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Sample records for approaches uncover increasing

  1. Genomic approaches uncover increasing complexities in the regulatory landscape at the human SCL (TAL1) locus

    OpenAIRE

    Dhami, P.; Bruce, A. W.; Jim, J.H.; Dillon, S. C.; Hall, A; Cooper, J. L.; Bonhoure, N.; Chiang, K.; Ellis, P D; Langford, C; Andrews, R.M.; Vetrie, D

    2010-01-01

    The SCL (TAL1) transcription factor is a critical regulator of haematopoiesis and its expression is tightly controlled by multiple cis-acting regulatory elements. To elaborate further the DNA elements which control its regulation, we used genomic tiling microarrays covering 256 kb of the human SCL locus to perform a concerted analysis of chromatin structure and binding of regulatory proteins in human haematopoietic cell lines. This approach allowed us to characterise further or redefine known...

  2. Uncovering transcriptional interactions via an adaptive fuzzy logic approach

    Directory of Open Access Journals (Sweden)

    Chen Chung-Ming

    2009-12-01

    Full Text Available Abstract Background To date, only a limited number of transcriptional regulatory interactions have been uncovered. In a pilot study integrating sequence data with microarray data, a position weight matrix (PWM performed poorly in inferring transcriptional interactions (TIs, which represent physical interactions between transcription factors (TF and upstream sequences of target genes. Inferring a TI means that the promoter sequence of a target is inferred to match the consensus sequence motifs of a potential TF, and their interaction type such as AT or RT is also predicted. Thus, a robust PWM (rPWM was developed to search for consensus sequence motifs. In addition to rPWM, one feature extracted from ChIP-chip data was incorporated to identify potential TIs under specific conditions. An interaction type classifier was assembled to predict activation/repression of potential TIs using microarray data. This approach, combining an adaptive (learning fuzzy inference system and an interaction type classifier to predict transcriptional regulatory networks, was named AdaFuzzy. Results AdaFuzzy was applied to predict TIs using real genomics data from Saccharomyces cerevisiae. Following one of the latest advances in predicting TIs, constrained probabilistic sparse matrix factorization (cPSMF, and using 19 transcription factors (TFs, we compared AdaFuzzy to four well-known approaches using over-representation analysis and gene set enrichment analysis. AdaFuzzy outperformed these four algorithms. Furthermore, AdaFuzzy was shown to perform comparably to 'ChIP-experimental method' in inferring TIs identified by two sets of large scale ChIP-chip data, respectively. AdaFuzzy was also able to classify all predicted TIs into one or more of the four promoter architectures. The results coincided with known promoter architectures in yeast and provided insights into transcriptional regulatory mechanisms. Conclusion AdaFuzzy successfully integrates multiple types of

  3. Feminist Approaches to Triangulation: Uncovering Subjugated Knowledge and Fostering Social Change in Mixed Methods Research

    Science.gov (United States)

    Hesse-Biber, Sharlene

    2012-01-01

    This article explores the deployment of triangulation in the service of uncovering subjugated knowledge and promoting social change for women and other oppressed groups. Feminist approaches to mixed methods praxis create a tight link between the research problem and the research design. An analysis of selected case studies of feminist praxis…

  4. Increasing productivity: Another approach

    Energy Technology Data Exchange (ETDEWEB)

    Norton, F.J.

    1996-06-10

    An engineering information (EI) and information technology (IT) organization that must improve its productivity should work to further its business goals. This paper explores a comprehensive model for increasing EI/IT productivity by supporting organizational objectives.

  5. Uncovering the Factors behind Comparative Regional Economic Performance: A Dynamic CGE Approach

    OpenAIRE

    James A. Giesecke; John R Madden

    2006-01-01

    Recently a new method has emerged for uncovering the factors driving regional disparities in growth performance. The method involves historical analysis with a multiregional computable general equilibrium model. This paper has three main aims. The first is to demonstrate the capacity of the CGE historical technique to decompose the causes of regional divergence into clearly-specified economic factors. The second is to provide a generic miniature model that can be used as a template for adapti...

  6. Systems-level approach to uncovering diffusive states and their transitions from single particle trajectories

    CERN Document Server

    Koo, Peter K

    2016-01-01

    The stochastic motions of a diffusing particle contain information concerning the particle's interactions with binding partners and with its local environment. However, accurate determination of the underlying diffusive properties, beyond normal diffusion, has remained challenging when analyzing particle trajectories on an individual basis. Here, we introduce the maximum likelihood estimator (MLE) for confined diffusion and fractional Brownian motion. We demonstrate that this MLE yields improved estimation over traditional mean square displacement analyses. We also introduce a model selection scheme (that we call mleBIC) that classifies individual trajectories to a given diffusion mode. We demonstrate the statistical limitations of classification via mleBIC using simulated data. To overcome these limitations, we introduce a new version of perturbation expectation-maximization (pEMv2), which simultaneously analyzes a collection of particle trajectories to uncover the system of interactions which give rise to u...

  7. HIV/AIDS orphans as farmers: uncovering pest knowledge differences through an ethnobiological approach in Benin

    OpenAIRE

    Fagbémissi, R.C.; Price, L. L.

    2008-01-01

    The erosion of local/indigenous firming knowledge in the face of HIV/AIDS deaths in Africa has been noted as a point of concerti in the literature and by organizations such as the Food and Agriculture Organization of the United Nations. These concerns are about a break in the transmission of knowledge from adults (deceased parents) to children (orphans). Ultimately, erosion of fanning knowledge is implied. This paper examines one aspect of knowledge, using an ethnobiological approach that is ...

  8. Kinds versus continua: a review of psychometric approaches to uncover the structure of psychiatric constructs.

    Science.gov (United States)

    Borsboom, D; Rhemtulla, M; Cramer, A O J; van der Maas, H L J; Scheffer, M; Dolan, C V

    2016-06-01

    The question of whether psychopathology constructs are discrete kinds or continuous dimensions represents an important issue in clinical psychology and psychiatry. The present paper reviews psychometric modelling approaches that can be used to investigate this question through the application of statistical models. The relation between constructs and indicator variables in models with categorical and continuous latent variables is discussed, as are techniques specifically designed to address the distinction between latent categories as opposed to continua (taxometrics). In addition, we examine latent variable models that allow latent structures to have both continuous and categorical characteristics, such as factor mixture models and grade-of-membership models. Finally, we discuss recent alternative approaches based on network analysis and dynamical systems theory, which entail that the structure of constructs may be continuous for some individuals but categorical for others. Our evaluation of the psychometric literature shows that the kinds-continua distinction is considerably more subtle than is often presupposed in research; in particular, the hypotheses of kinds and continua are not mutually exclusive or exhaustive. We discuss opportunities to go beyond current research on the issue by using dynamical systems models, intra-individual time series and experimental manipulations. PMID:26997244

  9. Peptide library approach to uncover phosphomimetic inhibitors of the BRCA1 C-terminal domain.

    Science.gov (United States)

    White, E Railey; Sun, Luxin; Ma, Zhong; Beckta, Jason M; Danzig, Brittany A; Hacker, David E; Huie, Melissa; Williams, David C; Edwards, Ross A; Valerie, Kristoffer; Glover, J N Mark; Hartman, Matthew C T

    2015-05-15

    Many intracellular protein-protein interactions are mediated by the phosphorylation of serine, and phosphoserine-containing peptides can inhibit these interactions. However, hydrolysis of the phosphate by phosphatases, and the poor cell permeability associated with phosphorylated peptides has limited their utility in cellular and in vivo contexts. Compounding the problem, strategies to replace phosphoserine in peptide inhibitors with easily accessible mimetics (such as Glu or Asp) routinely fail. Here, we present an in vitro selection strategy for replacement of phosphoserine. Using mRNA display, we created a 10 trillion member structurally diverse unnatural peptide library. From this library, we found a peptide that specifically binds to the C-terminal domain (BRCT)2 of breast cancer associated protein 1 (BRCA1) with an affinity comparable to phosphorylated peptides. A crystal structure of the peptide bound reveals that the pSer-x-x-Phe motif normally found in BRCA1 (BRCT)2 binding partners is replaced by a Glu-x-x-4-fluoroPhe and that the peptide picks up additional contacts on the protein surface not observed in cognate phosphopeptide binding. Expression of the peptide in human cells led to defects in DNA repair by homologous recombination, a process BRCA1 is known to coordinate. Overall, this work validates a new in vitro selection approach for the development of inhibitors of protein-protein interactions mediated by serine phosphorylation. PMID:25654734

  10. Meta-analysis of cancer transcriptomes: A new approach to uncover molecular pathological events in different cancer tissues

    Directory of Open Access Journals (Sweden)

    Sundus Iqbal

    2014-03-01

    Full Text Available To explore secrets of metastatic cancers, individual expression of true sets of respective genes must spread across the tissue. In this study, meta-analysis for transcriptional profiles of oncogenes was carried out to hunt critical genes or networks helping in metastasizing cancers. For this, transcriptomic analysis of different cancerous tissues causing leukemia, lung, liver, spleen, colorectal, colon, breast, bladder, and kidney cancers was performed by extracting microarray expression data from online resource; Gene Expression Omnibus. A newly developed bioinformatics technique; Dynamic Impact Approach (DIA was applied for enrichment analysis of transcriptional profiles using Database for Annotation Visualization and Integrated Discovery (DAVID. Furthermore, oPOSSUM (v. 2.0 and Cytoscape (v. 2.8.2 were used for in-depth analysis of transcription factors and regulatory gene networks respectively. DAVID analysis uncovered the most significantly enriched pathways in molecular functions that were 'Ubiquitin thiolesterase activity' up regulated in blood, breast, bladder, colorectal, lung, spleen, prostrate cancer. 'Transforming growth factor beta receptor activity' was inhibited in all cancers except leukemia, colon and liver cancer. oPOSSUM further revealed highly over-represented Transcription Factors (TFs; Broad-complex_3, Broad-complex_4, and Foxd3 except for leukemia and bladder cancer. From these findings, it is possible to target genes and networks, play a crucial role in the development of cancer. In the future, these transcription factors can serve as potential candidates for the therapeutic drug targets which can impede the deadly spread.

  11. Buffering mechanisms in aging: a systems approach toward uncovering the genetic component of aging.

    Directory of Open Access Journals (Sweden)

    Aviv Bergman

    2007-08-01

    Full Text Available An unrealized potential to understand the genetic basis of aging in humans, is to consider the immense survival advantage of the rare individuals who live 100 years or more. The Longevity Gene Study was initiated in 1998 at the Albert Einstein College of Medicine to investigate longevity genes in a selected population: the "oldest old" Ashkenazi Jews, 95 years of age and older, and their children. The study proved the principle that some of these subjects are endowed with longevity-promoting genotypes. Here we reason that some of the favorable genotypes act as mechanisms that buffer the deleterious effect of age-related disease genes. As a result, the frequency of deleterious genotypes may increase among individuals with extreme lifespan because their protective genotype allows disease-related genes to accumulate. Thus, studies of genotypic frequencies among different age groups can elucidate the genetic determinants and pathways responsible for longevity. Borrowing from evolutionary theory, we present arguments regarding the differential survival via buffering mechanisms and their target age-related disease genes in searching for aging and longevity genes. Using more than 1,200 subjects between the sixth and eleventh decades of life (at least 140 subjects in each group, we corroborate our hypotheses experimentally. We study 66 common allelic site polymorphism in 36 candidate genes on the basis of their phenotype. Among them we have identified a candidate-buffering mechanism and its candidate age-related disease gene target. Previously, the beneficial effect of an advantageous cholesteryl ester transfer protein (CETP-VV genotype on lipoprotein particle size in association with decreased metabolic and cardiovascular diseases, as well as with better cognitive function, have been demonstrated. We report an additional advantageous effect of the CETP-VV (favorable genotype in neutralizing the deleterious effects of the lipoprotein(a (LPA gene

  12. Uncovering ultrastructural defences in Daphnia magna--an interdisciplinary approach to assess the predator-induced fortification of the carapace.

