined in the three core subjects and compared with known national norms. Possible predictors of performance were measured, including language ability at ages 7 and 11, educational placement type, and performance IQ. Outcomes & Results Children with SLI, compared with national norms, were found to be at a disadvantage in core school subjects. Nevertheless, some children attained the levels expected of TD peers. Performance was poorest in English; relative strengths were indicated in Science and, to a lesser extent, in Mathematics. Language skills were significant predictors of performance in all three core subjects. PIQ was the strongest predictor for Mathematics. For Science, both early language skills at 7 years and PIQ made significant contributions. Conclusions & Implications Language impacts on the school performance of children with SLI, but differentially across subjects. English for these children is the most challenging of the core subjects, reflecting the high levels of language demand it incurs. Science is an area of relative strength and mathematics appears to be intermediate, arguably because some tasks in these subjects can be performed with less reliance on verbal processing. Many children

  7. Characterization of the sterol 14α-demethylases of Fusarium graminearum identifies a novel genus-specific CYP51 function.

    Science.gov (United States)

    Fan, Jieru; Urban, Martin; Parker, Josie E; Brewer, Helen C; Kelly, Steven L; Hammond-Kosack, Kim E; Fraaije, Bart A; Liu, Xili; Cools, Hans J

    2013-05-01

    CYP51 encodes the cytochrome P450 sterol 14α-demethylase, an enzyme essential for sterol biosynthesis and the target of azole fungicides. In Fusarium species, including pathogens of humans and plants, three CYP51 paralogues have been identified with one unique to the genus. Currently, the functions of these three genes and the rationale for their conservation within the genus Fusarium are unknown. Three Fusarium graminearum CYP51s (FgCYP51s) were heterologously expressed in Saccharomyces cerevisiae. Single and double FgCYP51 deletion mutants were generated and the functions of the FgCYP51s were characterized in vitro and in planta. FgCYP51A and FgCYP51B can complement yeast CYP51 function, whereas FgCYP51C cannot. FgCYP51A deletion increases the sensitivity of F. graminearum to the tested azoles. In ΔFgCYP51B and ΔFgCYP51BC mutants, ascospore formation is blocked, and eburicol and two additional 14-methylated sterols accumulate. FgCYP51C deletion reduces virulence on host wheat ears. FgCYP51B encodes the enzyme primarily responsible for sterol 14α-demethylation, and plays an essential role in ascospore formation. FgCYP51A encodes an additional sterol 14α-demethylase, induced on ergosterol depletion and responsible for the intrinsic variation in azole sensitivity. FgCYP51C does not encode a sterol 14α-demethylase, but is required for full virulence on host wheat ears. This is the first example of the functional diversification of a fungal CYP51. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  8. Species-specific considerations in using the fish embryo test as an alternative to identify endocrine disruption.

    Science.gov (United States)

    Schiller, Viktoria; Zhang, Xiaowei; Hecker, Markus; Schäfers, Christoph; Fischer, Rainer; Fenske, Martina

    2014-10-01

    A number of regulations have been implemented that aim to control the release of potentially adverse endocrine disrupters into the aquatic environment based on evidence from laboratory studies. Currently, such studies rely on testing approaches with adult fish because reliable alternatives have not been validated so far. Fish embryo tests have been proposed as such an alternative, and here we compared two species (medaka and zebrafish) to determine their suitability for the assessment of substances with estrogenic and anti-androgenic activity. Changes in gene expression (in here the phrase gene expression is used synonymously to gene transcription, although it is acknowledged that gene expression is additionally regulated, e.g., by translation and protein stability) patterns between the two species were compared in short term embryo exposure tests (medaka: 7-day post fertilization [dpf]; zebrafish: 48 and 96h post fertilization [hpf]) by using relative quantitative real-time RT-PCR. The tested genes were related to the hypothalamic-gonadal-axis and early steroidogenesis. Test chemicals included 17α-ethinylestradiol and flutamide as estrogenic and anti-androgenic reference compounds, respectively, as well as five additional substances with endocrine activities, namely bisphenol A, genistein, prochloraz, linuron and propanil. Estrogenic responses were comparable in 7-dpf medaka and 48/96-hpf zebrafish embryos and included transcriptional upregulation of aromatase b, vitellogenin 1 as well as steroidogenic genes, suggesting that both species reliably detected exposure to estrogenic compounds. However, anti-androgenic responses differed between the two species, with each species providing specific information concerning the mechanism of anti-androgenic disruption in fish embryos. Although small but significant changes in the expression of selected genes was observed in 48-hpf zebrafish embryos, exposure prolonged to 96hpf was necessary to obtain a response indicative

  9. Core subjects at the end of primary school: identifying and explaining relative strengths of children with specific language impairment (SLI).

    Science.gov (United States)

    Durkin, Kevin; Mok, Pearl L H; Conti-Ramsden, Gina

    2015-01-01

    In general, children with specific language impairment (SLI) tend to fall behind their typically developing (TD) peers in educational attainment. Less is known about how children with SLI fare in particular areas of the curriculum and what predicts their levels of performance. To compare the distributions of performance of children with SLI in three core school subjects (English, Mathematics and Science); to test the possibility that performance would vary across the core subjects; and to examine the extent to which language impairment predicts performance. This study was conducted in England and reports historical data on educational attainments. Teacher assessment and test scores of 176 eleven-year-old children with SLI were examined in the three core subjects and compared with known national norms. Possible predictors of performance were measured, including language ability at ages 7 and 11, educational placement type, and performance IQ. Children with SLI, compared with national norms, were found to be at a disadvantage in core school subjects. Nevertheless, some children attained the levels expected of TD peers. Performance was poorest in English; relative strengths were indicated in Science and, to a lesser extent, in Mathematics. Language skills were significant predictors of performance in all three core subjects. PIQ was the strongest predictor for Mathematics. For Science, both early language skills at 7 years and PIQ made significant contributions. Language impacts on the school performance of children with SLI, but differentially across subjects. English for these children is the most challenging of the core subjects, reflecting the high levels of language demand it incurs. Science is an area of relative strength and mathematics appears to be intermediate, arguably because some tasks in these subjects can be performed with less reliance on verbal processing. Many children with SLI do have the potential to reach or exceed educational targets that are set

  10. General Aspects and First Progress Report on a Frame of a Research on Specific Professional Knowledge of Chemistry Teachers Associated with the Notion of Chemical Nomenclature

    Directory of Open Access Journals (Sweden)

    Gerardo Andrés Perafán Echeverri

    2014-04-01

    Full Text Available Within the framework of research about professional teacher’s knowledge, our business is to identify and to characterize with case study method, a kind of specific professional teacher´s knowledge of Chemistry professorate, associated to the chemical nomenclature notion. This kind of research guides the sight to the teaching contents, but it postulates the teacher as an essential actor of that knowledge, rather than ignore of the other actors (didactic community, researchers, specialists, students, etc. our research realizes the specific construction that the teacher makes, beyond the «spontaneous epistemologies» category, between others, which seems to deny an academic and discipline character of the built knowledge by the teachers. First, we show a brief reference to the research program on professional teacher´s knowledge which frames in the development of research line about Specific Professional Teacher´s Knowledge associated with Particular Categories, which belongs to the research group «Por las Aulas Colombianas- INVAUCOL». After that, we show a short justification about the choice of the particular category: chemical nomenclature, as a studied object, besides the historical importance that it has to the professional teaching consolidation, recognizing the teacher´s specific contributions to discipline body construction of school knowledge. Finally, weset in consideration some general methodological criteria defined in this research, and we show too, some preliminary reflections derived from field work in thepresent state of the project.

  11. Neuropsychopharmacology and neurogenetic aspects of executive functioning: should reward gene polymorphisms constitute a diagnostic tool to identify individuals at risk for impaired judgment?

    Science.gov (United States)

    Bowirrat, Abdalla; Chen, Thomas J H; Oscar-Berman, Marlene; Madigan, Margaret; Chen, Amanda Lh; Bailey, John A; Braverman, Eric R; Kerner, Mallory; Giordano, John; Morse, Siobhan; Downs, B William; Waite, Roger L; Fornari, Frank; Armaly, Zaher; Blum, Kenneth

    2012-04-01

    Executive functions are processes that act in harmony to control behaviors necessary for maintaining focus and achieving outcomes. Executive dysfunction in neuropsychiatric disorders is attributed to structural or functional pathology of brain networks involving prefrontal cortex (PFC) and its connections with other brain regions. The PFC receives innervations from different neurons associated with a number of neurotransmitters, especially dopamine (DA). Here we review findings on the contribution of PFC DA to higher-order cognitive and emotional behaviors. We suggest that examination of multifactorial interactions of an individual's genetic history, along with environmental risk factors, can assist in the characterization of executive functioning for that individual. Based upon the results of genetic studies, we also propose genetic mapping as a probable diagnostic tool serving as a therapeutic adjunct for augmenting executive functioning capabilities. We conclude that preservation of the neurological underpinnings of executive functions requires the integrity of complex neural systems including the influence of specific genes and associated polymorphisms to provide adequate neurotransmission.

  12. Neuropsychopharmacology and Neurogenetic Aspects of Executive Functioning: Should Reward Gene Polymorphisms Constitute a Diagnostic Tool to Identify Individuals at Risk for Impaired Judgment?

    Science.gov (United States)

    Bowirrat, Abdalla; Chen, Thomas JH; Oscar-Berman, Marlene; Madigan, Margaret; Chen, Amanda LH; Bailey, John A.; Braverman, Eric R.; Kerner, Mallory; Giordano, John; Morse, Siohban; Downs, B. William; Waite, Roger L.; Fornari, Frank; Armaly, Zaher; Blum, Kenneth

    2013-01-01

    Executive functions are processes that act in harmony to control behaviors necessary for maintaining focus and achieving outcomes. Executive dysfunction in neuropsychiatric disorders is attributed to structural or functional pathology of brain networks involving prefrontal cortex (PFC) and its connections with other brain regions. The PFC receives innervations from different neurons associated with a number of neurotransmitters, especially dopamine (DA). Here we review findings on the contribution of PFC DA to higher-order cognitive and emotional behaviors. We suggest examination of multifactorial interactions of an individual’s genetic history, along with environmental risk factors, can assist in the characterization of executive functioning for that individual. Based upon the results of genetic studies we also propose genetic mapping as a probable diagnostic tool serving as a therapeutic adjunct for augmenting executive functioning capabilities. We conclude that preservation of the neurological underpinnings of executive functions requires the integrity of complex neural systems including the influence of specific genes and associated polymorphisms to provide adequate neurotransmission. PMID:22371275

  13. Identifying Conformational-Selection and Induced-Fit Aspects in the Binding-Induced Folding of PMI from Markov State Modeling of Atomistic Simulations.

    Science.gov (United States)

    Paul, Fabian; Noé, Frank; Weikl, Thomas R

    2018-03-27

    Unstructured proteins and peptides typically fold during binding to ligand proteins. A challenging problem is to identify the mechanism and kinetics of these binding-induced folding processes in experiments and atomistic simulations. In this Article, we present a detailed picture for the folding of the inhibitor peptide PMI into a helix during binding to the oncoprotein fragment 25-109 Mdm2 obtained from atomistic, explicit-water simulations and Markov state modeling. We find that binding-induced folding of PMI is highly parallel and can occur along a multitude of pathways. Some pathways are induced-fit-like with binding occurring prior to PMI helix formation, while other pathways are conformational-selection-like with binding after helix formation. On the majority of pathways, however, binding is intricately coupled to folding, without clear temporal ordering. A central feature of these pathways is PMI motion on the Mdm2 surface, along the binding groove of Mdm2 or over the rim of this groove. The native binding groove of Mdm2 thus appears as an asymmetric funnel for PMI binding. Overall, binding-induced folding of PMI does not fit into the classical picture of induced fit or conformational selection that implies a clear temporal ordering of binding and folding events. We argue that this holds in general for binding-induced folding processes because binding and folding events in these processes likely occur on similar time scales and do exhibit the time-scale separation required for temporal ordering.

  14. Sparse feature selection identifies H2A.Z as a novel, pattern-specific biomarker for asymmetrically self-renewing distributed stem cells

    Directory of Open Access Journals (Sweden)

    Yang Hoon Huh

    2015-03-01

    Full Text Available There is a long-standing unmet clinical need for biomarkers with high specificity for distributed stem cells (DSCs in tissues, or for use in diagnostic and therapeutic cell preparations (e.g., bone marrow. Although DSCs are essential for tissue maintenance and repair, accurate determination of their numbers for medical applications has been problematic. Previous searches for biomarkers expressed specifically in DSCs were hampered by difficulty obtaining pure DSCs and by the challenges in mining complex molecular expression data. To identify such useful and specific DSC biomarkers, we combined a novel sparse feature selection method with combinatorial molecular expression data focused on asymmetric self-renewal, a conspicuous property of DSCs. The analysis identified reduced expression of the histone H2A variant H2A.Z as a superior molecular discriminator for DSC asymmetric self-renewal. Subsequent molecular expression studies showed H2A.Z to be a novel “pattern-specific biomarker” for asymmetrically self-renewing cells, with sufficient specificity to count asymmetrically self-renewing DSCs in vitro and potentially in situ.

  15. Geriatric-specific triage criteria are more sensitive than standard adult criteria in identifying need for trauma center care in injured older adults.

    Science.gov (United States)

    Ichwan, Brian; Darbha, Subrahmanyam; Shah, Manish N; Thompson, Laura; Evans, David C; Boulger, Creagh T; Caterino, Jeffrey M

    2015-01-01

    We evaluate the sensitivity of Ohio's 2009 emergency medical services (EMS) geriatric trauma triage criteria compared with the previous adult triage criteria in identifying need for trauma center care among older adults. We studied a retrospective cohort of injured patients aged 16 years or older in the 2006 to 2011 Ohio Trauma Registry. Patients aged 70 years or older were considered geriatric. We identified whether each patient met the geriatric and the adult triage criteria. The outcome measure was need for trauma center care, defined by surrogate markers: Injury Severity Score greater than 15, operating room in fewer than 48 hours, any ICU stay, and inhospital mortality. We calculated sensitivity and specificity of both triage criteria for both age groups. We included 101,577 patients; 33,379 (33%) were geriatric. Overall, 57% of patients met adult criteria and 68% met geriatric criteria. Using Injury Severity Score, for older adults geriatric criteria were more sensitive for need for trauma center care (93%; 95% confidence interval [CI] 92% to 93%) than adult criteria (61%; 95% CI 60% to 62%). Geriatric criteria decreased specificity in older adults from 61% (95% CI 61% to 62%) to 49% (95% CI 48% to 49%). Geriatric criteria in older adults (93% sensitivity, 49% specificity) performed similarly to the adult criteria in younger adults (sensitivity 87% and specificity 44%). Similar patterns were observed for other outcomes. Standard adult EMS triage guidelines provide poor sensitivity in older adults. Ohio's geriatric trauma triage guidelines significantly improve sensitivity in identifying Injury Severity Score and other surrogate markers of the need for trauma center care, with modest decreases in specificity for older adults. Copyright © 2014 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  16. Women-specific HIV/AIDS services: identifying and defining the components of holistic service delivery for women living with HIV/AIDS.

    Science.gov (United States)

    Carter, Allison J; Bourgeois, Sonya; O'Brien, Nadia; Abelsohn, Kira; Tharao, Wangari; Greene, Saara; Margolese, Shari; Kaida, Angela; Sanchez, Margarite; Palmer, Alexis K; Cescon, Angela; de Pokomandy, Alexandra; Loutfy, Mona R

    2013-01-11

    The increasing proportion of women living with HIV has evoked calls for tailored services that respond to women's specific needs. The objective of this investigation was to explore the concept of women-specific HIV/AIDS services to identify and define what key elements underlie this approach to care. A comprehensive review was conducted using online databases (CSA Social Service Abstracts, OvidSP, Proquest, Psycinfo, PubMed, CINAHL), augmented with a search for grey literature. In total, 84 articles were retrieved and 30 were included for a full review. Of these 30, 15 were specific to HIV/AIDS, 11 for mental health and addictions and four stemmed from other disciplines. The review demonstrated the absence of a consensual definition of women-specific HIV/AIDS services in the literature. We distilled this concept into its defining features and 12 additional dimensions (1) creating an atmosphere of safety, respect and acceptance; (2) facilitating communication and interaction among peers; (3) involving women in the planning, delivery and evaluation of services; (4) providing self-determination opportunities; (5) providing tailored programming for women; (6) facilitating meaningful access to care through the provision of social and supportive services; (7) facilitating access to women-specific and culturally sensitive information; (8) considering family as the unit of intervention; (9) providing multidisciplinary integration and coordination of a comprehensive array of services; (10) meeting women "where they are"; (11) providing gender-, culture- and HIV-sensitive training to health and social care providers; and (12) conducting gendered HIV/AIDS research. This review highlights that the concept of women-specific HIV/AIDS services is a complex and multidimensional one that has been shaped by diverse theoretical perspectives. Further research is needed to better understand this emerging concept and ultimately assess the effectiveness of women-specific services on HIV

  17. Women-specific HIV/AIDS services: identifying and defining the components of holistic service delivery for women living with HIV/AIDS

    Science.gov (United States)

    Carter, Allison J; Bourgeois, Sonya; O'Brien, Nadia; Abelsohn, Kira; Tharao, Wangari; Greene, Saara; Margolese, Shari; Kaida, Angela; Sanchez, Margarite; Palmer, Alexis K; Cescon, Angela; de Pokomandy, Alexandra; Loutfy, Mona R

    2013-01-01

    Introduction The increasing proportion of women living with HIV has evoked calls for tailored services that respond to women's specific needs. The objective of this investigation was to explore the concept of women-specific HIV/AIDS services to identify and define what key elements underlie this approach to care. Methods A comprehensive review was conducted using online databases (CSA Social Service Abstracts, OvidSP, Proquest, Psycinfo, PubMed, CINAHL), augmented with a search for grey literature. In total, 84 articles were retrieved and 30 were included for a full review. Of these 30, 15 were specific to HIV/AIDS, 11 for mental health and addictions and four stemmed from other disciplines. Results and discussion The review demonstrated the absence of a consensual definition of women-specific HIV/AIDS services in the literature. We distilled this concept into its defining features and 12 additional dimensions (1) creating an atmosphere of safety, respect and acceptance; (2) facilitating communication and interaction among peers; (3) involving women in the planning, delivery and evaluation of services; (4) providing self-determination opportunities; (5) providing tailored programming for women; (6) facilitating meaningful access to care through the provision of social and supportive services; (7) facilitating access to women-specific and culturally sensitive information; (8) considering family as the unit of intervention; (9) providing multidisciplinary integration and coordination of a comprehensive array of services; (10) meeting women “where they are”; (11) providing gender-, culture- and HIV-sensitive training to health and social care providers; and (12) conducting gendered HIV/AIDS research. Conclusions This review highlights that the concept of women-specific HIV/AIDS services is a complex and multidimensional one that has been shaped by diverse theoretical perspectives. Further research is needed to better understand this emerging concept and ultimately

  18. Using c-Jun to identify fear extinction learning-specific patterns of neural activity that are affected by single prolonged stress.

    Science.gov (United States)

    Knox, Dayan; Stanfield, Briana R; Staib, Jennifer M; David, Nina P; DePietro, Thomas; Chamness, Marisa; Schneider, Elizabeth K; Keller, Samantha M; Lawless, Caroline

    2018-04-02

    Neural circuits via which stress leads to disruptions in fear extinction is often explored in animal stress models. Using the single prolonged stress (SPS) model of post traumatic stress disorder and the immediate early gene (IEG) c-Fos as a measure of neural activity, we previously identified patterns of neural activity through which SPS disrupts extinction retention. However, none of these stress effects were specific to fear or extinction learning and memory. C-Jun is another IEG that is sometimes regulated in a different manner to c-Fos and could be used to identify emotional learning/memory specific patterns of neural activity that are sensitive to SPS. Animals were either fear conditioned (CS-fear) or presented with CSs only (CS-only) then subjected to extinction training and testing. C-Jun was then assayed within neural substrates critical for extinction memory. Inhibited c-Jun levels in the hippocampus (Hipp) and enhanced functional connectivity between the ventromedial prefrontal cortex (vmPFC) and basolateral amygdala (BLA) during extinction training was disrupted by SPS in the CS-fear group only. As a result, these effects were specific to emotional learning/memory. SPS also disrupted inhibited Hipp c-Jun levels, enhanced BLA c-Jun levels, and altered functional connectivity among the vmPFC, BLA, and Hipp during extinction testing in SPS rats in the CS-fear and CS-only groups. As a result, these effects were not specific to emotional learning/memory. Our findings suggest that SPS disrupts neural activity specific to extinction memory, but may also disrupt the retention of fear extinction by mechanisms that do not involve emotional learning/memory. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. LC-QTOF-MS identification of porcine-specific peptide in heat treated pork identifies candidate markers for meat species determination.

    Science.gov (United States)

    Sarah, S A; Faradalila, W N; Salwani, M S; Amin, I; Karsani, S A; Sazili, A Q

    2016-05-15

    The purpose of this study was to identify porcine-specific peptide markers from thermally processed meat that could differentiate pork from beef, chevon and chicken meat. In the initial stage, markers from tryptic digested protein of chilled, boiled and autoclaved pork were identified using LC-QTOF-MS. An MRM method was then established for verification. A thorough investigation of LC-QTOF-MS data showed that only seven porcine-specific peptides were consistently detected. Among these peptides, two were derived from lactate dehydrogenase, one from creatine kinase, and four from serum albumin protein. However, MRM could only detect four peptides (EVTEFAK, LVVITAGAR, FVIER and TVLGNFAAFVQK) that were consistently present in pork samples. In conclusion, meat species determination through a tandem mass spectrometry platform shows high potential in providing scientifically valid and reliable results even at peptide level. Besides, the specificity and selectivity offered by the proteomics approach also provide a robust platform for Halal authentication. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Prognostic factors for specific lower extremity and spinal musculoskeletal injuries identified through medical screening and training load monitoring in professional football (soccer): a systematic review

    Science.gov (United States)

    Sergeant, Jamie C; Parkes, Matthew J; Callaghan, Michael J

    2017-01-01

    Background Medical screening and load monitoring procedures are commonly used in professional football to assess factors perceived to be associated with injury. Objectives To identify prognostic factors (PFs) and models for lower extremity and spinal musculoskeletal injuries in professional/elite football players from medical screening and training load monitoring processes. Methods The MEDLINE, AMED, EMBASE, CINAHL Plus, SPORTDiscus and PubMed electronic bibliographic databases were searched (from inception to January 2017). Prospective and retrospective cohort studies of lower extremity and spinal musculoskeletal injury incidence in professional/elite football players aged between 16 and 40 years were included. The Quality in Prognostic Studies appraisal tool and the modified Grading of Recommendations Assessment, Development and Evaluation synthesis approach was used to assess the quality of the evidence. Results Fourteen studies were included. 16 specific lower extremity injury outcomes were identified. No spinal injury outcomes were identified. Meta-analysis was not possible due to heterogeneity and study quality. All evidence related to PFs and specific lower extremity injury outcomes was of very low to low quality. On the few occasions where multiple studies could be used to compare PFs and outcomes, only two factors demonstrated consensus. A history of previous hamstring injuries (HSI) and increasing age may be prognostic for future HSI in male players. Conclusions The assumed ability of medical screening tests to predict specific musculoskeletal injuries is not supported by the current evidence. Screening procedures should currently be considered as benchmarks of function or performance only. The prognostic value of load monitoring modalities is unknown. PMID:29177074

  1. The Outwardly Rectifying Current of Layer 5 Neocortical Neurons that was Originally Identified as "Non-Specific Cationic" Is Essentially a Potassium Current.

    Directory of Open Access Journals (Sweden)

    Omer Revah

    Full Text Available In whole-cell patch clamp recordings from layer 5 neocortical neurons, blockade of voltage gated sodium and calcium channels leaves a cesium current that is outward rectifying. This current was originally identified as a "non-specific cationic current", and subsequently it was hypothesized that it is mediated by TRP channels. In order to test this hypothesis, we used fluorescence imaging of intracellular sodium and calcium indicators, and found no evidence to suggest that it is associated with influx of either of these ions to the cell body or dendrites. Moreover, the current is still prominent in neurons from TRPC1-/- and TRPC5-/- mice. The effects on the current of various blocking agents, and especially its sensitivity to intracellular tetraethylammonium, suggest that it is not a non-specific cationic current, but rather that it is generated by cesium-permeable delayed rectifier potassium channels.

  2. Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

    DEFF Research Database (Denmark)

    Jones, Gregory T; Tromp, Gerard; Kuivaniemi, Helena

    2017-01-01

    studies (GWAS). Through a meta-analysis of 6 GWAS datasets and a validation study totalling 10,204 cases and 107,766 controls we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches we observed no new...... associations between the lead AAA SNPs and coronary artery disease, blood pressure, lipids or diabetes. Network analyses identified ERG, IL6R and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. The 4 new risk loci for AAA appear to be specific for AAA compared with other...

  3. Discussion about the use of the volume-specific surface area (VSSA) as criteria to identify nanomaterials according to the EU definition

    International Nuclear Information System (INIS)

    Lecloux, André J.

    2015-01-01

    In the EU regulation, a material containing particles is considered as nano if, for 50 % or more of the particles in the number size distribution, one or more external dimensions is in the size range 1–100 nm. Due to the difficulty to measure in a reliable way the number particle size distribution, it is suggested to use the volume-specific surface area (VSSA) >60 m 2 /cm 3 as simple screening criterion to identify nanomaterials. This threshold corresponds to monodispersed spherical particles with a size of 100 nm. In this paper, a theoretical study is carried out to identify the effect of the particle shape, polydispersity, agglomeration and aggregation on the VSSA threshold. It appears that the VSSA approach is overprotective because a lot of samples are identified as nanomaterials even if less than 50 % of the particles have a size lower than 100 nm, this 50 % in number criterion being the main identification criterion in the EU definition. Even if the VSSA is leading to many false positive results, it can be used to identify non-nanomaterials as soon as its value is lower than the threshold at the condition to take into account the shape of the particles and their external surface area. This conclusion is true for monomodal distributions of particles but is subject to some restrictions for bimodal distributions

  4. Discussion about the use of the volume-specific surface area (VSSA) as criteria to identify nanomaterials according to the EU definition

    Energy Technology Data Exchange (ETDEWEB)

    Lecloux, André J., E-mail: alecloux@nanocyl.com, E-mail: envicat@skynet.be [ENVICAT Consulting (Belgium)

    2015-11-15

    In the EU regulation, a material containing particles is considered as nano if, for 50 % or more of the particles in the number size distribution, one or more external dimensions is in the size range 1–100 nm. Due to the difficulty to measure in a reliable way the number particle size distribution, it is suggested to use the volume-specific surface area (VSSA) >60 m{sup 2}/cm{sup 3} as simple screening criterion to identify nanomaterials. This threshold corresponds to monodispersed spherical particles with a size of 100 nm. In this paper, a theoretical study is carried out to identify the effect of the particle shape, polydispersity, agglomeration and aggregation on the VSSA threshold. It appears that the VSSA approach is overprotective because a lot of samples are identified as nanomaterials even if less than 50 % of the particles have a size lower than 100 nm, this 50 % in number criterion being the main identification criterion in the EU definition. Even if the VSSA is leading to many false positive results, it can be used to identify non-nanomaterials as soon as its value is lower than the threshold at the condition to take into account the shape of the particles and their external surface area. This conclusion is true for monomodal distributions of particles but is subject to some restrictions for bimodal distributions.

  5. Trans-ethnic fine-mapping of lipid loci identifies population-specific signals and allelic heterogeneity that increases the trait variance explained.

    Directory of Open Access Journals (Sweden)

    Ying Wu

    2013-03-01

    Full Text Available Genome-wide association studies (GWAS have identified ~100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG, high-density lipoprotein cholesterol (HDL-C, and low-density lipoprotein cholesterol (LDL-C, respectively, in individuals of African American (n = 6,832, East Asian (n = 9,449, and European (n = 10,829 ancestry. We aimed to identify the variants with strongest association at each locus, identify additional and population-specific signals, refine association signals, and assess the relative significance of previously described functional variants. Among the 58 loci, 33 exhibited evidence of association at P<1 × 10(-4 in at least one ancestry group. Sequential conditional analyses revealed that ten, nine, and four loci in African Americans, Europeans, and East Asians, respectively, exhibited two or more signals. At these loci, accounting for all signals led to a 1.3- to 1.8-fold increase in the explained phenotypic variance compared to the strongest signals. Distinct signals across ancestry groups were identified at PCSK9 and APOA5. Trans-ethnic analyses narrowed the signals to smaller sets of variants at GCKR, PPP1R3B, ABO, LCAT, and ABCA1. Of 27 variants reported previously to have functional effects, 74% exhibited the strongest association at the respective signal. In conclusion, trans-ethnic high-density genotyping and analysis confirm the presence of allelic heterogeneity, allow the identification of population-specific variants, and limit the number of candidate SNPs for functional studies.

  6. Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs

    Directory of Open Access Journals (Sweden)

    Chan Zhou

    2017-08-01

    Full Text Available N6-methyladenosine (m6A is the most abundant internal modification of mRNAs and is implicated in all aspects of post-transcriptional RNA metabolism. However, little is known about m6A modifications to circular (circ RNAs. We developed a computational pipeline (AutoCirc that, together with depletion of ribosomal RNA and m6A immunoprecipitation, defined thousands of m6A circRNAs with cell-type-specific expression. The presence of m6A circRNAs is corroborated by interaction between circRNAs and YTHDF1/YTHDF2, proteins that read m6A sites in mRNAs, and by reduced m6A levels upon depletion of METTL3, the m6A writer. Despite sharing m6A readers and writers, m6A circRNAs are frequently derived from exons that are not methylated in mRNAs, whereas mRNAs that are methylated on the same exons that compose m6A circRNAs exhibit less stability in a process regulated by YTHDF2. These results expand our understanding of the breadth of m6A modifications and uncover regulation of circRNAs through m6A modification.

  7. Innovation and rational use of energy: general problems and specific aspects in the brick production sector. L'innovazione e l'uso razionale dell'energia: problematiche generali e aspetti specifici del settore dei laterizi

    Energy Technology Data Exchange (ETDEWEB)

    Tomassetti, M

    1988-03-01

    Innovation in the traditional sectors is a very complex phenomena: technological, scientific, social and managerial aspects are involved. The report considers the evaluation of traditional Italian research and the opportunity for synergy between innovation and energy saving. The specific situation of the brick production sector is analized and prospectives given for more efficient production and factory innovation.

  8. Genome-wide analysis of the CCCH zinc finger family identifies tissue specific and stress responsive candidates in chickpea (Cicer arietinum L.).

    Science.gov (United States)

    Pradhan, Seema; Kant, Chandra; Verma, Subodh; Bhatia, Sabhyata

    2017-01-01

    The CCCH zinc finger is a group of proteins characterised by a typical motif consisting of three cysteine residues and one histidine residue. These proteins have been reported to play important roles in regulation of plant growth, developmental processes and environmental responses. In the present study, genome wide analysis of the CCCH zinc finger gene family was carried out in the available chickpea genome. Various bioinformatics tools were employed to predict 58 CCCH zinc finger genes in chickpea (designated CarC3H1-58), which were analysed for their physio-chemical properties. Phylogenetic analysis classified the proteins into 12 groups in which members of a particular group had similar structural organization. Further, the numbers as well as the types of CCCH motifs present in the CarC3H proteins were compared with those from Arabidopsis and Medicago truncatula. Synteny analysis revealed valuable information regarding the evolution of this gene family. Tandem and segmental duplication events were identified and their Ka/Ks values revealed that the CarC3H gene family in chickpea had undergone purifying selection. Digital, as well as real time qRT-PCR expression analysis was performed which helped in identification of several CarC3H members that expressed preferentially in specific chickpea tissues as well as during abiotic stresses (desiccation, cold, salinity). Moreover, molecular characterization of an important member CarC3H45 was carried out. This study provides comprehensive genomic information about the important CCCH zinc finger gene family in chickpea. The identified tissue specific and abiotic stress specific CCCH genes could be potential candidates for further characterization to delineate their functional roles in development and stress.

  9. A screen for kinase inhibitors identifies antimicrobial imidazopyridine aminofurazans as specific inhibitors of the Listeria monocytogenes PASTA kinase PrkA.

    Science.gov (United States)

    Schaenzer, Adam J; Wlodarchak, Nathan; Drewry, David H; Zuercher, William J; Rose, Warren E; Striker, Rob; Sauer, John-Demian

    2017-10-13

    Bacterial signaling systems such as protein kinases and quorum sensing have become increasingly attractive targets for the development of novel antimicrobial agents in a time of rising antibiotic resistance. The family of bacterial P enicillin-binding-protein A nd S erine/ T hreonine kinase- A ssociated (PASTA) kinases is of particular interest due to the role of these kinases in regulating resistance to β-lactam antibiotics. As such, small-molecule kinase inhibitors that target PASTA kinases may prove beneficial as treatments adjunctive to β-lactam therapy. Despite this interest, only limited progress has been made in identifying functional inhibitors of the PASTA kinases that have both activity against the intact microbe and high kinase specificity. Here, we report the results of a small-molecule screen that identified GSK690693, an imidazopyridine aminofurazan-type kinase inhibitor that increases the sensitivity of the intracellular pathogen Listeria monocytogenes to various β-lactams by inhibiting the PASTA kinase PrkA. GSK690693 potently inhibited PrkA kinase activity biochemically and exhibited significant selectivity for PrkA relative to the Staphylococcus aureus PASTA kinase Stk1. Furthermore, other imidazopyridine aminofurazans could effectively inhibit PrkA and potentiate β-lactam antibiotic activity to varying degrees. The presence of the 2-methyl-3-butyn-2-ol (alkynol) moiety was important for both biochemical and antimicrobial activity. Finally, mutagenesis studies demonstrated residues in the back pocket of the active site are important for GSK690693 selectivity. These data suggest that targeted screens can successfully identify PASTA kinase inhibitors with both biochemical and antimicrobial specificity. Moreover, the imidazopyridine aminofurazans represent a family of PASTA kinase inhibitors that have the potential to be optimized for selective PASTA kinase inhibition.

  10. Constructing disease-specific gene networks using pair-wise relevance metric: Application to colon cancer identifies interleukin 8, desmin and enolase 1 as the central elements

    Directory of Open Access Journals (Sweden)

    Jiang Wei

    2008-08-01

    Full Text Available Abstract Background With the advance of large-scale omics technologies, it is now feasible to reversely engineer the underlying genetic networks that describe the complex interplays of molecular elements that lead to complex diseases. Current networking approaches are mainly focusing on building genetic networks at large without probing the interaction mechanisms specific to a physiological or disease condition. The aim of this study was thus to develop such a novel networking approach based on the relevance concept, which is ideal to reveal integrative effects of multiple genes in the underlying genetic circuit for complex diseases. Results The approach started with identification of multiple disease pathways, called a gene forest, in which the genes extracted from the decision forest constructed by supervised learning of the genome-wide transcriptional profiles for patients and normal samples. Based on the newly identified disease mechanisms, a novel pair-wise relevance metric, adjusted frequency value, was used to define the degree of genetic relationship between two molecular determinants. We applied the proposed method to analyze a publicly available microarray dataset for colon cancer. The results demonstrated that the colon cancer-specific gene network captured the most important genetic interactions in several cellular processes, such as proliferation, apoptosis, differentiation, mitogenesis and immunity, which are known to be pivotal for tumourigenesis. Further analysis of the topological architecture of the network identified three known hub cancer genes [interleukin 8 (IL8 (p ≈ 0, desmin (DES (p = 2.71 × 10-6 and enolase 1 (ENO1 (p = 4.19 × 10-5], while two novel hub genes [RNA binding motif protein 9 (RBM9 (p = 1.50 × 10-4 and ribosomal protein L30 (RPL30 (p = 1.50 × 10-4] may define new central elements in the gene network specific to colon cancer. Gene Ontology (GO based analysis of the colon cancer-specific gene network and

  11. Constructing disease-specific gene networks using pair-wise relevance metric: application to colon cancer identifies interleukin 8, desmin and enolase 1 as the central elements.

    Science.gov (United States)

    Jiang, Wei; Li, Xia; Rao, Shaoqi; Wang, Lihong; Du, Lei; Li, Chuanxing; Wu, Chao; Wang, Hongzhi; Wang, Yadong; Yang, Baofeng

    2008-08-10

    With the advance of large-scale omics technologies, it is now feasible to reversely engineer the underlying genetic networks that describe the complex interplays of molecular elements that lead to complex diseases. Current networking approaches are mainly focusing on building genetic networks at large without probing the interaction mechanisms specific to a physiological or disease condition. The aim of this study was thus to develop such a novel networking approach based on the relevance concept, which is ideal to reveal integrative effects of multiple genes in the underlying genetic circuit for complex diseases. The approach started with identification of multiple disease pathways, called a gene forest, in which the genes extracted from the decision forest constructed by supervised learning of the genome-wide transcriptional profiles for patients and normal samples. Based on the newly identified disease mechanisms, a novel pair-wise relevance metric, adjusted frequency value, was used to define the degree of genetic relationship between two molecular determinants. We applied the proposed method to analyze a publicly available microarray dataset for colon cancer. The results demonstrated that the colon cancer-specific gene network captured the most important genetic interactions in several cellular processes, such as proliferation, apoptosis, differentiation, mitogenesis and immunity, which are known to be pivotal for tumourigenesis. Further analysis of the topological architecture of the network identified three known hub cancer genes [interleukin 8 (IL8) (p approximately 0), desmin (DES) (p = 2.71 x 10(-6)) and enolase 1 (ENO1) (p = 4.19 x 10(-5))], while two novel hub genes [RNA binding motif protein 9 (RBM9) (p = 1.50 x 10(-4)) and ribosomal protein L30 (RPL30) (p = 1.50 x 10(-4))] may define new central elements in the gene network specific to colon cancer. Gene Ontology (GO) based analysis of the colon cancer-specific gene network and the sub-network that

  12. Enzyme-labeled Antigen Method: Development and Application of the Novel Approach for Identifying Plasma Cells Locally Producing Disease-specific Antibodies in Inflammatory Lesions

    International Nuclear Information System (INIS)

    Mizutani, Yasuyoshi; Shiogama, Kazuya; Onouchi, Takanori; Sakurai, Kouhei; Inada, Ken-ichi; Tsutsumi, Yutaka

    2016-01-01

    In chronic inflammatory lesions of autoimmune and infectious diseases, plasma cells are frequently observed. Antigens recognized by antibodies produced by the plasma cells mostly remain unclear. A new technique identifying these corresponding antigens may give us a breakthrough for understanding the disease from a pathophysiological viewpoint, simply because the immunocytes are seen within the lesion. We have developed an enzyme-labeled antigen method for microscopic identification of the antigen recognized by specific antibodies locally produced in plasma cells in inflammatory lesions. Firstly, target biotinylated antigens were constructed by the wheat germ cell-free protein synthesis system or through chemical biotinylation. Next, proteins reactive to antibodies in tissue extracts were screened and antibody titers were evaluated by the AlphaScreen method. Finally, with the enzyme-labeled antigen method using the biotinylated antigens as probes, plasma cells producing specific antibodies were microscopically localized in fixed frozen sections. Our novel approach visualized tissue plasma cells that produced 1) autoantibodies in rheumatoid arthritis, 2) antibodies against major antigens of Porphyromonas gingivalis in periodontitis or radicular cyst, and 3) antibodies against a carbohydrate antigen, Strep A, of Streptococcus pyogenes in recurrent tonsillitis. Evaluation of local specific antibody responses expectedly contributes to clarifying previously unknown processes in inflammatory disorders

  13. Weighted gene co-expression network analysis of expression data of monozygotic twins identifies specific modules and hub genes related to BMI.

    Science.gov (United States)

    Wang, Weijing; Jiang, Wenjie; Hou, Lin; Duan, Haiping; Wu, Yili; Xu, Chunsheng; Tan, Qihua; Li, Shuxia; Zhang, Dongfeng

    2017-11-13

    The therapeutic management of obesity is challenging, hence further elucidating the underlying mechanisms of obesity development and identifying new diagnostic biomarkers and therapeutic targets are urgent and necessary. Here, we performed differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) to identify significant genes and specific modules related to BMI based on gene expression profile data of 7 discordant monozygotic twins. In the differential gene expression analysis, it appeared that 32 differentially expressed genes (DEGs) were with a trend of up-regulation in twins with higher BMI when compared to their siblings. Categories of positive regulation of nitric-oxide synthase biosynthetic process, positive regulation of NF-kappa B import into nucleus, and peroxidase activity were significantly enriched within GO database and NF-kappa B signaling pathway within KEGG database. DEGs of NAMPT, TLR9, PTGS2, HBD, and PCSK1N might be associated with obesity. In the WGCNA, among the total 20 distinct co-expression modules identified, coral1 module (68 genes) had the strongest positive correlation with BMI (r = 0.56, P = 0.04) and disease status (r = 0.56, P = 0.04). Categories of positive regulation of phospholipase activity, high-density lipoprotein particle clearance, chylomicron remnant clearance, reverse cholesterol transport, intermediate-density lipoprotein particle, chylomicron, low-density lipoprotein particle, very-low-density lipoprotein particle, voltage-gated potassium channel complex, cholesterol transporter activity, and neuropeptide hormone activity were significantly enriched within GO database for this module. And alcoholism and cell adhesion molecules pathways were significantly enriched within KEGG database. Several hub genes, such as GAL, ASB9, NPPB, TBX2, IL17C, APOE, ABCG4, and APOC2 were also identified. The module eigengene of saddlebrown module (212 genes) was also significantly

  14. Increasing organizational energy conservation behaviors: Comparing the theory of planned behavior and reasons theory for identifying specific motivational factors to target for change

    Science.gov (United States)

    Finlinson, Scott Michael

    Social scientists frequently assess factors thought to underlie behavior for the purpose of designing behavioral change interventions. Researchers commonly identify these factors by examining relationships between specific variables and the focal behaviors being investigated. Variables with the strongest relationships to the focal behavior are then assumed to be the most influential determinants of that behavior, and therefore often become the targets for change in a behavioral change intervention. In the current proposal, multiple methods are used to compare the effectiveness of two theoretical frameworks for identifying influential motivational factors. Assessing the relative influence of all factors and sets of factors for driving behavior should clarify which framework and methodology is the most promising for identifying effective change targets. Results indicated each methodology adequately predicted the three focal behaviors examined. However, the reasons theory approach was superior for predicting factor influence ratings compared to the TpB approach. While common method variance contamination had minimal impact on the results or conclusions derived from the present study's findings, there were substantial differences in conclusions depending on the questionnaire design used to collect the data. Examples of applied uses of the present study are discussed.

  15. Systemic approaches identify a garlic-derived chemical, Z-ajoene, as a glioblastoma multiforme cancer stem cell-specific targeting agent.

    Science.gov (United States)

    Jung, Yuchae; Park, Heejoo; Zhao, Hui-Yuan; Jeon, Raok; Ryu, Jae-Ha; Kim, Woo-Young

    2014-07-01

    Glioblastoma multiforme (GBM) is one of the most common brain malignancies and has a very poor prognosis. Recent evidence suggests that the presence of cancer stem cells (CSC) in GBM and the rare CSC subpopulation that is resistant to chemotherapy may be responsible for the treatment failure and unfavorable prognosis of GBM. A garlic-derived compound, Z-ajoene, has shown a range of biological activities, including anti-proliferative effects on several cancers. Here, we demonstrated for the first time that Z-ajoene specifically inhibits the growth of the GBM CSC population. CSC sphere-forming inhibition was achieved at a concentration that did not exhibit a cytotoxic effect in regular cell culture conditions. The specificity of this inhibitory effect on the CSC population was confirmed by detecting CSC cell surface marker CD133 expression and biochemical marker ALDH activity. In addition, stem cell-related mRNA profiling and real-time PCR revealed the differential expression of CSC-specific genes, including Notch, Wnt, and Hedgehog, upon treatment with Z-ajoene. A proteomic approach, i.e., reverse-phase protein array (RPPA) and Western blot analysis, showed decreased SMAD4, p-AKT, 14.3.3 and FOXO3A expression. The protein interaction map (http://string-db.org/) of the identified molecules suggested that the AKT, ERK/p38 and TGFβ signaling pathways are key mediators of Z-ajoene's action, which affects the transcriptional network that includes FOXO3A. These biological and bioinformatic analyses collectively demonstrate that Z-ajoene is a potential candidate for the treatment of GBM by specifically targeting GBM CSCs. We also show how this systemic approach strengthens the identification of new therapeutic agents that target CSCs.

  16. Identifying Patient-Specific Epstein-Barr Nuclear Antigen-1 Genetic Variation and Potential Autoreactive Targets Relevant to Multiple Sclerosis Pathogenesis.

    Directory of Open Access Journals (Sweden)

    Monika Tschochner

    Full Text Available Epstein-Barr virus (EBV infection represents a major environmental risk factor for multiple sclerosis (MS, with evidence of selective expansion of Epstein-Barr Nuclear Antigen-1 (EBNA1-specific CD4+ T cells that cross-recognize MS-associated myelin antigens in MS patients. HLA-DRB1*15-restricted antigen presentation also appears to determine susceptibility given its role as a dominant risk allele. In this study, we have utilised standard and next-generation sequencing techniques to investigate EBNA-1 sequence variation and its relationship to HLA-DR15 binding affinity, as well as examining potential cross-reactive immune targets within the central nervous system proteome.Sanger sequencing was performed on DNA isolated from peripheral blood samples from 73 Western Australian MS cases, without requirement for primary culture, with additional FLX 454 Roche sequencing in 23 samples to identify low-frequency variants. Patient-derived viral sequences were used to predict HLA-DRB1*1501 epitopes (NetMHCII, NetMHCIIpan and candidates were evaluated for cross recognition with human brain proteins.EBNA-1 sequence variation was limited, with no evidence of multiple viral strains and only low levels of variation identified by FLX technology (8.3% nucleotide positions at a 1% cut-off. In silico epitope mapping revealed two known HLA-DRB1*1501-restricted epitopes ('AEG': aa 481-496 and 'MVF': aa 562-577, and two putative epitopes between positions 502-543. We identified potential cross-reactive targets involving a number of major myelin antigens including experimentally confirmed HLA-DRB1*15-restricted epitopes as well as novel candidate antigens within myelin and paranodal assembly proteins that may be relevant to MS pathogenesis.This study demonstrates the feasibility of obtaining autologous EBNA-1 sequences directly from buffy coat samples, and confirms divergence of these sequences from standard laboratory strains. This approach has identified a number of

  17. From viral genome to specific peptide epitopes: methods for identifying porcine T cell epitopes based on in silico predictions, in vitro identification and ex vivo verification

    DEFF Research Database (Denmark)

    Pedersen, Lasse Eggers; Rasmussen, Michael; Harndah, Mikkel

    2013-01-01

    to predict likely candidates for peptide-SLA binding. These results were combined with binding predictions generated by the algorithm, NetMHCpan (http://www.cbs.dtu.dk/services/NetMHCpan/) in order to select peptide candidates for in vitro analysis. The correlation between high affinity and high stability.......000 peptides. T cell epitopes were identified using peptide-SLA complexes assembled into fluorescent tetramers to stain swine influenza specific CTLs derived from immunized animals and MHC-defined pigs vaccinated against foot-and-mouth disease virus. These results demonstrate the broad applicability of methods...... originally developed for analysis of human leukocyte antigen (HLA) presentation of peptides. The methods presented provide a timely and cost-effective approach to CTL epitope discovery that can be applied to diseases of swine and of other mammalian species of interest....

  18. The Interferon-signature of Sjögren’s Syndrome: How Unique Biomarkers Can Identify Underlying Inflammatory and Immunopathological Mechanisms of Specific Diseases

    Directory of Open Access Journals (Sweden)

    Cuong eNguyen

    2013-07-01

    Full Text Available Innate immune responses direct the nature and specificity of downstream adaptive responses in autoimmune diseases. One of the strongest markers of innate immunity is the up-regulated expression of interferon (IFN and IFN-responsive/stimulated genes (IRGs/ISGs. While multiple IRGs are induced during the innate phase of host responses, transcriptome data suggest unique IRG-signatures for different diseases. Sjögren’s syndrome (SjS is characterized by chronic immune attacks against exocrine glands leading to exocrine dysfunction, plus strong up-regulated expressions of IFN IRG transcripts. Genome-wide transcriptome analyses indicate that differentially-expressed IRGs are restricted during disease development and therefore define underlying etiopathological mechanisms. Here we review the innate immune-associated IFN-signature of SjS and show how differential gene expressions of IRG/ISG sets interact molecularly and biologically to identify critical details of SjS etiopathogenesis.

  19. Flash visual evoked potentials are not specific enough to identify parieto-occipital lobe involvement in term neonates after significant hypoglycaemia.

    Science.gov (United States)

    Hu, Liyuan; Gu, Qiufang; Zhu, Zhen; Yang, Chenhao; Chen, Chao; Cao, Yun; Zhou, Wenhao

    2014-08-01

    Hypoglycaemia is a significant problem in high-risk neonates and predominant parieto-occipital lobe involvement has been observed after severe hypoglycaemic insult. We explored the use of flash visual evoked potentials (FVEP) in detecting parieto-occipital lobe involvement after significant hypoglycaemia. Full-term neonates (n = 15) who underwent FVEP from January 2008 to May 2013 were compared with infants (n = 11) without hypoglycaemia or parietal-occipital lobe injury. Significant hypoglycaemia was defined as being symptomatic or needing steroids, glucagon or a glucose infusion rate of ≥12 mg/kg/min. The hypoglycaemia group exhibited delayed latency of the first positive waveform on FVEP. The initial detected time for hypoglycaemia was later in the eight subjects with seizures (median 51-h-old) than those without (median 22-h-old) (P = 0.003). Magnetic resonance imaging showed that 80% of the hypoglycaemia group exhibited occipital-lobe injuries, and they were more likely to exhibit abnormal FVEP morphology (P = 0.007) than the controls. FVEP exhibited 100% sensitivity, but only 25% specificity, for detecting injuries to the parieto-occipital lobes. Flash visual evoked potential (FVEP) was sensitive, but not sufficiently specific, in identifying parieto-occipital lobe injuries among term neonates exposed to significant hypoglycaemia. Larger studies exploring the potential role of FVEP in neonatal hypoglycaemia are required. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  20. A trans-ethnic genome-wide association study identifies gender-specific loci influencing pediatric aBMD and BMC at the distal radius.

    Science.gov (United States)

    Chesi, Alessandra; Mitchell, Jonathan A; Kalkwarf, Heidi J; Bradfield, Jonathan P; Lappe, Joan M; McCormack, Shana E; Gilsanz, Vicente; Oberfield, Sharon E; Hakonarson, Hakon; Shepherd, John A; Kelly, Andrea; Zemel, Babette S; Grant, Struan F A

    2015-09-01

    Childhood fractures are common, with the forearm being the most common site. Genome-wide association studies (GWAS) have identified more than 60 loci associated with bone mineral density (BMD) in adults but less is known about genetic influences specific to bone in childhood. To identify novel genetic factors that influence pediatric bone strength at a common site for childhood fractures, we performed a sex-stratified trans-ethnic genome-wide association study of areal BMD (aBMD) and bone mineral content (BMC) Z-scores measured by dual energy X-ray absorptiometry at the one-third distal radius, in a cohort of 1399 children without clinical abnormalities in bone health. We tested signals with P BMC-Z). Signals at the CPED1-WNT16-FAM3C locus have been previously associated with BMD at other skeletal sites in adults and children. Our result at the distal radius underscores the importance of this locus at multiple skeletal sites. The 9p21.3 locus is within a gene desert, with the nearest gene flanking each side being MIR31HG and MTAP, neither of which has been implicated in BMD or BMC previously. These findings suggest that genetic determinants of childhood bone accretion at the radius, a skeletal site that is primarily cortical bone, exist and also differ by sex. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. ERIC-PCR fingerprinting-based community DNA hybridization to pinpoint genome-specific fragments as molecular markers to identify and track populations common to healthy human guts.

    Science.gov (United States)

    Wei, Guifang; Pan, Li; Du, Huimin; Chen, Junyi; Zhao, Liping

    2004-10-01

    Bacterial populations common to healthy human guts may play important roles in human health. A new strategy for discovering genomic sequences as markers for these bacteria was developed using Enterobacterial Repetitive Intergenic Consensus (ERIC)-PCR fingerprinting. Structural features within microbial communities are compared with ERIC-PCR followed by DNA hybridization to identify genomic fragments shared by samples from healthy human individuals. ERIC-PCR profiles of fecal samples from 12 diseased or healthy human and piglet subjects demonstrated stable, unique banding patterns for each individual tested. Sequence homology of DNA fragments in bands of identical size was examined between samples by hybridization under high stringency conditions with DIG-labeled ERIC-PCR products derived from the fecal sample of one healthy child. Comparative analysis of the hybridization profiles with the original agarose fingerprints identified three predominant bands as signatures for populations associated with healthy human guts with sizes of 500, 800 and 1000 bp. Clone library profiling of the three bands produced 17 genome fragments, three of which showed high similarity only with regions of the Bacteroides thetaiotaomicron genome, while the remainder were orphan sequences. Association of these sequences with healthy guts was validated by sequence-selective PCR experiments, which showed that a single fragment was present in all 32 healthy humans and 13 healthy piglets tested. Two fragments were present in the healthy human group and in 18 children with non-infectious diarrhea but not in eight children with infectious diarrhea. Genome fragments identified with this novel strategy may be used as genome-specific markers for dynamic monitoring and sequence-guided isolation of functionally important bacterial populations in complex communities such as human gut microflora.

  2. Genome-Wide Association Study Identifies Two Novel Loci with Sex-Specific Effects for Type 2 Diabetes Mellitus and Glycemic Traits in a Korean Population

    Directory of Open Access Journals (Sweden)

    Min Jin Go

    2014-10-01

    Full Text Available BackgroundUntil recently, genome-wide association study (GWAS-based findings have provided a substantial genetic contribution to type 2 diabetes mellitus (T2DM or related glycemic traits. However, identification of allelic heterogeneity and population-specific genetic variants under consideration of potential confounding factors will be very valuable for clinical applicability. To identify novel susceptibility loci for T2DM and glycemic traits, we performed a two-stage genetic association study in a Korean population.MethodsWe performed a logistic analysis for T2DM, and the first discovery GWAS was analyzed for 1,042 cases and 2,943 controls recruited from a population-based cohort (KARE, n=8,842. The second stage, de novo replication analysis, was performed in 1,216 cases and 1,352 controls selected from an independent population-based cohort (Health 2, n=8,500. A multiple linear regression analysis for glycemic traits was further performed in a total of 14,232 nondiabetic individuals consisting of 7,696 GWAS and 6,536 replication study participants. A meta-analysis was performed on the combined results using effect size and standard errors estimated for stage 1 and 2, respectively.ResultsA combined meta-analysis for T2DM identified two new (rs11065756 and rs2074356 loci reaching genome-wide significance in CCDC63 and C12orf51 on the 12q24 region. In addition, these variants were significantly associated with fasting plasma glucose and homeostasis model assessment of β-cell function. Interestingly, two independent single nucleotide polymorphisms were associated with sex-specific stratification in this study.ConclusionOur study showed a strong association between T2DM and glycemic traits. We further observed that two novel loci with multiple diverse effects were highly specific to males. Taken together, these findings may provide additional insights into the clinical assessment or subclassification of disease risk in a Korean population.

  3. Aspects of spirituality in medical doctors and their relation to specific views of illness and dealing with their patients' individual situation

    DEFF Research Database (Denmark)

    Büssing, Arndt; Hirdes, Almut Tabea; Baumann, Klaus

    2013-01-01

    . Data from an anonymous survey enrolling 237 medical doctors from Germany (mean age 45.7 +/- 9.6, 58% male, 42% female) indicated that secular forms of spirituality scored highest, while specific religious orientation had the lowest scores. Physicians with a specific specialization in complementary...

  4. Prototyping and Composing Aspect Languages: using an Aspect Interpreter Framework

    NARCIS (Netherlands)

    Havinga, W.K.; Bergmans, Lodewijk; Aksit, Mehmet

    2008-01-01

    Domain specific aspect languages (DSALs) are becoming more popular because they can be designed to represent recurring concerns in a way that is optimized for a specific domain. However, the design and implementation of even a limited domain-specific aspect language can be a tedious job. To address

  5. Discussion about the use of the volume specific surface area (VSSA) as a criterion to identify nanomaterials according to the EU definition. Part two: experimental approach.

    Science.gov (United States)

    Lecloux, André J; Atluri, Rambabu; Kolen'ko, Yury V; Deepak, Francis Leonard

    2017-10-12

    The first part of this study was dedicated to the modelling of the influence of particle shape, porosity and particle size distribution on the volume specific surface area (VSSA) values in order to check the applicability of this concept to the identification of nanomaterials according to the European Commission Recommendation. In this second part, experimental VSSA values are obtained for various samples from nitrogen adsorption isotherms and these values were used as a screening tool to identify and classify nanomaterials. These identification results are compared to the identification based on the 50% of particles with a size below 100 nm criterion applied to the experimental particle size distributions obtained by analysis of electron microscopy images on the same materials. It is concluded that the experimental VSSA values are able to identify nanomaterials, without false negative identification, if they have a mono-modal particle size, if the adsorption data cover the relative pressure range from 0.001 to 0.65 and if a simple, qualitative image of the particles by transmission or scanning electron microscopy is available to define their shape. The experimental conditions to obtain reliable adsorption data as well as the way to analyze the adsorption isotherms are described and discussed in some detail in order to help the reader in using the experimental VSSA criterion. To obtain the experimental VSSA values, the BET surface area can be used for non-porous particles, but for porous, nanostructured or coated nanoparticles, only the external surface of the particles, obtained by a modified t-plot approach, should be considered to determine the experimental VSSA and to avoid false positive identification of nanomaterials, only the external surface area being related to the particle size. Finally, the availability of experimental VSSA values together with particle size distributions obtained by electron microscopy gave the opportunity to check the

  6. The Use of Patient-Specific Induced Pluripotent Stem Cells (iPSCs to Identify Osteoclast Defects in Rare Genetic Bone Disorders

    Directory of Open Access Journals (Sweden)

    I-Ping Chen

    2014-12-01

    Full Text Available More than 500 rare genetic bone disorders have been described, but for many of them only limited treatment options are available. Challenges for studying these bone diseases come from a lack of suitable animal models and unavailability of skeletal tissues for studies. Effectors for skeletal abnormalities of bone disorders may be abnormal bone formation directed by osteoblasts or anomalous bone resorption by osteoclasts, or both. Patient-specific induced pluripotent stem cells (iPSCs can be generated from somatic cells of various tissue sources and in theory can be differentiated into any desired cell type. However, successful differentiation of hiPSCs into functional bone cells is still a challenge. Our group focuses on the use of human iPSCs (hiPSCs to identify osteoclast defects in craniometaphyseal dysplasia. In this review, we describe the impact of stem cell technology on research for better treatment of such disorders, the generation of hiPSCs from patients with rare genetic bone disorders and current protocols for differentiating hiPSCs into osteoclasts.

  7. Socio-epidemiologic aspects and cutaneous side effects of permanent tattoos in Germany – Tattoos are not restricted to a specific social phenotype

    Science.gov (United States)

    Müller, Cornelia Sigrid Lissi; Oertel, Angela; Körner, Rebecca; Pföhler, Claudia; Vogt, Thomas

    2017-01-01

    ABSTRACT Background: More and more people of all age classes have a tattoo. Intriguingly, there are multiple prejudices in the general population and published data that concern tattooed persons, such as being criminals, having a low education, being alcohol or drug abusers, or more risky in their life style. Objective: To obtain and to evaluate sociodemographic data on tattooed persons, to investigate the incidence of tattoo-related cutaneous complications and to define personal risk factors and course of the persons after being tattooed concerning behavior of personal environment. Patients and Methods: We interviewed 426 participants with already existing tattoos and 20 participants just before getting a new tattoo by using an online questionnaire. The participators were asked about socio-epidemiologic aspects of tattoos in general and special aspects of their own tattoo(s) in particular. There were no exclusion criteria. Results: Tattoos are interesting for people seeking popular body art, esp. university graduates and financially-secure individuals. 446 persons participated in this study. Most of the persons were female with a mean age of 35. Local pruritus around the tattooed area was the most common cutaneous side effect among the participants. 93.5% of the participants did not want a tattoo removal. Intriguingly, most of the participants experienced no career problems related to the tattoo(s). Limitations: The study population is not representative as we included only persons being tattooed prior to or getting newly tattooed. Furthermore, there is a potential selection bias as the participation in this study was voluntary. Only persons that felt involved by the flyer did answer the questionnaire. Conclusion: The present data shows that common tattooed persons are not low educated criminals with any drug or alcohol abuse or with risky life style. Nowadays being tattooed encompasses a kind of body art and displays a certain kind of lifestyle habit. PMID

  8. Socio-epidemiologic aspects and cutaneous side effects of permanent tattoos in Germany - Tattoos are not restricted to a specific social phenotype.

    Science.gov (United States)

    Müller, Cornelia Sigrid Lissi; Oertel, Angela; Körner, Rebecca; Pföhler, Claudia; Vogt, Thomas

    2017-01-01

    Background : More and more people of all age classes have a tattoo. Intriguingly, there are multiple prejudices in the general population and published data that concern tattooed persons, such as being criminals, having a low education, being alcohol or drug abusers, or more risky in their life style. Objective : To obtain and to evaluate sociodemographic data on tattooed persons, to investigate the incidence of tattoo-related cutaneous complications and to define personal risk factors and course of the persons after being tattooed concerning behavior of personal environment. Patients and Methods : We interviewed 426 participants with already existing tattoos and 20 participants just before getting a new tattoo by using an online questionnaire. The participators were asked about socio-epidemiologic aspects of tattoos in general and special aspects of their own tattoo(s) in particular. There were no exclusion criteria. Results : Tattoos are interesting for people seeking popular body art, esp. university graduates and financially-secure individuals. 446 persons participated in this study. Most of the persons were female with a mean age of 35. Local pruritus around the tattooed area was the most common cutaneous side effect among the participants. 93.5% of the participants did not want a tattoo removal. Intriguingly, most of the participants experienced no career problems related to the tattoo(s). Limitations : The study population is not representative as we included only persons being tattooed prior to or getting newly tattooed. Furthermore, there is a potential selection bias as the participation in this study was voluntary. Only persons that felt involved by the flyer did answer the questionnaire. Conclusion : The present data shows that common tattooed persons are not low educated criminals with any drug or alcohol abuse or with risky life style. Nowadays being tattooed encompasses a kind of body art and displays a certain kind of lifestyle habit.

  9. A multi-level approach to travel mode choice - How person characteristics and situation specific aspects determine car use in a student sample

    OpenAIRE

    Kløckner, Christian; Friedrichsmeier, Thomas

    2011-01-01

    The presented study analyses travel mode choice in a student sample on four frequent trips: To the university, to work, to the favourite leisure activity, and to the favourite shop. The decision to use the car in contrast to alternative travel modes is modelled for each individual trip using a two-level structural equation model with trip specific attributes on Level 1 and person specific attributes on Level 2. Data was gathered in an online travel survey on a student sample of the Ruhr-Unive...

  10. A novel type of peptidoglycan-binding domain highly specific for amidated D-Asp cross-bridge, identified in Lactobacillus casei bacteriophage endolysins.

    Science.gov (United States)

    Regulski, Krzysztof; Courtin, Pascal; Kulakauskas, Saulius; Chapot-Chartier, Marie-Pierre

    2013-07-12

    Peptidoglycan hydrolases (PGHs) are responsible for bacterial cell lysis. Most PGHs have a modular structure comprising a catalytic domain and a cell wall-binding domain (CWBD). PGHs of bacteriophage origin, called endolysins, are involved in bacterial lysis at the end of the infection cycle. We have characterized two endolysins, Lc-Lys and Lc-Lys-2, identified in prophages present in the genome of Lactobacillus casei BL23. These two enzymes have different catalytic domains but similar putative C-terminal CWBDs. By analyzing purified peptidoglycan (PG) degradation products, we showed that Lc-Lys is an N-acetylmuramoyl-L-alanine amidase, whereas Lc-Lys-2 is a γ-D-glutamyl-L-lysyl endopeptidase. Remarkably, both lysins were able to lyse only Gram-positive bacterial strains that possess PG with D-Ala(4)→D-Asx-L-Lys(3) in their cross-bridge, such as Lactococcus casei, Lactococcus lactis, and Enterococcus faecium. By testing a panel of L. lactis cell wall mutants, we observed that Lc-Lys and Lc-Lys-2 were not able to lyse mutants with a modified PG cross-bridge, constituting D-Ala(4)→L-Ala-(L-Ala/L-Ser)-L-Lys(3); moreover, they do not lyse the L. lactis mutant containing only the nonamidated D-Asp cross-bridge, i.e. D-Ala(4)→D-Asp-L-Lys(3). In contrast, Lc-Lys could lyse the ampicillin-resistant E. faecium mutant with 3→3 L-Lys(3)-D-Asn-L-Lys(3) bridges replacing the wild-type 4→3 D-Ala(4)-D-Asn-L-Lys(3) bridges. We showed that the C-terminal CWBD of Lc-Lys binds PG containing mainly D-Asn but not PG with only the nonamidated D-Asp-containing cross-bridge, indicating that the CWBD confers to Lc-Lys its narrow specificity. In conclusion, the CWBD characterized in this study is a novel type of PG-binding domain targeting specifically the D-Asn interpeptide bridge of PG.

  11. High IL-17E and low IL-17C dermal expression identifies a fibrosis-specific motif common to morphea and systemic sclerosis.

    Directory of Open Access Journals (Sweden)

    Paola Adele Lonati

    identifies a fibrosis-specific motif. The specific IL-17C/IL-17E cytokine combination may thus play a role in the development of fibrosis.

  12. Quantitative Non-canonical Amino Acid Tagging (QuaNCAT) Proteomics Identifies Distinct Patterns of Protein Synthesis Rapidly Induced by Hypertrophic Agents in Cardiomyocytes, Revealing New Aspects of Metabolic Remodeling*

    Science.gov (United States)

    Liu, Rui; Kenney, Justin W.; Manousopoulou, Antigoni; Johnston, Harvey E.; Kamei, Makoto; Woelk, Christopher H.; Xie, Jianling; Schwarzer, Michael; Proud, Christopher G.

    2016-01-01

    Cardiomyocytes undergo growth and remodeling in response to specific pathological or physiological conditions. In the former, myocardial growth is a risk factor for cardiac failure and faster protein synthesis is a major factor driving cardiomyocyte growth. Our goal was to quantify the rapid effects of different pro-hypertrophic stimuli on the synthesis of specific proteins in ARVC and to determine whether such effects are caused by alterations on mRNA abundance or the translation of specific mRNAs. Cardiomyocytes have very low rates of protein synthesis, posing a challenging problem in terms of studying changes in the synthesis of specific proteins, which also applies to other nondividing primary cells. To study the rates of accumulation of specific proteins in these cells, we developed an optimized version of the Quantitative Noncanonical Amino acid Tagging LC/MS proteomic method to label and selectively enrich newly synthesized proteins in these primary cells while eliminating the suppressive effects of pre-existing and highly abundant nonisotope-tagged polypeptides. Our data revealed that a classical pathologic (phenylephrine; PE) and the recently identified insulin stimulus that also contributes to the development of pathological cardiac hypertrophy (insulin), both increased the synthesis of proteins involved in, e.g. glycolysis, the Krebs cycle and beta-oxidation, and sarcomeric components. However, insulin increased synthesis of many metabolic enzymes to a greater extent than PE. Using a novel validation method, we confirmed that synthesis of selected candidates is indeed up-regulated by PE and insulin. Synthesis of all proteins studied was up-regulated by signaling through mammalian target of rapamycin complex 1 without changes in their mRNA levels, showing the key importance of translational control in the rapid effects of hypertrophic stimuli. Expression of PKM2 was up-regulated in rat hearts following TAC. This isoform possesses specific regulatory

  13. Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors

    DEFF Research Database (Denmark)

    Melin, Beatrice S; Barnholtz-Sloan, Jill S; Wrensch, Margaret R

    2017-01-01

    Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,496 cases and 18,190 controls. We identified fi...

  14. Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

    NARCIS (Netherlands)

    Jones, G.T.; Tromp, G.; Kuivaniemi, H.; Gretarsdottir, S.; Baas, A.F.; Giusti, B.; Strauss, E.; Hof, F.N. van 't; Webb, T.R.; Erdman, R.; Ritchie, M.D.; Elmore, J.R.; Verma, A.; Pendergrass, S.; Kullo, I.J.; Ye, Z.; Peissig, P.L.; Gottesman, O.; Verma, S.S.; Malinowski, J.; Rasmussen-Torvik, L.J.; Borthwick, K.M.; Smelser, D.T.; Crosslin, D.R.; Andrade, M. de; Ryer, E.J.; McCarty, C.A.; Bottinger, E.P.; Pacheco, J.A.; Crawford, D.C.; Carrell, D.S.; Gerhard, G.S.; Franklin, D.P.; Carey, D.J.; Phillips, V.L.; Williams, M.J.; Wei, W.; Blair, R.; Hill, A.A.; Vasudevan, T.M.; Lewis, D.R.; Thomson, I.A.; Krysa, J.; Hill, G.B.; Roake, J.; Merriman, T.R.; Oszkinis, G.; Galora, S.; Saracini, C.; Abbate, R.; Pulli, R.; Pratesi, C.; Saratzis, A.; Verissimo, A.R.; Bumpstead, S.; Badger, S.A.; Clough, R.E.; Cockerill, G.; Hafez, H.; Scott, D.J.; Futers, T.S.; Romaine, S.P.; Bridge, K.; Griffin, K.J.; Bailey, M.A.; Smith, A.; Thompson, M.M.; Bockxmeer, F.M. van; Matthiasson, S.E.; Thorleifsson, G.; Thorsteinsdottir, U.; Blankensteijn, J.D.; Teijink, J.A.; Wijmenga, C.; Graaf, J. de; Kiemeney, L.A.L.M.; Lindholt, J.S.; Hughes, A.; Bradley, D.T.; Stirrups, K.; Golledge, J.; Norman, P.E.; Powell, J.T.; Humphries, S.E.; Hamby, S.E.; Goodall, A.H.; Nelson, C.P.; Sakalihasan, N.; Courtois, A.; Ferrell, R.E.; Eriksson, P.; Folkersen, L.; Franco-Cereceda, A.; Eicher, J.D.; Johnson, A.D.; Betsholtz, C.; Ruusalepp, A.; Franzen, O.; Schadt, E.E.; Bjorkegren, J.L.; et al.,

    2017-01-01

    RATIONALE: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. OBJECTIVE: To identify additional AAA risk loci using data from all available

  15. A genome survey sequencing of the Java mouse deer (Tragulus javanicus) adds new aspects to the evolution of lineage specific retrotransposons in Ruminantia (Cetartiodactyla).

    Science.gov (United States)

    Gallus, S; Kumar, V; Bertelsen, M F; Janke, A; Nilsson, M A

    2015-10-25

    Ruminantia, the ruminating, hoofed mammals (cow, deer, giraffe and allies) are an unranked artiodactylan clade. Around 50-60 million years ago the BovB retrotransposon entered the ancestral ruminantian genome through horizontal gene transfer. A survey genome screen using 454-pyrosequencing of the Java mouse deer (Tragulus javanicus) and the lesser kudu (Tragelaphus imberbis) was done to investigate and to compare the landscape of transposable elements within Ruminantia. The family Tragulidae (mouse deer) is the only representative of Tragulina and phylogenetically important, because it represents the earliest divergence in Ruminantia. The data analyses show that, relative to other ruminantian species, the lesser kudu genome has seen an expansion of BovB Long INterspersed Elements (LINEs) and BovB related Short INterspersed Elements (SINEs) like BOVA2. In comparison the genome of Java mouse deer has fewer BovB elements than other ruminants, especially Bovinae, and has in addition a novel CHR-3 SINE most likely propagated by LINE-1. By contrast the other ruminants have low amounts of CHR SINEs but high numbers of actively propagating BovB-derived and BovB-propagated SINEs. The survey sequencing data suggest that the transposable element landscape in mouse deer (Tragulina) is unique among Ruminantia, suggesting a lineage specific evolutionary trajectory that does not involve BovB mediated retrotransposition. This shows that the genomic landscape of mobile genetic elements can rapidly change in any lineage. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Detectable end of radiation prostate specific antigen assists in identifying men with unfavorable intermediate-risk prostate cancer at high risk of distant recurrence and cancer-specific mortality.