    Directory of Open Access Journals (Sweden)

    Max Rabus

    Full Text Available The development of structural defences, such as the fortification of shells or exoskeletons, is a widespread strategy to reduce predator attack efficiency. In unpredictable environments these defences may be more pronounced in the presence of a predator. The cladoceran Daphnia magna (Crustacea: Branchiopoda: Cladocera has been shown to develop a bulky morphotype as an effective inducible morphological defence against the predatory tadpole shrimp Triops cancriformis (Crustacea: Branchiopoda: Notostraca. Mediated by kairomones, the daphnids express an increased body length, width and an elongated tail spine. Here we examined whether these large scale morphological defences are accompanied by additional ultrastructural defences, i.e. a fortification of the exoskeleton. We employed atomic force microscopy (AFM based nanoindentation experiments to assess the cuticle hardness along with tapping mode AFM imaging to visualise the surface morphology for predator exposed and non-predator exposed daphnids. We used semi-thin sections of the carapace to measure the cuticle thickness, and finally, we used fluorescence microscopy to analyse the diameter of the pillars connecting the two carapace layers. We found that D. magna indeed expresses ultrastructural defences against Triops predation. The cuticle in predator exposed individuals is approximately five times harder and two times thicker than in control daphnids. Moreover, the pillar diameter is significantly increased in predator exposed daphnids. These predator-cue induced changes in the carapace architecture should provide effective protection against being crushed by the predator's mouthparts and may add to the protective effect of bulkiness. This study highlights the potential of interdisciplinary studies to uncover new and relevant aspects even in extensively studied fields of research.

  13. Increasing Efficiency: A Process-Oriented Approach.

    Science.gov (United States)

    Harbour, Jerry L.

    1993-01-01

    Discussion of the need to increase efficiency focuses on a process-oriented approach for systematically identifying and minimizing non-value-adding process steps to analyze and improve tasks, services, and production. Highlights include a historical perspective, a discussion of wasted efforts, and a case study. (Contains 16 references.) (LRW)

  14. Uncovering the Role of Metal Catalysis in Tetrazole Formation by an In Situ Cycloaddition Reaction: An Experimental Approach.

    Science.gov (United States)

    Zhong, Di-Chang; Wen, Ya-Qiong; Deng, Ji-Hua; Luo, Xu-Zhong; Gong, Yun-Nan; Lu, Tong-Bu

    2015-09-28

    Using an experimental approach, the role of metal catalysis has been investigated in the in situ cycloaddition reaction of nitrile with azide to form tetrazoles. It has been shown that metal catalysis serves to activate the cyano group in the nitrile reagent by a coordinative interaction. PMID:26293313

  15. Rational and evolutionary engineering approaches uncover a small set of genetic changes efficient for rapid xylose fermentation in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Soo Rin Kim

    Full Text Available Economic bioconversion of plant cell wall hydrolysates into fuels and chemicals has been hampered mainly due to the inability of microorganisms to efficiently co-ferment pentose and hexose sugars, especially glucose and xylose, which are the most abundant sugars in cellulosic hydrolysates. Saccharomyces cerevisiae cannot metabolize xylose due to a lack of xylose-metabolizing enzymes. We developed a rapid and efficient xylose-fermenting S. cerevisiae through rational and inverse metabolic engineering strategies, comprising the optimization of a heterologous xylose-assimilating pathway and evolutionary engineering. Strong and balanced expression levels of the XYL1, XYL2, and XYL3 genes constituting the xylose-assimilating pathway increased ethanol yields and the xylose consumption rates from a mixture of glucose and xylose with little xylitol accumulation. The engineered strain, however, still exhibited a long lag time when metabolizing xylose above 10 g/l as a sole carbon source, defined here as xylose toxicity. Through serial-subcultures on xylose, we isolated evolved strains which exhibited a shorter lag time and improved xylose-fermenting capabilities than the parental strain. Genome sequencing of the evolved strains revealed that mutations in PHO13 causing loss of the Pho13p function are associated with the improved phenotypes of the evolved strains. Crude extracts of a PHO13-overexpressing strain showed a higher phosphatase activity on xylulose-5-phosphate (X-5-P, suggesting that the dephosphorylation of X-5-P by Pho13p might generate a futile cycle with xylulokinase overexpression. While xylose consumption rates by the evolved strains improved substantially as compared to the parental strain, xylose metabolism was interrupted by accumulated acetate. Deletion of ALD6 coding for acetaldehyde dehydrogenase not only prevented acetate accumulation, but also enabled complete and efficient fermentation of xylose as well as a mixture of glucose and

  16. A joint modeling approach for uncovering associations between gene expression, bioactivity and chemical structure in early drug discovery to guide lead selection and genomic biomarker development.

    Science.gov (United States)

    Perualila-Tan, Nolen; Kasim, Adetayo; Talloen, Willem; Verbist, Bie; Göhlmann, Hinrich W H; Shkedy, Ziv

    2016-08-01

    The modern drug discovery process involves multiple sources of high-dimensional data. This imposes the challenge of data integration. A typical example is the integration of chemical structure (fingerprint features), phenotypic bioactivity (bioassay read-outs) data for targets of interest, and transcriptomic (gene expression) data in early drug discovery to better understand the chemical and biological mechanisms of candidate drugs, and to facilitate early detection of safety issues prior to later and expensive phases of drug development cycles. In this paper, we discuss a joint model for the transcriptomic and the phenotypic variables conditioned on the chemical structure. This modeling approach can be used to uncover, for a given set of compounds, the association between gene expression and biological activity taking into account the influence of the chemical structure of the compound on both variables. The model allows to detect genes that are associated with the bioactivity data facilitating the identification of potential genomic biomarkers for compounds efficacy. In addition, the effect of every structural feature on both genes and pIC50 and their associations can be simultaneously investigated. Two oncology projects are used to illustrate the applicability and usefulness of the joint model to integrate multi-source high-dimensional information to aid drug discovery. PMID:27269248

  17. Increasing rice production in Malaysia: Department of Agriculture approach

    International Nuclear Information System (INIS)

    Increasing rice productivity will continue to be an important agenda in the agricultural development program of the country. This represents a challenge to the Department of Agriculture. To address this challenge, it calls for creativity, innovation, ideas and initiatives in the use of technologies that consist of land leveling, in the field water management, Integrated Pest Management (IPM), production and distribution of quality seeds, effective fertilizer usage and value added activities. Rice areas which have been leveled using laser guided technology have shown yield increase from 3.3 t/ha to 5.1 t/ha. In-field water management increases rice yield, reduces water wastage and ensures timeliness of operations and improve soil water bearing capacity. IPM has proven highly beneficial in the control of field rats, reducing the incidence of diseases such as rice blast, lowering the occurrence of insect pest outbreaks and weed infestation. Fish rearing and fattening of ducklings to adulthood in the rice fields have also been undertaken as profitable enterprises in the rice farming system. In its effort to modernise and increase rice productivity, the Department of Agriculture approach in acquisition of technology from research agencies, and its adaptation and adoption are discussed. Any technology promoted must be economically viable, socially acceptable and technologically feasible for effective implementation. (Author)

  18. Integrated system approach for increase of engine combined cycle efficiency

    International Nuclear Information System (INIS)

    Highlights: ► A new approach for the optimization of engine combined cycle systems is presented. ► The efficiency can be increased by integrating all available waste heat sources. ► The optimization of the ICE cooling system towards higher temperatures is examined. ► Higher engine cooling water temperatures increase the combined cycle efficiency. ► The costs of electricity generation can be decreased by five integrated system. - Abstract: Internal combustion engines (ICEs) are widely used as independent power producers due to their high electrical efficiency (up to 47%), which can be further enhanced by operating them in combined cycle mode with a water/steam cycle as bottoming cycle. This study presents an integrated approach to optimize the combined cycle overall system efficiency. Therefore, not only the most favorable design of the waste heat recovery (WHR) cycle, but also the optimal configuration of the ICE cooling system have to be investigated, in order to integrate both available engine waste heat sources (exhaust gas, 300–400 °C, engine cooling water, 90 °C) into the waste heat recovery cycle. For the definition of the most favourable temperature level of the engine cooling water three variants of engine cooling systems are examined, with respect to technical limitations given by the ICE. In order to determine the types of engines for which this optimization approach is suitable, three types of engines with different characteristics (fuel, exhaust gas parameters) combined with a water/steam cycle are simulated, by using the calculation tools Excel and Ebsilon Professional. An energetic, exergetic and economic analysis is conducted. These reveal the impacts of the temperature level to the WHR system and to the design of the engine cooling system. The calculations performed, showed that up to 19% of the engine cooling water heat can be efficiently recovered compared to a portion of 6% in the standard system. The better recovery leads to a 5

  19. Uncovering Research Topics of Academic Communities of Scientific Collaboration Network

    OpenAIRE

    Hongqi Han; Shuo Xu; Jie Gui; Xiaodong Qiao; Lijun Zhu; Han Zhang

    2014-01-01

    In order to improve the quality of applications, such as recommendation or retrieval in knowledge-based service system, it is very helpful to uncover research topics of academic communities in scientific collaboration network (SCN). Previous research mainly focuses on network characteristics measurement and community evolution, but it remains largely understudied on how to uncover research topics of each community. This paper proposes a nonjoint approach, consisting of three simple steps: (1)...

  20. A systems biology approach uncovers cellular strategies used by Methylobacterium extorquens AM1 during the switch from multi- to single-carbon growth.

    Directory of Open Access Journals (Sweden)

    Elizabeth Skovran

    Full Text Available BACKGROUND: When organisms experience environmental change, how does their metabolic network reset and adapt to the new condition? Methylobacterium extorquens is a bacterium capable of growth on both multi- and single-carbon compounds. These different modes of growth utilize dramatically different central metabolic pathways with limited pathway overlap. METHODOLOGY/PRINCIPAL FINDINGS: This study focused on the mechanisms of metabolic adaptation occurring during the transition from succinate growth (predicted to be energy-limited to methanol growth (predicted to be reducing-power-limited, analyzing changes in carbon flux, gene expression, metabolites and enzymatic activities over time. Initially, cells experienced metabolic imbalance with excretion of metabolites, changes in nucleotide levels and cessation of cell growth. Though assimilatory pathways were induced rapidly, a transient block in carbon flow to biomass synthesis occurred, and enzymatic assays suggested methylene tetrahydrofolate dehydrogenase as one control point. This "downstream priming" mechanism ensures that significant carbon flux through these pathways does not occur until they are fully induced, precluding the buildup of toxic intermediates. Most metabolites that are required for growth on both carbon sources did not change significantly, even though transcripts and enzymatic activities required for their production changed radically, underscoring the concept of metabolic setpoints. CONCLUSIONS/SIGNIFICANCE: This multi-level approach has resulted in new insights into the metabolic strategies carried out to effect this shift between two dramatically different modes of growth and identified a number of potential flux control and regulatory check points as a further step toward understanding metabolic adaptation and the cellular strategies employed to maintain metabolic setpoints.

  1. Uncovering undetected hypoglycemic events

    Directory of Open Access Journals (Sweden)

    Unger J

    2012-03-01

    Full Text Available Jeff UngerCatalina Research Institute, Chino, CA, USAAbstract: Hypoglycemia is the rate-limiting factor that often prevents patients with diabetes from safely and effectively achieving their glycemic goals. Recent studies have reported that severe hypoglycemia is associated with a significant increase in the adjusted risks of major macrovascular events, major microvascular events, and mortality. Minor hypoglycemic episodes can also have serious implications for patient health, psychological well being, and adherence to treatment regimens. Hypoglycemic events can impact the health economics of the patient, their employer, and third-party payers. Insulin treatment is a key predictor of hypoglycemia, with one large population-based study reporting an overall prevalence of 7.1% (type 1 diabetes mellitus and 7.3% (type 2 diabetes mellitus in insulin-treated patients, compared with 0.8% in patients with type 2 diabetes treated with an oral sulfonylurea. Patients with type 1 diabetes typically experience symptomatic hypoglycemia on average twice weekly and severe hypoglycemia once annually. The progressive loss of islet cell function in patients with type 2 diabetes results in a higher risk of both symptomatic and unrecognized hypoglycemia over time. Patients with diabetes who become hypoglycemic are also more susceptible to developing defective counter-regulation, also known as hypoglycemia awareness autonomic failure, which is life-threatening and must be aggressively addressed. In patients unable to recognize hypoglycemia symptoms, frequent home monitoring or use of continuous glucose sensors are critical. Primary care physicians play a key role in the prevention and management of hypoglycemia in patients with diabetes, particularly in those requiring intensive insulin therapy, yet physicians are often unaware of the multitude of consequences of hypoglycemia or how to deal with them. Careful monitoring, adherence to guidelines, and use of optimal

  2. Comprehensive Approach to Increase Cyber Security and Resilience

    OpenAIRE

    Yautsiukhin, Artsiom; Choras, Michal; Kozik, Rafal; Bruna, Maria Pilar Torres; Churchill, Andrew; Maciejewska, Iwona; Eguinoa, Irene; Jomni, Adel

    2015-01-01

    In this paper the initial results of the European project CAMINO in terms of the realistic roadmap to counter cyber crime and cyber terrorism are presented. The roadmap is built in accordance to so called CAMINO THOR approach, where cyber security is perceived comprehensively in 4 dimensions: Technical, Human, Organizational, and Regulatory.

  3. DANGER INCREASING WITH APPROACHING SUMMER: SUN RELATED UV RAYS

    Directory of Open Access Journals (Sweden)

    Omer Faruk TEKBAS

    2005-04-01

    Full Text Available Notwithstanding the sun is a regulator for all that maintaining their biological lives, it is a source of energy which spreaded UV radiation that can be made a harmful effects. The Ozone layer, which is being in the stratosphere, is very important filter to keeping against the harmful effects of UV radiations. The increase of tears, which occurs in the ozone layer cause the increase of non-melanoma, skin cancer and melanoma cancer cases. The best way of protecting from the sun’s harmful effects, which particularly increase in the summer, is avoiding from it. [TAF Prev Med Bull 2005; 4(2.000: 98-107

  4. Increasing Forests and Quadrangulations via a Bijective Approach

    CERN Document Server

    Bettinelli, Jérémie

    2012-01-01

    In this work, we expose four bijections each allowing to increase (or decrease) one parameter in either uniform random forests with a fixed number of edges and trees, or quadrangulations with a boundary having a fixed number of faces and a fixed boundary length. In particular, this gives a way to sample a uniform quadrangulation with n + 1 faces from a uniform quadrangulation with n faces.

  5. Clinical role modelling: uncovering hidden knowledge.

    Science.gov (United States)

    Davies, E

    1993-04-01

    Those responsible for the education of nurses are well aware of the need to reconcile the art and science of nursing so that future practitioners can be prepared to offer a humanistic and professional service to society. One way to assist students in this integration is to provide them with opportunities for role modelling as a means of discovering the knowledge embedded in clinical practice. A study of first-year undergraduate students undertaking a course which provides such opportunities in a number of practice settings was carried out to determine whether the observation of clinical role models does lead to knowledge discovery. The study, which used a grounded theory approach, indicated that the major aspect of nursing uncovered by the students through observation of clinical role models was that of provision of direct care. They articulated their values in relation to 'good' and 'bad' care and identified those attributes of nurses which they considered contributed to these care positions. In addition, they were able to recognize creativity and flexibility in practitioners and to relate these attributes to the ability to provide individualized, context-specific care. There was some uncovering of aspects of the nurse's role in maintaining their own professional competence, socializing neophytes into the profession and collaborating with the members of the multi-disciplinary health care team. PMID:8496511

  6. Revelando sentidos na prática docente: a abordagem de corpus na análise do discurso Uncovering meanings in pedagogical practice: the corpus approach in discourse analysis

    Directory of Open Access Journals (Sweden)

    Vander Viana

    2011-01-01

    Full Text Available Este artigo discute a viabilidade da utilização de ferramentas da Linguística de Corpus na análise do discurso pedagógico. Para tanto, são apresentados dois estudos de caso. O primeiro focaliza o discurso de professores de língua inglesa de um renomado curso de idiomas do Rio de Janeiro acerca da implementação de recursos tecnológicos na sala de aula. O segundo estudo, por sua vez, busca perceber qual é o posicionamento de professores universitários de literaturas em língua inglesa sobre literatura e seu ensino. Os resultados apontam para a riqueza dos dados contextuais que podem ser depreendidos a partir de uma análise linguística de base empírica. Em última análise, o artigo revela a importância e a flexibilidade da abordagem de corpus na análise do discurso, que pode ser aplicada a inúmeros contextos.This paper discusses the feasibility of using Corpus Linguistics tools in the analysis of pedagogic discourse. For doing this, two case studies are presented. The first one focuses on the discourse of English language teachers of a well-known languages course in Rio de Janeiro about the implementation of technological resources in the classroom. The second study, in its turn, seeks to realize the position held by university professors of literatures in English language with regard to literature and its teaching. The results point out to the richness of contextual data which can be inferred from a linguistic analysis with an empirical basis. All in all, the paper uncovers the importance and flexibility of the corpus approach in discourse analysis, which may be applied to several contexts.

  7. Massively Increasing TIMEX3 Resources: A Transduction Approach

    CERN Document Server

    Derczynski, Leon; Saquete, Estela

    2012-01-01

    Automatic annotation of temporal expressions is a research challenge of great interest in the field of information extraction. Gold standard temporally-annotated resources are limited in size, which makes research using them difficult. Standards have also evolved over the past decade, so not all temporally annotated data is in the same format. We vastly increase available human-annotated temporal expression resources by converting older format resources to TimeML/TIMEX3. This task is difficult due to differing annotation methods. We present a robust conversion tool and a new, large temporal expression resource. Using this, we evaluate our conversion process by using it as training data for an existing TimeML annotation tool, achieving a 0.87 F1 measure -- better than any system in the TempEval-2 timex recognition exercise.

  8. Weaving Social Foundations through Dance Pedagogy: A Pedagogy of Uncovering

    Science.gov (United States)

    Barr, Sherrie; Risner, Doug

    2014-01-01

    Today's dance educators enter classrooms populated by increasingly diverse students in which teachers' pedagogical knowledge necessitates heightened understandings of race, ethnicity, social class, gender, and sexuality. Uncovering taken-for-granted assumptions, dominant stereotypes, and educational structures that reproduce social…

  9. Uncovering Plagiarism - Author Profiling at PAN

    OpenAIRE

    Rosso, Paolo; RANGEL PARDO, FRANCISCO MANUEL

    2014-01-01

    PAN is a yearly workshop and evaluation lab on uncovering plagiarism, authorship, and social software misuse. Since 2009, PAN has been organizing benchmark activities on uncovering plagiarism, authorship, and social software misuse . An additional task - author profiling - has also recently been proposed. Author profiling, instead of focusing on individual authors, studies how language is shared by a class of people. Author profiling is a problem of growing importance in applications in foren...

  10. The Uncovered Interest Parity in the Foreign Exchange (FX Markets

    Directory of Open Access Journals (Sweden)

    Silvio Ricardo Micheloto

    2004-12-01

    Full Text Available This work verifies the uncovered interest rates parity (UIP in the FX (foreign exchange emerging markets by using the panel cointegration technique. The data involves several developing countries that compose the EMBI+ Global Index. We compare the results of several panel estimators: OLS (ordinary list square, DOLS (dynamic OLS and FMOLS (fully modified OLS. This new panel technique can handle problems of either non-stationary series (spurious regression or small problem. This latter problem has being considered one of the main causes for distorting the UIP empirical results. By using this approach, we check the UIP in the FX (foreign exchange emerging markets. These markets are more critical because they have been subjected to changing FX regimes and speculative attacks. Our results do not corroborate the uncovered interest parity for the developing countries in the recent years. Thus, the forward premium puzzle may hold in the FX emergent markets.

  11. Assessment of Credit Risk Approaches in Relation with Competitiveness Increase of the Banking Sector

    Directory of Open Access Journals (Sweden)

    Cipovová Eva

    2012-06-01

    Full Text Available The article is focused on a presentation and analysis of selected methods of credit risk management in relation with competitiveness increase of the banking sector. The article is defined credit risk approaches under the Basel III gradually. Aim of this contribution constitutes various methods of credit risk management and effects of their usage on regulatory capital amount in respect of corporate exposures. Optimal equity amount in relation to the risk portfolio presents an essential prerequisite of performance and competitiveness growth of commercial banks. Gradually capital requirements using Standardized Approach and Internal Based Approach in a case of used and unused techniques of credit risk reduce has been quantified. We presume that sophisticated approach means significant saving for bank’s equity which increases competitiveness of banking sector also. Within the article, quantification of capital savings in case of Standardized (with and without assigned external ratings and Foundation Internal Based Approach at the selected credit portfolio has been effected.

  12. Disordered Collarettes and Uncovered Tables

    DEFF Research Database (Denmark)

    Nørgaard, Nina

    2007-01-01

    This article examines the use of negative polarity as a stylistic device in James Joyce's short story, "Two Gallants" (1992 [1914]). The article begins with a brief account of various approaches to negative polarity, focusing in particular on theoretical paradigms that favour the pragmatic...