    Science.gov (United States)

    Hayman, Jonathan; Phillips, Ryan; Chen, Di; Perin, Jamie; Narang, Amol K; Trieu, Janson; Radwan, Noura; Greco, Stephen; Deville, Curtiland; McNutt, Todd; Song, Daniel Y; DeWeese, Theodore L; Tran, Phuoc T

    2018-06-01

    Undetectable End of Radiation PSA (EOR-PSA) has been shown to predict improved survival in prostate cancer (PCa). While validating the unfavorable intermediate-risk (UIR) and favorable intermediate-risk (FIR) stratifications among Johns Hopkins PCa patients treated with radiotherapy, we examined whether EOR-PSA could further risk stratify UIR men for survival. A total of 302 IR patients were identified in the Johns Hopkins PCa database (178 UIR, 124 FIR). Kaplan-Meier curves and multivariable analysis was performed via Cox regression for biochemical recurrence free survival (bRFS), distant metastasis free survival (DMFS), and overall survival (OS), while a competing risks model was used for PCa specific survival (PCSS). Among the 235 patients with known EOR-PSA values, we then stratified by EOR-PSA and performed the aforementioned analysis. The median follow-up time was 11.5 years (138 months). UIR was predictive of worse DMFS and PCSS (P = 0.008 and P = 0.023) on multivariable analysis (MVA). Increased radiation dose was significant for improved DMFS (P = 0.016) on MVA. EOR-PSA was excluded from the models because it did not trend towards significance as a continuous or binary variable due to interaction with UIR, and we were unable to converge a multivariable model with a variable to control for this interaction. However, when stratifying by detectable versus undetectable EOR-PSA, UIR had worse DMFS and PCSS among detectable EOR-PSA patients, but not undetectable patients. UIR was significant on MVA among detectable EOR-PSA patients for DMFS (P = 0.021) and PCSS (P = 0.033), while RT dose also predicted PCSS (P = 0.013). EOR-PSA can assist in predicting DMFS and PCSS among UIR patients, suggesting a clinically meaningful time point for considering intensification of treatment in clinical trials of intermediate-risk men. © 2018 Wiley Periodicals, Inc.

  17. Competitive Enzyme-Linked Immunosorbent Assay Based on a Rhoptry-Associated Protein 1 Epitope Specifically Identifies Babesia bovis-Infected Cattle

    Science.gov (United States)

    Goff, Will L.; McElwain, Terry F.; Suarez, Carlos E.; Johnson, Wendell C.; Brown, Wendy C.; Norimine, Junzo; Knowles, Donald P.

    2003-01-01

    The competitive enzyme-linked immunosorbent assay (cELISA) format has proven to be an accurate, reliable, easily standardized, and high-throughput method for detecting hemoparasite infections. In the present study, a species-specific, broadly conserved, and tandemly repeated B-cell epitope within the C terminus of the rhoptry-associated protein 1 of the hemoparasite Babesia bovis was cloned and expressed as a histidine-tagged thioredoxin fusion peptide and used as antigen in a cELISA. The assay was optimized with defined negative and positive bovine sera, where positive sera inhibited the binding of the epitope-specific monoclonal antibody BABB75A4. The cELISA accurately differentiated animals with B. bovis-specific antibodies from uninfected animals and from animals with antibodies against other tick-borne hemoparasites (98.7% specificity). In addition, B. bovis-specific sera from Australia, Argentina, Bolivia, Puerto Rico, and Morocco inhibited the binding of BABB75A4, confirming conservation of the epitope. The assay first detected experimentally infected animals between 13 and 17 days postinfection, and with sera from naturally infected carrier cattle, was comparable to indirect immunofluorescence (98.3% concordance). The assay appears to have the characteristics necessary for an epidemiologic and disease surveillance tool. PMID:12522037

  18. Applying Machine Learning to Workers' Compensation Data to Identify Industry-Specific Ergonomic and Safety Prevention Priorities: Ohio, 2001 to 2011.

    Science.gov (United States)

    Meyers, Alysha R; Al-Tarawneh, Ibraheem S; Wurzelbacher, Steven J; Bushnell, P Timothy; Lampl, Michael P; Bell, Jennifer L; Bertke, Stephen J; Robins, David C; Tseng, Chih-Yu; Wei, Chia; Raudabaugh, Jill A; Schnorr, Teresa M

    2018-01-01

    This study leveraged a state workers' compensation claims database and machine learning techniques to target prevention efforts by injury causation and industry. Injury causation auto-coding methods were developed to code more than 1.2 million Ohio Bureau of Workers' Compensation claims for this study. Industry groups were ranked for soft-tissue musculoskeletal claims that may have been preventable with biomechanical ergonomic (ERGO) or slip/trip/fall (STF) interventions. On the basis of the average of claim count and rate ranks for more than 200 industry groups, Skilled Nursing Facilities (ERGO) and General Freight Trucking (STF) were the highest risk for lost-time claims (>7 days). This study created a third, major causation-specific U.S. occupational injury surveillance system. These findings are being used to focus prevention resources on specific occupational injury types in specific industry groups, especially in Ohio. Other state bureaus or insurers may use similar methods.

  19. Environmental Aspects, Objectives and Targets Identification Process

    International Nuclear Information System (INIS)

    Green, R.

    2002-01-01

    The purpose of this report is to document the environmental aspects and associated environmental impacts of the Bechtel SAIC Company (BSC) scope of work, evaluate the significance of those environmental aspects based on established criteria, and establish environmental objectives and targets for specific environmental aspects. This report is intended to be used by environmental staff in the evaluation of BSC work packages during the annual risk-based planning process. This report shall be fully reviewed and revised annually during the annual work planning process to reflect changes in BSC operations, facilities, and scope of work. Planned BSC work will be evaluated to determine if the work is covered by a previously defined activity, product or service (see Table 2); if work activities require redefinition or addition of a new activity; and if the significant evaluation for each environment aspect is still valid based on scope of planned work. New workscope initiated during the fiscal year through the Baseline Change Proposal process (i.e., not as part of the annual work plan) also will be reviewed for new environmental aspects and determination of whether the new workscope would change the significance rating of any environmental aspect. If a new environmental aspect is identified in a new work activity, product, or service but the aspect is not determined to be significant (see Section 4), then this report can be changed through an interim change notice (ICN). This report can be changed five times through an ICN before a full revision is required. However, if new workscope causes an environmental aspect to be graded as significant using the evaluation process in Section 4, this report shall be revised though a full review and revision

  20. Exome chip meta-analysis identifies novel loci and East Asian-specific coding variants that contribute to lipid levels and coronary artery disease

    DEFF Research Database (Denmark)

    Lu, Xiangfeng; Peloso, Gina M; Liu, Dajiang J

    2017-01-01

    Most genome-wide association studies have been of European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we used a...

  1. Dlx1 and Rgs5 in the ductus arteriosus: vessel-specific genes identified by transcriptional profiling of laser-capture microdissected endothelial and smooth muscle cells

    NARCIS (Netherlands)

    Bokenkamp, R.; Brempt, R. van; Munsteren, J.C. van; Wijngaert, I. van den; Hoogt, R. de; Finos, L.; Goeman, J.J.; Groot, A.C de; Poelmann, R.E.; Blom, N.A.; DeRuiter, M.C.

    2014-01-01

    Closure of the ductus arteriosus (DA) is a crucial step in the transition from fetal to postnatal life. Patent DA is one of the most common cardiovascular anomalies in children with significant clinical consequences especially in premature infants. We aimed to identify genes that specify the DA in

  2. Validity of the Male Depression Risk Scale in a representative Canadian sample: sensitivity and specificity in identifying men with recent suicide attempt.

    Science.gov (United States)

    Rice, Simon M; Ogrodniczuk, John S; Kealy, David; Seidler, Zac E; Dhillon, Haryana M; Oliffe, John L

    2017-12-22

    Clinical practice and literature has supported the existence of a phenotypic sub-type of depression in men. While a number of self-report rating scales have been developed in order to empirically test the male depression construct, psychometric validation of these scales is limited. To confirm the psychometric properties of the multidimensional Male Depression Risk Scale (MDRS-22) and to develop clinical cut-off scores for the MDRS-22. Data were obtained from an online sample of 1000 Canadian men (median age (M) = 49.63, standard deviation (SD) = 14.60). Confirmatory factor analysis (CFA) was used to replicate the established six-factor model of the MDRS-22. Psychometric values of the MDRS subscales were comparable to the widely used Patient Health Questionnaire-9. CFA model fit indices indicated adequate model fit for the six-factor MDRS-22 model. ROC curve analysis indicated the MDRS-22 was effective for identifying those with a recent (previous four-weeks) suicide attempt (area under curve (AUC) values = 0.837). The MDRS-22 cut-off identified proportionally more (84.62%) cases of recent suicide attempt relative to the PHQ-9 moderate range (53.85%). The MDRS-22 is the first male-sensitive depression scale to be psychometrically validated using CFA techniques in independent and cross-nation samples. Additional studies should identify differential item functioning and evaluate cross-cultural effects.

  3. Organisational aspects of care.

    Science.gov (United States)

    Bloomfield, Jacqueline; Pegram, Anne

    2015-03-04

    Organisational aspects of care, the second essential skills cluster, identifies the need for registered nurses to systematically assess, plan and provide holistic patient care in accordance with individual needs. Safeguarding, supporting and protecting adults and children in vulnerable situations; leading, co-ordinating and managing care; functioning as an effective and confident member of the multidisciplinary team; and managing risk while maintaining a safe environment for patients and colleagues, are vital aspects of this cluster. This article discusses the roles and responsibilities of the newly registered graduate nurse. Throughout their education, nursing students work towards attaining this knowledge and these skills in preparation for their future roles as nurses.

  4. Specific aspects of insurance of nuclear risks

    International Nuclear Information System (INIS)

    Angelici, C.

    1980-03-01

    The following questions are discussed in connection with the insurance of nuclear risks: insurance techniques, the nuclear operator's limitation of liability in amount and in time, its channelling, the principle of sole liability and exonerations, the insurers' position, the cover provided and state intervention beyond that amount. (NEA) [fr

  5. Sex-specific aspects of venous thrombosis

    NARCIS (Netherlands)

    Roach, Rachel Elizabeth Jo

    2014-01-01

    Venous thrombosis is a disease that occurs in 1-2 per 1000 people per year. At the time of their first venous thrombosis, approximately 50% of women are exposed to reproductive risk factors (oral contraception, postmenopausal hormone therapy, pregnancy and the puerperium). In this thesis, we showed

  6. Distribution channels: Specific aspects and new technologies

    Directory of Open Access Journals (Sweden)

    Lovrić Dražen

    2005-01-01

    Full Text Available Products and services distribution is aimed to a basic purpose of marketing - to satisfy needs of people and to distribute products to different types of customers, in necessary quantities, to designed destinations with competitive prices and in time when it is needed. For a effective distribution to take place it is necessary to have several resources from different profiles of organizations and to coordinate their knowledge.

  7. OOAspectZ and aspect-oriented UML class diagrams for Aspect-oriented software modelling (AOSM

    Directory of Open Access Journals (Sweden)

    Cristian Vidal Silva

    2013-09-01

    Full Text Available Regarding modularised software development, Aspect-oriented programming (AOP identifies and represents individually crosscutting concerns during the software development cycle’s programming stage. This article proposes and applies OOAspectZ to formal Aspect-oriented requirement specifications for prior stages of the software development cycle. It particularly concerns requirement specification and the structural design of data and behaviour, along with describing and applying Aspect-oriented UML class diagrams to designing classes, aspects and associations among classes and aspects during Aspect-oriented software development (AOSD.OOAspectZ is a language integrating both Object-Z and AspectZ formal languages whereas Aspect-oriented UML class diagrams represent AOP code, object class and crosscutting concern class structure by means of stereotypes. This article shows and applies the main OOAspectZ and AO UML class diagram characteristics to Aspect-oriented software modelling (AOSM using a classic example of AOP. Ideas for future work concerning an actual AOP version are also indicated.

  8. Weighted gene co-expression network analysis of expression data of monozygotic twins identifies specific modules and hub genes related to BMI

    DEFF Research Database (Denmark)

    Wang, Weijing; Jiang, Wenjie; Hou, Lin

    2017-01-01

    BACKGROUND: The therapeutic management of obesity is challenging, hence further elucidating the underlying mechanisms of obesity development and identifying new diagnostic biomarkers and therapeutic targets are urgent and necessary. Here, we performed differential gene expression analysis......) were with a trend of up-regulation in twins with higher BMI when compared to their siblings. Categories of positive regulation of nitric-oxide synthase biosynthetic process, positive regulation of NF-kappa B import into nucleus, and peroxidase activity were significantly enriched within GO database...

  9. Organisational aspects, research required, educational aspects

    International Nuclear Information System (INIS)

    Rueterjans, H.

    1987-01-01

    In addition to the clinical testing of NMR imaging, there were activities for studying the basic principles of NMR spectroscopy, also for routine applications in university clinics and larger hospitals. Equipment is available now at different places; research projects should be coordinated in order to ensure direct access to the equipment for a sufficient, task-specific period of time. There is demand for research in this field in the Federal Republic of Germany. Education and further training should be organised taking into account physical and medical aspects. (TRV) [de

  10. Bacterial indicator occurrence and the use of an F+ specific RNA coliphage assay to identify fecal sources in Homosassa Springs, Florida

    Science.gov (United States)

    Griffin, Dale W.; Stokes, Rodger; Rose, J.B.; Paul, J.H.

    2000-01-01

    A microbiological water quality study of Homosassa Springs State Wildlife Park (HSSWP) and surrounding areas was undertaken. Samples were collected in November of 1997 (seven sites) and again in November of 1998 (nine sites). Fecal bacterial concentrations (total and fecal coliforms, Clostridium perfringens, and enterococci) were measured as relative indicators of fecal contamination. F+-specific coliphage genotyping was performed to determine the source of fecal contamination at the study sites. Bacterial levels were considerably higher at most sites in the 1997 sampling compared to the 1998 sampling, probably because of the greater rainfall that year. In November of 1997, 2 of the 7 sites were in violation of all indicator standards and guidance levels. In November of 1998, 1 of 9 sites was in violation of all indicator standard and guidance levels. The highest concentrations of all fecal indicators were found at a station downstream of the animal holding pens in HSSWP. The lowest levels of indicators were found at the Homosassa Main Spring vent. Levels of fecal indicators downstream of HSSWP (near the point of confluence with the river) were equivalent to those found in the Southeastern Fork and areas upstream of the park influences. F+ specific RNA coliphage analysis indicated that fecal contamination at all sites that tested positive was from animal sources (mammals and birds). These results suggest that animal (indigenous and those in HSSWP) and not human sources influenced microbial water quality in the area of Homosassa River covered by this study.

  11. Anti-citrullinated heat shock protein 90 antibodies identified in bronchoalveolar lavage fluid are a marker of lung-specific immune responses.

    Science.gov (United States)

    Harlow, Lisa; Gochuico, Bernadette R; Rosas, Ivan O; Doyle, Tracy J; Osorio, Juan C; Travers, Timothy S; Camacho, Carlos C; Oddis, Chester V; Ascherman, Dana P

    2014-11-01

    Previous work has demonstrated a correlation between serum anti-citrullinated HSP90 antibodies and rheumatoid arthritis-associated interstitial lung disease (RA-ILD). To further investigate this potential pathogenic relationship, we used ELISA-based techniques to assess anti-citrullinated HSP90 antibody profiles in bronchoalveolar lavage fluid (BALF) of patients with different stages of RA-ILD. 9/21 RA-derived BALF specimens demonstrated IgG and/or IgA antibodies targeting citrullinated HSP90 proteins/peptides, highlighting disease specific responses (with a predilection for RA-ILD) that did not occur in IPF patients (0/5) or healthy control subjects (0/5). Comparison of antibody profiles between BALF and matching serum specimens revealed various recognition patterns favoring predominant production of anti-citrullinated HSP90 antibodies within the lung microenvironment-further supporting the connection between this antibody specificity and parenchymal lung disease. Equally important, qualitative as well as quantitative differences in anti-citrullinated HSP90 profiles between BALF and serum indicate that the lung plays a direct role in shaping the immune repertoire of RA/RA-ILD. Published by Elsevier Inc.

  12. Small RNA analysis in Petunia hybrida identifies unusual tissue-specific expression patterns of conserved miRNAs and of a 24mer RNA

    Science.gov (United States)

    Tedder, Philip; Zubko, Elena; Westhead, David R.; Meyer, Peter

    2009-01-01

    Two pools of small RNAs were cloned from inflorescences of Petunia hybrida using a 5′-ligation dependent and a 5′-ligation independent approach. The two libraries were integrated into a public website that allows the screening of individual sequences against 359,769 unique clones. The library contains 15 clones with 100% identity and 53 clones with one mismatch to miRNAs described for other plant species. For two conserved miRNAs, miR159 and miR390, we find clear differences in tissue-specific distribution, compared with other species. This shows that evolutionary conservation of miRNA sequences does not necessarily include a conservation of the miRNA expression profile. Almost 60% of all clones in the database are 24-nucleotide clones. In accordance with the role of 24mers in marking repetitive regions, we find them distributed across retroviral and transposable element sequences but other 24mers map to promoter regions and to different transcript regions. For one target region we observe tissue-specific variation of matching 24mers, which demonstrates that, as for 21mers, 24mer concentrations are not necessarily identical in different tissues. Asymmetric distribution of a putative novel miRNA in the two libraries suggests that the cloning method can be selective for the representation of certain small RNAs in a collection. PMID:19369427

  13. Genomic, Epigenomic, and Transcriptomic Profiling towards Identifying Omics Features and Specific Biomarkers That Distinguish Uterine Leiomyosarcoma and Leiomyoma at Molecular Levels

    Directory of Open Access Journals (Sweden)

    Tomoko Miyata

    2015-01-01

    Full Text Available Uterine leiomyosarcoma (LMS is the worst malignancy among the gynecologic cancers. Uterine leiomyoma (LM, a benign tumor of myometrial origin, is the most common among women of childbearing age. Because of their similar symptoms, it is difficult to preoperatively distinguish the two conditions only by ultrasound and pelvic MRI. While histopathological diagnosis is currently the main approach used to distinguish them postoperatively, unusual histologic variants of LM tend to be misdiagnosed as LMS. Therefore, development of molecular diagnosis as an alternative or confirmatory means will help to diagnose LMS more accurately. We adopted omics-based technologies to identify genome-wide features to distinguish LMS from LM and revealed that copy number, gene expression, and DNA methylation profiles successfully distinguished these tumors. LMS was found to possess features typically observed in malignant solid tumors, such as extensive chromosomal abnormalities, overexpression of cell cycle-related genes, hypomethylation spreading through large genomic regions, and frequent hypermethylation at the polycomb group target genes and protocadherin genes. We also identified candidate expression and DNA methylation markers, which will facilitate establishing postoperative molecular diagnostic tests based on conventional quantitative assays. Our results demonstrate the feasibility of establishing such tests and the possibility of developing preoperative and noninvasive methods.

  14. Lung cancer risk and cancer-specific mortality in subjects undergoing routine imaging test when stratified with and without identified lung nodule on imaging study

    Energy Technology Data Exchange (ETDEWEB)

    Gomez-Saez, Noemi [Miguel Hernandez University, Public Health, History of Science and Ginecology Department, Alicante (Spain); Hernandez-Aguado, Ildefonso; Pastor Valero, Maria; Parker, Lucy Anne; Lumbreras, Blanca [Miguel Hernandez University, Public Health, History of Science and Ginecology Department, Alicante (Spain); CIBER en Epidemiologia y Salud Publica, Madrid (Spain); Vilar, Jose; Domingo, Maria Luisa [Peset Hospital, Radiodiagnostic Department, Valencia (Spain); Gonzalez-Alvarez, Isabel; Lorente, Maria Fermina [San Juan Hospital, Radiodiagnostic Department, San Juan de Alicante (Spain)

    2015-12-15

    To assess the risk of lung cancer and specific mortality rate in patients with and without solitary pulmonary nodules (SPN) on chest radiograph and CT. This prospective study included 16,078 patients ≥35 years old (893 of them had an SPN detected with either chest radiograph or CT) and 15,185 without SPN. Patients were followed up for 18 months or until being diagnosed with lung cancer. Risk and mortality lung cancer were calculated in both groups with Poisson regression. In patients with SPN, incidence of lung cancer was 8.3 % (95 % CI 6.0-11.2) on radiograph and 12.4 % (95 % CI 9.3-15.9) on CT. A chronic obstructive pulmonary disease in patients with radiographs (odds ratio 2.62; 95 % CI 1.03, 6.67) and smoking habit (odds ratio 20.63; 95 % CI 3.84, 110.77) in patients with CT were associated with a higher probability of lung cancer. Large nodule size and spiculated edge were associated with lung cancer on both CT and radiograph. Lung cancer-specific mortality was lower in patients with SPN than in those without SPN (1.73/1000 person-years, 95 % CI 1.08-2.88 vs. 2.15/1000 person-years, 95 % CI 1.25-3.96). The risk of lung cancer for patients with SPN is higher in clinical populations than in screening studies. Moreover, patients with SPN showed lower mortality than those without SPN. (orig.)

  15. Computational prediction of the Crc regulon identifies genus-wide and species-specific targets of catabolite repression control in Pseudomonas bacteria

    Directory of Open Access Journals (Sweden)

    O'Gara Fergal

    2010-11-01

    Full Text Available Abstract Background Catabolite repression control (CRC is an important global control system in Pseudomonas that fine tunes metabolism in order optimise growth and metabolism in a range of different environments. The mechanism of CRC in Pseudomonas spp. centres on the binding of a protein, Crc, to an A-rich motif on the 5' end of an mRNA resulting in translational down-regulation of target genes. Despite the identification of several Crc targets in Pseudomonas spp. the Crc regulon has remained largely unexplored. Results In order to predict direct targets of Crc, we used a bioinformatics approach based on detection of A-rich motifs near the initiation of translation of all protein-encoding genes in twelve fully sequenced Pseudomonas genomes. As expected, our data predict that genes related to the utilisation of less preferred nutrients, such as some carbohydrates, nitrogen sources and aromatic carbon compounds are targets of Crc. A general trend in this analysis is that the regulation of transporters is conserved across species whereas regulation of specific enzymatic steps or transcriptional activators are often conserved only within a species. Interestingly, some nucleoid associated proteins (NAPs such as HU and IHF are predicted to be regulated by Crc. This finding indicates a possible role of Crc in indirect control over a subset of genes that depend on the DNA bending properties of NAPs for expression or repression. Finally, some virulence traits such as alginate and rhamnolipid production also appear to be regulated by Crc, which links nutritional status cues with the regulation of virulence traits. Conclusions Catabolite repression control regulates a broad spectrum of genes in Pseudomonas. Some targets are genus-wide and are typically related to central metabolism, whereas other targets are species-specific, or even unique to particular strains. Further study of these novel targets will enhance our understanding of how Pseudomonas

  16. Computational prediction of the Crc regulon identifies genus-wide and species-specific targets of catabolite repression control in Pseudomonas bacteria.

    Science.gov (United States)

    Browne, Patrick; Barret, Matthieu; O'Gara, Fergal; Morrissey, John P

    2010-11-25

    Catabolite repression control (CRC) is an important global control system in Pseudomonas that fine tunes metabolism in order optimise growth and metabolism in a range of different environments. The mechanism of CRC in Pseudomonas spp. centres on the binding of a protein, Crc, to an A-rich motif on the 5' end of an mRNA resulting in translational down-regulation of target genes. Despite the identification of several Crc targets in Pseudomonas spp. the Crc regulon has remained largely unexplored. In order to predict direct targets of Crc, we used a bioinformatics approach based on detection of A-rich motifs near the initiation of translation of all protein-encoding genes in twelve fully sequenced Pseudomonas genomes. As expected, our data predict that genes related to the utilisation of less preferred nutrients, such as some carbohydrates, nitrogen sources and aromatic carbon compounds are targets of Crc. A general trend in this analysis is that the regulation of transporters is conserved across species whereas regulation of specific enzymatic steps or transcriptional activators are often conserved only within a species. Interestingly, some nucleoid associated proteins (NAPs) such as HU and IHF are predicted to be regulated by Crc. This finding indicates a possible role of Crc in indirect control over a subset of genes that depend on the DNA bending properties of NAPs for expression or repression. Finally, some virulence traits such as alginate and rhamnolipid production also appear to be regulated by Crc, which links nutritional status cues with the regulation of virulence traits. Catabolite repression control regulates a broad spectrum of genes in Pseudomonas. Some targets are genus-wide and are typically related to central metabolism, whereas other targets are species-specific, or even unique to particular strains. Further study of these novel targets will enhance our understanding of how Pseudomonas bacteria integrate nutritional status cues with the regulation

  17. Lung cancer risk and cancer-specific mortality in subjects undergoing routine imaging test when stratified with and without identified lung nodule on imaging study

    International Nuclear Information System (INIS)

    Gomez-Saez, Noemi; Hernandez-Aguado, Ildefonso; Pastor Valero, Maria; Parker, Lucy Anne; Lumbreras, Blanca; Vilar, Jose; Domingo, Maria Luisa; Gonzalez-Alvarez, Isabel; Lorente, Maria Fermina

    2015-01-01

    To assess the risk of lung cancer and specific mortality rate in patients with and without solitary pulmonary nodules (SPN) on chest radiograph and CT. This prospective study included 16,078 patients ≥35 years old (893 of them had an SPN detected with either chest radiograph or CT) and 15,185 without SPN. Patients were followed up for 18 months or until being diagnosed with lung cancer. Risk and mortality lung cancer were calculated in both groups with Poisson regression. In patients with SPN, incidence of lung cancer was 8.3 % (95 % CI 6.0-11.2) on radiograph and 12.4 % (95 % CI 9.3-15.9) on CT. A chronic obstructive pulmonary disease in patients with radiographs (odds ratio 2.62; 95 % CI 1.03, 6.67) and smoking habit (odds ratio 20.63; 95 % CI 3.84, 110.77) in patients with CT were associated with a higher probability of lung cancer. Large nodule size and spiculated edge were associated with lung cancer on both CT and radiograph. Lung cancer-specific mortality was lower in patients with SPN than in those without SPN (1.73/1000 person-years, 95 % CI 1.08-2.88 vs. 2.15/1000 person-years, 95 % CI 1.25-3.96). The risk of lung cancer for patients with SPN is higher in clinical populations than in screening studies. Moreover, patients with SPN showed lower mortality than those without SPN. (orig.)

  18. Computational prediction of the Crc regulon identifies genus-wide and species-specific targets of catabolite repression control in Pseudomonas bacteria

    LENUS (Irish Health Repository)

    Browne, Patrick

    2010-11-25

    Abstract Background Catabolite repression control (CRC) is an important global control system in Pseudomonas that fine tunes metabolism in order optimise growth and metabolism in a range of different environments. The mechanism of CRC in Pseudomonas spp. centres on the binding of a protein, Crc, to an A-rich motif on the 5\\' end of an mRNA resulting in translational down-regulation of target genes. Despite the identification of several Crc targets in Pseudomonas spp. the Crc regulon has remained largely unexplored. Results In order to predict direct targets of Crc, we used a bioinformatics approach based on detection of A-rich motifs near the initiation of translation of all protein-encoding genes in twelve fully sequenced Pseudomonas genomes. As expected, our data predict that genes related to the utilisation of less preferred nutrients, such as some carbohydrates, nitrogen sources and aromatic carbon compounds are targets of Crc. A general trend in this analysis is that the regulation of transporters is conserved across species whereas regulation of specific enzymatic steps or transcriptional activators are often conserved only within a species. Interestingly, some nucleoid associated proteins (NAPs) such as HU and IHF are predicted to be regulated by Crc. This finding indicates a possible role of Crc in indirect control over a subset of genes that depend on the DNA bending properties of NAPs for expression or repression. Finally, some virulence traits such as alginate and rhamnolipid production also appear to be regulated by Crc, which links nutritional status cues with the regulation of virulence traits. Conclusions Catabolite repression control regulates a broad spectrum of genes in Pseudomonas. Some targets are genus-wide and are typically related to central metabolism, whereas other targets are species-specific, or even unique to particular strains. Further study of these novel targets will enhance our understanding of how Pseudomonas bacteria integrate

  19. Identifying specific profiles in patients with different degrees of painful knee osteoarthritis based on serological biochemical and mechanistic pain biomarkers: a diagnostic approach based on cluster analysis.

    Science.gov (United States)

    Egsgaard, Line Lindhardt; Eskehave, Thomas Navndrup; Bay-Jensen, Anne C; Hoeck, Hans Christian; Arendt-Nielsen, Lars

    2015-01-01

    Biochemical and pain biomarkers can be applied to patients with painful osteoarthritis profiles and may provide more details compared with conventional clinical tools. The aim of this study was to identify an optimal combination of biochemical and pain biomarkers for classification of patients with different degrees of knee pain and joint damage. Such profiling may provide new diagnostic and therapeutic options. A total of 216 patients with different degrees of knee pain (maximal pain during the last 24 hours rated on a visual analog scale [VAS]) (VAS 0-100) and 64 controls (VAS 0-9) were recruited. Patients were separated into 3 groups: VAS 10 to 39 (N = 81), VAS 40 to 69 (N = 70), and VAS 70 to 100 (N = 65). Pressure pain thresholds, temporal summation to pressure stimuli, and conditioning pain modulation were measured from the peripatellar and extrasegmental sites. Biochemical markers indicative for autoinflammation and immunity (VICM, CRP, and CRPM), synovial inflammation (CIIIM), cartilage loss (CIIM), and bone degradation (CIM) were analyzed. WOMAC, Lequesne, and pain catastrophizing scores were collected. Principal component analysis was applied to select the optimal variable subset, and cluster analysis was applied to this subset to create distinctly different knee pain profiles. Four distinct knee pain profiles were identified: profile A (N = 27), profile B (N = 59), profile C (N = 85), and profile D (N = 41). Each knee pain profile had a unique combination of biochemical markers, pain biomarkers, physical impairments, and psychological factors that may provide the basis for mechanism-based diagnosis, individualized treatment, and selection of patients for clinical trials evaluating analgesic compounds. These results introduce a new profiling for knee OA and should be regarded as preliminary.

  20. Structure-function relationship of a plant NCS1 member - Homology modeling and mutagenesis identified residues critical for substrate specificity of PLUTO, a nucleobase transporter from arabidopsis

    KAUST Repository

    Witz, Sandra

    2014-03-12

    Plastidic uracil salvage is essential for plant growth and development. So far, PLUTO, the plastidic nucleobase transporter from Arabidopsis thaliana is the only known uracil importer at the inner plastidic membrane which represents the permeability barrier of this organelle. We present the first homology model of PLUTO, the sole plant NCS1 member from Arabidopsis based on the crystal structure of the benzyl hydantoin transporter MHP1 from Microbacterium liquefaciens and validated by molecular dynamics simulations. Polar side chains of residues Glu-227 and backbones of Val-145, Gly-147 and Thr-425 are proposed to form the binding site for the three PLUTO substrates uracil, adenine and guanine. Mutational analysis and competition studies identified Glu-227 as an important residue for uracil and to a lesser extent for guanine transport. A differential response in substrate transport was apparent with PLUTO double mutants E227Q G147Q and E227Q T425A, both of which most strongly affected adenine transport, and in V145A G147Q, which markedly affected guanine transport. These differences could be explained by docking studies, showing that uracil and guanine exhibit a similar binding mode whereas adenine binds deep into the catalytic pocket of PLUTO. Furthermore, competition studies confirmed these results. The present study defines the molecular determinants for PLUTO substrate binding and demonstrates key differences in structure-function relations between PLUTO and other NCS1 family members. 2014 Witz et al.

  1. Efficient Culture Adaptation of Hepatitis C Virus Recombinants with Genotype-Specific Core-NS2 by Using Previously Identified Mutations

    DEFF Research Database (Denmark)

    Scheel, Troels Kasper Høyer; Gottwein, Judith M; Carlsen, Thomas H R

    2011-01-01

    Hepatitis C virus (HCV) is an important cause of chronic liver disease, and interferon-based therapy cures only 40 to 80% of patients, depending on HCV genotype. Research was accelerated by genotype 2a (strain JFH1) infectious cell culture systems. We previously developed viable JFH1-based...... (HC-TN and DH6), 1b (DH1 and DH5), and 3a (DBN) isolates, using previously identified adaptive mutations. Introduction of mutations from isolates of the same subtype either led to immediate efficient virus production or accelerated culture adaptation. The DH6 and DH5 recombinants without introduced...... mutations did not adapt to culture. Universal adaptive effects of mutations in NS3 (Q1247L, I1312V, K1398Q, R1408W, and Q1496L) and NS5A (V2418L) were investigated for JFH1-based genotype 1 to 5 core-NS2 recombinants; several mutations conferred adaptation to H77C (1a), J4 (1b), S52 (3a), and SA13 (5a...

  2. The use of sterol distributions combined with compound specific isotope analyses as a tool to identify the origin of fecal contamination in rivers.

    Science.gov (United States)

    Biache, Coralie; Philp, R Paul

    2013-03-01

    The sterol distributions of 9 sediment samples from the Illinois River Basin (OK and AR, USA) were examined in order to identify the source of fecal contamination. The samples were extracted with organic solvent using sonication and the fractions containing the sterols were isolated and analyzed by gas chromatography-mass spectrometry. The sterol distributions of the Illinois River samples were dominated by phytosterols. They were compared to those of different animal feces and manures using a principal component analysis and correspondence appeared between the sediments and one group of chicken feces samples. Gas chromatography-isotope ratio mass spectrometry analyses were also performed to determine the δ(13)C values for the phytosterols and to get an indication of their origin based on the C(3)/C(4) plant signatures. The δ(13)C values obtained ranged from -30.6 ‰ to -17.4 ‰ (VPDB) corresponding to a mixed signature between C(3) and C(4) plants, indicating a C(4) plant contribution to the C(3) plant natural background. These observations indicate that a proportion of the phytosterols originated from chicken feces. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Jacqueline Zoe-Munn Chan

    2014-10-01

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

  4. Reciprocal Genetics: Identifying QTL for General and Specific Combining Abilities in Hybrids Between Multiparental Populations from Two Maize (Zea mays L.) Heterotic Groups.

    Science.gov (United States)

    Giraud, Héloïse; Bauland, Cyril; Falque, Matthieu; Madur, Delphine; Combes, Valérie; Jamin, Philippe; Monteil, Cécile; Laborde, Jacques; Palaffre, Carine; Gaillard, Antoine; Blanchard, Philippe; Charcosset, Alain; Moreau, Laurence

    2017-11-01

    Several plant and animal species of agricultural importance are commercialized as hybrids to take advantage of the heterosis phenomenon. Understanding the genetic architecture of hybrid performances is therefore of key importance. We developed two multiparental maize ( Zea mays L.) populations, each corresponding to an important heterotic group (dent or flint) and comprised of six connected biparental segregating populations of inbred lines (802 and 822 lines for each group, respectively) issued from four founder lines. Instead of using "testers" to evaluate their hybrid values, segregating lines were crossed according to an incomplete factorial design to produce 951 dent-flint hybrids, evaluated for four biomass production traits in eight environments. QTL detection was carried out for the general-combining-ability (GCA) and specific-combining-ability (SCA) components of hybrid value, considering allelic effects transmitted from each founder line. In total, 42 QTL were detected across traits. We detected mostly QTL affecting GCA, 31% (41% for dry matter yield) of which also had mild effects on SCA. The small impact of dominant effects is consistent with the known differentiation between the dent and flint heterotic groups and the small percentage of hybrid variance due to SCA observed in our design (∼20% for the different traits). Furthermore, most (80%) of GCA QTL were segregating in only one of the two heterotic groups. Relative to tester-based designs, use of hybrids between two multiparental populations appears highly cost efficient to detect QTL in two heterotic groups simultaneously. This presents new prospects for selecting superior hybrid combinations with markers. Copyright © 2017 by the Genetics Society of America.

  5. TargetM6A: Identifying N6-Methyladenosine Sites From RNA Sequences via Position-Specific Nucleotide Propensities and a Support Vector Machine.

    Science.gov (United States)

    Li, Guang-Qing; Liu, Zi; Shen, Hong-Bin; Yu, Dong-Jun

    2016-10-01

    As one of the most ubiquitous post-transcriptional modifications of RNA, N 6 -methyladenosine ( [Formula: see text]) plays an essential role in many vital biological processes. The identification of [Formula: see text] sites in RNAs is significantly important for both basic biomedical research and practical drug development. In this study, we designed a computational-based method, called TargetM6A, to rapidly and accurately target [Formula: see text] sites solely from the primary RNA sequences. Two new features, i.e., position-specific nucleotide/dinucleotide propensities (PSNP/PSDP), are introduced and combined with the traditional nucleotide composition (NC) feature to formulate RNA sequences. The extracted features are further optimized to obtain a much more compact and discriminative feature subset by applying an incremental feature selection (IFS) procedure. Based on the optimized feature subset, we trained TargetM6A on the training dataset with a support vector machine (SVM) as the prediction engine. We compared the proposed TargetM6A method with existing methods for predicting [Formula: see text] sites by performing stringent jackknife tests and independent validation tests on benchmark datasets. The experimental results show that the proposed TargetM6A method outperformed the existing methods for predicting [Formula: see text] sites and remarkably improved the prediction performances, with MCC = 0.526 and AUC = 0.818. We also provided a user-friendly web server for TargetM6A, which is publicly accessible for academic use at http://csbio.njust.edu.cn/bioinf/TargetM6A.

  6. Post-genome wide association studies and functional analyses identify association of MPP7 gene variants with site-specific bone mineral density.

    Science.gov (United States)

    Xiao, Su-Mei; Kung, Annie Wai Chee; Gao, Yi; Lau, Kam-Shing; Ma, Alvin; Zhang, Zhen-Lin; Liu, Jian-Min; Xia, Wiebo; He, Jin-Wei; Zhao, Lin; Nie, Min; Fu, Wei-Zhen; Zhang, Min-Jia; Sun, Jing; Kwan, Johnny S H; Tso, Gloria Hoi Wan; Dai, Zhi-Jie; Cheung, Ching-Lung; Bow, Cora H; Leung, Anskar Yu Hung; Tan, Kathryn Choon Beng; Sham, Pak Chung

    2012-04-01

    Our previous genome-wide association study (GWAS) in a Hong Kong Southern Chinese population with extreme bone mineral density (BMD) scores revealed suggestive association with MPP7, which ranked second after JAG1 as a candidate gene for BMD. To follow-up this suggestive signal, we replicated the top single-nucleotide polymorphism rs4317882 of MPP7 in three additional independent Asian-descent samples (n= 2684). The association of rs4317882 reached the genome-wide significance in the meta-analysis of all available subjects (P(meta)= 4.58 × 10(-8), n= 4204). Site heterogeneity was observed, with a larger effect on spine than hip BMD. Further functional studies in a zebrafish model revealed that vertebral bone mass was lower in an mpp7 knock-down model compared with the wide-type (P= 9.64 × 10(-4), n= 21). In addition, MPP7 was found to have constitutive expression in human bone-derived cells during osteogenesis. Immunostaining of murine MC3T3-E1 cells revealed that the Mpp7 protein is localized in the plasma membrane and intracytoplasmic compartment of osteoblasts. In an assessment of the function of identified variants, an electrophoretic mobility shift assay demonstrated the binding of transcriptional factor GATA2 to the risk allele 'A' but not the 'G' allele of rs4317882. An mRNA expression study in human peripheral blood mononuclear cells confirmed that the low BMD-related allele 'A' of rs4317882 was associated with lower MPP7 expression (P= 9.07 × 10(-3), n= 135). Our data suggest a genetic and functional association of MPP7 with BMD variation.

  7. Modeling Submarine Lava Flow with ASPECT

    Science.gov (United States)

    Storvick, E. R.; Lu, H.; Choi, E.

    2017-12-01

    Submarine lava flow is not easily observed and experimented on due to limited accessibility and challenges posed by the fast solidification of lava and the associated drastic changes in rheology. However, recent advances in numerical modeling techniques might address some of these challenges and provide unprecedented insight into the mechanics of submarine lava flow and conditions determining its wide-ranging morphologies. In this study, we explore the applicability ASPECT, Advanced Solver for Problems in Earth's ConvecTion, to submarine lava flow. ASPECT is a parallel finite element code that solves problems of thermal convection in the Earth's mantle. We will assess ASPECT's capability to model submarine lava flow by observing models of lava flow morphology simulated with GALE, a long-term tectonics finite element analysis code, with models created using comparable settings and parameters in ASPECT. From these observations we will contrast the differing models in order to identify the benefits of each code. While doing so, we anticipate we will learn about the conditions required for end-members of lava flow morphology, for example, pillows and sheet flows. With ASPECT specifically we focus on 1) whether the lava rheology can be implemented; 2) how effective the AMR is in resolving morphologies of the solidified crust; 3) whether and under what conditions the end-members of the lava flow morphologies, pillows and sheets, can be reproduced.

  8. Delusion disorder: Neuropsychological aspects

    Directory of Open Access Journals (Sweden)

    Leposavić Ivana

    2004-01-01

    Full Text Available Previous studies concerned with neuropsychological aspect of delusions, were mainly focused on specific forms of this disorder. Comparatively small number of investigations were concerned with cognitive deficiencies accompanying the delusions. The substance of this study includes the detection of neuropsychological disfunctions in patients with persistent delusion disorder, and in tracing of these cognitive distortions to appropriate brain regions. Besides, characteristics of attribution style in these patients are analysed, from the aspect of their connections with unadjusted localized input for their reasoning system. The investigation is designed as a comparative study. The sample includes: a group of patients with persistent delusion disorder; a group of patients with paranoid schizophrenia; a group of healthy individuals. The participants have been tested by a neuropsychological battery that represents the following cognitive functions: attention, memory, vizuospatial and vizuoconstruction organization, executive ability, verbal divergent thinking. Projective Rorschach's method was used for estimation of attribution style.

  9. Haematoxylin and eosin staining identifies medium to large bacterial aggregates with a reliable specificity: A comparative analysis of follicular bacterial aggregates in axillary biopsies using peptide nucleic acid-fluorescence in situ hybridization and haematoxylin and eosin staining

    DEFF Research Database (Denmark)

    Ring, Hans Christian; Riis, Peter Theut; Bay, Lene

    2017-01-01

    between bacterial aggregates identified by haematoxylin and eosin (HE) staining vs bacterial aggregates in corresponding PNA-FISH samples. Axillary biopsies were obtained in 24 healthy controls. HE-stained and PNA-FISH samples were investigated using traditional light microscopy and CLSM, respectively....... The data demonstrate that HE staining identifies large bacterial aggregates (>10 μm) with a sensitivity of 0.43 and specificity of 1. The methods, however, are not equivalent as demonstrated by a McNemar's test (P=.04). Where bacterial aggregates >10 μm in diameter, HE staining may offer a rapid...... and practical low-cost tool to evaluate bacterial aggregates....

  10. Nuclear medicine software: safety aspects

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    A brief editorial discusses the safety aspects of nuclear medicine software. Topics covered include some specific features which should be incorporated into a well-written piece of software, some specific points regarding software testing and legal liability if inappropriate medical treatment was initiated as a result of information derived from a piece of clinical apparatus incorporating a malfunctioning computer program. (U.K.)

  11. Cosmological aspects of superstring models

    International Nuclear Information System (INIS)

    Binetruy, P.

    1986-10-01

    I consider more specifically the cosmological aspects of supersymmetry breaking in ''superstring models'' (grand unified models which are believed to describe the effective theory obtained by compactification of superstring theories). The most interesting aspects are related to the presence of flat directions in the scalar potential (vacuum degeneracies). These flat directions are discussed both in the hidden sector of these models (do they give rise to inflation) and in the observable sector of quarks, leptons and Higgs particles, in connection with baryogenesis

  12. AspectKE*

    DEFF Research Database (Denmark)

    Yang, Fan; Masuhara, Hidehiko; Aotani, Tomoyuki

    2010-01-01

    Enforcing security policies to distributed systems is difficult, in particular, when a system contains untrusted components. We designed AspectKE*, a distributed AOP language based on a tuple space, to tackle this issue. In AspectKE*, aspects can enforce access control policies that depend......KE*, and demonstrate usefulness of AspectKE* through a security aspect for a distributed chat system....

  13. Tense and aspect in Lamnsoʹ

    Directory of Open Access Journals (Sweden)

    Lendzemo Constantine Yuka

    2012-12-01

    Full Text Available Yuka (1997 has identified three broad tenses in Lamnso’2. A closer look at these tenses and their specification of time reference willreveal a more complex tense structure of multiple past and future timeallusions that distinguish different degrees of remoteness to the pastand future tense categories. This paper seeks to determine the variousdegrees of remoteness to a given tense category exhibited in Lamnso’. This paper investigates the relative relationship(s between a tense marker that denotes the time of an action and the time reference preceding or following that action within the clause. It also examines aspect, interpreted as the way of conceiving the flow of an event (Comrie, 1976. This study identifies seven tense forms for Lamnso’ (P3, P2, P1, P0, F1, F2 and F3., which specify time distinctions from the remote past (P3 to the remote future (F3 and three aspect forms. These ten tense and aspect forms combine with distinctive tones and time adverbials to derive a time reference structure whose cut-off points are sometimes fluid and non-rigid.

  14. Some global aspects regarding nuclear spent fuel management

    International Nuclear Information System (INIS)

    Ohai, Dumitru; Postoaca, Marius Marcel

    2002-01-01

    The globalization means the worldwide extension of certain aspects of social or economic processes, structural or environmental changes, or concerning working methodologies, technical activity, industrial production, etc. At present the emergence of global aspects is more frequently observed, being determined by the rapid development of computerized systems and of transfer of information, by the development of big transnational companies and due to the increasing international co-operation. Some of the manifested global aspects could be beneficial for the development of the human society, other could be not. It is necessary to perform an adequate analysis from this view point and to promote appropriate measures to enhance the positive global aspects and to mitigate the negative global aspects. These measures can have a good efficiency only if they are pursued at global level, but for this it is necessary to build an adequate international coordinating body, having the corresponding instruments for action. The global aspects identified in the field of nuclear power may be divided into two categories, namely: - related to the main features of nuclear power; - regarding the specific features of some subdivisions of the field, as for example, spent fuel management. In the paper both categories are discussed. The influence of the global aspects on the development of nuclear power and particularly on the back end activities of the fuel cycle, is also presented. At the same time, some possible actions for enhancing nuclear power development are proposed

  15. Aspects and Polymorphism in AspectJ

    DEFF Research Database (Denmark)

    Lorenz, David Harel; Ernst, Erik

    2003-01-01

    There are two important points of view on inclusion or subtype polymorphism in object-oriented programs, namely polymorphic access and dynamic dispatch. These features are essential for object-oriented programming, and it is worthwhile to consider whether they are supported in aspect-oriented......J as the basis for the presentation. The results are not exclusive to AspectJ---aspectual polymorphism may make aspects in any comparable AOSD language more expressive and reusable across programs, while preserving safety....

  16. “Drug mules” as a radiological challenge: Sensitivity and specificity in identifying internal cocaine in body packers, body pushers and body stuffers by computed tomography, plain radiography and Lodox

    Energy Technology Data Exchange (ETDEWEB)

    Flach, Patricia M., E-mail: patricia.flach@irm.uzh.ch [Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Bern, Buehlstrasse 20, 3012 Bern (Switzerland); Department of Neuroradiology, Inselspital Bern, University of Bern, 3010 Bern (Switzerland); Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Department of Radiology, University Hospital USZ, University of Zurich, Raemistrasse 100, 8091 Zurich (Switzerland); Ross, Steffen G. [Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Bern, Buehlstrasse 20, 3012 Bern (Switzerland); Ampanozi, Garyfalia; Ebert, Lars [Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Bern, Buehlstrasse 20, 3012 Bern (Switzerland); Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Germerott, Tanja; Hatch, Gary M. [Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Bern, Buehlstrasse 20, 3012 Bern (Switzerland); Thali, Michael J. [Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Bern, Buehlstrasse 20, 3012 Bern (Switzerland); Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Patak, Michael A. [Department of Radiology, Inselspital Bern, University of Bern, 3010 Bern (Switzerland); Department of Radiology, University Hospital USZ, University of Zurich, Raemistrasse 100, 8091 Zurich (Switzerland)

    2012-10-15

    Purpose: The purpose of our study was to retrospectively evaluate the specificity, sensitivity and accuracy of computed tomography (CT), digital radiography (DR) and low-dose linear slit digital radiography (LSDR, Lodox{sup ®}) in the detection of internal cocaine containers. Methods: Institutional review board approval was obtained. The study collectively consisted of 83 patients (76 males, 7 females, 16–45 years) suspected of having incorporated cocaine drug containers. All underwent radiological imaging; a total of 135 exams were performed: nCT = 35, nDR = 70, nLSDR = 30. An overall calculation of all “drug mules” and a specific evaluation of body packers, pushers and stuffers were performed. The gold standard was stool examination in a dedicated holding cell equipped with a drug toilet. Results: There were 54 drug mules identified in this study. CT of all drug carriers showed the highest diagnostic accuracy 97.1%, sensitivity 100% and specificity 94.1%. DR in all cases was 71.4% accurate, 58.3% sensitive and 85.3% specific. LSDR of all patients with internal cocaine was 60% accurate, 57.9% sensitive and 63.4% specific. Conclusions: CT was the most accurate test studied. Therefore, the detection of internal cocaine drug packs should be performed by CT, rather than by conventional X-ray, in order to apply the most sensitive exam in the medico-legal investigation of suspected drug carriers. Nevertheless, the higher radiation applied by CT than by DR or LSDR needs to be considered. Future studies should include evaluation of low dose CT protocols in order to address germane issues and to reduce dosage.

  17. “Drug mules” as a radiological challenge: Sensitivity and specificity in identifying internal cocaine in body packers, body pushers and body stuffers by computed tomography, plain radiography and Lodox

    International Nuclear Information System (INIS)

    Flach, Patricia M.; Ross, Steffen G.; Ampanozi, Garyfalia; Ebert, Lars; Germerott, Tanja; Hatch, Gary M.; Thali, Michael J.; Patak, Michael A.

    2012-01-01

    Purpose: The purpose of our study was to retrospectively evaluate the specificity, sensitivity and accuracy of computed tomography (CT), digital radiography (DR) and low-dose linear slit digital radiography (LSDR, Lodox ® ) in the detection of internal cocaine containers. Methods: Institutional review board approval was obtained. The study collectively consisted of 83 patients (76 males, 7 females, 16–45 years) suspected of having incorporated cocaine drug containers. All underwent radiological imaging; a total of 135 exams were performed: nCT = 35, nDR = 70, nLSDR = 30. An overall calculation of all “drug mules” and a specific evaluation of body packers, pushers and stuffers were performed. The gold standard was stool examination in a dedicated holding cell equipped with a drug toilet. Results: There were 54 drug mules identified in this study. CT of all drug carriers showed the highest diagnostic accuracy 97.1%, sensitivity 100% and specificity 94.1%. DR in all cases was 71.4% accurate, 58.3% sensitive and 85.3% specific. LSDR of all patients with internal cocaine was 60% accurate, 57.9% sensitive and 63.4% specific. Conclusions: CT was the most accurate test studied. Therefore, the detection of internal cocaine drug packs should be performed by CT, rather than by conventional X-ray, in order to apply the most sensitive exam in the medico-legal investigation of suspected drug carriers. Nevertheless, the higher radiation applied by CT than by DR or LSDR needs to be considered. Future studies should include evaluation of low dose CT protocols in order to address germane issues and to reduce dosage

  18. Haematoxylin and eosin staining identifies medium to large bacterial aggregates with a reliable specificity: A comparative analysis of follicular bacterial aggregates in axillary biopsies using peptide nucleic acid-fluorescence in situ hybridization and haematoxylin and eosin staining.

    Science.gov (United States)

    Ring, Hans Christian; Theut Riis, Peter; Bay, Lene; Kallenbach, Klaus; Bjarnsholt, Thomas; Jemec, Gregor B E

    2017-10-01

    Although peptide nucleic acid (PNA), fluorescence in situ hybridization (FISH) and confocal laser scanning microscopy (CLSM) are the reference tools in the study of bacterial aggregates/biofilms, it may also be rather time-consuming. This study aimed to investigate the sensitivity and specificity between bacterial aggregates identified by haematoxylin and eosin (HE) staining vs bacterial aggregates in corresponding PNA-FISH samples. Axillary biopsies were obtained in 24 healthy controls. HE-stained and PNA-FISH samples were investigated using traditional light microscopy and CLSM, respectively. The data demonstrate that HE staining identifies large bacterial aggregates (>10 μm) with a sensitivity of 0.43 and specificity of 1. The methods, however, are not equivalent as demonstrated by a McNemar's test (P=.04). Where bacterial aggregates >10 μm in diameter, HE staining may offer a rapid and practical low-cost tool to evaluate bacterial aggregates. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Coordiantion by using Product Specifications in Product Development

    DEFF Research Database (Denmark)

    Terkelsen, Søren Bendix

    1997-01-01

    This paper is based on a case study. It treats the coordination by generating product specifications in product development. This paper contains three very important aspects, which cause a need for coordination, and call attention to the coordination mechanisms. The three aspects are task...... uncertainty, task complexity, and dependencies between activities. If one want to select coordination mechanisms, which improve the performance in product development, it is very important to have a knowledge about these three aspects. In the following the aspects are identified in the literature...

  20. Formal aspects of resilience

    Directory of Open Access Journals (Sweden)

    Diana-Maria Drigă

    2015-12-01

    Full Text Available The concept of resilience has represented during the recent years a leading concern both in Romania, within the European Union and worldwide. Specialists in economics, management, finance, legal sciences, political sciences, sociology, psychology, grant a particular interest to this concept. Multidisciplinary research of resilience has materialized throughout the time in multiple conceptualizations and theorizing, but without being a consensus between specialists in terms of content, specificity and scope. Through this paper it is intended to clarify the concept of resilience, achieving an exploration of the evolution of this concept in ecological, social and economic environment. At the same time, the paper presents aspects of feedback mechanisms and proposes a formalization of resilience using the logic and mathematical analysis.

  1. Legal aspects of dosimetry

    International Nuclear Information System (INIS)

    Pomarola, H.

    1976-01-01

    The use of ionizing radiations is regulated in France in all fields of application. The main principles governing inspection activities in the food industry are outlined. Conventional preservation methods are mentioned, after which a discussion is devoted to the preservation of food products by irradiation treatment and the increasing importance given to this technique. Consumer protection automatically implies the obligatory use of dosimetry by inspection organisms if the irradiated merchandise is likely to serve for human or animal consumption. Irradiation treatment permits are granted in a context of specific statutory texts mentioned here. Supervision is constant, but always both realistic and flexible. Each aspect of this treatment is discussed in maximum detail if not quite exhaustively, with special emphasis on dosimetry as an indispensable safety factor [fr

  2. Computational Aspects of Asynchronous CA

    OpenAIRE

    Chandesris, Jérôme; Dennunzio, Alberto; Formenti, Enrico; Manzoni, Luca

    2011-01-01

    This work studies some aspects of the computational power of fully asynchronous cellular automata (ACA). We deal with some notions of simulation between ACA and Turing Machines. In particular, we characterize the updating sequences specifying which are "universal", i.e., allowing a (specific family of) ACA to simulate any TM on any input. We also consider the computational cost of such simulations.

  3. Early Aspects at ICSE 2007: Workshop on Aspect-Oriented Requirements Engineering and Architecture Design

    NARCIS (Netherlands)

    Chitchyan, R; Rashid, A.; Moreira, A; Araujo, J.; Clements, P.; Baniassad, E.; Tekinerdogan, B.

    2007-01-01

    The “Early Aspects @ ICSE’07��? is the 11th workshop in the series of Early Aspects workshops [1] which focuses on aspect identification during the requirements engineering and architecture derivation activities. The specific aim of the present workshop is twofold: (a) to initiate creation of an

  4. Identifying Aboriginal-specific AUDIT-C and AUDIT-3 cutoff scores for at-risk, high-risk, and likely dependent drinkers using measures of agreement with the 10-item Alcohol Use Disorders Identification Test.

    Science.gov (United States)

    Calabria, Bianca; Clifford, Anton; Shakeshaft, Anthony P; Conigrave, Katherine M; Simpson, Lynette; Bliss, Donna; Allan, Julaine

    2014-09-01

    The Alcohol Use Disorders Identification Test (AUDIT) is a 10-item alcohol screener that has been recommended for use in Aboriginal primary health care settings. The time it takes respondents to complete AUDIT, however, has proven to be a barrier to its routine delivery. Two shorter versions, AUDIT-C and AUDIT-3, have been used as screening instruments in primary health care. This paper aims to identify the AUDIT-C and AUDIT-3 cutoff scores that most closely identify individuals classified as being at-risk drinkers, high-risk drinkers, or likely alcohol dependent by the 10-item AUDIT. Two cross-sectional surveys were conducted from June 2009 to May 2010 and from July 2010 to June 2011. Aboriginal Australian participants (N = 156) were recruited through an Aboriginal Community Controlled Health Service, and a community-based drug and alcohol treatment agency in rural New South Wales (NSW), and through community-based Aboriginal groups in Sydney NSW. Sensitivity, specificity, and positive and negative predictive values of each score on the AUDIT-C and AUDIT-3 were calculated, relative to cutoff scores on the 10-item AUDIT for at-risk, high-risk, and likely dependent drinkers. Receiver operating characteristic (ROC) curve analyses were conducted to measure the detection characteristics of AUDIT-C and AUDIT-3 for the three categories of risk. The areas under the receiver operating characteristic (AUROC) curves were high for drinkers classified as being at-risk, high-risk, and likely dependent. Recommended cutoff scores for Aboriginal Australians are as follows: at-risk drinkers AUDIT-C ≥ 5, AUDIT-3 ≥ 1; high-risk drinkers AUDIT-C ≥ 6, AUDIT-3 ≥ 2; and likely dependent drinkers AUDIT-C ≥ 9, AUDIT-3 ≥ 3. Adequate sensitivity and specificity were achieved for recommended cutoff scores. AUROC curves were above 0.90.

  5. Link between Research, Development and Demonstration (RD and D) and Stakeholder Confidence: the Specific Aspect of Long-term Safety. Proceedings of a Topical Session, Issy-les-Moulineaux, France 6-8 June 2007

    International Nuclear Information System (INIS)

    2008-01-01

    The Forum on Stakeholder Confidence (FSC) was created under a mandate from the OECD Nuclear Energy Agency's Radioactive Waste Management Committee (RWMC) to facilitate the sharing of international experience in addressing the societal dimension of radioactive waste management. It explores means of ensuring an effective dialogue with the public, and considers ways to strengthen confidence in decision-making processes. NEA member countries nominate participants. The FSC today includes representatives of national regulators, implementing agencies, policy makers, and R and D scientists from 16 OECD countries and two international organisations. Each has experience in and/or responsibility for stakeholder interaction. The Forum was launched in August 2000, in Paris, and convenes a series of alternating regular meetings and workshops. The FSC is expected to identify specific issues of interest on which stakeholders can learn from one another and provide a platform for discussing and exchanging those issues. This topical session's emphasis on long-term safety is meant to complement the Programme of Work of the RWMC in this area and to create a bridge between the FSC and the more technically oriented groups of the RWMC, e.g., the Integration Group for the Safety Case (IGSC) and the Regulators' Forum. These Proceedings are meant to provide a record that can be used by a wide spectrum of stakeholders and decision-makers. They include: a) An executive summary of the topical presentations, and of the discussion they sparked within the FSC; b) Texts and Power Point presentations provided by the speakers at the Topical Session

  6. Gender specific analysis of occupational diseases of the low back caused by carrying, lifting or extreme trunk flexion—use of a prevention index to identify occupations with high prevention needs

    Science.gov (United States)

    Thiede, Markus; Liebers, Falk; Seidler, Andreas; Gravemeyer, Stefan; Latza, Ute

    2014-01-01

    Background Gender specific analysis of the occupational disease of the lumbar spine caused by carrying, lifting, or extreme trunk flexion in Germany (OD No.2108) with the aim to identify areas of focus for prevention and research with a prevention index (PI). Methods Data from the German Statutory Accident Insurance stratified by gender are shown. Results From 2002 until 2009 there were 2,877 confirmed cases of an OD No. 2108 (40.1% male and 59.1% female). The PI indicated the highest prevention need for female nursing/midwifery associate professionals and male building frame and related trades workers. Patient transfer and working in extremely bent posture were the most frequent exposures. Conclusions The identified occupations with high need for prevention among men come from nearly all major occupational groups whereas women cluster in occupational groups from the health and care sectors. Am. J. Ind. Med. 57:233–244, 2014. © 2013 The Authors. American Journal of Industrial Medicine Published by Wiley Periodicals, Inc. PMID:24243091

  7. Genetic and molecular risk factors within the newly identified primate-specific exon of the SAP97/DLG1 gene in the 3q29 schizophrenia-associated locus.

    Science.gov (United States)

    Uezato, Akihito; Yamamoto, Naoki; Jitoku, Daisuke; Haramo, Emiko; Hiraaki, Eri; Iwayama, Yoshimi; Toyota, Tomoko; Umino, Masakazu; Umino, Asami; Iwata, Yasuhide; Suzuki, Katsuaki; Kikuchi, Mitsuru; Hashimoto, Tasuku; Kanahara, Nobuhisa; Kurumaji, Akeo; Yoshikawa, Takeo; Nishikawa, Toru

    2017-12-01

    The synapse-associated protein 97/discs, large homolog 1 of Drosophila (DLG1) gene encodes synaptic scaffold PDZ proteins interacting with ionotropic glutamate receptors including the N-methyl-D-aspartate type glutamate receptor (NMDAR) that is presumed to be hypoactive in brains of patients with schizophrenia. The DLG1 gene resides in the chromosomal position 3q29, the microdeletion of which confers a 40-fold increase in the risk for schizophrenia. In the present study, we performed genetic association analyses for DLG1 gene using a Japanese cohort with 1808 schizophrenia patients and 2170 controls. We detected an association which remained significant after multiple comparison testing between schizophrenia and the single nucleotide polymorphism (SNP) rs3915512 that is located within the newly identified primate-specific exon (exon 3b) of the DLG1 gene and constitutes the exonic splicing enhancer sequence. When stratified by onset age, although it did not survive multiple comparisons, the association was observed in non-early onset schizophrenia, whose onset-age selectivity is consistent with our recent postmortem study demonstrating a decrease in the expression of the DLG1 variant in early-onset schizophrenia. Although the present study did not demonstrate the previously reported association of the SNP rs9843659 by itself, a meta-analysis revealed a significant association between DLG1 gene and schizophrenia. These findings provide a valuable clue for molecular mechanisms on how genetic variations in the primate-specific exon of the gene in the schizophrenia-associated 3q29 locus affect its regulation in the glutamate system and lead to the disease onset around a specific stage of brain development. © 2017 Wiley Periodicals, Inc.

  8. Legal aspects of radiactive installations

    International Nuclear Information System (INIS)

    Malheiros, T.M.M.; Knoefell, T.M.J.

    1988-01-01

    The goal of this paper is to discuss the main legal aspects related to the application of ionizing radiation in the industry, medicine, agriculture, scientific activities to envisage from the in force legislation the competence and responsibility for the control of radiation facilities comprising regulation, licensing and inspection. Legislation does not embrace all the aspects related to radiation facilities regarding to the specific provisions on civil liability concerning damages caused by non nuclear radiological accidents. The law nr.6.453 is applied only to nuclear accident, as defined in its rules. (author) [pt

  9. Identifying Aboriginal-specific AUDIT-C and AUDIT-3 cutoff scores for at-risk, high-risk, and likely dependent drinkers using measures of agreement with the 10-item Alcohol Use Disorders Identification Test

    Science.gov (United States)

    2014-01-01

    Background The Alcohol Use Disorders Identification Test (AUDIT) is a 10-item alcohol screener that has been recommended for use in Aboriginal primary health care settings. The time it takes respondents to complete AUDIT, however, has proven to be a barrier to its routine delivery. Two shorter versions, AUDIT-C and AUDIT-3, have been used as screening instruments in primary health care. This paper aims to identify the AUDIT-C and AUDIT-3 cutoff scores that most closely identify individuals classified as being at-risk drinkers, high-risk drinkers, or likely alcohol dependent by the 10-item AUDIT. Methods Two cross-sectional surveys were conducted from June 2009 to May 2010 and from July 2010 to June 2011. Aboriginal Australian participants (N = 156) were recruited through an Aboriginal Community Controlled Health Service, and a community-based drug and alcohol treatment agency in rural New South Wales (NSW), and through community-based Aboriginal groups in Sydney NSW. Sensitivity, specificity, and positive and negative predictive values of each score on the AUDIT-C and AUDIT-3 were calculated, relative to cutoff scores on the 10-item AUDIT for at-risk, high-risk, and likely dependent drinkers. Receiver operating characteristic (ROC) curve analyses were conducted to measure the detection characteristics of AUDIT-C and AUDIT-3 for the three categories of risk. Results The areas under the receiver operating characteristic (AUROC) curves were high for drinkers classified as being at-risk, high-risk, and likely dependent. Conclusions Recommended cutoff scores for Aboriginal Australians are as follows: at-risk drinkers AUDIT-C ≥ 5, AUDIT-3 ≥ 1; high-risk drinkers AUDIT-C ≥ 6, AUDIT-3 ≥ 2; and likely dependent drinkers AUDIT-C ≥ 9, AUDIT-3 ≥ 3. Adequate sensitivity and specificity were achieved for recommended cutoff scores. AUROC curves were above 0.90. PMID:25179547

  10. Structures of Preferred Human IgV Genes-Based Protective Antibodies Identify How Conserved Residues Contact Diverse Antigens and Assign Source of Specificity to CDR3 Loop Variation.

    Science.gov (United States)

    Bryson, Steve; Thomson, Christy A; Risnes, Louise F; Dasgupta, Somnath; Smith, Kenneth; Schrader, John W; Pai, Emil F

    2016-06-01

    The human Ab response to certain pathogens is oligoclonal, with preferred IgV genes being used more frequently than others. A pair of such preferred genes, IGVK3-11 and IGVH3-30, contributes to the generation of protective Abs directed against the 23F serotype of the pneumonococcal capsular polysaccharide of Streptococcus pneumoniae and against the AD-2S1 peptide of the gB membrane protein of human CMV. Structural analyses of Fab fragments of mAbs 023.102 and pn132p2C05 in complex with portions of the 23F polysaccharide revealed five germline-encoded residues in contact with the key component, l-rhamnose. In the case of the AD-2S1 peptide, the KE5 Fab fragment complex identified nine germline-encoded contact residues. Two of these germline-encoded residues, Arg91L and Trp94L, contact both the l-rhamnose and the AD-2S1 peptide. Comparison of the respective paratopes that bind to carbohydrate and protein reveals that stochastic diversity in both CDR3 loops alone almost exclusively accounts for their divergent specificity. Combined evolutionary pressure by human CMV and the 23F serotype of S. pneumoniae acted on the IGVK3-11 and IGVH3-30 genes as demonstrated by the multiple germline-encoded amino acids that contact both l-rhamnose and AD-2S1 peptide. Copyright © 2016 by The American Association of Immunologists, Inc.

  11. Cross-cultural aspects of anxiety disorders.

    Science.gov (United States)

    Hofmann, Stefan G; Hinton, Devon E

    2014-06-01

    A person's cultural background influences the experience and expression of emotions. In reviewing the recent literature on cross-cultural aspects of anxiety disorders, we identified some culturally related ethnopsychology/ethnophysiology factors (the culture's conceptualizations of how the mind and body function) and contextual factors that influence anxiety disorders. Ethnopsychology/ethnophysiology factors include the person's ideas about the mental and bodily processes (and their interaction), whereas contextual factors are associated with the social norms and rules that may contribute to anxiety, including individualism vs. collectivism and self-construals. From the perspective of ethnopsychology/ethnophysiology and contextual factors, we will discuss "khyâl cap" ("wind attacks"), taijin kyofusho, and ataques de nervios, three prominent examples of culture-specific expressions of anxiety disorders that have all been included in the DSM-5 list of cultural concepts of distress.

  12. Epistemological risk aspects

    Directory of Open Access Journals (Sweden)

    Ardashkin I.B.

    2016-01-01

    Full Text Available The paper considers risk in the context of the main characteristics of non-classical epistemology. It states that non-classical epistemology is characterized by transformation, according to which the major priority of cognitive activity shifts the focus from the present to the past. In this situation a subject is keen not on what he or she has learnt but on what can be learnt. Truth being a crucial criterion of scientific knowledge is becoming of less priority, while risk is becoming more and more significant and acts as one of the major epistemology measurements. Risk is gaining the status of epistemological phenomenon, which shows a growing degree of uncertainty as a cognitive process background and the necessity for a subject to learn the world (make decisions under the conditions of uncertainty degree strengthening. The author states that risk is a comprehensive notion and it obtains a base value for all other aspects of its application, specifically, in the role of epistemological phenomenon.

  13. Electrical aspects of rainout

    International Nuclear Information System (INIS)

    Rosenkilde, C.E.

    1981-01-01

    Rainout commonly denotes the aggregate of phenomena associated with precipitation scavenging of radioactivity from a cloud of nuclear debris that is within a natural rain cloud. (In contrast, the term, washout, is applicable when the nuclear cloud is below the rain cloud and the term, fallout, commonly denotes the direct gravitational settling of contaminated solid material from a nuclear cloud.) Nuclear debris aerosols may be scavenged within natural clouds by a variety of different physical processes which may involve diffusion, convection, impaction, nucleation, phoresis, turbulence, and/or electricity among others. Processes which involve electrical aspects are scrutinized for their susceptibility to the intimate presence of the radioactive-cloud environment. This particular choice of electrical processes is not accidental. Nearly all of the listed processes were examined earlier by Williams. His rough estimates suggested that electrical effects, and to a lesser extent turbulence, could enhance the scavenging of those submicron aerosols which reside in the size-range that bridges the minimum in the scavenging rate coefficient which is commonly called the Greenfield gap. This minimum in the scavenging-rate coefficient is created by the simultaneous reduction of scavenging via diffusion and the reduction of scavenging via inertial impaction. However, Williams omitted the specific influence of a radioactive environment. This report aims to remedy this omission

  14. Gestational surrogacy: Psychosocial aspects

    Directory of Open Access Journals (Sweden)

    Nicolás Ruiz-Robledillo

    2016-12-01

    Full Text Available Innovation in assisted reproductive technologies together with increased infertility and new family structures are increasing the use of gestational surrogacy as a means to have children. Before, during and after the process, it is necessary to study the psychosocial characteristics of triad members: the gestational surrogate, intended parents, and offspring. Research has indicated positive adaptation to the process and benefits for all members of the triad. Altruism is the main motivation of surrogates. Notably, psychological well-being has been found to be higher in individuals who have become parents through surrogacy than in those who have used egg donation or have followed a natural process of conception. Moreover, no differences in psychosocial characteristics have been observed in the offspring, compared with children born through natural conception or egg donation. Results highlight the positive aspects of surrogacy. Future research should investigate psychosocial factors that modulate the process, acting as risk and protective factors for well-being of the triad members, and identify the optimal profiles of surrogates for the process to be a success.

  15. Operational Radiological Protection and Aspects of Optimisation

    International Nuclear Information System (INIS)

    Lazo, E.; Lindvall, C.G.