  13. Mind the gap: Increasing associations between the self and Blacks with approach behaviors.

    Science.gov (United States)

    Phills, Curtis E; Kawakami, Kerry; Tabi, Emmanuel; Nadolny, Daniel; Inzlicht, Michael

    2011-02-01

    Although perceived differences between outgroup social categories and the self are often cited as a major contributor to prejudice and intergroup tension, surprisingly few studies have examined ways to improve associations between the self and racial outgroups. The present research investigated one strategy to increase these associations-approach training. Specifically, 3 studies investigated the impact of training participants to conceptually approach Blacks on 3 separate measures: 2 response latency measures indexing the strength of association between the self and Blacks and a psychophysiological measure indexing brain activity in response to Blacks in the context of the self. A fourth study examined the link between earlier research on the impact of approach training on implicit prejudice against Blacks and the current results related to self-Black associations. Together, these findings provided consistent evidence that training in approaching Blacks increases associations between the self and Blacks that in turn reduce implicit prejudice against Blacks. PMID:21299313

  14. Consumption of palatable food primes food approach behavior by rapidly increasing synaptic density in the VTA

    OpenAIRE

    Liu, Shuai; Globa, Andrea K.; Mills, Fergil; Naef, Lindsay; Qiao, Min; Bamji, Shernaz X.; Borgland, Stephanie L.

    2016-01-01

    Consumption of palatable food or food-related advertising can prime increased food intake, potentially leading to overeating. We show that short-term exposure to palatable foods induces long-lasting synaptic plasticity in mesolimbic dopamine neurons. Furthermore, short-term exposure to sweetened high-fat food can drive food approach behaviors and consumption days after the initial exposure. Suppressing excitatory synaptic transmission in the ventral tegmental area can reverse increased food a...

  15. Some Specification Tests of Uncovered Interest Parity

    OpenAIRE

    Ian D. McAVINCHEY; Ronald MacDONALD

    1990-01-01

    Exchange rate theory has recently been concerned with versions of the uncovered interest rate parity (UIP) condition, as an alternative to purchasing power parity. The UIP condition is examined, for the U.S. Dollar, the Deutschemark, the Yen, and the Swiss Franc all against the Pound Sterling, using dynamic specification tests based on residual from the LUS and OLS classes, and selected error orthogonality tests. Market errors for one currency may have an information role for other currencies...

  16. Lead exposure at uncovered outdoor firing ranges

    Energy Technology Data Exchange (ETDEWEB)

    Goldberg, R.L.; Hicks, A.M.; O' Leary, L.M.; London, S. (University of Southern California School of Medicine, Los Angeles (USA))

    1991-06-01

    Excessive lead exposure in shooting instructors at indoor firing ranges and covered outdoor firing ranges has been documented. The City of Los Angeles assessed exposure of its full-time shooting instructors at uncovered outdoor ranges via air monitoring and blood lead-level measurements. Results of these tests revealed that significant lead exposure and absorption can occur at outdoor firing ranges. The use of copper-jacketed ammunition may decrease air lead levels and decrease lead absorption by range instructors.

  17. 'Mystery shoppers' can uncover ED weaknesses.

    Science.gov (United States)

    2006-12-01

    One veteran "mystery shopper" has uncovered several common ED practices that can hurt patient satisfaction. You can learn from her observations to improve your ED's customer service: Be sure to let all of your patients know how long they might expect to wait before seeing a doctor. Wash your hands where the patient can see you, so they can be confident you are practicing good hygiene. Clearly explain all forms and discharge instructions to help ensure patient compliance. PMID:17209484

  18. Uncovering student ideas in physical science

    CERN Document Server

    Keeley, Page

    2014-01-01

    If you and your students can't get enough of a good thing, Volume 2 of Uncovering Student Ideas in Physical Science is just what you need. The book offers 39 new formative assessment probes, this time with a focus on electric charge, electric current, and magnets and electromagnetism. It can help you do everything from demystify electromagnetic fields to explain the real reason balloons stick to the wall after you rub them on your hair.

  19. Approaches for increasing the cooperation between Member States and IAEA under SSS

    International Nuclear Information System (INIS)

    With introduction of the Strengthened Safeguards System (SSS), both the IAEA and Member States are concerned about the limited resources to carry out the SSS activity and the potential increase of additional cost and burdens. Even though the IAEA has recently prepared a procedure of the generalized New Partnership Approach (NPA), its wider application to the general Member States is difficult at the present time. For the generalized NPA necessitates that SSACs of the Member States have sufficient technical capability in safeguards to carry out the necessary activities. Unfortunately a few Member States seem to be qualified to have the sufficient technical capability that the IAEA desires. In this topic, a new approach to increase the cooperation between Member States and IAEA under SSS is proposed such that effective supports can be provided to all of its Member States that are not technically competent in terms of safeguards experience. This is realized by so called 'tunneling effort', meaning that desired goals are accomplished by efforts from both Member States and the IAEA. The Member States having high technical competence in safeguards provide technical assistance to the Member States that are not competent until they attain to a certain level in technical capability, while the IAEA provides the guidelines, and coordinates the process. The formal introduction of the Quality Control concept to the safeguards management is proposed as well so as to efficiently reduce burdens from the implementation of the SSS. (author)

  20. Consumption of palatable food primes food approach behavior by rapidly increasing synaptic density in the VTA.

    Science.gov (United States)

    Liu, Shuai; Globa, Andrea K; Mills, Fergil; Naef, Lindsay; Qiao, Min; Bamji, Shernaz X; Borgland, Stephanie L

    2016-03-01

    In an environment with easy access to highly palatable and energy-dense food, food-related cues drive food-seeking regardless of satiety, an effect that can lead to obesity. The ventral tegmental area (VTA) and its mesolimbic projections are critical structures involved in the learning of environmental cues used to predict motivationally relevant outcomes. Priming effects of food-related advertising and consumption of palatable food can drive food intake. However, the mechanism by which this effect occurs, and whether these priming effects last days after consumption, is unknown. Here, we demonstrate that short-term consumption of palatable food can prime future food approach behaviors and food intake. This effect is mediated by the strengthening of excitatory synaptic transmission onto dopamine neurons that is initially offset by a transient increase in endocannabinoid tone, but lasts days after an initial 24-h exposure to sweetened high-fat food (SHF). This enhanced synaptic strength is mediated by a long-lasting increase in excitatory synaptic density onto VTA dopamine neurons. Administration of insulin into the VTA, which suppresses excitatory synaptic transmission onto dopamine neurons, can abolish food approach behaviors and food intake observed days after 24-h access to SHF. These results suggest that even a short-term exposure to palatable foods can drive future feeding behavior by "rewiring" mesolimbic dopamine neurons. PMID:26884159

  1. An Axiomatic Approach to Increase End-of-Life Recovery Profit

    Directory of Open Access Journals (Sweden)

    Guang Beng Lee

    2015-10-01

    Full Text Available This paper aims at examining the feasibility of using Axiomatic Design (AD for the purpose of increasing end-of-life (EOL recovery profit of a product. A case study that involves keypad assemblies of a mobile phone is presented to demonstrate the usage of AD in this area. Product recovery considerations are only involved in the second part of the case study. As a result, two different handset assemblies are produced. An evaluation of design was performed to determine the approximate EOL recovery profit by utilizing a methodology presented by Kwak et al. (2010. This is followed by a verification of evaluation results using multiple service action (MSA algorithm proposed by S.W. Lye et al. (2000. Both evaluation approaches yield identical and conclusive results: when recovery-related requirements are omitted, application of AD produces a keypad assembly that fulfills the functional requirements derived from customer needs but a more complicated product network is obtained. In contrast, when recovery-related requirements are included during problem definition using axiomatic approach, the disassemblability of the resulted keypad is improved and thus increasing recovery potential in the event of replacing defective keypad, while satisfying product-related requirements.

  2. Modelling the impact of increasing soil sealing on runoff coefficients at regional scale: a hydropedological approach

    Directory of Open Access Journals (Sweden)

    Ungaro Fabrizio

    2014-03-01

    Full Text Available Soil sealing is the permanent covering of the land surface by buildings, infrastructures or any impermeable artificial material. Beside the loss of fertile soils with a direct impact on food security, soil sealing modifies the hydrological cycle. This can cause an increased flooding risk, due to urban development in potential risk areas and to the increased volumes of runoff. This work estimates the increase of runoff due to sealing following urbanization and land take in the plain of Emilia Romagna (Italy, using the Green and Ampt infiltration model for two rainfall return periods (20 and 200 years in two different years, 1976 and 2008. To this goal a hydropedological approach was adopted in order to characterize soil hydraulic properties via locally calibrated pedotransfer functions (PTF. PTF inputs were estimated via sequential Gaussian simulations coupled with a simple kriging with varying local means, taking into account soil type and dominant land use. Results show that in the study area an average increment of 8.4% in sealed areas due to urbanization and sprawl induces an average increment in surface runoff equal to 3.5 and 2.7% respectively for 20 and 200-years return periods, with a maximum > 20% for highly sealed coast areas.

  3. Nicotine reduction as an increase in the unit price of cigarettes: a behavioral economics approach.

    Science.gov (United States)

    Smith, Tracy T; Sved, Alan F; Hatsukami, Dorothy K; Donny, Eric C

    2014-11-01

    Urgent action is needed to reduce the harm caused by smoking. Product standards that reduce the addictiveness of cigarettes are now possible both in the U.S. and in countries party to the Framework Convention on Tobacco Control. Specifically, standards that required substantially reduced nicotine content in cigarettes could enable cessation in smokers and prevent future smoking among current non-smokers. Behavioral economics uses principles from the field of microeconomics to characterize how consumption of a reinforcer changes as a function of the unit price of that reinforcer (unit price=cost/reinforcer magnitude). A nicotine reduction policy might be considered an increase in the unit price of nicotine because smokers are paying more per unit of nicotine. This perspective allows principles from behavioral economics to be applied to nicotine reduction research questions, including how nicotine consumption, smoking behavior, use of other tobacco products, and use of other drugs of abuse are likely to be affected. This paper reviews the utility of this approach and evaluates the notion that a reduction in nicotine content is equivalent to a reduction in the reinforcement value of smoking-an assumption made by the unit price approach. PMID:25025523

  4. Increasing orthodontic and orthognathic surgery treatment efficiency with a modified surgery-first approach.

    Science.gov (United States)

    Uribe, Flavio; Agarwal, Sachin; Shafer, David; Nanda, Ravindra

    2015-11-01

    This case report describes the treatment of a 33-year-old white man who had a skeletal Class III and dental Class II subdivision malocclusion caused by a retrognathic maxilla, with severe maxillary crowding, a highly placed maxillary left canine, mild mandibular crowding, and a bilateral posterior crossbite. Treatment was performed with a modified surgery-first approach, which included a short presurgical alignment phase for the correction of the significant maxillary crowding while controlling the incisal angulation, followed by LeFort I maxillary advancement surgery. The short presurgical orthodontic phase aimed at eliminating the anterior dental interferences before the maxillary advancement, and the use of the inherent increased bone turnover in the postsurgical phase helped to reduce the total orthodontic treatment time to 12 months. Pleasing esthetic results and a good functional occlusion were achieved. PMID:26522045

  5. APPROACHES TO INCREASE THE AVAILABILITY AND EFFECTIVENESS OF PRE-HOSPITAL THROMBOLYSIS IN REAL CLINICAL PRACTICE

    Directory of Open Access Journals (Sweden)

    L. A. Ostroumova

    2015-12-01

    Full Text Available Aim. To identify the factors of the increasing the availability and effectiveness of pre-hospital thrombolytic therapy of patients with ST segment elevation acute coronary syndrome (STEACS. Material and methods. STEACS patients (n=70 were included in the study and stratified into two groups. Patients of the 1st group (n=30 received emergency medical assistance from the feldsher teams and patients of the 2nd group (n=40 — from the doctor teams. Expert estimation approach was used for the real practice assessment. Results. The hospital-matched diagnose rate was 97.5% in the doctor teams in comparison with 76.7% in feldsher teams (p<0.05. The efficiency of pre-hospital thrombolysis in 90 minutes after its beginning was 60.1% for the doctor teams versus 73.3% for the feldsher teams (p>0.05. The deviation from the standard operating procedure of the medical care for myocardial infarction patients was observed more often in the doctor teams in comparison with this in the feldsher teams. Time for the decision about pre-hospital thrombolysis start, the rate of unreasonable use or unreasonable refusal of thrombolysis did not differ significantly in feldsher and doctor teams. Conclusion. To increase the effectiveness of pre-hospital thrombolysis therapy it is necessary to follow strictly the standard of the medical care for patients with acute coronary syndrome. One of the main approaches to improve the availability of up to date medical care technologies in STEACS treatment is implementation of pre-hospital thrombolysis in practice of feldsher teams.