    2005-01-01

    Since 1992, the Nuclear Energy Agency (NEA), along with the International Atomic Energy Agency (IAEA), has sponsored the Information System on Occupational Exposure (ISOE). ISOE collects and analyses occupational exposure data and experience from over 400 nuclear power plants around the world and is a forum for radiological protection experts from both nuclear power plants and regulatory authorities to share lessons learned and best practices in the management of worker radiation exposures. In connection to the ongoing work of the International Commission on Radiological Protection (ICRP) to develop new recommendations, the ISOE programme has been interested in how the new recommendations would affect operational radiological protection application at nuclear power plants. Bearing in mind that the ICRP is developing, in addition to new general recommendations, a new recommendation specifically on optimisation, the ISOE programme created a working group to study the operational aspects of optimisation, and to identify the key factors in optimisation that could usefully be reflected in ICRP recommendations. In addition, the Group identified areas where further ICRP clarification and guidance would be of assistance to practitioners, both at the plant and the regulatory authority. The specific objective of this ISOE work was to provide operational radiological protection input, based on practical experience, to the development of new ICRP recommendations, particularly in the area of optimisation. This will help assure that new recommendations will best serve the needs of those implementing radiation protection standards, for the public and for workers, at both national and international levels. (author)

  16. Aspect-Oriented Programming

    NARCIS (Netherlands)

    Bergmans, Lodewijk; Videira Lopes, Cristina; Moreira, Ana; Demeyer, Serge

    1999-01-01

    Aspect-oriented programming is a promising idea that can improve the quality of software by reduce the problem of code tangling and improving the separation of concerns. At ECOOP'97, the first AOP workshop brought together a number of researchers interested in aspect-orientation. At ECOOP'98, during

  17. Conjugated Polymers and Oligomers: Structural and Soft Matter Aspects

    DEFF Research Database (Denmark)

    This book identifies modern topics and current trends of structural and soft matter aspects of conjugated polymers and oligomers. Each chapter recognizes an active research line where structural perspective dominates research and therefore the book covers fundamental aspects of persistent...

  18. Cultural Aspects of Suicide

    Directory of Open Access Journals (Sweden)

    Hari D. Maharajh

    2005-01-01

    Full Text Available Undefined cultural factors cannot be dismissed and significantly contribute to the worldwide incidence of death by suicide. Culture is an all embracing term and defines the relationship of an individual to his environment. This study seeks to investigate the effect of culture on suicide both regionally and internationally. Culture-bound syndrome with suicidal behaviours specific to a particular culture or geographical region are discussed. Opinions are divided as to the status of religious martyrs. The law itself is silent on many aspects of suicidal behaviour and despite decriminalization of suicide as self-murder, the latter remains on the statutes of many developing countries. The Caribbean region is of concern due to its steady rise in mean suicide rate, especially in Trinidad and Tobago where socio-cultural factors are instrumental in influencing suicidal behaviour. These include transgenerational cultural conflicts, psycho-social problems, media exposure, unemployment, social distress, religion and family structure. The methods used are attributed to accessibility and lethality. Ingestion of poisonous substances is most popular followed by hanging. The gender differences seen with regard to suicidality can also be attributed to gender related psychopathology and psychosocial differences in help-seeking behaviour. These are influenced by the cultural environment to which the individual is exposed. Culture provides coping strategies to individuals; as civilization advances many of these coping mechanisms are lost unclothing the genetic predisposition of vulnerable groups. In the management of suicidal behaviour, a system of therapeutic re-culturation is needed with an emphasis on relevant culture- based therapies.

  19. Identifying Topics in Microblogs Using Wikipedia.

    Directory of Open Access Journals (Sweden)

    Ahmet Yıldırım

    Full Text Available Twitter is an extremely high volume platform for user generated contributions regarding any topic. The wealth of content created at real-time in massive quantities calls for automated approaches to identify the topics of the contributions. Such topics can be utilized in numerous ways, such as public opinion mining, marketing, entertainment, and disaster management. Towards this end, approaches to relate single or partial posts to knowledge base items have been proposed. However, in microblogging systems like Twitter, topics emerge from the culmination of a large number of contributions. Therefore, identifying topics based on collections of posts, where individual posts contribute to some aspect of the greater topic is necessary. Models, such as Latent Dirichlet Allocation (LDA, propose algorithms for relating collections of posts to sets of keywords that represent underlying topics. In these approaches, figuring out what the specific topic(s the keyword sets represent remains as a separate task. Another issue in topic detection is the scope, which is often limited to specific domain, such as health. This work proposes an approach for identifying domain-independent specific topics related to sets of posts. In this approach, individual posts are processed and then aggregated to identify key tokens, which are then mapped to specific topics. Wikipedia article titles are selected to represent topics, since they are up to date, user-generated, sophisticated articles that span topics of human interest. This paper describes the proposed approach, a prototype implementation, and a case study based on data gathered during the heavily contributed periods corresponding to the four US election debates in 2012. The manually evaluated results (0.96 precision and other observations from the study are discussed in detail.

  20. Identifying Topics in Microblogs Using Wikipedia.

    Science.gov (United States)

    Yıldırım, Ahmet; Üsküdarlı, Suzan; Özgür, Arzucan

    2016-01-01

    Twitter is an extremely high volume platform for user generated contributions regarding any topic. The wealth of content created at real-time in massive quantities calls for automated approaches to identify the topics of the contributions. Such topics can be utilized in numerous ways, such as public opinion mining, marketing, entertainment, and disaster management. Towards this end, approaches to relate single or partial posts to knowledge base items have been proposed. However, in microblogging systems like Twitter, topics emerge from the culmination of a large number of contributions. Therefore, identifying topics based on collections of posts, where individual posts contribute to some aspect of the greater topic is necessary. Models, such as Latent Dirichlet Allocation (LDA), propose algorithms for relating collections of posts to sets of keywords that represent underlying topics. In these approaches, figuring out what the specific topic(s) the keyword sets represent remains as a separate task. Another issue in topic detection is the scope, which is often limited to specific domain, such as health. This work proposes an approach for identifying domain-independent specific topics related to sets of posts. In this approach, individual posts are processed and then aggregated to identify key tokens, which are then mapped to specific topics. Wikipedia article titles are selected to represent topics, since they are up to date, user-generated, sophisticated articles that span topics of human interest. This paper describes the proposed approach, a prototype implementation, and a case study based on data gathered during the heavily contributed periods corresponding to the four US election debates in 2012. The manually evaluated results (0.96 precision) and other observations from the study are discussed in detail.

  1. Department of Energy: some aspects of basic research in the chemical sciences

    International Nuclear Information System (INIS)

    1979-01-01

    The basic research needs pertinent to DOE's specific mission are identified in the fields of combustion science, coal chemistry, reprocessing of reactor fuel and the disposal of radioactive waste, and analytical chemistry. Aspects of these fields which do not need DOE support are also identified in some cases. In addition recommendations are made on review procedures and funding, use of DOE laboratories by university and other extramural chemists, isotope availability, and critically evaluated data

  2. [Headache: Otorhinolaryngological aspects].

    Science.gov (United States)

    Michel, O

    2016-01-01

    Headache is the main symptom in a wide variety of diseases of which ear, nose and throat (ENT) entities are only a small fraction but are not reflected in the number of patients. Comprehensive knowledge of the clinical signs of the most common primary headaches, e. g. migraine, is therefore essential for the ENT specialist because the few patients with secondary headache from ENT-related causes must be identified. Reasons for confusing primary headache with e. g. sinusitis are mostly symptoms mediated by the trigeminal nerve, such as nasal obstruction and rhinorrhea because branches of the trigeminal nerve also innervate the meninges. The ENT-specific origin of headaches is characterized by clinical findings of physical organ disease; therefore, from an ENT perspective imaging should be part of the diagnostic procedure as normal imaging findings are indicative of primary headache, which would not normally be treated by an ENT specialist.

  3. NADiA ProsVue prostate-specific antigen slope is an independent prognostic marker for identifying men at reduced risk of clinical recurrence of prostate cancer after radical prostatectomy.

    Science.gov (United States)

    Moul, Judd W; Lilja, Hans; Semmes, O John; Lance, Raymond S; Vessella, Robert L; Fleisher, Martin; Mazzola, Clarisse; Sarno, Mark J; Stevens, Barbara; Klem, Robert E; McDermed, Jonathan E; Triebell, Melissa T; Adams, Thomas H

    2012-12-01

    To validate the hypothesis that men displaying serum prostate-specific antigen (PSA) slopes ≤ 2.0 pg/mL/mo after prostatectomy, measured using a new immuno-polymerase chain reaction diagnostic test (NADiA ProsVue), have a reduced risk of clinical recurrence as determined by positive biopsy, imaging findings, or death from prostate cancer. From 4 clinical sites, we selected a cohort of 304 men who had been followed up for 17.6 years after prostatectomy for clinical recurrence. We assessed the prognostic value of a PSA slope cutpoint of 2.0 pg/mL/mo against established risk factors to identify men at low risk of clinical recurrence using uni- and multivariate Cox proportional hazards regression and Kaplan-Meier analyses. The univariate hazard ratio of a PSA slope >2.0 pg/mL/mo was 18.3 (95% confidence interval 10.6-31.8) compared with a slope ≤ 2.0 pg/mL/mo (P free survival interval was 4.8 years vs >10 years in the 2 groups (P <.0001). The multivariate hazard ratio for PSA slope with the covariates of preprostatectomy PSA, pathologic stage, and Gleason score was 9.8 (95% confidence interval 5.4-17.8), an 89.8% risk reduction for men with PSA slopes ≤ 2.0 pg/mL/mo (P <.0001). The Gleason score (<7 vs ≥ 7) was the only other significant predictor (hazard ratio 5.4, 95% confidence interval 2.1-13.8, P = .0004). Clinical recurrence after radical prostatectomy is difficult to predict using established risk factors. We have demonstrated that a NADiA ProsVue PSA slope of ≤ 2.0 pg/mL/mo after prostatectomy is prognostic for a reduced risk of prostate cancer recurrence and adds predictive power to the established risk factors. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Genome-wide methylation profiling identifies an essential role of reactive oxygen species in pediatric glioblastoma multiforme and validates a methylome specific for H3 histone family 3A with absence of G-CIMP/isocitrate dehydrogenase 1 mutation.

    Science.gov (United States)

    Jha, Prerana; Pia Patric, Irene Rosita; Shukla, Sudhanshu; Pathak, Pankaj; Pal, Jagriti; Sharma, Vikas; Thinagararanjan, Sivaarumugam; Santosh, Vani; Suri, Vaishali; Sharma, Mehar Chand; Arivazhagan, Arimappamagan; Suri, Ashish; Gupta, Deepak; Somasundaram, Kumaravel; Sarkar, Chitra

    2014-12-01

    Pediatric glioblastoma multiforme (GBM) is rare, and there is a single study, a seminal discovery showing association of histone H3.3 and isocitrate dehydrogenase (IDH)1 mutation with a DNA methylation signature. The present study aims to validate these findings in an independent cohort of pediatric GBM, compare it with adult GBM, and evaluate the involvement of important functionally altered pathways. Genome-wide methylation profiling of 21 pediatric GBM cases was done and compared with adult GBM data (GSE22867). We performed gene mutation analysis of IDH1 and H3 histone family 3A (H3F3A), status evaluation of glioma cytosine-phosphate-guanine island methylator phenotype (G-CIMP), and Gene Ontology analysis. Experimental evaluation of reactive oxygen species (ROS) association was also done. Distinct differences were noted between methylomes of pediatric and adult GBM. Pediatric GBM was characterized by 94 hypermethylated and 1206 hypomethylated cytosine-phosphate-guanine (CpG) islands, with 3 distinct clusters, having a trend to prognostic correlation. Interestingly, none of the pediatric GBM cases showed G-CIMP/IDH1 mutation. Gene Ontology analysis identified ROS association in pediatric GBM, which was experimentally validated. H3F3A mutants (36.4%; all K27M) harbored distinct methylomes and showed enrichment of processes related to neuronal development, differentiation, and cell-fate commitment. Our study confirms that pediatric GBM has a distinct methylome compared with that of adults. Presence of distinct clusters and an H3F3A mutation-specific methylome indicate existence of epigenetic subgroups within pediatric GBM. Absence of IDH1/G-CIMP status further indicates that findings in adult GBM cannot be simply extrapolated to pediatric GBM and that there is a strong need for identification of separate prognostic markers. A possible role of ROS in pediatric GBM pathogenesis is demonstrated for the first time and needs further evaluation. © The Author(s) 2014

  5. Toxicological aspects of energy production

    International Nuclear Information System (INIS)

    Sanders, C.L.

    1986-01-01

    Part I reviews the principles of toxicology, describes the biological fate of chemicals in the body, discusses basic pathobiology, and reviews short-term toxicity tests. Part II describes the toxicology and pathology of pollutants in several important organ systems. The greatest emphasis is placed on the respiratory tract because of its high probability as a route of exposure to pollutants from energy technologies and its high sensitivity to pollutant related tissue damage. Part III describes the toxicological aspects of specific chemical classes associated with fossil fuels; these include polycyclic hydrocarbons, gases and metals. Part IV describes the biomedical effects associated with each energy technology, including coal and oil, fossil fuel and biomass conversions, solar and geothermal and radiological health aspects associated with uranium mining, nuclear fission and fusion, and with nonionising radiations and electromagnetic fields

  6. Selected aspects of fusion reactions

    International Nuclear Information System (INIS)

    Lacroix, D.

    2003-01-01

    In this lecture, we present selected aspects of nuclear fusion. The importance of the initial geometry of the reaction and its relation to fusion barrier are first discussed. The effect of deformation leading to the notion of barrier distribution is then illustrated. After a brief overview of the advantages of macroscopic theories, the dynamics of nuclear system under large amplitude motion is reviewed. The di-nuclear concept is presented to understand the competition between fusion and quasi-fission. This concept is then generalized to account for the dissipative dynamics in multidimensional collective space. The last part of this lecture is devoted to new aspects encountered with radioactive beams specific properties of very extended neutron rich system, influence of pygmy or soft dipole resonances and charge exchange far from stability are discussed. (author)

  7. Summary on Theoretical Aspects

    CERN Document Server

    Soffer, Jacques

    2010-01-01

    During the five days of this conference a very dense scientific program has enlighted our research fields, with the presentation of large number of interesting lectures. I will try to summarize the theoretical aspects of some of these new results.

  8. General safety aspects

    International Nuclear Information System (INIS)

    1998-01-01

    In this part next aspects are described: (1) Priority to safety; (2) Financial and human resources;; (3) Human factor; (4) Operator's quality assurance system; (5) Safety assessment and Verification; (6) Radiation protection and (7) Emergency preparedness

  9. Identifying vehicle descriptions in microblogging text with the aim of reducing or predicting crime

    CSIR Research Space (South Africa)

    Featherstone, Coral

    2013-11-01

    Full Text Available in the fight against crime, to the specific problem of identifying the description of vehicles in microblog text. As this problem has many aspects, especially in terms of data gathering and identification, an initial search is performed on preset keywords...

  10. Criminal aspects domestic violence

    OpenAIRE

    Smetanová, Kristina

    2013-01-01

    Smetanová, Kristina. Criminal aspects of domestic violence The topic of this thesis is the criminal aspects of domestic violence. The aim of the thesis is to describe this dangerous and complicated social problem and focus on outlining the possibilities of protection under Czech criminal law. The thesis consists of eight chapters. The first chapter explains what the domestic violence is and which sources, types and characters does it have.The second chapter shows who can be the violent person...

  11. Foundational aspects of security

    DEFF Research Database (Denmark)

    Chatzikokolakis, Konstantinos; Mödersheim, Sebastian Alexander; Palamidessi, Catuscia

    2014-01-01

    This Special Issue of the Journal of Computer Security focuses on foundational aspects of security, which in recent years have helped change much of the way we think about and approach system security.......This Special Issue of the Journal of Computer Security focuses on foundational aspects of security, which in recent years have helped change much of the way we think about and approach system security....

  12. Performance of CT ASPECTS and Collateral Score in Risk Stratification: Can Target Perfusion Profiles Be Predicted without Perfusion Imaging?

    Science.gov (United States)

    Dehkharghani, S; Bammer, R; Straka, M; Bowen, M; Allen, J W; Rangaraju, S; Kang, J; Gleason, T; Brasher, C; Nahab, F

    2016-08-01

    Endovascular trials suggest that revascularization benefits a subset of acute ischemic stroke patients with large-artery occlusion and small-core infarct volumes. The objective of our study was to identify thresholds of noncontrast CT-ASPECTS and collateral scores on CT angiography that best predict ischemic core volume thresholds quantified by CT perfusion among patients with acute ischemic stroke. Fifty-four patients with acute ischemic stroke (collateral score of 3 had 100% specificity for identifying patients with a CBF core volume of ≤50 mL. NCCT-ASPECTS of ≤6 had 100% specificity for identifying patients with a CBF core volume of >50 mL. In our cohort, 44 (81%) patients had an NCCT-ASPECTS of ≥9, a CTA collateral score of 3, or an NCCT-ASPECTS of ≤6. Using an NCCT-ASPECTS of ≥9 or a CTA collateral score of 3 best predicts CBF core volume infarct of ≤50 mL, while an NCCT-ASPECTS of ≤6 best predicts a CBF core volume infarct of >50 mL. Together these thresholds suggest that a specific population of patients with acute ischemic stroke not meeting such profiles may benefit most from CTP imaging to determine candidacy for revascularization. © 2016 by American Journal of Neuroradiology.

  13. Identifying a size-specific hazard of silica nanoparticles after intravenous administration and its relationship to the other hazards that have negative correlations with the particle size in mice

    Science.gov (United States)

    Handa, Takayuki; Hirai, Toshiro; Izumi, Natsumi; Eto, Shun-ichi; Tsunoda, Shin-ichi; Nagano, Kazuya; Higashisaka, Kazuma; Yoshioka, Yasuo; Tsutsumi, Yasuo

    2017-03-01

    Many of the beneficial and toxic biological effects of nanoparticles have been shown to have a negative correlation with particle size. However, few studies have demonstrated biological effects that only occur at specific nanoparticle sizes. Further elucidation of the size-specific biological effects of nanoparticles may reveal not only unknown toxicities, but also novel benefits of nanoparticles. We used surface-unmodified silica particles with a wide range of diameters and narrow size intervals between the diameters (10, 30, 50, 70, 100, 300, and 1000 nm) to investigate the relationship between particle size and acute toxicity after intravenous administration in mice. Negative correlations between particle size and thrombocytopenia, liver damage, and lethal toxicity were observed. However, a specific size-effect was observed for the severity of hypothermia, where silica nanoparticles with a diameter of 50 nm induced the most severe hypothermia. Further investigation revealed that this hypothermia was mediated not by histamine, but by platelet-activating factor, and it was independent of the thrombocytopenia and the liver damage. In addition, macrophages/Kupffer cells and platelets, but not neutrophils, play a critical role in the hypothermia. The present results reveal that silica nanoparticles have particle size-specific toxicity in mice, suggesting that other types of nanoparticles may also have biological effects that only manifest at specific particle sizes. Further study of the size-specific effects of nanoparticles is essential for safer and more effective nanomedicines.

  14. Five aspects of maximizing objectivity from perceptual evaluations of loudspeakers

    DEFF Research Database (Denmark)

    Volk, Christer Peter; Bech, Søren; Pedersen, Torben H.

    2015-01-01

    of data from the listening evaluations. This paper addresses the following subset of aspects for increasing the objectivity of data from listening tests: The choice of perceptual attributes, relevance of perceptual attributes, choice of loudness equalisation strategy, optimum listening room specifications......A literature study was conducted focusing on maximizing objectivity of results from listening evaluations aimed at establishing the relationship between physical and perceptual measurements of loudspeakers. The purpose of the study was to identify and examine factors influencing the objectivity......, as well as loudspeaker listening in-situ vs. listening to recordings of loudspeakers over headphones....

  15. Three-Dimensional Structural Aspects of Protein–Polysaccharide Interactions

    Directory of Open Access Journals (Sweden)

    Masamichi Nagae

    2014-03-01

    Full Text Available Linear polysaccharides are typically composed of repeating mono- or disaccharide units and are ubiquitous among living organisms. Polysaccharide diversity arises from chain-length variation, branching, and additional modifications. Structural diversity is associated with various physiological functions, which are often regulated by cognate polysaccharide-binding proteins. Proteins that interact with linear polysaccharides have been identified or developed, such as galectins and polysaccharide-specific antibodies, respectively. Currently, data is accumulating on the three-dimensional structure of polysaccharide-binding proteins. These proteins are classified into two types: exo-type and endo-type. The former group specifically interacts with the terminal units of polysaccharides, whereas the latter with internal units. In this review, we describe the structural aspects of exo-type and endo-type protein-polysaccharide interactions. Further, we discuss the structural basis for affinity and specificity enhancement in the face of inherently weak binding interactions.

  16. Catharsis – Philosophical and Spiritual Aspects of Long-Distance Running

    Directory of Open Access Journals (Sweden)

    Nemec Marcel

    2016-05-01

    Full Text Available The purpose of the study was to identify and analyze the occurrence of cathartic states in a sample of long-distance runners. Data collected via questionnaires were used to evaluate quantitative variables complemented by heuristics while aiming at qualitatively categorize the areas of cathartic states in the context of philosophical and spiritual aspects of long-distance running. The study findings objectify philosophical and spiritual aspects affecting personalities of long-distance runners. The study findings have shown that catharsis represents a relevant philosophical and spiritual aspect affecting long-distance running. We assume that authentic experience of catharsis and its effects motivates runners to perform regular physical activity. The analysis of philosophical and spiritual aspects of long-distance running has revealed a multi-spectral holistic relevance based on the transfer affecting a specific way of life, spectrum of values, ethical personality traits, and also the quality of long-distance runners’ lives.

  17. Cognitive aspects of color

    Science.gov (United States)

    Derefeldt, Gunilla A. M.; Menu, Jean-Pierre; Swartling, Tiina

    1995-04-01

    This report surveys cognitive aspects of color in terms of behavioral, neuropsychological, and neurophysiological data. Color is usually defined as psychophysical color or as perceived color. Behavioral data on categorical color perception, absolute judgement of colors, color coding, visual search, and visual awareness refer to the more cognitive aspects of color. These are of major importance in visual synthesis and spatial organization, as already shown by the Gestalt psychologists. Neuropsychological and neurophysiological findings provide evidence for an interrelation between cognitive color and spatial organization. Color also enhances planning strategies, as has been shown by studies on color and eye movements. Memory colors and the color- language connections in the brain also belong among the cognitive aspects of color.

  18. Internally readable identifying tag

    International Nuclear Information System (INIS)

    Jefferts, K.B.; Jefferts, E.R.

    1980-01-01

    A method of identifying non-metallic objects by means of X-ray equipment is described in detail. A small metal pin with a number of grooves cut in a pre-determined equi-spaced pattern is implanted into the non-metallic object and by decoding the groove patterns using X-ray equipment, the object is uniquely identified. A specific example of such an application is in studying the migratory habits of fish. The pin inserted into the snout of the fish is 0.010 inch in diameter, 0.040 inch in length with 8 possible positions for grooves if spaced 0.005 inch apart. With 6 of the groove positions available for data, the capacity is 2 6 or 64 combinations; clearly longer pins would increase the data capacity. This method of identification is a major advance over previous techniques which necessitated destruction of the fish in order to recover the identification tag. (UK)

  19. Tense, aspect, and modality

    NARCIS (Netherlands)

    Pfau, R.; Steinbach, M.; Woll, B.; Pfau, R.; Steinbach, M.; Woll, B.

    2012-01-01

    Cross-linguistically, the grammatical categories tense, aspect, and modality - when they are overtly expressed - are generally realized by free morphemes (such as adverbials and auxiliaries) or by bound inflectional markers. The discussion in this chapter will make clear that this generalization

  20. Toxicological aspects of water

    International Nuclear Information System (INIS)

    Garcia Puertas, P.

    1991-01-01

    Different toxicological aspects of water have been studied, remarking the activity of various chemical substances in the organism. These substances are divided in: trace metals (Sb, As, Cd, Zn, Cu, Cr, Fe, Mn, Hg, Ni, Pb, Se), other contaminants (CN-, polycyclic aromatic hydrocarbons, phenols, pesticides, detergents) and radioactivity. Finally, some considerations on this subject are made [es

  1. Aspects of strangeness

    International Nuclear Information System (INIS)

    Dover, C.B.

    1995-01-01

    We review various aspects of strangeness production in relativistic heavy ion collisions from AGS to CERN energies. The experimental data are briefly summarized and various possible theoretical interpretations of these data are evaluated, such as quark-gluon- plasma (QGP), hadron gas (HG) thermal models, or event generators (cascade models). Some comments on the production of strange clusters are offered

  2. Aspect-Oriented Programming

    NARCIS (Netherlands)

    Lopes, C.; Bergmans, Lodewijk; Lopes, C.

    1999-01-01

    Aspect-oriented programming is a promising idea that can improve the quality of software by reduce the problem of code tangling and improving the separation of concerns. At ECOOP’97, the first AOP workshop brought together a number of researchers interested in aspectorientation. At ECOOP’98, during

  3. Gout. Radiological aspects

    International Nuclear Information System (INIS)

    Restrepo Suarez, Jose Felix; Pena Cortes, Mario; Rondon Herrera, Federico; Iglesias Gamarra, Antonio; Calvo Paramo, Enrique

    2000-01-01

    In this paper we reviewed the clinical and radiological aspects of gout, showing the most frequent radiological findings that can guide to the correct diagnosis of the disease. The cases that we presented here have been analyzed for many years in our rheumatology service, Universidad Nacional de Colombia, Hospital San Juan de Dios, Bogota

  4. Medical Aspects of Surfing.

    Science.gov (United States)

    Renneker, Mark

    1987-01-01

    The medical aspects of surfing include ear and eye injuries and sprains and strains of the lower back and neck, as well as skin cancer from exposure to the sun. Treatment, rehabilitation, and prevention of these problems are discussed. Surfing is recommended as part of an exercise program for reasonably healthy people. (Author/MT)

  5. EMS and process of identification and evaluation of environmental aspects: a proposal methodology

    International Nuclear Information System (INIS)

    Perotto, E.

    2006-01-01

    The Environmental Management System (EMS) is an instrument to manage the interaction between the organization and the environment. The scope od EMS is to reduce the environmental impact and to achieve improvements in overall performances. In particular, the focus point of EMS implementation is the method for identifying and assessing significant environmental aspects. The results of the literature and regulation reviews (Perotto 2006) have shown that rigourous repeatable and transparent methodologies do not exist. This paper presents a proposal method for identifying and assessing significant environmental aspects, that has all three of these important characteristics. In particular, the proposal methodology for assessing aspects is based on some criteria that are combined in a specific algorithm. It is important to specify that to make a correct application of the method a preliminary rigorous approach to investigating the environment and the activities of organizations is necessary [it

  6. RNA-Seq analysis and annotation of a draft blueberry genome assembly identifies candidate genes involved in fruit ripening, biosynthesis of bioactive compounds, and stage-specific alternative splicing.

    Science.gov (United States)

    Gupta, Vikas; Estrada, April D; Blakley, Ivory; Reid, Rob; Patel, Ketan; Meyer, Mason D; Andersen, Stig Uggerhøj; Brown, Allan F; Lila, Mary Ann; Loraine, Ann E

    2015-01-01

    Blueberries are a rich source of antioxidants and other beneficial compounds that can protect against disease. Identifying genes involved in synthesis of bioactive compounds could enable the breeding of berry varieties with enhanced health benefits. Toward this end, we annotated a previously sequenced draft blueberry genome assembly using RNA-Seq data from five stages of berry fruit development and ripening. Genome-guided assembly of RNA-Seq read alignments combined with output from ab initio gene finders produced around 60,000 gene models, of which more than half were similar to proteins from other species, typically the grape Vitis vinifera. Comparison of gene models to the PlantCyc database of metabolic pathway enzymes identified candidate genes involved in synthesis of bioactive compounds, including bixin, an apocarotenoid with potential disease-fighting properties, and defense-related cyanogenic glycosides, which are toxic. Cyanogenic glycoside (CG) biosynthetic enzymes were highly expressed in green fruit, and a candidate CG detoxification enzyme was up-regulated during fruit ripening. Candidate genes for ethylene, anthocyanin, and 400 other biosynthetic pathways were also identified. Homology-based annotation using Blast2GO and InterPro assigned Gene Ontology terms to around 15,000 genes. RNA-Seq expression profiling showed that blueberry growth, maturation, and ripening involve dynamic gene expression changes, including coordinated up- and down-regulation of metabolic pathway enzymes and transcriptional regulators. Analysis of RNA-seq alignments identified developmentally regulated alternative splicing, promoter use, and 3' end formation. We report genome sequence, gene models, functional annotations, and RNA-Seq expression data that provide an important new resource enabling high throughput studies in blueberry.

  7. Screening for HIV-related PTSD: sensitivity and specificity of the 17-item Posttraumatic Stress Diagnostic Scale (PDS) in identifying HIV-related PTSD among a South African sample.

    Science.gov (United States)

    Martin, L; Fincham, D; Kagee, A

    2009-11-01

    The identification of HIV-positive patients who exhibit criteria for Posttraumatic Stress Disorder (PTSD) and related trauma symptomatology is of clinical importance in the maintenance of their overall wellbeing. This study assessed the sensitivity and specificity of the 17-item Posttraumatic Stress Diagnostic Scale (PDS), a self-report instrument, in the detection of HIV-related PTSD. An adapted version of the PTSD module of the Composite International Diagnostic Interview (CIDI) served as the gold standard. 85 HIV-positive patients diagnosed with HIV within the year preceding data collection were recruited by means of convenience sampling from three HIV clinics within primary health care facilities in the Boland region of South Africa. A significant association was found between the 17-item PDS and the adapted PTSD module of the CIDI. A ROC curve analysis indicated that the 17-item PDS correctly discriminated between PTSD caseness and non-caseness 74.9% of the time. Moreover, a PDS cut-off point of > or = 15 yielded adequate sensitivity (68%) and 1-specificity (65%). The 17-item PDS demonstrated a PPV of 76.0% and a NPV of 56.7%. The 17-item PDS can be used as a brief screening measure for the detection of HIV-related PTSD among HIV-positive patients in South Africa.

  8. The complete genome sequencing of Prevotella intermedia strain OMA14 and a subsequent fine-scale, intra-species genomic comparison reveal an unusual amplification of conjugative and mobile transposons and identify a novel Prevotella-lineage-specific repeat.

    Science.gov (United States)

    Naito, Mariko; Ogura, Yoshitoshi; Itoh, Takehiko; Shoji, Mikio; Okamoto, Masaaki; Hayashi, Tetsuya; Nakayama, Koji

    2016-02-01

    Prevotella intermedia is a pathogenic bacterium involved in periodontal diseases. Here, we present the complete genome sequence of a clinical strain, OMA14, of this bacterium along with the results of comparative genome analysis with strain 17 of the same species whose genome has also been sequenced, but not fully analysed yet. The genomes of both strains consist of two circular chromosomes: the larger chromosomes are similar in size and exhibit a high overall linearity of gene organizations, whereas the smaller chromosomes show a significant size variation and have undergone remarkable genome rearrangements. Unique features of the Pre. intermedia genomes are the presence of a remarkable number of essential genes on the second chromosomes and the abundance of conjugative and mobilizable transposons (CTns and MTns). The CTns/MTns are particularly abundant in the second chromosomes, involved in its extensive genome rearrangement, and have introduced a number of strain-specific genes into each strain. We also found a novel 188-bp repeat sequence that has been highly amplified in Pre. intermedia and are specifically distributed among the Pre. intermedia-related species. These findings expand our understanding of the genetic features of Pre. intermedia and the roles of CTns and MTns in the evolution of bacteria. © The Author 2015. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

  9. SPECIFIC ASPECTS OF INTERACTION OF PLATELETS WITH THE HEPARINIZED MATERIALS

    Directory of Open Access Journals (Sweden)

    E.A. Nemets

    2012-01-01

    Full Text Available Comparative analysis of anticoagulant nature on medical materials testing was done. It was found that change of citrate by heparin is accompanied by significant changes in platelet adhesion and activation. This results allowed us to arrive at a conclusion about reasonability of heparin usage as anticoagulant in in vitro testing. 

  10. Collective regulatory focus predicts specific aspects of team innovation

    NARCIS (Netherlands)

    Rietzschel, E.F.

    Much innovative work in organizations takes place in teams. Because organizational demands are complex and resources are limited, teams need to regulate their collective efforts to perform optimally. Based on previous research and a stage-based approach to innovation, it was hypothesized that

  11. Aspects of temporary specific anergy to tuberculin in Vietnamese refugees

    NARCIS (Netherlands)

    Veen, Jacob

    1992-01-01

    De vragen die in het onderzoek beantwoord dienden te worden waren: 1) Kan bevestigd worden dat bij Vietnamese vluchtelingen een groot aantal negatieve tuberculine huidtesten na herhaling van de test een positief resultaat vertoont (Mantoux-omslag) ; 2) Kunnen deze omslagen worden verklaard door een

  12. Aspects of B physics

    International Nuclear Information System (INIS)

    Gaillard, M.K.

    1987-01-01

    Various aspects of weak decays are commented on. Probing of the standard model and of phenomena beyond the standard model are discussed, followed by a theoretical view of B mesons and some experimental observations on B mesons. The point is made that any data on B decay would be interesting in that it would provide powerful new constraints in analyses of the standard model and extensions thereof

  13. LNG project - contractual aspects

    Energy Technology Data Exchange (ETDEWEB)

    Goncalves, Bruno Almeida

    2008-07-01

    This paper intends to provide from the legal point of view an outline of the main challenges of a LNG project in the upstream, regulatory aspects, liquefaction, financing and midstream through a basic checklist; an overview of the contractual complexity of a LNG project; some basic discussion of particular LNG contract clauses; and a comparative analysis between the classic clauses of a Gas Transportation Agreement (GTA) through a gas pipeline and LNG logistic. (author)

  14. Rectenna session: Micro aspects

    Science.gov (United States)

    Gutmann, R. J.

    1980-01-01

    Two micro aspects of rectenna design are discussed: evaluation of the degradation in net rectenna RF to DC conversion efficiency due to power density variations across the rectenna (power combining analysis) and design of Yagi-Uda receiving elements to reduce rectenna cost by decreasing the number of conversion circuits (directional receiving elements). The first of these involves resolving a fundamental question of efficiency potential with a rectenna, while the second involves a design modification with a large potential cost saving.

  15. MARKETING MIX THEORETICAL ASPECTS

    OpenAIRE

    Margarita Išoraitė

    2016-01-01

    Aim of article is to analyze marketing mix theoretical aspects. The article discusses that marketing mix is one of the main objectives of the marketing mix elements for setting objectives and marketing budget measures. The importance of each element depends not only on the company and its activities, but also on the competition and time. All marketing elements are interrelated and should be seen in the whole of their actions. Some items may have greater importance than others; it depends main...

  16. Futurological aspects of globalisation

    OpenAIRE

    Kostić Aleksandar V.

    2013-01-01

    The author examines futurological aspects of globalization having in mind various models of historical processes. He describes the changes as "futuroshock", thus presenting a dilemma whether the changes are only a momentum or a pre-planned concept. He especially stresses the Toffler’s conclusion that turns a new page in futurology - examining the dangers that follow the changes. According to him, predictions are made with the help of practically all the sciences in two basic directions: explo...

  17. ETHICAL ASPECTS OF SUSTAINABILITY

    OpenAIRE

    Amantova-Salmane, Liene

    2015-01-01

    Ethics can be defined as a reflection on nature and a definition of “the good”. Individuals value qualities and things dissimilarly, most visibly, but they also value their goods in different ways, in different relations to each other, for different reasons, and to different ends. These differences are very applicable to sustainability. In other words, sustainability cannot be achieved without attention to its ethical dimensions. The aim of this research is to examine the ethical aspects of s...

  18. MANAGING CHANGE: SOME THEORETICAL AND APPLICATIVE ASPECTS

    Directory of Open Access Journals (Sweden)

    Botezat Elena

    2012-07-01

    Full Text Available The strategic organizational change aims is the change of procedures and systems, organizational structures and responsibilities but especially acquiring new knowledge and skills. Significant authors (Drucker: 1999; Kotter: 1996; Buckingham n Clifton: 2001, supporters of the theory of strategic leadership show an inclination for the idea of optimal management of an organization, which depends on circumstantial factors as place and time, the individual and the context in which it acts. Many experts who studied organizational change saw as possible the future replacement of the current state, desired only after completion of specific phases, in a certain sequence. In this article we will focus our attention on the reduction phase of resistance to change. The research objectives targeted both theoretical aspects consisting in bringing to the forefront the relevant aspects related to organizational change in the current context and practical aspects related to identifying and analyzing the main elements that make it possible or on the contrary act as brakes in way of introduction and implementation of change. To achieve the research objectives, we used the method of direct observation and the questionnaire method supported by the gathering of more information from the organization's documents (Beton Construct SRL and support discussions with the employees. Data processing and analysis revealed that in the organization certain factors exist and manifest that constitute obstacles or inhibit organizational change, namely: the goal of the change is not clear, the rewards of change are not related to the effort needed to make them happen, change determines fear of failure, change is often imposed by coercion, change requires effort and commitment required for employees that think they do not have resources anymore. Summarizing the results of usage for certain methods and techniques to implement change, we can say that the actions of an authoritarian

  19. Criminal Aspects of Artificial Abortion

    OpenAIRE

    Hartmanová, Leona

    2016-01-01

    Criminal Aspects of Artificial Abortion This diploma thesis deals with the issue of artificial abortion, especially its criminal aspects. Legal aspects are not the most important aspects of artificial abortion. Social, ethical or ideological aspects are of the same importance but this diploma thesis cannot analyse all of them. The main issue with artificial abortion is whether it is possible to force a pregnant woman to carry a child and give birth to a child when she cannot or does not want ...

  20. Aspect as a Communicative Category

    DEFF Research Database (Denmark)

    Durst-Andersen, Per

    2018-01-01

    On the basis of internal evidence from primarily the use of imperfective forms and external evidence from primarily first language acquisition, it is argued that English, Russian, and French aspect differ from one another, because they go back to an obligatory choice among three possible communic......On the basis of internal evidence from primarily the use of imperfective forms and external evidence from primarily first language acquisition, it is argued that English, Russian, and French aspect differ from one another, because they go back to an obligatory choice among three possible...... communicative directions: should a grammatical category be grounded in the speaker's experience of a situation, in the situation referred to or in the hearer as information about the situation? The progressive vs. non-progressive distinction in English is acquired in the present tense of atelic (simplex) verbs...... to the meta-distinction between atelic (simplex) and telic (complex) verbs. It is second-person oriented. The specific order arrived at reflects the Peircean categories of Firstness, Secondness, and Thirdness and their predictions. This can account for the fact that the English and Russian types can be found...

  1. PRACTICAL ASPECTS REGARDING FIDUCIARY OPERATIONS

    Directory of Open Access Journals (Sweden)

    Bazil Oglindă

    2016-11-01

    Full Text Available The trusts have been frequently used in the countries which function under the Anglo-Saxon law system, but it most certainly represents an innovation in the new Romanian legislation. For this reason, in this paper, we tried to highlight the main differences between the trust regulated in the Romanian Civil code and its corespondent in other legal systems. Observing that the trust in an institution that is mainly theoretical, and the reluctance of practicioners in using it, we tried to analyze the trust, regarding its practical side. In this paper, we will take into consideration the following aspects: the rights that the trustee acquires after establishing the trust, that will be explained through the new regulations regarding the division of assets, the quality of the parties and the limits in which the trustee may be held liable. Other important aspects are: the means that the new regulations provide in order to protect the interests of the creditors and at the same time, the fiduciary assets; the formalities which the law requires and the means of termination of the contract. In the end, in order to identify alternative solutions, we will compare the trust (regulated in the Civil code with the management of assets that belong to a third party.

  2. QTLs and potential candidate genes for heat stress tolerance identified from the mapping populations specifically segregating for Fv/Fm in wheat

    DEFF Research Database (Denmark)

    Sharma, Dew Kumari; Torp, Anna Maria; Rosenqvist, Eva

    2017-01-01

    Despite the fact that F-v/F-m (maximum quantum efficiency of photosystem II) is the most widely used parameter for a rapid non-destructive measure of stress detection in plants, there are barely any studies on the genetic understanding of this trait under heat stress. Our aim was to identify...... quantitative trait locus (QTL) and the potential candidate genes linked to F-v/F-m for improved photosynthesis under heat stress in wheat (Triticum aestivum L.). Three bi-parental F-2 mapping populations were generated by crossing three heat tolerant male parents (origin: Afghanistan and Pakistan) selected...... for high F-v/F-m with a common heat susceptible female parent (origin: Germany) selected for lowest F-v/F-m out of a pool of 1274 wheat cultivars of diverse geographic origin. Parents together with 140 F-2 individuals in each population were phenotyped by F-v/F-m under heat stress (40 degrees C for 3 days...

  3. Biomechanical aspects of nonspecific back pain

    Directory of Open Access Journals (Sweden)

    Ridwan Harrianto

    2010-12-01

    Full Text Available Low back pain (LBP is a common problem in adult life, since despite its benign nature it is commonly associated with incapacity, productivity loss due to sick leave, and correspondingly high costs to the individual worker. Psychosocial and lifestyle factors and work-place exposures have been implicated in the onset of symptoms. Heavy physical work, static work postures, frequent bending and twisting, lifting and postural movements, repetitive work, and whole body vibrations are occupational factors associated with LBP. The usual classification of LBP is related to the duration of the complaints (acute, subacute, and chronic. However, these terms fail to take into account several clinically important aspects of the course of LBP, which is frequently recurrent and thus neither acute nor chronic. More realistically, LBP should be classified as specific and nonspecific. Approximately 90% of LBP cases have no identifiable cause and is designated nonspecific LBP. However, despite its high prevalence, the etiology and nature of nonspecific LBP are not yet well understood. Its pathophysiology remains complex and multifaceted. Multiple anatomic structures and elements of the lumbar spine (e.g. bones, ligaments, tendons, discs, and muscles are all suspected of playing a role. Many of these components of the lumbar spine have sensory innervations that can generate nociceptive signals in response to tissue-damaging stimuli. Other causes could be neuropathic (e.g. sciatica. Some cases of LBP most likely involve mixed nociceptive and neuropathic etiologies.

  4. ASPECTE SPECIFICE COMPORTAMENTULUI CONSUMATORULUI DE SERVICII

    Directory of Open Access Journals (Sweden)

    Natalia REMEŞOVSCHI

    2018-03-01

    Full Text Available Natura și conținutul serviciilor dau procesului de luare a deciziei de cumpărare și consum a serviciilor o altă semnificație, în comparație cu decizia de cumpărare a bunurilor. Aceasta se datorează impactului caracteristicilor serviciilor, complexităţii şi diferenţei influenţei factorilor de comportament. Ceea ce ne-a determinat să constatăm că particularitatea distinsă a comportamentului consumatorului de servicii ține de rolul pe care îl poate avea specialistul de marketing în înțelegerea și interactivitatea cu clientul.THE SPECIFIC ASPECTS OF THE BEHAVIOR OF THE SERVICE CONSUMER The nature and content of the services give to the decision-making process of purchasing and consuming services a different meaning compared to the decision to purchase the goods. This is due to the impact of the services characteristics, complexity and difference in behavioral factors. Which has made us identify the distinctive particularity of the service consumer's behavior is the role that the marketing specialist can have in understanding and interaction with the customer.

  5. Aspects of grand unification in higher dimensions

    Energy Technology Data Exchange (ETDEWEB)

    Wingerter, A.

    2005-07-01

    We consider various aspects of string phenomenology in the context of heterotic orbifold constructions, where special emphasis is laid on the connection between GUT models in extra dimensions and their relation to string theory. We investigate orbifold models with more general structure than the Z{sub 3} orbifold, on which most of the past research had focused. The picture of the heterotic brane world which naturally emerges allows us to make contact to field theoretic orbifold constructions in five and six dimensions, which have recently attracted much attention. We present a classification scheme for inequivalent orbifold models and apply the results to the case of Z{sub 6}-II point group. We develop the mathematical background for a stringy Higgs mechanism which allows us to lower the rank of the gauge group in the higher dimensions, which cannot be achieved by contemporary orbifold constructions. We provide all the calculational methods needed to unambiguously identify the gauge symmetry and to construct the matter representations. For specific model constructions, we focus on two promising gauge groups, namely on SO(10) and E{sub 6}. In the latter case, we derive a GUT model in six dimensions which has a standard model like gauge symmetry SU(3) x SU (2) x U(1) x U(1)' in four dimensions, and discuss its embedding into string theory. (orig.)

  6. AspectJ in action practical aspect-oriented programming

    CERN Document Server

    Laddad, Ramnivas

    2003-01-01

    A guide to aspect-oriented programming and the AspectJ language, this book provides code examples that enable quick implementation of functionality in a system. Thorough introductions to AOP and AspectJ will help developers learn or advance their knowledge of AspectJ. Examples of everyday situations in which AspectJ solutions can be applied, such as logging, policy enforcement, resource pooling, business logic, thread-safety, authentication and authorization, and transaction management are provided. In addition, design patterns and idioms are covered, as is business rule implementation. The latest technologies, such as JEES, JAAS, and log4j, are explained and connected with AspectJ.

  7. Long-term radiological aspects of management of wastes from uranium mining and milling

    International Nuclear Information System (INIS)

    1984-09-01

    Due to the contamination of uranium mill tailings by long-lived natural radionuclides, their management presents specific radiation protection aspects in the long term. This report presents several examples of the application of the International Commission of Radiological Protection (ICRP) methodology for the optimisation of radiation protection to these types of waste. The advantages and disadvantages of such an approach are discussed and several important limitations are identified

  8. Immune Aspects of Female Infertility

    Directory of Open Access Journals (Sweden)

    Andrea Brazdova

    2016-05-01

    Full Text Available Immune infertility, in terms of reproductive failure, has become a serious health issue involving approximately 1 out of 5 couples at reproductive age. Semen that is defined as a complex fluid containing sperm, cellular vesicles and other cells and components, could sensitize the female genital tract. The immune rejection of male semen in the female reproductive tract is explained as the failure of natural tolerance leading to local and/or systemic immune response. Present active immune mechanism may induce high levels of anti-seminal/sperm antibodies. It has already been proven that iso-immunization is associated with infertility. Comprehensive studies with regards to the identification of antibody-targets and the determination of specific antibody class contribute to the development of effective immuno-therapy and, on the other hand, potential immuno-contraception, and then of course to complex patient diagnosis. This review summarizes the aspects of female immune infertility.

  9. Legal aspects of nuclear energy

    International Nuclear Information System (INIS)

    Kraut, A.

    1981-01-01

    The legal basis for the use of nuclear energy is generally given by an Atomic Energy Act. Additionally, however, a system of regulations and standards has to be set up to lay down more detailed requirements. The fundamental philosophy and strategy has to be specified by governmental organizations. For the specification and implementation of the requirements some minimum organizational arrangements are necessary, which are not only restricted to governmental organizations. Furthermore procedural regulations have to be laid down before the implementation phase. This includes aspects like public participation in the licensing procedure. In practice, however, the implementation of the legal requirements always shows some weakness of the basic legal requirements. To learn from this experience some examples are presented, which gave rise to difficulties in the implementation procedure. (orig./RW)

  10. Environmental, legal and managerial aspects

    International Nuclear Information System (INIS)

    1978-09-01

    This U.S. contribution to the syllabus for Subgroup 5C treats with environmental and ecological aspects specific to fast breeder reactors, physical protection and safeguarding of the FBR cycle, fuel cycle centers (site selection problems for different degrees of collocation) and administrative and legal problems. Decommissioning of an FBR power plant, syllabus item C.1.7, is treated in separate contribution, more information on advanced safeguards for the fast breeder fyel cycle is contained in the contribution, USA WG 5C-tbd. A key conclusion of this is that with safeguards planning initiated early in the development of the FBR fuel cycle, time is available to develop, evaluate, and implement improved safeguards techniques and incorporate them into the design phase of all FBR cycle facilities

  11. Knockout reactions: experimental aspects

    Energy Technology Data Exchange (ETDEWEB)

    Cortina Gil, D. [Santiago de Compostela Univ. (Spain)

    2007-07-01

    The availability of radioactive beams has given rise to intense activity in the field of direct reactions. The removal of one(two)-nucleon (referred to as nucleon knockout in this text) from a fast exotic projectile has been extensively investigated. This lecture provides a general overview of the experimental results achieved using this technique. The sensitivity of the method to different experimental aspects is illustrated with a few examples. Special attention is given to the application of nucleon-knockout reactions as a general purpose spectroscopic tool. (author)

  12. Strategic Aspects of Bundling

    International Nuclear Information System (INIS)

    Podesta, Marion

    2008-01-01

    The increase of bundle supply has become widespread in several sectors (for instance in telecommunications and energy fields). This paper review relates strategic aspects of bundling. The main purpose of this paper is to analyze profitability of bundling strategies according to the degree of competition and the characteristics of goods. Moreover, bundling can be used as price discrimination tool, screening device or entry barriers. In monopoly case bundling strategy is efficient to sort consumers in different categories in order to capture a maximum of surplus. However, when competition increases, the profitability on bundling strategies depends on correlation of consumers' reservations values. (author)

  13. Aspects of nuclear science

    International Nuclear Information System (INIS)

    Hageboe, E.; Salbu, B.

    1987-01-01

    The aspects of nuclear science presented in this book result from a symposium that was held in Oslo in October 1985. On this special occasion the rapid development of nuclear science as an interdisciplinary field was illustrated with brief presentations of some selected areas. These areas represent parts of the main interests of the Section for Nuclear Chemistry in the Department of Chemistry at the University of Oslo. This section has for decades been among the leading laboratories for nuclear chemistry in Scandinavia, thanks to its founder and inspiring leader professor Alexis C. Pappas

  14. Ethical aspects of business

    OpenAIRE

    Konečná, Lucie

    2013-01-01

    This thesis covers the topic of the ethical aspects of business. The paper defines what an ethics and a business ethics are and it describes selected tools of business ethics. The practical part focuses on building company called Skanska and on its view of business ethics. This part consists of an interview with managing director of Skanska SK a.s. and of a questionnaire survey. The main goal of this thesis is to analyze the level of the business ethics in this building company. The main rese...

  15. Analytic aspects of convexity

    CERN Document Server

    Colesanti, Andrea; Gronchi, Paolo

    2018-01-01

    This book presents the proceedings of the international conference Analytic Aspects in Convexity, which was held in Rome in October 2016. It offers a collection of selected articles, written by some of the world’s leading experts in the field of Convex Geometry, on recent developments in this area: theory of valuations; geometric inequalities; affine geometry; and curvature measures. The book will be of interest to a broad readership, from those involved in Convex Geometry, to those focusing on Functional Analysis, Harmonic Analysis, Differential Geometry, or PDEs. The book is a addressed to PhD students and researchers, interested in Convex Geometry and its links to analysis.

  16. Radiographic aspects of xeroradiography

    International Nuclear Information System (INIS)

    Rao, G.U.V.; Fatouros, P.P.

    1980-01-01

    The quality of a conventional radiographic image can be characterized in terms of five basic parameters; density, contrast, latitude, resolution and noise. Since xeroradiographic images exhibit very limited broad area contrasts, and image formation is predominantly due to edge enhancement, a straightforward description of image quality using the same five parameters is not adequate. A detailed study was made of the radiographic aspects of xeroradiography with special reference to mammography, and a summary of major findings to date with appropriate references to published papers is presented

  17. Radiological aspects of Arthroplasties

    International Nuclear Information System (INIS)

    Garcia, Sara Eugenia; Barragan, John Henry; Narvaez, Jorge Andres

    2008-01-01

    The development of new surgical techniques, of new prosthetic materials, and the increase in life expectancy with greater coverage of health services has ugmented the performance of hip replacements in our country. The radiologist should be familiar with the different surgical techniques and prosthetic devices, the evaluation of its components and associated complications. The most frequently performed arthroplasties are: shoulder, elbow, hip and knee replacement. This article reviews the most frequent prosthetic devices used, the radiological aspects of arthroplasties and their most common complications.

  18. Knockout reactions: experimental aspects

    International Nuclear Information System (INIS)

    Cortina Gil, D.

    2007-01-01

    The availability of radioactive beams has given rise to intense activity in the field of direct reactions. The removal of one(two)-nucleon (referred to as nucleon knockout in this text) from a fast exotic projectile has been extensively investigated. This lecture provides a general overview of the experimental results achieved using this technique. The sensitivity of the method to different experimental aspects is illustrated with a few examples. Special attention is given to the application of nucleon-knockout reactions as a general purpose spectroscopic tool. (author)

  19. Practical aspects on a Marx generator construction

    International Nuclear Information System (INIS)

    Diniz, R.; Sudano, J.P.

    1991-01-01

    The practical aspects of Marx generator construction has been studied. The problems and the ways to solve them are related, once the tests with the Marx generator will continue until the specification with the 16 capacitors. (L.C.J.A.). 7 refs, 6 figs

  20. Fungal peroxidases : molecular aspects and applications

    NARCIS (Netherlands)

    Conesa, A.; Punt, P.J.; Hondel, C.A.M.J.J.

    2002-01-01

    Peroxidases are oxidoreductases that utilize hydrogen peroxide to catalyze oxidative reactions. A large number of peroxidases have been identified in fungal species and are being characterized at the molecular level. In this manuscript we review the current knowledge on the molecular aspects of this

  1. Aspects of an ecological theory of language

    DEFF Research Database (Denmark)

    Bang, J. C.; Trampe, W.

    2014-01-01

    Our aim and knowledge-constitutive interest is to identify some central aspects of an ecological theory of language. In our understanding of building an integrative ecological theory of language, it seems useful to look first for roots of a special ecological understanding of language. Here...

  2. Simple New Method of Detecting Lies By Identifying Invisible Unique Physiological Reflex Response Appearing Often Less Than 10-15 Seconds on the Specific Parts of Face of Lying Person; Quick Screening of Potential Murderers & Problematic Persons.

    Science.gov (United States)

    Omura, Yoshiaki; Nihrane, Abdallah; Lu, Dominic; Jones, Marilyn K; Shimotsuura, Yasuhiro; Ohki, Motomu

    2015-01-01

    Frequently, we cannot find any significant visible changes when somebody lies, but we found there are significant invisible changes appearing in specific areas of the face when somebody lies and their location often depends on whether the lie is serious with or without physical violence involvement. These abnormalities were detected non-invasively at areas: 1) lobules and c) a small round area of each upper lateral side of forehead; 2) the skin between the base of the 2 orifices of the nose and the upper end of upper lip and 3) Alae of both sides of nose. These invisible significant changes usually last less than 15 seconds after telling a lie. In these areas, Bi-Digital O-Ring Test (BDORT), which received a U.S. Patent in 1993, became significantly weak with an abnormal value of (-)7 and TXB2, measured non-invasively, was increased from 0.125-0.5ng to 12.5-15ng (within the first 5 seconds) and then went back down to less than 1ng (after 15 seconds). These unique changes can be documented semi-permanently by taking photographs of the face of people who tell a lie, within as short as 10 seconds after saying a lying statement. These abnormal responses appear in one or more of the above-mentioned 3 areas 1), 2) & 3). At least one abnormal pupil with BDORT of (-)8-(-)12 & marked reduction in Acetylcholine and abnormal increase in any of 3 Alzheimer's disease associated factors Apolipoprotein (Apo) E4, β-Amyloid (1-42), Tau protein, viral and bacterial infections were detected in both pupils and forehead of murderers and people who often have problems with others. Analysis of well-known typical examples of recent mass murderers was presented as examples. Using these findings, potential murderers and people who are very likely to develop problems with others can be screened within 5-10 minutes by examining their facial photographs and signatures before school admission or employment.

  3. Energy and social aspects

    International Nuclear Information System (INIS)

    Perez, D.; Gomez, Y.

    2008-01-01

    In this section, the social aspects of Cuba's energy system are described, based on the accessibility and availability of energy services and the affordability and acceptance of these energy services by the population. Accessibility refers to the existence of modern energy services and supporting infrastructures that allow the population, regardless of income level, place of residence, race, religion, etc., the use of modern fuels. Logistics and the economy determine the amount and kinds of energy and energy services available in each place. Even if energy services are accessible to the population, problems with their availability during particular time periods may exist; thus, this section discusses the problems of availability of modern fuels in Cuba. Affordability relates to the ability of the population to pay for the energy services that are accessible and available. Energy prices should be low enough (without affecting the profitability of the producing companies) to enable everyone's minimum requirements for modern energy services to be satisfied. Acceptability concerns the social and/or environmental problems related to energy chains, ranging from production and use to the disposal of waste generated by energy production. Making an assessment of the acceptability of an energy option is often difficult and sometimes involves many issues, including social, environmental, cultural, economic and religious aspects at local and regional levels

  4. Diabetic patients: Psychological aspects.

    Science.gov (United States)

    Adili, Fatemeh; Larijani, Bagher; Haghighatpanah, Mohammadreza

    2006-11-01

    This study was undertaken to consider the psychological aspect of diabetes with regard to improving clinical outcomes. The review was limited to literature reports on the causes, solutions, and treatments of some common psychological problems known to complicate diabetes management. A literature search was undertaken using Pub-Med, CINAHL, Proquest, Elsevier, Blackwell Synergy, Ovid, Ebsco, Rose net, and Google websites, including studies published in English journals between 1995 and 2006. Therefore about 88 articles were selected based on the inclusion criteria. In earlier studies, relatively little empirical research was found to substantiate the effect of psychological counseling in complicated diabetes. The greatest deficits were seen in areas of mental health, self-esteem parent impact, and family cohesion. There were some different factors, which influence the psychological aspect of diabetic patients, such as age, gender, place of living, familial and social support, motivation, energy, life satisfaction, and lifestyle. There are various types of solutions for coping with the psychological problems in diabetic clients. The most essential solution lies in educating the patients and healthcare providers on the subject. Before initiating each educational intervention, a thorough assessment would be crucial. Treatment plans may benefit from cognitive behavior therapy (CBT), behavior family therapy, improving family communication, problem-solving skills, and providing motivation for diabetic patients. Moreover, it seems that the close collaboration between diabetologists and psychologists would be fruitful.

  5. Ecological aspects of parasitology

    National Research Council Canada - National Science Library

    Kennedy, Clive Russell

    1976-01-01

    .... The second section is concerned with the specific problems and difficulties posed by the major organs and tissues occupied by parasites, and the tactical solutions adopted by parasites in each...

  6. MACROECONOMIC ASPECTS OF COMPETITIVENESS

    Directory of Open Access Journals (Sweden)

    Oleg Hooke

    2017-09-01

    Full Text Available In the process of globalization of world economic processes, the role of individual national economies increases, comparative advantages of the development of a country are formed, and their competitiveness is ensured. That is why it is worth emphasizing the importance of increasing the competitiveness of each individual country, based on its internal capacity. In a broad aspect, the competitiveness of the national economy is perceived as the ability of the country to ensure the balance of its external proportions and to avoid those constraints imposed by the foreign economic sphere, to self-organizing the improvement of their world economic ties. The competitiveness of the economy at the macro level is associated with the duration of the cycle of reproduction of the main productive assets and, accordingly, the jobs, productive forces of society and determined by the overall economic efficiency of investment. The criteria of competitiveness of the national economy are the growth of social productivity of labor, increase of social and economic efficiency of production and standard of living of the population. The competitiveness of the national economy determines sustainable socio-economic development of the country, as well as sustainable development predetermines the competitiveness of not only the country, but also all its levels. Scientific results are obtained using special methods of research of economic objects and phenomena, that is, based on the correlation and regressive, comparative analysis (establishing the relationship between the indicator factor, as well as economic modeling. Findings. Generalizing analysis and the importance of the macroeconomic aspect of competitiveness were used in the research paper, which will allow to better respond to the economic situation, in accordance with the trends of the “green” transformation of the economy; which in turn will solve important problems of the development and implementation of its

  7. Identifying subgroups of CERME affect research papers

    OpenAIRE

    Hannula, Markku S.; Garcia Moreno-Esteva, Enrique

    2017-01-01

    Research in mathematics related affect uses a variety of theoretical frameworks. Three different dimensions have been suggested as significant to characterize concepts in this area: (1) emotional, motivational, and cognitive aspects of affect, (2) state and trait aspects of affect, and (3) physiological, psychological, and sociological level of theorizing affect. In this study, we used the information in reference lists and graph theory to identify Graph Communities (coherent clusters) of res...

  8. Political and economic aspects

    International Nuclear Information System (INIS)

    O'Neil, C.

    1997-01-01

    The political and socio-economic aspects of oil and gas exploration in Canada's Arctic and the Beaufort Sea were reviewed. The federal government was very interested in developing the North because they saw oil and gas development in the North as a means of strengthening sovereignty claims. The projected profits from Northern oil and gas development were also very attractive, and after dealing with environmental and social concerns, the government granted the necessary drilling permits. The federal government also made allowances for huge tax incentives for the oil and gas companies to encourage exploration. Although oil has been found, large-scale production in the Beaufort Sea never materialized. During the period from 1984 to 1988, world prices for oil fell and it was no longer economical to undertake frontier production. Beaufort Sea operation were shut down as the oil industry changed its focus to more cost-effective reservoirs in southern Canada. 1 fig

  9. Technological Aspects: High Voltage

    International Nuclear Information System (INIS)

    Faircloth, D C

    2013-01-01

    This paper covers the theory and technological aspects of high-voltage design for ion sources. Electric field strengths are critical to understanding high-voltage breakdown. The equations governing electric fields and the techniques to solve them are discussed. The fundamental physics of high-voltage breakdown and electrical discharges are outlined. Different types of electrical discharges are catalogued and their behaviour in environments ranging from air to vacuum are detailed. The importance of surfaces is discussed. The principles of designing electrodes and insulators are introduced. The use of high-voltage platforms and their relation to system design are discussed. The use of commercially available high-voltage technology such as connectors, feedthroughs and cables are considered. Different power supply technologies and their procurement are briefly outlined. High-voltage safety, electric shocks and system design rules are covered. (author)

  10. CUSTOMER LOYALTY THEORETICAL ASPECTS

    Directory of Open Access Journals (Sweden)

    Margarita IŠORAITĖ

    2016-08-01

    Full Text Available Customer loyalty - is a voluntary user solution for a long time to build relationships with the company. Loyalty is the user's desire for a long time to continue their relationship with a particular company, because loyal customers are those who purchase goods/services of the company from time to time. Loyalty can be treated as a customer desire, willingness to be a regular customer for a long time, buying and using the goods of the chosen companies by recommending them to friends and colleagues. Loyalty can be seen as a multi-dimension, covering behavioral and positional components, where positional aspect reflects customers' approach to business, while the behavioral dimension reveals a frequent and regular shopping, purchase quantity, size, range, availability, etc.

  11. Pecan cultivation: general aspects

    Directory of Open Access Journals (Sweden)

    Diniz Fronza

    2018-02-01

    Full Text Available ABSTRACT: Given the increasing investment in the pecan production in southern Brazil, it becomes necessary researches, assisting in solve problems and proposition of technical and methodology to enhance this production chain. Thus, the present review aimed to survey the existing information about the culture, both on the world and the Brazilian scene. Issues related to botany, climate and soil requirements, alignment and planting density, cultivars, pests and diseases, among other technical aspects of this culture will be addressed. Pecan nut presents nutraceutical properties that are beneficial to human health, which has increased its demand from consumers. However, there are few research results with pecan nut in Brazil and there are many gaps in scientific knowledge about this culture, especially as regards the management of pests and diseases control, irrigation and nutrition, in Brazilian conditions.

  12. Technological Aspects: High Voltage

    CERN Document Server

    Faircloth, D.C.

    2013-12-16

    This paper covers the theory and technological aspects of high-voltage design for ion sources. Electric field strengths are critical to understanding high-voltage breakdown. The equations governing electric fields and the techniques to solve them are discussed. The fundamental physics of high-voltage breakdown and electrical discharges are outlined. Different types of electrical discharges are catalogued and their behaviour in environments ranging from air to vacuum are detailed. The importance of surfaces is discussed. The principles of designing electrodes and insulators are introduced. The use of high-voltage platforms and their relation to system design are discussed. The use of commercially available high-voltage technology such as connectors, feedthroughs and cables are considered. Different power supply technologies and their procurement are briefly outlined. High-voltage safety, electric shocks and system design rules are covered.

  13. Aspects, Wrappers and Events

    Science.gov (United States)

    Filman, Robert E.

    2003-01-01

    This viewgraph presentation provides information on Object Infrastructure Framework (OIF), an Aspect-Oriented Programming (AOP) system. The presentation begins with an introduction to the difficulties and requirements of distributed computing, including functional and non-functional requirements (ilities). The architecture of Distributed Object Technology includes stubs, proxies for implementation objects, and skeletons, proxies for client applications. The key OIF ideas (injecting behavior, annotated communications, thread contexts, and pragma) are discussed. OIF is an AOP mechanism; AOP is centered on: 1) Separate expression of crosscutting concerns; 2) Mechanisms to weave the separate expressions into a unified system. AOP is software engineering technology for separately expressing systematic properties while nevertheless producing running systems that embody these properties.

  14. ADTT safety aspects

    International Nuclear Information System (INIS)

    Thedeen, T.

    1997-01-01

    Beside the technical problems of ADTT which remain to be solved it is crucial for the ADTT progress that safety and economical aspects are considered already during the research and planning phases. Safety here stands for the converse of risk, negative consequences for human life and health and the environment together with the corresponding probabilities. The system to be considered includes all phases of an ADTT plant, a life cycle analysis (LCA). The risk analysis is useful for two purposes: comparison with other ways of handling nuclear waste, e.g. geological repository and for valuation of different construction designs. Due to lack of precise plans and adequate data the analysis will be more of a qualitative than quantitative type. The main risks appear in connection with repair and replacement work. 2 refs., 1 fig

  15. Psychiatric aspects of burn

    Directory of Open Access Journals (Sweden)

    Dalal P

    2010-10-01

    Full Text Available Burn injuries and their subsequent treatment cause one of the most excruciating forms of pain imaginable. The psychological aspects of burn injury have been researched in different parts of the world, producing different outcomes. Studies have shown that greater levels of acute pain are associated with negative long-term psychological effects such as acute stress disorder, depression, suicidal ideation, and post-traumatic stress disorder for as long as 2 years after the initial burn injury. The concept of allostatic load is presented as a potential explanation for the relationship between acute pain and subsequent psychological outcomes. A biopsychosocial model is also presented as a means of obtaining better inpatient pain management and helping to mediate this relationship.

  16. ROBOTIC SURGERY: BIOETHICAL ASPECTS.

    Science.gov (United States)

    Siqueira-Batista, Rodrigo; Souza, Camila Ribeiro; Maia, Polyana Mendes; Siqueira, Sávio Lana

    2016-01-01

    The use of robots in surgery has been increasingly common today, allowing the emergence of numerous bioethical issues in this area. To present review of the ethical aspects of robot use in surgery. Search in Pubmed, SciELO and Lilacs crossing the headings "bioethics", "surgery", "ethics", "laparoscopy" and "robotic". Of the citations obtained, were selected 17 articles, which were used for the preparation of the article. It contains brief presentation on robotics, its inclusion in health and bioethical aspects, and the use of robots in surgery. Robotic surgery is a reality today in many hospitals, which makes essential bioethical reflection on the relationship between health professionals, automata and patients. A utilização de robôs em procedimentos cirúrgicos tem sido cada vez mais frequente na atualidade, o que permite a emergência de inúmeras questões bioéticas nesse âmbito. Apresentar revisão sobre os aspectos éticos dos usos de robôs em cirurgia. Realizou-se revisão nas bases de dados Pubmed, SciELO e Lilacs cruzando-se os descritores "bioética", "cirurgia", "ética", "laparoscopia" e "robótica". Do total de citações obtidas, selecionou-se 17 artigos, os quais foram utilizados para a elaboração do artigo. Ele contém breve apresentação sobre a robótica, sua inserção na saúde e os aspectos bioéticos da utilização dos robôs em procedimentos cirúrgicos. A cirurgia robótica é uma realidade, hoje, em muitas unidades hospitalares, o que torna essencial a reflexão bioética sobre as relações entre profissionais da saúde, autômatos e pacientes.

  17. Chemical Aspects of Dentistry.

    Science.gov (United States)

    Helfman, Murry

    1982-01-01

    Dental caries (tooth decay) and periodontal (gum) disease are treated/prevented by procedures utilizing chemical expertise. Procedures and suggestions on how they might be incorporated into the high school chemistry curriculum are described. Specific topics discussed include dental caries, fluoride, diet, tooth decay prevention, silver amalgan,…

  18. Magnetic nanoparticles. Metrological aspects

    International Nuclear Information System (INIS)

    Nikiforov, V N; Nikiforov, A V; Oxengendler, B L; Turaeva, N N; Sredin, V G

    2011-01-01

    The experiments on influence of the iron oxide cluster size on the specific magnetic moment are performed. Both free and covered clusters are investigated. The experiments are interpreted on the base of core-shell model by analogy to Weizsaecker formula in the nuclear physics. Metrological parameters for the cluster size investigation are obtained.

  19. Aspects of Radar Polarimetry

    OpenAIRE

    LÜNEBURG, Ernst

    2002-01-01

    This contribution is a tutorial introduction to the phenomenological theory of radar polarimetry for the coherent scatter case emphasizing monostatic backscattering and forward scattering (transmission). Characteristic similarities and differences between radar polarimetry and optical polarimetry and the role of linear and antilinear operators (time-reversal) are pointed out and typical polarimetric invariants are identified.

  20. Developmental aspects of ADHD

    NARCIS (Netherlands)

    Belle, J. van

    2015-01-01

    It is increasingly recognized that ADHD is a heterogeneous disorder, both in its clinical presentation (phenotype) and the underlying aetiology. This heterogeneity makes it difficult to identify causal pathways that link the phenotype to brain structure and functioning. In an attempt to go beyond

  1. Combinatorial drug screening identifies Ewing sarcoma-specific sensitivities

    OpenAIRE

    Radic-Sarikas, Branka; Tsafou, Kalliopi P.; Emdal, Kristina B.; Papamarkou, Theodore; Huber, Kilian V.M.; Mutz, Cornelia; Toretsky, Jeffrey A.; Bennett, Keiryn L.; Olsen, Jesper V.; Brunak, Søren; Kovar, Heinrich; Superti-Furga, Giulio

    2017-01-01

    Improvements in survival for Ewing sarcoma pediatric and adolescent patients have been modest over the past 20 years. Combinations of anticancer agents endure as an option to overcome resistance to single treatments caused by compensatory pathways. Moreover, combinations are thought to lessen any associated adverse side effects through reduced dosing, which is particularly important in childhood tumors. Using a parallel phenotypic combinatorial screening approach of cells derived from three p...

  2. New St-chromosome-specific molecular markers for identifying ...

    Indian Academy of Sciences (India)

    et al. 1994) or JJsSt (Chen et al. 1998) was widely used in wheat breeding programme (Chen .... Japan). Table 1. The features of primers used in this study. Homologous ..... Redinbaugh M. G., Jones T. A. and Zhang Y. T. 2000 Ubiquity of.