  6. Uncovering Transcriptional Regulatory Networks by Sparse Bayesian Factor Model

    Directory of Open Access Journals (Sweden)

    Qi Yuan(Alan

    2010-01-01

    Full Text Available Abstract The problem of uncovering transcriptional regulation by transcription factors (TFs based on microarray data is considered. A novel Bayesian sparse correlated rectified factor model (BSCRFM is proposed that models the unknown TF protein level activity, the correlated regulations between TFs, and the sparse nature of TF-regulated genes. The model admits prior knowledge from existing database regarding TF-regulated target genes based on a sparse prior and through a developed Gibbs sampling algorithm, a context-specific transcriptional regulatory network specific to the experimental condition of the microarray data can be obtained. The proposed model and the Gibbs sampling algorithm were evaluated on the simulated systems, and results demonstrated the validity and effectiveness of the proposed approach. The proposed model was then applied to the breast cancer microarray data of patients with Estrogen Receptor positive ( status and Estrogen Receptor negative ( status, respectively.

  7. Uncovering Quantum Correlations with Time-Multiplexed Click Detection

    Science.gov (United States)

    Sperling, J.; Bohmann, M.; Vogel, W.; Harder, G.; Brecht, B.; Ansari, V.; Silberhorn, C.

    2015-07-01

    We report on the implementation of a time-multiplexed click detection scheme to probe quantum correlations between different spatial optical modes. We demonstrate that such measurement setups can uncover nonclassical correlations in multimode light fields even if the single mode reductions are purely classical. The nonclassical character of correlated photon pairs, generated by a parametric down-conversion, is immediately measurable employing the theory of click counting instead of low-intensity approximations with photoelectric detection models. The analysis is based on second- and higher-order moments, which are directly retrieved from the measured click statistics, for relatively high mean photon numbers. No data postprocessing is required to demonstrate the effects of interest with high significance, despite low efficiencies and experimental imperfections. Our approach shows that such novel detection schemes are a reliable and robust way to characterize quantum-correlated light fields for practical applications in quantum communications.

  8. Uncovering the Hidden Decisions that Shape Curricula

    Science.gov (United States)

    Harlow, Danielle Boyd

    2010-10-01

    Developing explanatory models is a central practice to scientific inquiry. When students create and test explanatory models for scientific phenomenon, they develop content knowledge, knowledge of the nature of science, and creative thinking skills. Unfortunately, such instruction rarely occurs in K-12 science. This is, in part, because teachers do not have the opportunity to develop sophisticated understandings of the process of modeling, but also because teaching in this way requires teachers to make real-time instructional decisions that are responsive to students' ideas. This is challenging for teachers, especially because this decision process is often invisible. In this talk, I will highlight the importance of providing opportunities for sophisticated science thinking for our youngest learners and consider how uncovering the decisions that shape physics courses for teachers may benefit their future students.

  9. A Framework to Uncover Multiple Alternative Clusterings

    DEFF Research Database (Denmark)

    Dang, Xuan-Hong; Bailey, James

    Clustering is often referred to as unsupervised learning which aims at uncovering hidden structures from data. Unfortunately, though widely being used as one of the principal tools to understand the data, most conventional clustering techniques are limited in achieving this goal since they only...... attempt to find a single clustering solution from the data. For many real-world applications, especially those being described in high dimensional data, it is common to see that the data can be grouped into different yet meaningful ways. This gives rise to the recently emerging research area of mining...... alternative clusterings. In this paper, we propose a framework named MACL that is capable of discovering multiple alternative clusterings from a given dataset.MACL seeks alternative clusterings in sequence and a novel solution is found by conditioning on all previously known clusterings. The framework takes a...

  10. Hepatitis C virus host cell interactions uncovered

    DEFF Research Database (Denmark)

    Gottwein, Judith; Bukh, Jens

    2007-01-01

      Insights into virus-host cell interactions as uncovered by Randall et al. (1) in a recent issue of PNAS further our understanding of the hepatitis C virus (HCV) life cycle, persistence, and pathogenesis and might lead to the identification of new therapeutic targets. HCV persistently infects 180...... million individuals worldwide, causing chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The only approved treatment, combination therapy with IFN- and ribavirin, targets cellular pathways (2); however, a sustained virologic response is achieved only in approximately half of the patients...... treated. Therefore, there is a pressing need for the identification of novel drugs against hepatitis C. Although most research focuses on the development of HCV-specific antivirals, such as protease and polymerase inhibitors (3), cellular targets could be pursued and might allow the development of broad...

  11. Theoretical and empirical approaches to using films as a means to increase communication efficiency.

    Directory of Open Access Journals (Sweden)

    Kiselnikova, N.V.

    2016-07-01

    Full Text Available The theoretical framework of this analytic study is based on studies in the field of film perception. Films are considered as a communicative system that is encrypted in an ordered series of shots, and decoding proceeds during perception. The shots are the elements of a cinematic message that must be “read” by viewer. The objective of this work is to analyze the existing theoretical approaches to using films in psychotherapy and education. An original approach to film therapy that is based on teaching clients to use new communicative sets and psychotherapeutic patterns through watching films is presented. The article specifies the main emphasized points in theories of film therapy and education. It considers the specifics of film therapy in the process of increasing the effectiveness of communication. It discusses the advantages and limitations of the proposed method. The contemporary forms of film therapy and the formats of cinema clubs are criticized. The theoretical assumptions and empirical research that could be used as a basis for a method of developing effective communication by means of films are discussed. Our studies demonstrate that the usage of film therapy must include an educational stage for more effective and stable results. This means teaching viewers how to recognize certain psychotherapeutic and communicative patterns in the material of films, to practice the skill of finding as many examples as possible for each pattern and to transfer the acquired schemes of analyzing and recognizing patterns into one’s own life circumstances. The four stages of the film therapeutic process as well as the effects that are achieved at each stage are described in detail. In conclusion, the conditions under which the usage of the film therapy method would be the most effective are observed. Various properties of client groups and psychotherapeutic scenarios for using the method of active film therapy are described.

  12. Increasing safer sexual behavior among Lao kathoy through an integrated social marketing approach

    Directory of Open Access Journals (Sweden)

    Longfield Kim

    2011-11-01

    Full Text Available Abstract Background Although HIV prevalence has remained low in Laos thus far, there is reason to be concerned that Lao male-to-female (MtF transgender persons (kathoy and their partners may facilitate the spread of HIV. Little is known about how to most effectively reach kathoy with HIV prevention programming. This paper evaluates an intervention with Lao kathoy with the objective of increasing safe sex with regular and casual partners. Methods Quantitative surveys were administered in November 2004 (n = 288 and June 2006 (n = 415 using time location sampling at venues where kathoy were known to congregate. Respondents were aged 15-35 and from three urban centers in Laos. UNIANOVA tests were used to compare baseline and follow-up survey data and to evaluate the impact of PSI's kathoy-specific interventions on items that changed significantly over time. Results Exposure to the intervention was associated with higher levels of condom use at last anal sex with casual partners and greater use of water-based lubricant. Exposure was also linked to improved perceptions of product availability for condoms and water-based lubricant. Knowledge about the importance of consistent condom use improved over time as well as the need to use condoms with regular partners. Some HIV knowledge decreased over time and the intention to use condoms with casual partners when water-based lubricant is available also declined. Conclusions Study results demonstrate the feasibility of reaching kathoy with an integrated social marketing approach; combining product promotion, peer education, and other types of interpersonal communication. The approach was successful at increasing condom use with casual partners and water-based lubricant use, but the importance of using condoms along with water-based lubricant must be emphasized and modified strategies are required for improving condom use with boyfriends. Future messages should emphasize consistent condom use with all types

  13. New approaches to increase intestinal length: Methods used for intestinal regeneration and bioengineering.

    Science.gov (United States)

    Shirafkan, Ali; Montalbano, Mauro; McGuire, Joshua; Rastellini, Cristiana; Cicalese, Luca

    2016-03-24

    Inadequate absorptive surface area poses a great challenge to the patients suffering a variety of intestinal diseases causing short bowel syndrome. To date, these patients are managed with total parenteral nutrition or intestinal transplantation. However, these carry significant morbidity and mortality. Currently, by emergence of tissue engineering, anticipations to utilize an alternative method to increase the intestinal absorptive surface area are increasing. In this paper, we will review the improvements made over time in attempting elongating the intestine with surgical techniques as well as using intestinal bioengineering. Performing sequential intestinal lengthening was the preliminary method applied in humans. However, these methods did not reach widespread use and has limited outcome. Subsequent experimental methods were developed utilizing scaffolds to regenerate intestinal tissue and organoids unit from the intestinal epithelium. Stem cells also have been studied and applied in all types of tissue engineering. Biomaterials were utilized as a structural support for naive cells to produce bio-engineered tissue that can achieve a near-normal anatomical structure. A promising novel approach is the elongation of the intestine with an acellular biologic scaffold to generate a neo-formed intestinal tissue that showed, for the first time, evidence of absorption in vivo. In the large intestine, studies are more focused on regeneration and engineering of sphincters and will be briefly reviewed. From the review of the existing literature, it can be concluded that significant progress has been achieved in these experimental methods but that these now need to be fully translated into a pre-clinical and clinical experimentation to become a future viable therapeutic option. PMID:27011901

  14. Uncovering the Geometry of Barrierless Reactions Using Lagrangian Descriptors.

    Science.gov (United States)

    Junginger, Andrej; Hernandez, Rigoberto

    2016-03-01

    Transition-state theories describing barrierless chemical reactions, or more general activated problems, are often hampered by the lack of a saddle around which the dividing surface can be constructed. For example, the time-dependent transition-state trajectory uncovering the nonrecrossing dividing surface in thermal reactions in the framework of the Langevin equation has relied on perturbative approaches in the vicinity of the saddle. We recently obtained an alternative approach using Lagrangian descriptors to construct time-dependent and recrossing-free dividing surfaces. This is a nonperturbative approach making no reference to a putative saddle. Here we show how the Lagrangian descriptor can be used to obtain the transition-state geometry of a dissipated and thermalized reaction across barrierless potentials. We illustrate the method in the case of a 1D Brownian motion for both barrierless and step potentials; however, the method is not restricted and can be directly applied to different kinds of potentials and higher dimensional systems. PMID:26524392

  15. Increasing oral absorption of polar neuraminidase inhibitors: a prodrug transporter approach applied to oseltamivir analogue.