  3. Psychiatric Aspects of Infertility

    Directory of Open Access Journals (Sweden)

    Hacer Sezgin

    2014-06-01

    Full Text Available Infertility can be defined as a crisis with cultural, religious, and class related aspects, which coexists with medical, psychiatric, psychological, and social problems. Relation between psychiatric and psychological factors stem from a mutual interaction of both. Family is an important institution in maintaining human existence and raising individuals in line with society's expectations. Fertility and reproduction are seen as universal functions unique to women with raising children as the expected result of the family institution. Incidence of infertility has increased recently and can become a life crisis for a couple. Even though not being able to have a child affects both sexes emotionally, women feel greater amounts of stress, pressure, anxiety, and depression.Consequences of infertility arise from short and long-term devastating effects on both individual's physical and mental health, and marital system. Many studies focus on infertility related psychological and psychiatric disorders (depression, anxiety, grief, marital conflict, gender differences, relation between the causes of infertility and psychopathology, the effects of psychiatric evaluation and intervention -when necessaryon the course of infertility treatment, pregnancy rates, and childbirth. The most important underlying causes of high levels of stress and anxiety that infertile women experience are the loss of maternity, reproduction, sense of self, and genetic continuity. In this review article is to investigate the relationship between medically unexplained symptoms and psychiatric symptoms. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(2.000: 165-185

  4. Neutronic and thermalhydraulic aspects

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, J.B. [CEA Centre d`Etudes de Saclay, 91 - Gif-sur-Yvette (France). Dept. de Mecanique et de Technologie; Bergeonneau, P. [CEA Centre d`Etudes de Cadarache, 13 - Saint-Paul-lez-Durance (France). Dept. d`Etudes des Reacteurs

    1995-12-31

    Precise computation of neutron flux in the core of a nuclear reactor represents one of the basic aspects of reactor design and operation. Neutron flux is computed by solving Boltzmann`s linear equation. Anyway, the direct solution of the equation involves too great a number of operations for practical application, leading up to TeraFlops or even PetaFlops supercomputing capabilities. Physical and mathematical models are then required to handle the extensive variety of configurations encountered. Numerical methods must be adapted to the rapid evolution of computer power, as also computer architecture: sequential, vector or parallel. Physical and mathematical models must allow for very fast estimation for online control and monitoring, adequate quantification for industrial studies and high-precision, best estimate computations. Coupling of neutronics to mechanics and two-phase flow thermohydraulics must be implemented in order to improve the accuracy in best-estimate computation schemes and to take into account the transient behaviour of the plant during normal operation or incidents. In this field of continuous improvement, the new methods applied in Reactor Physics lead obviously to good results and provide the improvements required in the future for the needs of efficiency, safety and advanced fuel cycle. This trend and the ``evolutionary`` implementation in large and modular software systems will be illustrated by the example of the SAPHYR system. (authors). 3 tabs.

  5. Neutronic and thermalhydraulic aspects

    International Nuclear Information System (INIS)

    Thomas, J.B.; Bergeonneau, P.

    1995-01-01

    Precise computation of neutron flux in the core of a nuclear reactor represents one of the basic aspects of reactor design and operation. Neutron flux is computed by solving Boltzmann's linear equation. Anyway, the direct solution of the equation involves too great a number of operations for practical application, leading up to TeraFlops or even PetaFlops supercomputing capabilities. Physical and mathematical models are then required to handle the extensive variety of configurations encountered. Numerical methods must be adapted to the rapid evolution of computer power, as also computer architecture: sequential, vector or parallel. Physical and mathematical models must allow for very fast estimation for online control and monitoring, adequate quantification for industrial studies and high-precision, best estimate computations. Coupling of neutronics to mechanics and two-phase flow thermohydraulics must be implemented in order to improve the accuracy in best-estimate computation schemes and to take into account the transient behaviour of the plant during normal operation or incidents. In this field of continuous improvement, the new methods applied in Reactor Physics lead obviously to good results and provide the improvements required in the future for the needs of efficiency, safety and advanced fuel cycle. This trend and the ''evolutionary'' implementation in large and modular software systems will be illustrated by the example of the SAPHYR system. (authors). 3 tabs

  6. HISTORICAL ASPECTS OF PHALLOPLASTY

    Directory of Open Access Journals (Sweden)

    P. S. Kyzlasov

    2017-01-01

    Full Text Available Reconstruction of the penis in transgender operations, amputation of the penis, congenital deformities and anomalies of the penis was and remains today an important issue in plastic surgery of the urogenital region. The only method to restore the penis is phalloplasty. In general, over the past decades, generations of clinicians have different ways and flaps for total fallouretheral reconstruction. Thus was formulated the characteristics of an ideal flap for the formation of neophallos, which should be safe, sensitive, without hair, and with long leg. However, despite the fact that the characteristics of a perfect flap, nowadays there is no “gold standard” in the formation of neophallos, as phalloplasty is a fairly complicated surgery, and the choice of method depends on many factors. The choice of methodology is determined by the plastics surgeon and to each patient is individual, depends on the etiology of the disease and the possibility of choosing the form of the donor’s transplant. This article presents a literature review devoted to the historical aspects of phalloplasty. In the article, in chronological order reflected the evolution of the different forming methods neofallos, phallourethrоplasty, describes their advantages and disadvantages.

  7. [Economic aspects of epilepsy].

    Science.gov (United States)

    Argumosa, A; Herranz, J L

    2000-06-01

    The economic magnitude of epilepsy is determined by its effect on the employment status of the patients, the cost of drug treatment for them and the healthcare system and the repercussion worldwide. Studies of the cost of the disease show that it has economic importance due to the sum of the direct and indirect costs caused by it. In the case of epilepsy, the results of studies in various countries led to the creation of a Commission on Economic Aspects of Epilepsy. The lack of epidemiological studies regarding epilepsy in Spain may explain the lack of publications on this subject in our country. The percentage of the total cost due to antiepileptic drugs is considerable and will probably increase in the future. The pharmaco-economic evaluation made by cost-benefit, cost-effectiveness, cost-usefulness analysis and studies to minimize costs should serve to use healthcare resources in the most effective manner and justify the rational use of the new antiepileptic drugs. The economic impact of epilepsy is added to the repercussion of the disease itself on the patient and his family. The different distribution of costs in children and adults with epilepsy suggest the need for intervention at an early age to try to reduce the long term economic and personal repercussions. The pharmaco-economic evaluation of the new antiepileptic drugs will make it clear whether their considerable cost is worth paying for their greater effectivity.

  8. Visual aspects in urban woodland management and planning

    OpenAIRE

    Ode, Åsa

    2003-01-01

    Urban woodland is an important component of people's everyday environment, both as an attractive environment to visit as well as being an intrinsic part of the surrounding landscape. This thesis focuses on one specific aspect of the urban woodland - the visual. The visual aspect is how most people experience the woodland, both when visiting and as part of their everyday landscape. In order to take visual aspects into account there is a need to have tools and approaches for analysing and descr...

  9. Identifying Causes of Construction Waste – Case of Central Region of Peninsula Malaysia

    OpenAIRE

    Sasitharan Nagapan; Ismail Abdul Rahman; Ade Asmi; Aftab Hameed Memon; Rosli Mohammad Zin

    2012-01-01

    Construction waste becomes a global issue facing by practitioners and researchers around the world. Waste can affects success of construction project significantly. More specifically, it has major impact on construction cost, construction time, productivity and sustainability aspects. This paper aims to identify various factors causing construction waste in Malaysia. Study was carried out through structured questionnaire focusing three major parties (i.e. clients, consultants and contractors)...

  10. Trustworthy persistent identifier systems of the future

    Science.gov (United States)

    Golodoniuc, Pavel; Klump, Jens; Car, Nicholas

    2016-04-01

    Over the last two decades, persistent identifier (PID) systems have seen some significant changes in their governance policies, system capabilities, and technology. The development of most systems was driven by two main application areas, namely archives and libraries. Guidelines and criteria for trustworthy PID systems have been clearly devised (Bütikofer, 2009) and many PID system implementations for the identification of static digital objects have been built (e.g., PURL). However systems delivering persistent identifiers for dynamic datasets are not yet mature. There has been a rapid proliferation of different PID systems caused by the specific technical or organisational requirements of various communities that could not be met by existing systems such as DOI, ISBN, and EAN. Many of these different systems were limited by their inability to provide native means of persistent identifier resolution. This has prompted a decoupling of PID-associated data from the resolution service and this is where the Handle system has played a significant role. The Handle allowed to build a distributed system of independently managed resolver services. A trustworthy PID system must be designed to outlive the objects it provides persistent identifiers for, which may cease to exist or otherwise be deprecated, and the technology used to implement it, which will certainly need to change with time. We propose that such a system should rest on four pillars of agreements - (i) definitions, (ii) policies, (iii) services, and (iv) data services, to ensure longevity. While we believe all four pillars are equally important, we intentionally leave regulating aspects of issuing of identifiers and their registration out of the scope of this paper and focus on the agreements that have to be established between PID resolver services and the data sources indicated by the persistent identifiers. We propose an approach to development of PID systems that combines the use of (a) the Handle system

  11. SOCIAL ASPECTS OF COMPETITIVENESS

    Directory of Open Access Journals (Sweden)

    Klimova A. V.

    2014-06-01

    Full Text Available One of the most important conditions of the existence of every organization, every enterprise is to insure the long-term sustainable development, one of the conditions of which is the increase of an organizational competitiveness. In modern economic conditions, social aspects of competitiveness are now in the foreground of interest, because just the strategy of social responsibility (SSR of modern enterprises can assure some commercial benefits, in responding, at the same time, to the social demands and in creating its well-being. Such an approach is in the basis of the notion of competitiveness. Along with «rigid parameters», such as price characteristics, the capability to deal with competitors, effective financial and production policies, «flexible factors» of competitiveness are of a big importance: a personnel potential, individual and collective competencies, organizational and managerial capabilities. As a result, we have formulated a research hypothesis: the organizational competitiveness is defined by individual and collective competencies of an organization, is based on socially responsible actions, confirms the demand for the object and insures its sustainable long-term development. Any organization should base all its actions aimed to increase its competitiveness on its intellectual potential, or on the management of individual and collective competencies that assure the sustainable development and the goal achievement. For every organizational strategic action, an effective combination of these competencies exists. So, we suggest a new definition of competitiveness: it is a social and economic category of understanding of the social responsibility, having as a central element individual and collective competencies, based on socially responsible actions of an enterprise, insuring its long-term sustainable development.

  12. INTERPERSONAL COMMUNICATION: PSYCHOLINGUISTIC ASPECT

    Directory of Open Access Journals (Sweden)

    Mitrofanova, I.I.

    2016-09-01

    Full Text Available The article considers language as the organization of the speech of any person in any situation, without which it is impossible to characterize the internal structure of the speech stream. Language is exactly a system of guidelines necessary for the activity in the social world. Communication is primarily nothing but as a way of making one or another correction in the image of the interlocutor’s world. In order for a language to serve as a means of communication, it must have a single or a similar understanding of reality behind it. Conversely, the unity of understanding the reality and the unity of coherence presuppose the possibility of adequate communication. A mandatory component of communication is the communicative act, that is, the act of sharing information between people. The speech, i.e. the natural sound language is an important means of conveying information that defines this aspect of the communication process as verbal communication. The idea of dialogue as the space, in which the exchange of information takes place, is defined as initial. Essentially, it is the dialogue that in this case acts as the backbone principle in dealing with problems of language. It is here that the essence of social and psychological transition to the analysis of communication is most visibly concentrated. An individual essentially "lives" in the world of Another person’s worlds, and studying the words of this person, he or she studies the "world" of Another person. Thus, the dialogue is not merely the interaction (verbal with another person, but, ultimately, the interaction with the world of culture.

  13. Sociological aspects of rhinoplasty.

    Science.gov (United States)

    Babuccu, Orhan; Latifoğlu, Osman; Atabay, Kenan; Oral, Nursen; Coşan, Behçet

    2003-01-01

    Although the psychological aspect of the rhinoplasty operation has been a subject of interest for a long time, with the exception of a few studies, sociological factors have been almost totally ignored. In this prospective study the personality characteristics and socioeconomic backgrounds of 216 rhinoplasty patients were evaluated. Between 1994 and 2000, a questionnaire and the Minnesota Multiphasic Personality Inventory (MMPI) were given preoperatively to 157 females and 59 males. The MMPI was also given to age-matched people as a control. Six months after surgery, patients were called on the telephone and asked to rate their satisfaction. According to questionnaire, a great majority of the rhinoplasty patients were young, unmarried women with high education levels. In the rhinoplasty group, one or more scales of the inventory were not in the normal ranges in 45% of the patients, whereas this proportion in the control group was 28% (p childish, highly active, impulsive, competitive, reactive, perfectionistic about themselves, talkative, and emotionally superficial. Male patients could be described as rigid, stubborn, over-sensitive, suspicious, perfectionistic, pessimistic, over-reactive, and having somatizations. Tension and anxiety with feelings of inferiority were found to be characteristics of the male patients. The satisfaction rate after six months was reported as 72%. There was no significant correlation between MMPI results and demographic variables, nor satisfaction rate. In conclusion, the rhinoplasty patients in our study are young people at the very beginning of their careers. It could be that their personalities and socioeconomic backgrounds combine to make aesthetic surgery rewarding enough, both socially and personally, to encourage them to follow through.

  14. SOCIO-ECONOMIC ASPECTS OF THE CONCEPT OF SUSTAINABLE DEVELOPMENT IN AZERBAIJAN REPUBLIC

    Directory of Open Access Journals (Sweden)

    Z. T. Imrani

    2016-01-01

    Full Text Available Aim. The aim is to determine the socio-economic aspects of sustainable development of the Republic of Azerbaijan taking into account economic, environmental, social and environmental opportunities of the country; to find the rationale for the concept of sustainable development to eliminate major differences specific to regional economic development, management of economic and social development of the regions.Methods. Historical and comparative analysis, system approach, analysis of statistical and mathematical materials.Findings. We identified the advantages of the concept of sustainable development; cunducted the analysis of the dynamics of development of the leading industries in the region; studied the most promising sectors of the regions from the economic and geographic point of view.Conclusion. We identified socio-economic aspects of sustainable development of the Republic of Azerbaijan.

  15. Brand Image Theoretical Aspects

    OpenAIRE

    Išoraitė, Maria

    2018-01-01

    The article analyzes the image of a brand and a brand image, brand value assessment methods, brand value, and benefits. A brand is a word or phrase that identifies and separates goods belonging to one person from belonging to another person. A brand is one of the elements of marketing, advertising. High-quality brand brings significant benefits to the manufacturer or the trader. A brand name may consist of a brand name and a brand symbol. There is several brand value evaluation model analyze ...

  16. Emotional aspects of hyperprolactinemia.

    Science.gov (United States)

    Sobrinho, L G

    1998-01-01

    Patients with hyperprolactinemia often present with emotional difficulties. These occasionally persist even after successful treatment. Insight into the roots of their diseased state makes a difference in the handling of all cases, but becomes crucial in the not-so-rare situations in which the normalization of hormonal levels is not followed by a feeling of cure. This chapter attempts to provide details, discuss and situate in context the following blocks of pertinent information: (1) prolactin acts upon the central nervous system and variations in its concentrations do affect mood, emotions and behavior; (2) most actions of prolactin are directed to metabolical and behavioral adaptation to pregnancy and the care of the young; (3) even in the absence of pregnancy prolactin secretion responds to environmental stimuli under specific conditions. Whether adaptive, as in the case of surrogate maternity, or pathological, as in the case of pseudopregnancy, prolactin responds to a perceived need to take care of a child; (4) the facts that the clinical onset of prolactinomas often follows life-events and that these tumors occur preferentially in women brought up under specific conditions suggest the possibility that psychological factors may predispose to prolactinomas; (5) dealing with individual cases requires the perception that the relations between prolactin, emotions and feelings are circular, i.e., prolactin affects the brain and mood but, on the other hand, personality traits and environmental factors may stimulate the secretion of prolactin and may play a role in the genesis of the disease.

  17. Large Aspect Ratio Tokamak Study

    International Nuclear Information System (INIS)

    Reid, R.L.; Holmes, J.A.; Houlberg, W.A.; Peng, Y.K.M.; Strickler, D.J.; Brown, T.G.; Wiseman, G.W.

    1980-06-01

    The Large Aspect Ratio Tokamak Study (LARTS) at Oak Ridge National Laboratory (ORNL) investigated the potential for producing a viable longburn tokamak reactor by enhancing the volt-second capability of the ohmic heating transformer through the use of high aspect ratio designs. The plasma physics, engineering, and economic implications of high aspect ratio tokamaks were assessed in the context of extended burn operation. Using a one-dimensional transport code plasma startup and burn parameters were addressed. The pulsed electrical power requirements for the poloidal field system, which have a major impact on reactor economics, were minimized by optimizing the startup and shutdown portions of the tokamak cycle. A representative large aspect ratio tokamak with an aspect ratio of 8 was found to achieve a burn time of 3.5 h at capital cost only approx. 25% greater than that of a moderate aspect ratio design tokamak

  18. Global aspects of gauge anomalies

    International Nuclear Information System (INIS)

    Zhang, H.

    1988-01-01

    This dissertation discusses the global aspects of gauge anomalies in even dimensions. After a very brief description of local gauge anomalies, the possible global gauge anomalies for various gauge theories are discussed using homotopy theory. One of the main results obtained in a general formula for the SU(n - k) global gauge anomaly coefficient in arbitrary 2n dimensions. The result is expressed in terms of the James number of the Stiefel manifold SU(n + 1)/SU(n - k) and the generalized Dynkin indices. From this, the possibilities of SU(n), SU(n - 1), and SU(2) global gauge anomalies in arbitrary 2n dimensions have been determined. We have also determined the possibilities of global gauge anomalies for the gauge groups SP(2N) and SO(N) in certain general dimensions, as well as for the exceptional gauge groups in specific dimensions. Moreover, several general propositions are formulated and proved which are very useful in the study of global gauge anomalies

  19. Multiple sclerosis: current immunological aspects

    Directory of Open Access Journals (Sweden)

    Carlos Cuevas-García

    2017-02-01

    Full Text Available Multiple sclerosis is the most common inflammatory, chronic and degenerative condition of the central nervous system, and represents the first cause of disability in young adults. In Mexico, 11 to 20 out of every 100 000 people suffer from this disease. The causes of multiple sclerosis remain unknown, but several theories have been proposed on its origin: the interaction of environmental factors, viral infectious factors and genetic and immune susceptibility of each individual patient, which induce an autoimmune response and promote neuronal/axonal degeneration. In this review, the immune reaction main components and neurodegeneration present in multiple sclerosis are analyzed, as well as the inflammatory cascade associated with demyelination. Available treatments’ main purpose is to modulate aspects related to the adaptive immune response (B and T cells. The therapeutic challenge will be antigen-specific immune-tolerance induction, for example, with the use of tolerance protocols with peptides or DNA or nanoparticles vaccines. Future therapies should aim to control innate components (microglia, macrophages, astrocytes and to promote remyelination. To optimize the treatment, a combined therapeutic approach targeting the control of inflammatory and neurodegenerative components of the disease and monitoring of biomarkers will be necessary.

  20. Linguistic aspects of writing for professional purposes

    Directory of Open Access Journals (Sweden)

    Greta Përgjegji

    2016-03-01

    Full Text Available Writing for Professional Purposes is considered as a means of communication between professionals who belong to two communities that have different languages, but share the same knowledge or expertise. The article gives a hint on how writing for specific purposes evolved to give rise to the creation of Writing for Professional Purposes. The social, cultural and cognitive aspects are an essential part of Writing for Professional Purposes since the physical act of writing cannot be considered only a result or product of the knowledge the individual possesses but also a social and cultural act. Therefore, the social and cultural aspects of writing explains the specificities and the intricacies of the effects these aspects have on writing for it is considered as an inseparable part of social and cultural groups. On the other hand, the cognitive aspect of writing explains and emphasizes the mental activities of the individual during the decision-making process while he/she is writing planning and editing their material having in mind the audience. On the same line of reasoning, writing for professional purposes in a second language means that the writer has to consider the audience twice; first, there is an audience who shares the same knowledge or expertise and second, the audience does not have the same language. Consequently, writing in another language that is not the first language with a specific jargon as well as a specific grammatical structure brings about a lot of difficulties. Hence, writing in professional contexts in the mother tongue implies only writing in a specialized version of a language already known to the writer, but writing in a target language means that the writer has to learn the target language and the specialized version of that language.

  1. Aspects of risk assessment, control and prevention

    OpenAIRE

    Larsson, Tore J; Hale, Andrew R

    2000-01-01

    The contributions to this Worklife 2000 workshop and special issue of the Safety Science Monitor touch upon several aspects crucial to safety management. The perspectives and concepts presented are from areas which include, but are not specifically dedicated to, occupational health and safety. Safety at work, however, represents the prime target area of the workshop and the discussion initiated here, and hopefully continuing through the year on this site, should be seen as an attempt to seek ...

  2. Environmental aspects of nuclear power

    International Nuclear Information System (INIS)

    Ward, D.P.

    1987-01-01

    Nuclear power provides the world with an important option for generating electricity. To successfully and safely utilize this power, engineering and environmental factors should be carefully considered throughout a nuclear power plant project, especially during the planning stages. This paper discusses the major environmental aspects of a nuclear power plant project from site selection to retirement. During the site selection process, both engineering and environmental resources must be identified and evaluated. Environmental resources include areas that support agricultural or aquatic commercial activities, habitats for commercial or endangered species, population centers, transportation systems, and recreational areas. Also, during the site selection process, the potential impacts of both construction and operating activities must be considered. In addition to the area actually disturbed by construction, construction activities also affect local services, such as transportation systems, housing, school systems, and other social services. Since nuclear power plants use a 'clean fuel,' generally the most significant operating activity having a potential environmental impact is the discharge of cooling water. The potential effect of this discharge on commercial activities and sensitive habitats should be thoroughly evaluated. Lastly, the method of decommissioning can affect long-range land use planning and should therefore be considered during the planning process. With appropriate planning, nuclear power plants can be constructed and operated with minimum environmental impact. (author)

  3. Molecular radiation biology: Future aspects

    International Nuclear Information System (INIS)

    Hagen, U.

    1990-01-01

    Future aspects of molecular radiation biology may be envisaged by looking for unsolved problems and ways to analyse them. Considering the endpoints of cellular radiation effects as cell inactivation, chromosome aberrations, mutation and transformation, the type of DNA damage in the irradiated cell and the mechanisms of DNA repair as excision repair, recombination repair and mutagenic repair are essential topics. At present, great efforts are made to identify, to clone and to sequence genes involved in the control of repair of DNA damage and to study their regulation. There are close relationships between DNA repair genes isolated from various organisms, which promises fast progress for the molecular analysis of repair processes in mammalian cells. More knowledge is necessary regarding the function of the gene products, i.e. enzymes and proteins involved in DNA repair. Effort should be made to analyse the enzymatic reactions, leading to an altered nucleotide sequence, encountered as a point mutation. Mislead mismatch repair and modulation of DNA polymerase might be possible mechanisms. (orig.)

  4. Biophysical aspects of photodynamic therapy.

    Science.gov (United States)

    Juzeniene, Asta; Nielsen, Kristian Pagh; Moan, Johan

    2006-01-01

    Over the last three decades photodynamic therapy (PDT) has been developed to a useful clinical tool, a viable alternative in the treatment of cancer and other diseases. Several disciplines have contributed to this development: chemistry in the development of new photosensitizing agents, biology in the elucidation of cellular processes involved in PDT, pharmacology and physiology in identifying the mechanisms of distribution of photosensitizers in an organism, and, last but not least, physics in the development of better light sources, dosimetric concepts and construction of imaging devices, optical sensors and spectroscopic methods for determining sensitizer concentrations in different tissues. Physics and biophysics have also helped to focus on the role of pH for sensitizer accumulation, dose rate effects, oxygen depletion, temperature, and optical penetration of light of different wavelengths into various types of tissue. These are all important parameters for optimally effective PDT. The present review will give a brief, physically based, overview of PDT and then discuss some of the main biophysical aspects of this therapeutic modality.

  5. Environmental aspects of nuclear power

    International Nuclear Information System (INIS)

    Ward, D.P.

    1988-01-01

    Nuclear power provides the world with an important option for generating electricity. To successfully and safely utilize this power, engineering and environmental factors should be carefully considered throughout a nuclear power plant project, especially during the planning stages. This paper discusses the major environmental aspects of a nuclear power plant project from site selection to retirement. During the site selection process, both engineering and environmental resources must be identified and evaluated. Environmental resources include areas that support agricultural or aquatic commercial activities, habitats for commercial or endangered species, population centers, transportation systems, and recreational areas. Also during the site selection process, the potential impacts of both construction and operating activities must be considered. In addition to the area actually disturbed by construction, construction activities also affect local services, such as transportation systems, housing, school systems, and other social services. Since nuclear power plants use a ''clean fuel,'' generally the most significant operating activity having a potential environmental impact is the discharge of cooling water. The potential effect of this discharge on commercial activities and sensitive habitats should be thoroughly evaluated. Lastly, the method of decommissioning can affect long-range land use planning and should therefore be considered during the planning process

  6. Criminological aspects of crime recidivism

    OpenAIRE

    Lelková, Helena

    2015-01-01

    Criminological aspects of criminal recidivism The topic of this thesis are the criminological aspects of criminal recidivism and goal is to present a complete outline of some of the basic ideas related to the concept of criminal recidivism and to introduce the reader to its selected criminological aspects. This thesis is divided into four chapters. The introductory chapter is focused on the concept of criminal recidivism itself, and similarly defines the various concepts with emphasis on the ...

  7. Financial aspects of decommissioning (key aspects of decommissioning costing)

    International Nuclear Information System (INIS)

    Danska, V.

    2009-01-01

    In this presentation the following aspects of NPPs decommissioning are discussed: Requirements and purpose of decommissioning costing; Decommissioning costing methodologies; Standardised decommissioning cost structure; Input data for cost estimate process; Waste management in cost estimate process; Grading aspects in cost estimating; Cost control in decommissioning projects; Summary of the cost estimation process; Conclusions and recommendations.

  8. Prototyping and Composing Aspect Languages: using an Aspect Interpreter Framework

    NARCIS (Netherlands)

    Havinga, W.K.; Bergmans, Lodewijk; Aksit, Mehmet

    2007-01-01

    Domain speci��?c aspect languages (DSALs) are becoming more popular because they can be designed to represent recurring concerns in a way that is optimized for a speci��?c domain. However, the design and implementation of even a limited domain-speci��?c aspect language can be a tedious job. To

  9. Economic aspects of decommissioning

    International Nuclear Information System (INIS)

    Jenne, C.

    1988-01-01

    Two viewpoints on decommissioning are quoted; the first suggests that decommissioning can be viewed as a technical detail that is of limited relevance whereas the second suggests that decommissioning is a key financial issue. Both are specifically relevant to United Kingdom nuclear power stations. This paper attempts to reconcile the two views. It suggests that decommissioning does raise some important issues for regulation and financing of a privatised industry but, despite this, the economics of nuclear do remain insensitive. The paper begins by examining the significance of decommissioning costs in a number of contexts, including nuclear unit generating costs and financing requirements. It then addresses the degree of uncertainty in the decommissioning cost estimates. With privatisation on the horizon, the paper considers the significance of decommissioning and the associated uncertainty for the investor; this last section considers regulatory issues raised in relation to funding, accounting policy and electricity pricing. (author)

  10. Safety aspects of the RECH-1 core conversion

    International Nuclear Information System (INIS)

    Wetherby, Jaime Riesle

    1998-01-01

    When the RECH-1 research reactor joined the core conversion program for low enrichment fuel, the need to review some safety related aspects, which are currently under way with different degrees of progress, became apparent. The mentioned aspects can be grouped into: evaluation of the technical specifications of the new fuel elements: the technical specifications were carefully verified and contrasted with the recommendations of the IAEA and with those of manufacturers which are widely known for their expertise. (author)

  11. Some theoretical aspects of hormone receptor determination

    International Nuclear Information System (INIS)

    Sluiter, W.J.

    1981-01-01

    Suitable antisera for determination of hormone receptors are not available for the majority of hormone receptors. Therefore, the determination of hormone receptors is mostly performed in terms of binding capacity for the appropriate hormone, using radioactive hormone labels. Some theoretical aspects of such a receptor determination are discussed including the length of incubation (total or unoccupied receptor concentration), single point or multiple point (Scatchard) analysis (regarding the influence of other specific binders), the correction procedure for non-specific binding and the influence of the circulating hormone level. (Auth.)

  12. Logistics aspects of petroleum pipeline operations

    Directory of Open Access Journals (Sweden)

    W. J. Pienaar

    2010-11-01

    Full Text Available The paper identifies, assesses and describes the logistics aspects of the commercial operation of petroleum pipelines. The nature of petroleum-product supply chains, in which pipelines play a role, is outlined and the types of petroleum pipeline systems are described. An outline is presented of the nature of the logistics activities of petroleum pipeline operations. The reasons for the cost efficiency of petroleum pipeline operations are given. The relative modal service effectiveness of petroleum pipeline transport, based on the most pertinent service performance measures, is offered. The segments in the petroleum-products supply chain where pipelines can play an efficient and effective role are identified.

  13. The stress of being chronically ill: from disease-specific to task-specific aspects.

    NARCIS (Netherlands)

    Heijmans, M.; Rijken, M.; Foets, M.; Ridder, D. de; Schreurs, K.; Bensing, J.

    2004-01-01

    The assumption that disease-related stressors are exclusive for particular diagnoses characterizes many studies of chronically ill patients. In this study the perceptions of 1305 patients from 10 different chronic disease categories were compared with respect to a number of important stressors.

  14. The stress of being chronically ill: from disease-specific to task-specific aspects

    NARCIS (Netherlands)

    Heijmans, M.; Rijken, M.; Foets, M.; Ridder, D.T.D. de; Schreurs, K.; Bensing, J.

    The assumption that disease-related stressors are exclusive for particular diagnoses characterizes many studies of chronically ill patients. In this study the perceptions of 1305 patients from 10 different chronic disease categories were compared with respect to a number of important stressors.

  15. Framework for systematic identification of ethical aspects of healthcare technologies: the SBU approach.

    Science.gov (United States)

    Heintz, Emelie; Lintamo, Laura; Hultcrantz, Monica; Jacobson, Stella; Levi, Ragnar; Munthe, Christian; Tranæus, Sofia; Östlund, Pernilla; Sandman, Lars

    2015-01-01

    Assessment of ethical aspects of a technology is an important component of health technology assessment (HTA). Nevertheless, how the implementation of ethical assessment in HTA is to be organized and adapted to specific regulatory and organizational settings remains unclear. The objective of this study is to present a framework for systematic identification of ethical aspects of health technologies. Furthermore, the process of developing and adapting the framework to a specific setting is described. The framework was developed based on an inventory of existing approaches to identification and assessment of ethical aspects in HTA. In addition, the framework was adapted to the Swedish legal and organizational healthcare context, to the role of the HTA agency and to the use of non-ethicists. The framework was reviewed by a group of ethicists working in the field as well as by a wider set of interested parties including industry, interest groups, and other potential users. The framework consists of twelve items with sub-questions, short explanations, and a concluding overall summary. The items are organized into four different themes: the effects of the intervention on health, its compatibility with ethical norms, structural factors with ethical implications, and long term ethical consequences of using the intervention. In this study, a framework for identifying ethical aspects of health technologies is proposed. The general considerations and methodological approach to this venture will hopefully inspire and present important insights to organizations in other national contexts interested in making similar adaptations.

  16. Aspects of Quadratic Gravity

    CERN Document Server

    Alvarez-Gaume, Luis; Kounnas, Costas; Lust, Dieter; Riotto, Antonio

    2016-01-01

    We discuss quadratic gravity where terms quadratic in the curvature tensor are included in the action. After reviewing the corresponding field equations, we analyze in detail the physical propagating modes in some specific backgrounds. First we confirm that the pure $R^2$ theory is indeed ghost free. Then we point out that for flat backgrounds the pure $R^2$ theory propagates only a scalar massless mode and no spin-two tensor mode. However, the latter emerges either by expanding the theory around curved backgrounds like de Sitter or anti-de Sitter, or by changing the long-distance dynamics by introducing the standard Einstein term. In both cases, the theory is modified in the infrared and a propagating graviton is recovered. Hence we recognize a subtle interplay between the UV and IR properties of higher order gravity. We also calculate the corresponding Newton's law for general quadratic curvature theories. Finally, we discuss how quadratic actions may be obtained from a fundamental theory like string- or M-...

  17. WHO - IPHECA: Epidemiological aspects

    International Nuclear Information System (INIS)

    Souchkevitch, G.

    1996-01-01

    In May 1991 the World Health Assembly endorsed the establishment of the International Programme on the Health Effects of the Chernobyl Accident (IPHECA) under the auspices of WHO. Five pilot projects have been carried out within IPHECA in the study territories of Belarus, Russian Federation and Ukraine in a period from 1991 to 1994. This pilot projects dealt with the detection and treatment of leukaemia and related diseases (Haematology Project), thyroid disorders (Thyroid project), brain damage during exposure 'in-utero' (Brain Damage 'in-Utero' project) and with the development of the Chernobyl registries (Epidemiological Registry Project). A fifth pilot project on oral health was performed only in Belarus. Epidemiological investigations have been an important component of all IPHECA pilot projects. Within 'Epidemiological Registry' Project such investigations have been the principal activity. But with respect to other IPHECA projects it was carried out in addition to main objectives relating to medical monitoring, early diagnosis and treatment of specific diseases included in project protocols. To support the epidemiological investigations within IPHECA, WHO supplied 41 computers in Belarus, Russian Federation and Ukraine and provided training for specialists from these countries in internationally recognized centres. The training programmes and host countries were as follows: standardization of epidemiological investigations (United Kingdom), radiation epidemiology (Russia), development of software (United Kingdom), principles of epidemiological investigations (The Czech Republic), cohort investigations (Japan)

  18. WHO - IPHECA: Epidemiological aspects

    Energy Technology Data Exchange (ETDEWEB)

    Souchkevitch, G [World Health Organization, Geneva (Swaziland)

    1996-07-01

    In May 1991 the World Health Assembly endorsed the establishment of the International Programme on the Health Effects of the Chernobyl Accident (IPHECA) under the auspices of WHO. Five pilot projects have been carried out within IPHECA in the study territories of Belarus, Russian Federation and Ukraine in a period from 1991 to 1994. This pilot projects dealt with the detection and treatment of leukaemia and related diseases (Haematology Project), thyroid disorders (Thyroid project), brain damage during exposure 'in-utero' (Brain Damage 'in-Utero' project) and with the development of the Chernobyl registries (Epidemiological Registry Project). A fifth pilot project on oral health was performed only in Belarus. Epidemiological investigations have been an important component of all IPHECA pilot projects. Within 'Epidemiological Registry' Project such investigations have been the principal activity. But with respect to other IPHECA projects it was carried out in addition to main objectives relating to medical monitoring, early diagnosis and treatment of specific diseases included in project protocols. To support the epidemiological investigations within IPHECA, WHO supplied 41 computers in Belarus, Russian Federation and Ukraine and provided training for specialists from these countries in internationally recognized centres. The training programmes and host countries were as follows: standardization of epidemiological investigations (United Kingdom), radiation epidemiology (Russia), development of software (United Kingdom), principles of epidemiological investigations (The Czech Republic), cohort investigations (Japan)

  19. Electronic textbooks: didactic aspect

    Directory of Open Access Journals (Sweden)

    Ivanova Elena O.

    2016-01-01

    Full Text Available The modern process of training proceeding in the information and education environment demands a textbook of a new format differing from that one of a traditional paper book. Research has shown that a new textbook is a specially designed subject information and education environment. Filling of this environment (the textbook - navigator, the textbook script, a set of materials for independent work, etc., structuring information (as the script of an educational process, the designer of a process of training, the integrator of the specified types is shown in the article. Characteristics of textbooks of a new generation are provided: orientation towards realizing the complete process of training from positing aims to a reflection of results, ensuring the maximum independence of pupils, accounting of specific features of pupils, granting opportunities of creation by pupils of an own educational product. Components of the subject information and education environment are presented: subject and target, substantial and organizational, estimated and reflexive components. The reformative and constructive tasks providing an activity orientation of the electronic textbook are considered.

  20. Marketing aspect of paramedical

    Directory of Open Access Journals (Sweden)

    Dugalić Sretenka L.

    2003-01-01

    Full Text Available That's how the primary medical and ecological reasons as the well being for humanity came out of the satisfaction of specific health needs. Through operationally of these outcomes it tried to prove the need and the intentions of the customers, and through methodologies and strategies which stand to our service. Further developing activity acted as a useful to the innovation of the product and vertical structure of marketing, through the change in the way of thinking of the medical and pharmaceutical profession. The paper is concepted so that the received material inserted to the content part, do the following: 1. Meaning, characteristics and developing possibilities of phytotherapy; 2. Dimensions of market in managing of phytotherapic assortment. By observing the final results, which were obtained through means of representative sources and other research of phytotherapic products, it can be expected that the same can be applicable to broader spectrum in practice with kind input to the marketing ideas. Models, presented here, is meant to be for innovative applications in the medical marketing concept, by the results of wide spending in the food service industry (domain of dietetics, at manufacture of food for children at the manufacture of 'medical cosmetics' and cosmetic-druggist assortments (products for hygiene, shampoos, soap, creams and bubbles for bath.