    Science.gov (United States)

    Gupta, Deepak; Varghese Gupta, Sheeba; Dahan, Arik; Tsume, Yasuhiro; Hilfinger, John; Lee, Kyung-Dall; Amidon, Gordon L

    2013-02-01

    Poor oral absorption is one of the limiting factors in utilizing the full potential of polar antiviral agents. The neuraminidase target site requires a polar chemical structure for high affinity binding, thus limiting oral efficacy of many high affinity ligands. The aim of this study was to overcome this poor oral absorption barrier, utilizing prodrug to target the apical brush border peptide transporter 1 (PEPT1). Guanidine oseltamivir carboxylate (GOCarb) is a highly active polar antiviral agent with insufficient oral bioavailability (4%) to be an effective therapeutic agent. In this report we utilize a carrier-mediated targeted prodrug approach to improve the oral absorption of GOCarb. Acyloxy(alkyl) ester based amino acid linked prodrugs were synthesized and evaluated as potential substrates of mucosal transporters, e.g., PEPT1. Prodrugs were also evaluated for their chemical and enzymatic stability. PEPT1 transport studies included [(3)H]Gly-Sar uptake inhibition in Caco-2 cells and cellular uptake experiments using HeLa cells overexpressing PEPT1. The intestinal membrane permeabilities of the selected prodrugs and the parent drug were then evaluated for epithelial cell transport across Caco-2 monolayers, and in the in situ rat intestinal jejunal perfusion model. Prodrugs exhibited a pH dependent stability with higher stability at acidic pHs. Significant inhibition of uptake (IC(50) 30-fold increase in affinity compared to GOCarb. The l-valyl prodrug exhibited significant enhancement of uptake in PEPT1/HeLa cells and compared favorably with the well-absorbed valacyclovir. Transepithelial permeability across Caco-2 monolayers showed that these amino acid prodrugs have a 2-5-fold increase in permeability as compared to the parent drug and showed that the l-valyl prodrug (P(app) = 1.7 × 10(-6) cm/s) has the potential to be rapidly transported across the epithelial cell apical membrane. Significantly, only the parent drug (GOCarb) appeared in the basolateral

  16. Increasing Oral Absorption of Polar Neuraminidase Inhibitors: A Prodrug Transporter Approach Applied to Oseltamivir Analogue

    Science.gov (United States)

    Gupta, Deepak; Gupta, Sheeba Varghese; Dahan, Arik; Tsume, Yasuhiro; Hilfinger, John; Lee, Kyung-Dall; Amidon, Gordon L.

    2013-01-01

    Poor oral absorption is one of the limiting factors in utilizing the full potential of polar antiviral agents. The neuraminidase target site requires a polar chemical structure for high affinity binding, thus limiting oral efficacy of many high affinity ligands. The aim of this study was to overcome this poor oral absorption barrier, utilizing prodrug to target the apical brush border peptide transporter 1 (PEPT1). Guanidine oseltamivir carboxylate (GOCarb) is a highly active polar antiviral agent (prodrug) with insufficient oral bioavailability (4%) to be an effective therapeutic agent. In this report we utilize a carrier-mediated targeted prodrug approach to improve the oral absorption of GOCarb. Acyloxy(alkyl) ester based amino acid linked prodrugs were synthesized and evaluated as potential substrates of mucosal transporters e.g. PEPT1. Prodrugs were also evaluated for their chemical and enzymatic stability. PEPT1 transport studies included [3H]Gly-Sar uptake inhibition and cellular uptake experiments using HeLa cells over-expressing PEPT1. The intestinal membrane permeability of the selected prodrugs and the parent drug were then evaluated for epithelial cell transport across Caco-2 monolayers, and in the in-situ rat intestinal jejunal perfusion model. Prodrugs exhibited a pH dependent stability with higher stability at acidic pHs. Significant inhibition of uptake (IC50 30 fold increase in affinity compared to GOCarb. The L-valyl prodrug exhibited significant enhancement of uptake in PEPT1/HeLa cells, and compared favorably with the well absorbed valacyclovir. Transepithelial permeability across Caco-2 monolayers showed that these amino acid prodrugs have a 2–5 fold increase in permeability as compared to the parent drug and showed that the L-valyl prodrug (Papp = 1.7×10−6 cm/sec) has the potential to be a rapidly transported across the epithelial cell apical membrane. Significantly, only the parent drug (GOCarb) appeared in the basolateral compartment

  17. A predictive modeling approach to increasing the economic effectiveness of disease management programs.

    Science.gov (United States)

    Bayerstadler, Andreas; Benstetter, Franz; Heumann, Christian; Winter, Fabian

    2014-09-01

    Predictive Modeling (PM) techniques are gaining importance in the worldwide health insurance business. Modern PM methods are used for customer relationship management, risk evaluation or medical management. This article illustrates a PM approach that enables the economic potential of (cost-) effective disease management programs (DMPs) to be fully exploited by optimized candidate selection as an example of successful data-driven business management. The approach is based on a Generalized Linear Model (GLM) that is easy to apply for health insurance companies. By means of a small portfolio from an emerging country, we show that our GLM approach is stable compared to more sophisticated regression techniques in spite of the difficult data environment. Additionally, we demonstrate for this example of a setting that our model can compete with the expensive solutions offered by professional PM vendors and outperforms non-predictive standard approaches for DMP selection commonly used in the market. PMID:23780751

  18. Uncovering Barriers to Teaching Assistants (TAs) Implementing Inquiry Teaching: Inconsistent Facilitation Techniques, Student Resistance, and Reluctance to Share Control over Learning with Students †

    Science.gov (United States)

    Gormally, Cara; Sullivan, Carol Subiño; Szeinbaum, Nadia

    2016-01-01

    Inquiry-based teaching approaches are increasingly being adopted in biology laboratories. Yet teaching assistants (TAs), often novice teachers, teach the majority of laboratory courses in US research universities. This study analyzed the perspectives of TAs and their students and used classroom observations to uncover challenges faced by TAs during their first year of inquiry-based teaching. Our study revealed three insights about barriers to effective inquiry teaching practices: 1) TAs lack sufficient facilitation skills; 2) TAs struggle to share control over learning with students as they reconcile long-standing teaching beliefs with newly learned approaches, consequently undermining their fledgling ability to use inquiry approaches; and 3) student evaluations reinforce teacher-centered behaviors as TAs receive positive feedback conflicting with inquiry approaches. We make recommendations, including changing instructional feedback to focus on learner-centered teaching practices. We urge TA mentors to engage TAs in discussions to uncover teaching beliefs underlying teaching choices and support TAs through targeted feedback and practice. PMID:27158302

  19. Uncovering Barriers to Teaching Assistants (TAs) Implementing Inquiry Teaching: Inconsistent Facilitation Techniques, Student Resistance, and Reluctance to Share Control over Learning with Students.

    Science.gov (United States)

    Gormally, Cara; Sullivan, Carol Subiño; Szeinbaum, Nadia

    2016-05-01

    Inquiry-based teaching approaches are increasingly being adopted in biology laboratories. Yet teaching assistants (TAs), often novice teachers, teach the majority of laboratory courses in US research universities. This study analyzed the perspectives of TAs and their students and used classroom observations to uncover challenges faced by TAs during their first year of inquiry-based teaching. Our study revealed three insights about barriers to effective inquiry teaching practices: 1) TAs lack sufficient facilitation skills; 2) TAs struggle to share control over learning with students as they reconcile long-standing teaching beliefs with newly learned approaches, consequently undermining their fledgling ability to use inquiry approaches; and 3) student evaluations reinforce teacher-centered behaviors as TAs receive positive feedback conflicting with inquiry approaches. We make recommendations, including changing instructional feedback to focus on learner-centered teaching practices. We urge TA mentors to engage TAs in discussions to uncover teaching beliefs underlying teaching choices and support TAs through targeted feedback and practice. PMID:27158302

  20. A Model Based Approach to Increase the Part Accuracy in Robot Based Incremental Sheet Metal Forming

    International Nuclear Information System (INIS)

    One main influence on the dimensional accuracy in robot based incremental sheet metal forming results from the compliance of the involved robot structures. Compared to conventional machine tools the low stiffness of the robot's kinematic results in a significant deviation of the planned tool path and therefore in a shape of insufficient quality. To predict and compensate these deviations offline, a model based approach, consisting of a finite element approach, to simulate the sheet forming, and a multi body system, modeling the compliant robot structure, has been developed. This paper describes the implementation and experimental verification of the multi body system model and its included compensation method.

  1. The Campus-Wide Presentation: An Experiential Approach to Increasing Student Learning, Growth and Marketability

    Science.gov (United States)

    Redcross, Natalie Ryder

    2015-01-01

    The purpose of this article is to describe and encourage an approach to a public relations course that can be applied to any discipline. Grounded in the experiential learning theory, students prepare for 16 weeks to present an issue-based campaign to a targeted, live audience at an oncampus venue. Using the course textbook and required readings as…

  2. A Case-Based Approach Increases Student Learning Outcomes and Comprehension of Cellular Respiration Concepts

    Science.gov (United States)

    Rybarczyk, Brian J.; Baines, Antonio T.; McVey, Mitch; Thompson, Joseph T.; Wilkins, Heather

    2007-01-01

    This study investigated student learning outcomes using a case-based approach focused on cellular respiration. Students who used the case study, relative to students who did not use the case study, exhibited a significantly greater learning gain, and demonstrated use of higher-order thinking skills. Preliminary data indicate that after engaging…

  3. THE SIGNIFICANCE OF CRIMINALISTIC THEORY OF INFORMATION FOR THE PROCESS OF UNCOVERING AND INVESTIGATION OF CRIMES

    OpenAIRE

    Pisarev, Evgeniy

    2014-01-01

    The article proves the necessity of development of general criminalistic theory of information and application of informational approach in the process of uncovering and investigation of the crimes. The place of criminalistic informatiology is determined in general theory of criminalistics as its element. The author proceeds from the fact that the evidence in criminal procedure legislation is determined as the data; this circumstance predetermines the process of collection of evidence as the ...

  4. Uncovering Special Nuclear Materials by Low-energy Nuclear Reaction Imaging

    OpenAIRE

    P. B. Rose; Erickson, A. S.; Mayer, M.; Nattress, J.; Jovanovic, I

    2016-01-01

    Weapons-grade uranium and plutonium could be used as nuclear explosives with extreme destructive potential. The problem of their detection, especially in standard cargo containers during transit, has been described as “searching for a needle in a haystack” because of the inherently low rate of spontaneous emission of characteristic penetrating radiation and the ease of its shielding. Currently, the only practical approach for uncovering well-shielded special nuclear materials is by use of act...

  5. Nanoparticle Formulation Increases Oral Bioavailability of Poorly Soluble Drugs: Approaches Experimental Evidences and Theory

    OpenAIRE

    Jia, Lee

    2005-01-01

    The increasing frequency at which poorly soluble new chemical entities are being discovered raises concerns in the pharmaceutical industry about drugability associated with erratic dissolution and low bioavailability of these hydrophobic compounds. Nanonization provides a plausible pharmaceutical basis for enhancing oral bioavailability and therapeutic effectiveness of these compounds by increasing their surface area. This paper surveys methods available to pharmaceutical manufacturing nanopa...

  6. Increasing secondary and renewable material use: a chance constrained modeling approach to manage feedstock quality variation.

    Science.gov (United States)

    Olivetti, Elsa A; Gaustad, Gabrielle G; Field, Frank R; Kirchain, Randolph E

    2011-05-01

    The increased use of secondary (i.e., recycled) and renewable resources will likely be key toward achieving sustainable materials use. Unfortunately, these strategies share a common barrier to economical implementation - increased quality variation compared to their primary and synthetic counterparts. Current deterministic process-planning models overestimate the economic impact of this increased variation. This paper shows that for a range of industries from biomaterials to inorganics, managing variation through a chance-constrained (CC) model enables increased use of such variable raw materials, or heterogeneous feedstocks (hF), over conventional, deterministic models. An abstract, analytical model and a quantitative model applied to an industrial case of aluminum recycling were used to explore the limits and benefits of the CC formulation. The results indicate that the CC solution can reduce cost and increase potential hF use across a broad range of production conditions through raw materials diversification. These benefits increase where the hFs exhibit mean quality performance close to that of the more homogeneous feedstocks (often the primary and synthetic materials) or have large quality variability. In terms of operational context, the relative performance grows as intolerance for batch error increases and as the opportunity to diversify the raw material portfolio increases. PMID:21466183

  7. Bayesian approach increases accuracy when selecting cowpea genotypes with high adaptability and phenotypic stability.

    Science.gov (United States)

    Barroso, L M A; Teodoro, P E; Nascimento, M; Torres, F E; Dos Santos, A; Corrêa, A M; Sagrilo, E; Corrêa, C C G; Silva, F A; Ceccon, G

    2016-01-01

    This study aimed to verify that a Bayesian approach could be used for the selection of upright cowpea genotypes with high adaptability and phenotypic stability, and the study also evaluated the efficiency of using informative and minimally informative a priori distributions. Six trials were conducted in randomized blocks, and the grain yield of 17 upright cowpea genotypes was assessed. To represent the minimally informative a priori distributions, a probability distribution with high variance was used, and a meta-analysis concept was adopted to represent the informative a priori distributions. Bayes factors were used to conduct comparisons between the a priori distributions. The Bayesian approach was effective for selection of upright cowpea genotypes with high adaptability and phenotypic stability using the Eberhart and Russell method. Bayes factors indicated that the use of informative a priori distributions provided more accurate results than minimally informative a priori distributions. PMID:26985961

  8. Adaptation policies to increase terrestrial ecosystem resilience. Potential utility of a multicriteria approach

    Energy Technology Data Exchange (ETDEWEB)

    de Bremond, Ariane [Univ. of Maryland, College Park, MD (United States); Joint Global Change Research Inst., College Park, MD (United States); Engle, Nathan L. [World Bank, Washington, DC (United States)

    2014-01-30

    Climate change is rapidly undermining terrestrial ecosystem resilience and capacity to continue providing their services to the benefit of humanity and nature. Because of the importance of terrestrial ecosystems to human well-being and supporting services, decision makers throughout the world are busy creating policy responses that secure multiple development and conservation objectives- including that of supporting terrestrial ecosystem resilience in the context of climate change. This article aims to advance analyses on climate policy evaluation and planning in the area of terrestrial ecosystem resilience by discussing adaptation policy options within the ecology-economy-social nexus. The paper evaluates these decisions in the realm of terrestrial ecosystem resilience and evaluates the utility of a set of criteria, indicators, and assessment methods, proposed by a new conceptual multi-criteria framework for pro-development climate policy and planning developed by the United Nations Environment Programme. Potential applications of a multicriteria approach to climate policy vis-A -vis terrestrial ecosystems are then explored through two hypothetical case study examples. The paper closes with a brief discussion of the utility of the multi-criteria approach in the context of other climate policy evaluation approaches, considers lessons learned as a result efforts to evaluate climate policy in the realm of terrestrial ecosystems, and reiterates the role of ecosystem resilience in creating sound policies and actions that support the integration of climate change and development goals.

  9. New approaches to increase intestinal length: Methods used for intestinal regeneration and bioengineering

    OpenAIRE

    Shirafkan, Ali; Montalbano, Mauro; McGuire, Joshua; Rastellini, Cristiana; Cicalese, Luca

    2016-01-01

    Inadequate absorptive surface area poses a great challenge to the patients suffering a variety of intestinal diseases causing short bowel syndrome. To date, these patients are managed with total parenteral nutrition or intestinal transplantation. However, these carry significant morbidity and mortality. Currently, by emergence of tissue engineering, anticipations to utilize an alternative method to increase the intestinal absorptive surface area are increasing. In this paper, we will review t...

  10. Uncovering Aberrant Mutant PKA Function with Flow Cytometric FRET.

    Science.gov (United States)

    Lee, Shin-Rong; Sang, Lingjie; Yue, David T

    2016-03-29

    Biology has been revolutionized by tools that allow the detection and characterization of protein-protein interactions (PPIs). Förster resonance energy transfer (FRET)-based methods have become particularly attractive as they allow quantitative studies of PPIs within the convenient and relevant context of living cells. We describe here an approach that allows the rapid construction of live-cell FRET-based binding curves using a commercially available flow cytometer. We illustrate a simple method for absolutely calibrating the cytometer, validating our binding assay against the gold standard isothermal calorimetry (ITC), and using flow cytometric FRET to uncover the structural and functional effects of the Cushing-syndrome-causing mutation (L206R) on PKA's catalytic subunit. We discover that this mutation not only differentially affects PKAcat's binding to its multiple partners but also impacts its rate of catalysis. These findings improve our mechanistic understanding of this disease-causing mutation, while illustrating the simplicity, general applicability, and power of flow cytometric FRET. PMID:26997269

  11. Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms.

    Science.gov (United States)

    Nyström, Alexander; Thriene, Kerstin; Mittapalli, Venugopal; Kern, Johannes S; Kiritsi, Dimitra; Dengjel, Jörn; Bruckner-Tuderman, Leena

    2015-09-01

    Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB)-a severe skin fragility disorder associated with lifelong blistering and disabling progressive soft tissue fibrosis. Causative therapies for this complex disorder face major hurdles, and clinical implementation remains elusive. Here, we report an alternative evidence-based approach to ameliorate fibrosis and relieve symptoms in RDEB. Based on the findings that TGF-β activity is elevated in injured RDEB skin, we targeted TGF-β activity with losartan in a preclinical setting. Long-term treatment of RDEB mice efficiently reduced TGF-β signaling in chronically injured forepaws and halted fibrosis and subsequent fusion of the digits. In addition, proteomics analysis of losartan- vs. vehicle-treated RDEB skin uncovered changes in multiple proteins related to tissue inflammation. In line with this, losartan reduced inflammation and diminished TNF-α and IL-6 expression in injured forepaws. Collectively, the data argue that RDEB fibrosis is a consequence of a cascade encompassing tissue damage, TGF-β-mediated inflammation, and matrix remodeling. Inhibition of TGF-β activity limits these unwanted outcomes and thereby substantially ameliorates long-term symptoms. PMID:26194911

  12. Uncovering Aberrant Mutant PKA Function with Flow Cytometric FRET

    Directory of Open Access Journals (Sweden)

    Shin-Rong Lee

    2016-03-01

    Full Text Available Biology has been revolutionized by tools that allow the detection and characterization of protein-protein interactions (PPIs. Förster resonance energy transfer (FRET-based methods have become particularly attractive as they allow quantitative studies of PPIs within the convenient and relevant context of living cells. We describe here an approach that allows the rapid construction of live-cell FRET-based binding curves using a commercially available flow cytometer. We illustrate a simple method for absolutely calibrating the cytometer, validating our binding assay against the gold standard isothermal calorimetry (ITC, and using flow cytometric FRET to uncover the structural and functional effects of the Cushing-syndrome-causing mutation (L206R on PKA’s catalytic subunit. We discover that this mutation not only differentially affects PKAcat’s binding to its multiple partners but also impacts its rate of catalysis. These findings improve our mechanistic understanding of this disease-causing mutation, while illustrating the simplicity, general applicability, and power of flow cytometric FRET.

  13. An Approach to Increase the Battery Time of a Mobile Phone Using Free Energy Harvesting

    DEFF Research Database (Denmark)

    Kirkegaard Jensen, Jesper; Jessen, Kasper; Laugesen, Kasper;

    2016-01-01

    The increasing market of mobile phones, has increased the need for electricity to power mobile phones, as well. This paper investigates the possibilities to charge a mobile phone by harvesting energy from the surroundings. Some technologies are better suited for this purpose than others. Through...... previous analyses solar cells and electromagnetic generator were found to be the most suitable solution. This paper will give a basic description of the operating conditions of solar cells and an electromagnetic generator. There will also be a short view on the electrical circuit needed for implementing...

  14. Approaches to Increase Arsenic Awareness in Bangladesh: An Evaluation of an Arsenic Education Program

    Science.gov (United States)

    George, Christine Marie; Factor-Litvak, Pam; Khan, Khalid; Islam, Tariqul; Singha, Ashit; Moon-Howard, Joyce; van Geen, Alexander; Graziano, Joseph H.

    2013-01-01

    The objective of this study was to design and evaluate a household-level arsenic education and well water arsenic testing intervention to increase arsenic awareness in Bangladesh. The authors randomly selected 1,000 study respondents located in 20 villages in Singair, Bangladesh. The main outcome was the change in knowledge of arsenic from…

  15. A participatory and integrative approach to increase productivity and comfort in assembly

    NARCIS (Netherlands)

    Looze, M. de; Rhijn, G. van; Tuinzaad, B.; Deursen, J. van

    2000-01-01

    Manufacturers of manually assembled products are more and more forced to improve the flow of assembly orders together with a more efficient employment, in order to meet increasing demands on short delivery times, high product variety, good quality and low manufacturing costs. At the same time, the h

  16. An ICT-Mediated Constructivist Approach for Increasing Academic Support and Teaching Critical Thinking Skills

    Science.gov (United States)

    Ng'ambi, Dick; Johnston, Kevin

    2006-01-01

    South African Universities are tasked with increasing student throughput by offering additional academic support. A second task is to teach students to challenge and question. One way of attempting to achieve these tasks is by using Information and Communication Technology (ICT). The focus of this paper is to examine the effect of using an ICT…

  17. Mammary stem cells: Novel markers and novel approaches to increase lactation efficiency

    Science.gov (United States)

    Mammary stem cells (MaSC) provide for net growth, renewal and turnover of mammary epithelial cells, and are therefore potential targets for strategies to increase production efficiency. Appropriate regulation of MaSC can potentially benefit milk yield, persistency, dry period management and tissue r...