  1. Obesity: epigenetic aspects.

    Science.gov (United States)

    Kaushik, Prashant; Anderson, James T

    2016-06-01

    Epigenetics, defined as inheritable and reversible phenomena that affect gene expression without altering the underlying base pair sequence has been shown to play an important role in the etiopathogenesis of obesity. Obesity is associated with extensive gene expression changes in tissues throughout the body. Epigenetics is emerging as perhaps the most important mechanism through which the lifestyle-choices we make can directly influence the genome. Considerable epidemiological, experimental and clinical data have been amassed showing that the risk of developing disease in later life is dependent on early life conditions, mainly operating within the normative range of developmental exposures. In addition to the 'maternal' interactions, there has been increasing interest in the epigenetic mechanisms through which 'paternal' influences on offspring development can be achieved. Nutrition, among many other environmental factors, is a key player that can induce epigenetic changes not only in the directly exposed organisms but also in subsequent generations through the transgenerational inheritance of epigenetic traits. Overall, significant progress has been made in the field of epigenetics and obesity and the first potential epigenetic markers for obesity that could be detected at birth have been identified. Fortunately, epigenetic phenomena are dynamic and rather quickly reversible with intensive lifestyle changes. This is a very promising and sustainable resolution to the obesity pandemic.

  2. Tense and Aspect in English

    DEFF Research Database (Denmark)

    Davidsen-Nielsen, Niels

    2013-01-01

    In the 1990's the author cooperated with Carl Bache on a grammar of English. It turned out that the views they had previously arrived at individually on tense and aspect could be combined by operating with a fused system involving four ordered choices resulting in sixteen tense-aspect forms...

  3. Distributed Persistent Identifiers System Design

    Directory of Open Access Journals (Sweden)

    Pavel Golodoniuc

    2017-06-01

    Full Text Available The need to identify both digital and physical objects is ubiquitous in our society. Past and present persistent identifier (PID systems, of which there is a great variety in terms of technical and social implementation, have evolved with the advent of the Internet, which has allowed for globally unique and globally resolvable identifiers. PID systems have, by in large, catered for identifier uniqueness, integrity, and persistence, regardless of the identifier’s application domain. Trustworthiness of these systems has been measured by the criteria first defined by Bütikofer (2009 and further elaborated by Golodoniuc 'et al'. (2016 and Car 'et al'. (2017. Since many PID systems have been largely conceived and developed by a single organisation they faced challenges for widespread adoption and, most importantly, the ability to survive change of technology. We believe that a cause of PID systems that were once successful fading away is the centralisation of support infrastructure – both organisational and computing and data storage systems. In this paper, we propose a PID system design that implements the pillars of a trustworthy system – ensuring identifiers’ independence of any particular technology or organisation, implementation of core PID system functions, separation from data delivery, and enabling the system to adapt for future change. We propose decentralisation at all levels — persistent identifiers and information objects registration, resolution, and data delivery — using Distributed Hash Tables and traditional peer-to-peer networks with information replication and caching mechanisms, thus eliminating the need for a central PID data store. This will increase overall system fault tolerance thus ensuring its trustworthiness. We also discuss important aspects of the distributed system’s governance, such as the notion of the authoritative source and data integrity

  4. Nutritional Aspects of Depression

    Directory of Open Access Journals (Sweden)

    Undine E. Lang

    2015-09-01

    Full Text Available Several nutrition, food and dietary compounds have been suggested to be involved in the onset and maintenance of depressive disorders and in the severity of depressive symptoms. Nutritional compounds might modulate depression associated biomarkers and parallel the development of depression, obesity and diabetes. In this context, recent studies revealed new mediators of both energy homeostasis and mood changes (i.e. IGF-1, NPY, BDNF, ghrelin, leptin, CCK, GLP-1, AGE, glucose metabolism and microbiota acting in gut brain circuits. In this context several healthy foods such as olive oil, fish, fruits, vegetables, nuts, legumes, poultry, dairy and unprocessed meat have been inversely associated with depression risk and even have been postulated to improve depressive symptoms. In contrast, unhealthy western dietary patterns including the consumption of sweetened beverage, refined food, fried food, processed meat, refined grain, and high fat diary, biscuits, snacking and pastries have been shown to be associated with an increased risk of depression in longitudinal studies. However, it is always difficult to conclude a real prospective causal relationship from these mostly retrospective studies as depressed individuals might also change their eating habits secondarily to their depression. Additionally specific selected nutritional compounds, e.g. calcium, chromium, folate, PUFAs, vitamin D, B12, zinc, magnesium and D-serine have been postulated to be used as ad-on strategies in antidepressant treatment. In this context, dietary and lifestyle interventions may be a desirable, effective, pragmatical and non-stigmatizing prevention and treatment strategy for depression. At last, several medications (pioglitazone, metformin, exenatide, atorvastatin, gram-negative antibiotics, which have traditionally been used to treat metabolic disorders showed a certain potential to treat depression in first randomized controlled clinical trials.

  5. Nutritional aspects of depression.

    Science.gov (United States)

    Lang, Undine E; Beglinger, Christoph; Schweinfurth, Nina; Walter, Marc; Borgwardt, Stefan

    2015-01-01

    Several nutrition, food and dietary compounds have been suggested to be involved in the onset and maintenance of depressive disorders and in the severity of depressive symptoms. Nutritional compounds might modulate depression associated biomarkers and parallel the development of depression, obesity and diabetes. In this context, recent studies revealed new mediators of both energy homeostasis and mood changes (i.e. IGF-1, NPY, BDNF, ghrelin, leptin, CCK, GLP-1, AGE, glucose metabolism and microbiota) acting in gut brain circuits. In this context several healthy foods such as olive oil, fish, fruits, vegetables, nuts, legumes, poultry, dairy and unprocessed meat have been inversely associated with depression risk and even have been postulated to improve depressive symptoms. In contrast, unhealthy western dietary patterns including the consumption of sweetened beverage, refined food, fried food, processed meat, refined grain, and high fat diary, biscuits, snacking and pastries have been shown to be associated with an increased risk of depression in longitudinal studies. However, it is always difficult to conclude a real prospective causal relationship from these mostly retrospective studies as depressed individuals might also change their eating habits secondarily to their depression. Additionally specific selected nutritional compounds, e.g. calcium, chromium, folate, PUFAs, vitamin D, B12, zinc, magnesium and D-serine have been postulated to be used as ad-on strategies in antidepressant treatment. In this context, dietary and lifestyle interventions may be a desirable, effective, pragmatical and non-stigmatizing prevention and treatment strategy for depression. At last, several medications (pioglitazone, metformin, exenatide, atorvastatin, gram-negative antibiotics), which have traditionally been used to treat metabolic disorders showed a certain potential to treat depression in first randomized controlled clinical trials. © 2015 The Author(s) Published by S

  6. Nano-material aspects of shock absorption in bone joints.

    Science.gov (United States)

    Tributsch, H; Copf, F; Copf, P; Hindenlang, U; Niethard, F U; Schneider, R

    2010-01-01

    This theoretical study is based on a nano-technological evaluation of the effect of pressure on the composite bone fine structure. It turned out, that the well known macroscopic mechano-elastic performance of bones in combination with muscles and tendons is just one functional aspect which is critically supported by additional micro- and nano- shock damping technology aimed at minimising local bone material damage within the joints and supporting spongy bone material. The identified mechanisms comprise essentially three phenomena localised within the three-dimensional spongy structure with channels and so called perforated flexible tensulae membranes of different dimensions intersecting and linking them. Kinetic energy of a mechanical shock may be dissipated within the solid-liquid composite bone structure into heat via the generation of quasi-chaotic hydromechanic micro-turbulence. It may generate electro-kinetic energy in terms of electric currents and potentials. And the resulting specific structural and surface electrochemical changes may induce the compressible intra-osseal liquid to build up pressure dependent free chemical energy. Innovative bone joint prostheses will have to consider and to be adapted to the nano-material aspects of shock absorption in the operated bones.

  7. The philosophical aspect of learning inverse problems of mathematical physics

    Directory of Open Access Journals (Sweden)

    Виктор Семенович Корнилов

    2018-12-01

    Full Text Available The article describes specific questions student learning inverse problems of mathematical physics. When teaching inverse problems of mathematical physics to the understanding of the students brought the information that the inverse problems of mathematical physics with a philosophical point of view are the problems of determining the unknown causes of known consequences, and the search for their solutions have great scientific and educational potential. The reasons are specified in the form of unknown coefficients, right side, initial conditions of the mathematical model of inverse problems, and as a consequence are functionals of the solution of this mathematical model. In the process of learning the inverse problems of mathematical physics focuses on the philosophical aspects of the phenomenon of information and identify cause-effect relations. It is emphasized that in the process of logical analysis applied and humanitarian character, students realize that information is always related to the fundamental philosophical questions that the analysis applied and the humanitarian aspects of the obtained results the inverse problem of mathematical physics allows students to make appropriate inferences about the studied process and to, ultimately, new information, to study its properties and understand its value. Philosophical understanding of the notion of information opens up to students a new methodological opportunities to comprehend the world and helps us to reinterpret existing science and philosophy of the theory related to the disclosure of the interrelationship of all phenomena of reality.

  8. Thoughts on identifiers

    CERN Multimedia

    CERN. Geneva

    2005-01-01

    As business processes and information transactions have become an inextricably intertwined with the Web, the importance of assignment, registration, discovery, and maintenance of identifiers has increased. In spite of this, integrated frameworks for managing identifiers have been slow to emerge. Instead, identification systems arise (quite naturally) from immediate business needs without consideration for how they fit into larger information architectures. In addition, many legacy identifier systems further complicate the landscape, making it difficult for content managers to select and deploy identifier systems that meet both the business case and long term information management objectives. This presentation will outline a model for evaluating identifier applications and the functional requirements of the systems necessary to support them. The model is based on a layered analysis of the characteristics of identifier systems, including: * Functional characteristics * Technology * Policy * Business * Social T...

  9. Identifiability in stochastic models

    CERN Document Server

    1992-01-01

    The problem of identifiability is basic to all statistical methods and data analysis, occurring in such diverse areas as Reliability Theory, Survival Analysis, and Econometrics, where stochastic modeling is widely used. Mathematics dealing with identifiability per se is closely related to the so-called branch of ""characterization problems"" in Probability Theory. This book brings together relevant material on identifiability as it occurs in these diverse fields.

  10. HOLIDAY: THEORETICAL ASPECTS

    Directory of Open Access Journals (Sweden)

    Cheban Yuliia

    2018-01-01

    Full Text Available The right to leave is part of the employee’s legal status. It has every employee who works under an employment contract. Ensuring the employee’s right to leave is guaranteed by the state. At the same time, the term “vacation” is a significant range of different phenomena that have features in different sectors of the economy, including agrarian space, different regions, different production conditions, etc. The foregoing complicates not only the basic definition of the term “vacation”, but also its organizational and accounting support. According to the legislation of Ukraine, the holiday is set by law, collective agreement or employment contract a certain number of calendar days of continuous rest, which are provided to the employee by the employer in a calendar year, with or without payment, with the preservation of the place of work (position by the employee at this time. The citizens of Ukraine, who are in labor relations with enterprises, institutions, organizations irrespective of the forms of ownership, type of activity and branch affiliation, are also entitled to leave, as well as work under an employment contract from an individual. The main features that are inherent to the overwhelming majority of the holidays are the following: the employee’s dismissal from performing labor duties, the preservation of the employee during the period of vacations of the place of work (position, payment. Domestic legislation, together with the scientific achievements of researchers, the concept of “vacation” is identified with the concept of “time”. The main characteristic features of the vacation include the guarantee of vacation by law; scope of leave; periodicity of holidays; definition of the length of leave in legislation; continuity of rest during the holiday period; connection of vacation with work experience; the main purpose of vacation; preservation of the place of work at the time of vacations; saving at the time of

  11. FACTORS OF NANOTECHNOLOGY AND BIODIVERSITY: ENVIRONMENTAL AND EDUCATIONAL ASPECTS

    Directory of Open Access Journals (Sweden)

    A. V. Kozachek

    2015-01-01

    Full Text Available The aim is to consider the features of impact of nanotechnology on biodiversity in the future.Methods. We suggest an approach, according to which nanotechnologies are viewed as key technologies of the sixth technological order. It is assumed that nanotechnology may be a potential source of environmental problems of the future, and the basis for the creation of new advanced types of environmental engineering and technology. Since all of the above is important both within the actual environmental performance and for the purposes of professional engineering and environmental training. We suggest in this paper to view the problem of the impact of nanotechnology on biodiversity and the state of the environment through environmental and educational aspects.Results. We considered and analyzed the environmental and educational aspects of the application of nanotechnology in the period of the sixth technological order. Implementing procedures for their analysis has contributed to the identification and systematization of the various impacts of nanotechnology on biodiversity and the state of the environment, and identification of options for the prevention of such factors. Based on the results of such studies we have identified educational aspects of training environmental engineers during the sixth technological order; defined a new focus of the training in the sixth technological order, which involves, in our opinion, the study of features of a rational and prudent use of natural resources with the use of appropriate innovative eco-oriented nanotechnology, education of students in terms of the understanding of the causes, consequences and ways to prevent the global resource crisis on the planet due to the emergence of a new class of nano-contamination.Main conclusions. The results can be recommended to be used in practice for more in-depth analysis of the specific environmental challenges of nanotechnology, and revising approaches to the design of the

  12. Immigrants in Slovenia: Integration Aspects

    Directory of Open Access Journals (Sweden)

    Janja Žitnik

    2004-09-01

    Full Text Available On the basis of the latest statistics, the author estimates the present share of first- and second-generation immigrants in Slovenia’s population. After examining the quantity and intensity of those public efforts in Slovenia that have been focused on unresolved problems of the immigrants’ social and cultural integration, she continues to question the equality of immigrant minorities in Slovenia, and the sufficiency of the existing programs aimed at facilitating their integration with Slovenian society at large. She explains her doubts about the general assumption that a very clear distinction should be made between the rights of the autochthonous minorities and those of the immigrant ones as far as their special protection is concerned. In the third section of this article, the author discusses the social-ethnic stratification of Slovenian society and tries to look into the psychological background of the nationality/ethnicity statistics. She presents some aspects of the immigrants’ daily experience in Slovenian social, cultural, educational and working milieu, and points to the authorities’ attitude toward them. She comments on the burning issue of the “deleted residents”, and illustrates it with the experience of one of the persons involved. The fourth section, in which the most regular symptoms of Slovenian xenophobia are presented, consists of first-hand observations and focuses on the daily human attitude of the national majority towards the immigrant minorities. Finally the author compares the nature of the specific needs of Slovenians as a “European national minority” with the needs of the immigrant minorities in Slovenia.

  13. Environmental aspects of recycling

    International Nuclear Information System (INIS)

    Jansma, R.; Van Gemert, F.

    2001-01-01

    .24 kg/TW e h) is not so efficient at reducing the quantities in the waste as the multirecycling with MIX fuel in LWRs. The monorecycling of MOX with respect to minimisation of waste production performs better than the standard once-through fuel cycle (OFC), but is outperformed by all other more advanced fuel cycle options. However, MOX is a proven technology for which facilities are available and successfully operating whereas all other advanced fuel cycle options studied are based on experiments or on limited industrial experience. Furthermore experience in Europe and specifically in France shows that the use of MOX is economically feasible. Multiple recycling in LWRs of MOX fuel is possible but is considered to be a rather unfeasible option because of the reprocessing limits of spent MOX fuel, the degradation of the plutonium quality and the increasing minor actinide content in fuel with each recycle loop. 19 refs

  14. A nonmusical paradigm for identifying absolute pitch possessors

    Science.gov (United States)

    Ross, David A.; Olson, Ingrid R.; Marks, Lawrence E.; Gore, John C.

    2004-09-01

    The ability to identify and reproduce sounds of specific frequencies is remarkable and uncommon. The etiology and defining characteristics of this skill, absolute pitch (AP), have been very controversial. One theory suggests that AP requires a specific type of early musical training and that the ability to encode and remember tones depends on these learned musical associations. An alternate theory argues that AP may be strongly dependent on hereditary factors and relatively independent of musical experience. To date, it has been difficult to test these hypotheses because all previous paradigms for identifying AP have required subjects to employ knowledge of musical nomenclature. As such, these tests are insensitive to the possibility of discovering AP in either nonmusicians or musicians of non-Western training. Based on previous literature in pitch memory, a paradigm is presented that is intended to distinguish between AP possessors and nonpossessors independent of the subjects' musical experience. The efficacy of this method is then tested with 20 classically defined AP possessors and 22 nonpossessors. Data from these groups strongly support the validity of the paradigm. The use of a nonmusical paradigm to identify AP may facilitate research into many aspects of this phenomenon.

  15. Special radiation protection aspects of medical accelerators

    CERN Document Server

    Silari, Marco

    2001-01-01

    Radiation protection aspects relevant to medical accelerators are discussed. An overview is first given of general safety requirements. Next. shielding and labyrinth design are discussed in some detail for the various types of accelerators, devoting more attention to hadron machines as they are far less conventional than electron linear accelerators. Some specific aspects related to patient protection are also addressed. Finally, induced radioactivity in accelerator components and shielding walls is briefly discussed. Three classes of machines are considered: (1) medical electron linacs for 'conventional' radiation therapy. (2) low energy cyclotrons for production of radionuclides mainly for medical diagnostics and (3) medium energy cyclotrons and synchrotrons for advanced radiation therapy with protons or light ion beams (hadron therapy). (51 refs).

  16. Socio-Psychological Aspects of Entrepreneurial Motivation

    Directory of Open Access Journals (Sweden)

    Luhova Viktoriia M.

    2017-12-01

    Full Text Available The aim of the article is to study entrepreneurial motivation and socio-psychological aspects that determine it. In the article, the urgency of the study of socio-psychological aspects of motivation is substantiated. The list and essence of concepts related to the concept “motivation” are specified. The features of personal needs of entrepreneurs are determined. The groups of entrepreneurial motives are considered. The psychological properties of an entrepreneur’s personality are examined. The role of the positive self-identity in providing entrepreneurial motivation is substantiated. The values and value orientations typical for entrepreneurs are determined. The peculiarities of the Ukrainian mentality that are most clearly traced in the activity and behavior of entrepreneurs are considered. Specific features of normative regulation of human behavior in modern society are determined.

  17. Recombinant vaccines: experimental and applied aspects

    DEFF Research Database (Denmark)

    Lorenzen, Niels

    1999-01-01

    Development of vaccines for aquaculture fish represent an important applied functional aspect of fish immunology research. Particularly in the case of recombinant vaccines, where a single antigen is usually expected to induce immunity to a specific pathogen, knowledge of mechanisms involved...... in induction of a protective immune response may become vital. The few recombinant vaccines licensd so far, despite much research during the last decade, illustrate that this is not a straightforward matter. However, as vaccine technology as well as our knowledge of the fish immune system is steadily improved......, these fields will open up a number of interesting research objectives of mutual benefit. Recent aspects of recombinant protein vaccines, live recombinant vaccines and DNA vaccines are discussed....

  18. Orbital computed tomography: technical aspects

    International Nuclear Information System (INIS)

    Beck, T.J.; Rosenbaum, A.E.; Miller, N.R.

    1982-01-01

    Computed tomographic scanning has revolutionized the diagnosis and management of orbital disease. The best use of this methodology requires knowledge of the principles and appropriate attention to scanning protocols. Computed tomographic scanning of the orbit is a demanding technique requiring thin sections through planes precisely positioned from the topographical anatomy. Ideally, orbital CT should include both transverse axial and coronal sections: The pathological condition and its plane of growth will influence the selection of the optimal plane or section. Coronal sections may be obtained either directly or indirectly by computer reconstruction from contiguous transverse images. Sagittal or oblique sections or both also are useful and may be obtained directly or indirectly. Difficulty in patient positioning may preclude direct sagittal imaging, however. The use of intravenous contrast enhancement is not necessary as a routine technique unless a mass is identified or suspected. Where surgical resection or biopsy of a space-occupying lesion is contemplated, contrast enhancement can be valuable in assessing relative vascularity and aiding diagnostic specificity. It should be continually emphasized that CT is a powerful technology which, in orbital diagnosis, produces the highest yield when clinician and radiologist collaborate in the radiodiagnostic workup. The clinical information supplied by the referring ophthalmologist is used by the radiologist both in the selection of the appropriate techniques for investigation and in striving to achieve the most specific conclusion

  19. Genetic Aspects of Alzheimer Disease

    Science.gov (United States)

    Williamson, Jennifer; Goldman, Jill; Marder, Karen S.

    2011-01-01

    Background Alzheimer disease (AD) is a genetically complex disorder. Mutations in 3 genes, presenilin 1, amyloid precursor protein, and presenilin 2, lead to early-onset familial AD in rare families with onset of disease occurring prior to age 65. Specific polymorphisms in apolipoprotein E are associated with the more common, late-onset AD occurring after age 65. In this review, we discuss current advances in AD genetics, the implications of the known AD genes, presenilin 1, presenilin 2, amyloid precursor protein, and apolipoprotein E, and other possible genes on the clinical diagnosis, treatment, and genetic counseling of patients and families with early- and late-onset AD. Review Summary In addition to the mutations in 4 known genes associated with AD, mutations in other genes may be implicated in the pathogenesis of the disease. Most recently, 2 different research groups have reported genetic association between 2 genes, sortilin-related receptor and GAB2, and AD. These associations have not changed the diagnostic and medical management of AD. Conclusions New research in the genetics of AD have implicated novel genes as having a role in the disease, but these findings have not been replicated nor have specific disease causing mutations been identified. To date, clinical genetic testing is limited to familial early-onset disease for symptomatic individuals and asymptomatic relatives and, although not recommended, amyloid precursor protein apolipoprotein E testing as an adjunct to diagnosis of symptomatic individuals. PMID:19276785

  20. Environmental Aspects of Load Management

    International Nuclear Information System (INIS)

    Abaravicius, Juozas

    2004-02-01

    This study approaches load management from an environmental perspective. It identifies and discusses the possible environmental benefits of load management and evaluates their significance, primary focusing on CO 2 emissions reduction. The analysis is carried out on two levels: national - the Swedish electricity market, and local - one electric utility in southern Sweden. Our results show the importance of considering the influence of site-specific or level-specific conditions on the environmental effects of load management. On the national level, load management measures can hardly provide significant environmental benefits, due to the high hydropower production in Sweden, which is the demand following production source. Emission reductions will rather be the result of energy efficiency measures, which will cut the load demand as well as the energy demand. However, when it comes to a local (utility) level, where load management is considered as an alternative to an installation of peak diesel power plant, the benefits are clear. It is demonstrated that significant CO 2 emissions savings can be achieved due to avoided peak diesel power production

  1. Verb aspect, alternations and quantification

    Directory of Open Access Journals (Sweden)

    Svetla Koeva

    2015-11-01

    Full Text Available Verb aspect, alternations and quantification In this paper we are briefly discuss the nature of Bulgarian verb aspect and argue that the verb aspect pairs are different lexical units with different (although related meaning, different argument structure (reflecting categories, explicitness and referential status of arguments and different sets of semantic and syntactic alternations. The verb prefixes resulting in perfective verbs derivation in some cases can be interpreted as lexical quantifiers as well. Thus the Bulgarian verb aspect is related (in different way both with the potential for the generation of alternations and with the prefixal lexical quantification. It is shown that the scope of the lexical quantification by means of verbal prefixes is the quantified verb phrase and the scope remains constant in all derived alternations. The paper concerns the basic issues of these complex problems, while the detailed description of the conditions satisfying particular alternation or particular lexical quantification are subject of a more detailed study.

  2. Large aspect ratio tokamak study

    International Nuclear Information System (INIS)

    Reid, R.L.; Holmes, J.A.; Houlberg, W.A.; Peng, Y.K.M.; Strickler, D.J.; Brown, T.G.; Sardella, C.; Wiseman, G.W.

    1979-01-01

    The Large Aspect Ratio Tokamak Study (LARTS) investigated the potential for producing a viable long burn tokamak reactor through enhanced volt-second capability of the ohmic heating transformer by employing high aspect ratio designs. The plasma physics, engineering, and economic implications of high aspect ratio tokamaks were accessed in the context of extended burn operation. Plasma startup and burn parameters were addressed using a one-dimensional transport code. The pulsed electrical power requirements for the poloidal field system, which have a major impact on reactor economics, were minimized by optimizing the field in the ohmic heating coil and the wave shape of the ohmic heating discharge. A high aspect ratio reference reactor was chosen and configured

  3. Topological Aspects of Information Retrieval.

    Science.gov (United States)

    Egghe, Leo; Rousseau, Ronald

    1998-01-01

    Discusses topological aspects of theoretical information retrieval, including retrieval topology; similarity topology; pseudo-metric topology; document spaces as topological spaces; Boolean information retrieval as a subsystem of any topological system; and proofs of theorems. (LRW)

  4. Aspect of the conformal invariance

    International Nuclear Information System (INIS)

    Bauer, M.

    1990-11-01

    This thesis is about the study of several physical and mathematical aspects of critical phenomena at two dimensions. These phenomena have remarkable symmetry properties in the coordonnates changes keeping the angles. They are named conformal theories

  5. Administrative Aspects of Human Experimentation.

    Science.gov (United States)

    Irvine, George W.

    1992-01-01

    The following administrative aspects of scientific experimentation with human subjects are discussed: the definition of human experimentation; the distinction between experimentation and treatment; investigator responsibility; documentation; the elements and principles of informed consent; and the administrator's role in establishing and…

  6. Novel aspects of plasma control in ITER

    Energy Technology Data Exchange (ETDEWEB)

    Humphreys, D.; Jackson, G.; Walker, M.; Welander, A. [General Atomics P.O. Box 85608, San Diego, California 92186-5608 (United States); Ambrosino, G.; Pironti, A. [CREATE/University of Naples Federico II, Napoli (Italy); Vries, P. de; Kim, S. H.; Snipes, J.; Winter, A.; Zabeo, L. [ITER Organization, St. Paul Lez durance Cedex (France); Felici, F. [Eindhoven University of Technology, Eindhoven (Netherlands); Kallenbach, A.; Raupp, G.; Treutterer, W. [Max-Planck Institut für Plasmaphysik, Garching (Germany); Kolemen, E. [Princeton Plasma Physics Laboratory, Princeton, New Jersey 08543-0451 (United States); Lister, J.; Sauter, O. [Centre de Recherches en Physique des Plasmas, Ecole Polytechnique Federale de Lausanne, Lausanne (Switzerland); Moreau, D. [CEA, IRFM, 13108 St. Paul-lez Durance (France); Schuster, E. [Lehigh University, Bethlehem, Pennsylvania (United States)

    2015-02-15

    ITER plasma control design solutions and performance requirements are strongly driven by its nuclear mission, aggressive commissioning constraints, and limited number of operational discharges. In addition, high plasma energy content, heat fluxes, neutron fluxes, and very long pulse operation place novel demands on control performance in many areas ranging from plasma boundary and divertor regulation to plasma kinetics and stability control. Both commissioning and experimental operations schedules provide limited time for tuning of control algorithms relative to operating devices. Although many aspects of the control solutions required by ITER have been well-demonstrated in present devices and even designed satisfactorily for ITER application, many elements unique to ITER including various crucial integration issues are presently under development. We describe selected novel aspects of plasma control in ITER, identifying unique parts of the control problem and highlighting some key areas of research remaining. Novel control areas described include control physics understanding (e.g., current profile regulation, tearing mode (TM) suppression), control mathematics (e.g., algorithmic and simulation approaches to high confidence robust performance), and integration solutions (e.g., methods for management of highly subscribed control resources). We identify unique aspects of the ITER TM suppression scheme, which will pulse gyrotrons to drive current within a magnetic island, and turn the drive off following suppression in order to minimize use of auxiliary power and maximize fusion gain. The potential role of active current profile control and approaches to design in ITER are discussed. Issues and approaches to fault handling algorithms are described, along with novel aspects of actuator sharing in ITER.

  7. Ethical aspects of nuclear power

    International Nuclear Information System (INIS)

    Streithofen, H.B.

    1989-01-01

    The nuclear controversy comprises many ethical aspects, e.g. the waste disposal problem. Nuclear opponents should not neglect the environmental protection aspect; for example, the use of nuclear power alone brought about an 8% reduction of the CO 2 burden in 1987. Our responsibility towards nature and humans in the Third World leaves us no alternative to nuclear power. On the other hand, the nuclear power debate should not become a matter of religious beliefs. (DG) [de

  8. Physical aspects of radioisotope brachytherapy

    International Nuclear Information System (INIS)

    1967-01-01

    The present report represents an attempt to provide, within a necessarily limited compass, an authoritative guide to all important physical aspects of the use of sealed gamma sources in radiotherapy. Within the report, reference is made wherever necessary to the more extensive but scattered literature on this subject. While this report attempts to cover all the physical aspects of radioisotope 'brachytherapy' it does not, of course, deal exhaustively with any one part of the subject. 384 refs, 3 figs, 6 tabs

  9. Identifying Strategic Scientific Opportunities

    Science.gov (United States)

    As NCI's central scientific strategy office, CRS collaborates with the institute's divisions, offices, and centers to identify research opportunities to advance NCI's vision for the future of cancer research.

  10. Identifying Breast Cancer Oncogenes

    Science.gov (United States)

    2011-10-01

    cells we observed that it promoted transformation of HMLE cells, suggesting a tumor suppressive role of Merlin in breast cancer (Figure 4B). A...08-1-0767 TITLE: Identifying Breast Cancer Oncogenes PRINCIPAL INVESTIGATOR: Yashaswi Shrestha...Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 W81XWH-08-1-0767 Identifying Breast Cancer Oncogenes Yashaswi Shrestha Dana-Farber

  11. Dream content: Individual and generic aspects.

    Science.gov (United States)

    Hobson, Allan; Kahn, David

    2007-12-01

    Dream reports were collected from normal subjects in an effort to determine the degree to which dream reports can be used to identify individual dreamers. Judges were asked to group the reports by their authors. The judges scored the reports correctly at chance levels. This finding indicated that dreams may be at least as much like each other as they are the signature of individual dreamers. Our results suggest that dream reports cannot be used to identify the individuals who produced them when identifiers like names and gender of friends and family members are removed from the dream report. In addition to using dreams to learn about an individual, we must look at dreams as telling us about important common or generic aspects of human consciousness.

  12. Ranking product aspects through sentiment analysis of online reviews

    Science.gov (United States)

    Wang, Wei; Wang, Hongwei; Song, Yuan

    2017-03-01

    The electronic word-of-mouth (e-WOM) is one of the most important among all the factors affecting consumers' behaviours. Opinions towards a product through online reviews will influence purchase decisions of other online consumers by changing their perceptions on the product quality. Furthermore, each product aspect may impact consumers' intentions differently. Thus, sentiment analysis and econometric models are incorporated to examine the relationship between purchase intentions and aspect-opinion pairs, which enable the weight estimation for each product aspect. We first identify product aspects and reduce dimensions to extract aspect-opinion pairs. Next the information gain is calculated for each aspect through entropy theory. Based on sentiment polarity and sentiment strength, we formulate an econometric model by integrating the information gain to measure the aspect's weight. In the experiment, we track 386 digital cameras on Amazon for 39 months, and results show that the aspect weight for digital cameras is detected more precisely than TF-ID and HAC algorithms. The results will bridge product aspects and consumption intention to facilitate e-WOM-based marketing.

  13. Specifying Specification.

    Science.gov (United States)

    Paulo, Norbert

    2016-03-01

    This paper tackles the accusation that applied ethics is no serious academic enterprise because it lacks theoretical bracing. It does so in two steps. In the first step I introduce and discuss a highly acclaimed method to guarantee stability in ethical theories: Henry Richardson's specification. The discussion shows how seriously ethicists take the stability of the connection between the foundational parts of their theories and their further development as well as their "application" to particular problems or cases. A detailed scrutiny of specification leads to the second step, where I use insights from legal theory to inform the debate around stability from that point of view. This view reveals some of specification's limitations. I suggest that, once specification is sufficiently specified, it appears astonishingly similar to deduction as used in legal theory. Legal theory also provides valuable insight into the functional range of deduction and its relation to other forms of reasoning. This leads to a richer understanding of stability in normative theories and to a smart division of labor between deduction and other forms of reasoning. The comparison to legal theory thereby provides a framework for how different methods such as specification, deduction, balancing, and analogy relate to one another.

  14. [Psychological aspects of induced abortion].

    Science.gov (United States)

    Mouniq, C; Moron, P

    1982-06-01

    Results are presented of a literature review to identify social and psychological aspects of abortion. The literature does not provide a true profile of women requesting abortions, but some characteristics emerge. Reasons for requesting abortion include economic problems, difficult previous pregnancies, general medical contraindications to pregnancy, marital conflicts, feelings of loneliness, professional aspirations, problems with existing children, and feelings of insecurity about the future. However, the same feelings are found among women carrying their pregnancies to term. Unplanned pregnancies are more common during periods of depression. Most authors have found about 1/2 of women seeking abortions to be single and about 1/2 to be under 25 years old. Religion does not appear to be a determining factor. 1 study of psychological factors in abortion seekers found that a large number of single women seeking abortion had suffered traumatic experiences in childhood and were seeking security in inappropriate amorous relationships. Helene Deutsch stressed the destructive impulses latent in all pregnancies. Others have cited the ambivalence of the desire for pregnancy and feelings of loss after abortion. Studies published after legalization of abortion in the US and France however have stressed the nearly total absence of moderate or severe psychiatric symptoms after abortion. Responses immediately after the abortion may include feelings of relief, guilt, indifference, or ambivalence. Secondary affects appear minor to most authors. Psychological effects do not appear to be influenced by age, marital status, parity, intelligence, occupation, existence of a later pregnancy, or concommitant sterilization. "Premorbidity" and coercion by spouse or family were most closely associated with psychological symptoms. Numerous authors have found about twice as many negative reactions among women undergoing abortion for medical reasons. Most patients undergoing abortions for

  15. Identifying Knowledge and Communication

    Directory of Open Access Journals (Sweden)

    Eduardo Coutinho Lourenço de Lima

    2006-12-01

    Full Text Available In this paper, I discuss how the principle of identifying knowledge which Strawson advances in ‘Singular Terms and Predication’ (1961, and in ‘Identifying Reference and Truth-Values’ (1964 turns out to constrain communication. The principle states that a speaker’s use of a referring expression should invoke identifying knowledge on the part of the hearer, if the hearer is to understand what the speaker is saying, and also that, in so referring, speakers are attentive to hearers’ epistemic states. In contrasting it with Russell’s Principle (Evans 1982, as well as with the principle of identifying descriptions (Donnellan 1970, I try to show that the principle of identifying knowledge, ultimately a condition for understanding, makes sense only in a situation of conversation. This allows me to conclude that the cooperative feature of communication (Grice 1975 and reference (Clark andWilkes-Gibbs 1986 holds also at the understanding level. Finally, I discuss where Strawson’s views seem to be unsatisfactory, and suggest how they might be improved.

  16. Identified adjustability dimensions when generating a product specific requirements specification by requirements reuse

    DEFF Research Database (Denmark)

    Hauksdóttir, Dagný; Mortensen, Niels Henrik; Nielsen, Poul Erik

    2014-01-01

    . An extensive state of the art is included to introduce the presented methods related to each adjustability dimensions. The options for implementing each adjustability dimensions in a requirement reuse approach are illustrated along with a discussion regarding the benefits and issues resulting from each option....... This discussion should help practitioners to better understand the possible methods that can be implemented and to design a user friendly and sustainable approach. A case study, describing how the dimensions are incorporated in two requirements reuse approaches, for Danfoss Solar Inverters (SI) and Danfoss...

  17. Tendering specification and contracting

    International Nuclear Information System (INIS)

    Koch, E. von

    1975-01-01

    The lecture tendering, specification and contracting is prepared in two parts: This first part deals with technical aspects while part two features the commercial and legal situation in the partnership of two: the supplier of the fuel bundles and the utility. In this lecture a look is given on the way how a suppli