  18. Macroscopic model for biological fixation and its uncover-ing idea in Chinese Mongolian traditional osteopathy

    Institute of Scientific and Technical Information of China (English)

    ZHAO Namula; LI Xue-en; WANG Mei; HU Da-lai

    2009-01-01

    Splintage external fixation in Chinese Mongolian oste-opathy is a biological macroscopic model. In this model, the ideas of self-life "unity of mind and body" and vital natural "correspondence of nature and human" combine the physi-ological and psychological self-fixation with supplementary external fixation of fracture using small splints. This model implies macroscopic ideas of uncovering fixation and healing: structural stability integrating geometrical "dy-namic" stability with mechanical "dynamic" equilibrium and the stability of state integrating statics with dynamics, and osteoblasts with osteoclasts, and psychological stability in-tegrating closed and open systems of human and nature. These ideas indicate a trend of development in modem osteopathy.

  19. Approaches to Increasing Ethical Compliance in China with Drug Trial Standards of Practice.

    Science.gov (United States)

    Rosenberg, Jacob

    2016-03-29

    Zeng et al.'s Ethics Review highlights some of the challenges associated with clinical research in China. They found that only a minority of published clinical trials of anti-dementia drugs reported that they fulfilled the basic ethical principles as outlined in the Declaration of Helsinki. With recent reports of scientific misconduct from China, there is an urgent need to find approaches to compel researchers to adhere to ethical research practices. This problem does not call for a simple solution, but if forces are joined with governmental regulations, education in ethics issues for medical researchers, and strong reinforcement by Chinese journal editors not to publish studies with these flaws, then research ethics and publication standards will probably improve. Other solutions to foster ethical practice of drug trials are discussed including Chinese initiatives directed at managing conflict of interest from the pharmaceutical industry and educating clinical researchers. PMID:27031489

  20. Changing the Curation Equation: A Data Lifecycle Approach to Lowering Costs and Increasing Value

    Science.gov (United States)

    Myers, J.; Hedstrom, M.; Plale, B. A.; Kumar, P.; McDonald, R.; Kooper, R.; Marini, L.; Kouper, I.; Chandrasekar, K.

    2013-12-01

    What if everything that researchers know about their data, and everything their applications know, were directly available to curators? What if all the information that data consumers discover and infer about data were also available? What if curation and preservation activities occurred incrementally, during research projects instead of after they end, and could be leveraged to make it easier to manage research data from the moment of its creation? These are questions that the Sustainable Environments - Actionable Data (SEAD) project, funded as part of the National Science Foundation's DataNet partnership, was designed to answer. Data curation is challenging, but it is made more difficult by the historical separation of data production, data use, and formal curation activities across organizations, locations, and applications, and across time. Modern computing and networking technologies allow a much different approach in which data and metadata can easily flow between these activities throughout the data lifecycle, and in which heterogeneous and evolving data and metadata can be managed. Sustainability research, SEAD's initial focus area, is a clear example of an area where the nature of the research (cross-disciplinary, integrating heterogeneous data from independent sources, small teams, rapid evolution of sensing and analysis techniques) and the barriers and costs inherent in traditional methods have limited adoption of existing curation tools and techniques, to the detriment of overall scientific progress. To explore these ideas and create a sustainable curation capability for communities such as sustainability research, the SEAD team has developed and is now deploying an interacting set of open source data services that demonstrate this approach. These services provide end-to-end support for management of data during research projects; publication of that data into long-term archives; and integration of it into community networks of publications, research

  1. Approaches to Increasing Ethical Compliance in China with Drug Trial Standards of Practice

    DEFF Research Database (Denmark)

    Rosenberg, Jacob

    2016-01-01

    Zeng et al.'s Ethics Review highlights some of the challenges associated with clinical research in China. They found that only a minority of published clinical trials of anti-dementia drugs reported that they fulfilled the basic ethical principles as outlined in the Declaration of Helsinki. With...... recent reports of scientific misconduct from China, there is an urgent need to find approaches to compel researchers to adhere to ethical research practices. This problem does not call for a simple solution, but if forces are joined with governmental regulations, education in ethics issues for medical...... researchers, and strong reinforcement by Chinese journal editors not to publish studies with these flaws, then research ethics and publication standards will probably improve. Other solutions to foster ethical practice of drug trials are discussed including Chinese initiatives directed at managing conflict of...

  2. Cultural/Favorite Recipe Day: Strengthening Approaches to Increase Culturally Diverse Foods Served in Head Start Meals

    Science.gov (United States)

    Hoffman, Jessica A.; Agrawal, Tara; Carter, Sonia; Grinder, AnnMarie; Castaneda-Sceppa, Carmen

    2012-01-01

    One approach to halting the childhood obesity epidemic has been the modification of foods available to children during the school day. In recent years there has been an increased focus on obesity prevention efforts among children ages birth to 5 and the role of child care settings in prevention efforts. Head Start serves as an important venue for…

  3. A pragmatic approach to increase expressive language skills in young autistic children.

    Science.gov (United States)

    Beisler, J M; Tsai, L Y

    1983-09-01

    This paper is a description of a pilot communication program for autistic children designed to increase communication skills in the context of establishing reciprocal communication exchanges. The methods involved intensive modeling of verbal responses within joint activity routines and using a reinforcement system based on fulfilling the intent of the child's communication. Five male subjects ranging in age from 36 to 68 months participated in the communication program for 6 weeks during an inpatient stay at the Iowa Autism Program, Child Psychiatry Service. Communication exchanges involving requests for actions and objects, descriptions of actions and objects, comments on existence and nonexistence, and requests for recurrence were targeted. Individual gains for each subject are outlined. Posttreatment results indicated a significant increase in the mean length of response, in the mean receptive language level, and in the mean number of semantic-grammatical rules expressed. Suggestions regarding future research are discussed. PMID:6643374

  4. White certificates in Italy - Part of an innovative approach to increasing energy efficiency

    International Nuclear Information System (INIS)

    This article takes a look at efforts being made in Italy to increase energy efficiency in the electricity area. Legislation, already formulated in 2001, is to be enforced as a result of several blackouts experienced in Italy in 2002. These were caused by increasing load during the summer months and the temperature-related reduced capacity of generation units. A ministerial decree sets national goals for the improvement of energy efficiency and for the reduction of primary energy consumption as well as the financing of the measures with the help of 'white certificates' that are freely tradable and valid for five years. The certificates are issued to producers that improve their performance with respect to primary energy consumption and can be purchased by those who have not fulfilled their obligations

  5. Increased microbe-receptor contact in early life – approaching immune regulation

    DEFF Research Database (Denmark)

    Bendtsen, Katja Maria Bangsgaard; Hansen, Camilla H. F.; Krych, Lukasz; Skovgaard, Kerstin; Vogensen, Finn K.; Hansen, Axel K.

    The crucial colonization in early life educates immune receptors and cells of the body to form the immune system that we depend on during maintenance, disease, and repair. When regulatory mechanisms fail and the system itself becomes the cause of disease, we should look to the proposed early window...... of opportunity, where it may be possible to affect the developing immune system towards tolerance. We hypothesize that increased contact in early life between immune receptors and microbial-associated molecular patterns (MAMP), like TLR-4 and LPS, favors a regulatory immune environment later in life....... Dextran Sulphate Sodium interrupts the barrier function of the gut wall by shaving the mucus layer. In low doses it may have the desired contact-increasing effect without inducing colitis-related disease. Following low-dose DSS treatment in early life of BALB/c mice, we did a gene expression screening in...

  6. Approaches to Increase Arsenic Awareness in Bangladesh: An Evaluation of an Arsenic Education Program

    OpenAIRE

    George, Christine Marie; Factor-Litvak, Pam; Khan, Khalid; ISLAM, Tariqul; Singha, Ashit; Moon-Howard, Joyce; van Geen, Alexander; Graziano, Joseph H.

    2012-01-01

    The objective of this study was to design and evaluate a household-level arsenic education and well water arsenic testing intervention to increase arsenic awareness in Bangladesh. The authors randomly selected 1,000 study respondents located in 20 villages in Singair, Bangladesh. The main outcome was the change in knowledge of arsenic from baseline to follow-up 4 to 6 months after the household received the intervention. This was assessed through a pre- and postintervention quiz concerning kn...

  7. Principles and approaches to increasing radionuclide excretion from human organism under chronical intake

    International Nuclear Information System (INIS)

    The main principles for increasing natural excretion of radioactive substances incorporated by a man are suggested. These are decreasing radionuclide intakes with food, water and phlegm, as well as their absorption from digestion tract. It is suggested to use specific compounds binding individual radionuclides (salt of alginic acid, ferrocene), nonspecific entersorbents (vegetable cellulose; substances containing pectin; carbonaceous sorbent); to enhance radionuclide excretions from places of deposition into blood and later into gastrointestinal tract, urination system, perspiration system. 13 refs

  8. Increasing student success, engagement and retention through a novel approach to mathematics support

    OpenAIRE

    Gallimore, Michael; Stewart, Jill; Lawrence, Jonathan

    2012-01-01

    The ever growing gap between secondary and university level mathematics is now becoming a major concern to higher education institutions. The increase in diversity of students’ background in mathematics, from students who have studied the more traditional A-level programmes to students with BTEC or international qualifications and part-time students who have been out of education for long periods, means that they are often unprepared for the marked shift in levels and catering for all abiliti...

  9. Rejection of Welded Connections According to EN ISO 10675: a New Approach to Increasing Objectivity

    Science.gov (United States)

    Aleshin, N. P.; Galkin, D. I.; Sorokin, A. S.; Khodzhaeva, A. V.

    2016-01-01

    The currently applied criteria of identification of imperfections based on results of Radiographic Testing have no unambiguous description in regulatory documents. Therefore, there is a lack of coherence between opinions of the experts who are interpreting images on radiographic films .Authors suggest dividing images of imperfections into classes, each of which includes imperfections with similar projections on radiographs. This allows to simplify the identification procedure and to increase repeatability of results of the interpretation which is carried out by different experts independently.

  10. Strategies for Increasing the Market Share of Recycled Products—A Games Theory Approach

    Science.gov (United States)

    Batzias, Dimitris F.; Pollalis, Yannis A.

    2009-08-01

    A methodological framework (including 28 activity stages and 10 decision nodes) has been designed under the form of an algorithmic procedure for the development of strategies for increasing the market share of recycled products within a games theory context. A case example is presented referring to a paper market, where a recycling company (RC) is in competition with a virgin-raw-material-using company (VC). The strategies of the VC, for increasing its market share, are the strengthening of (and advertisement based on) the high quality (VC1), the high reliability (VC2), the combination quality and reliability, putting emphasis on the first component (VC3), the combination quality and reliability, putting emphasis on the second component (VC4). The strategies of the RC, for increasing its market share, are proper advertisement based on the low price of produced recycled paper satisfying minimum quality requirements (RC1), the combination of low price with sensitization of the public as regards environmental and materials-saving issues, putting emphasis on the first component (RC2), the same combination, putting emphasis on the second component (RC3). Analysis of all possible situations for the case example under examination is also presented.

  11. Prematurity at birth and increased cardiovascular risk: is a metabolomic approach the right solution?

    Directory of Open Access Journals (Sweden)

    Pier Paolo Bassareo

    2013-04-01

    Full Text Available In recent decades, steady progress in the field of physiopathology and the use of increasingly sophisticated technological procedures have resulted in an increase in the survival rates of babies born preterm. However, some of these individuals, although surviving, may at times be faced with severe consequences. Some conditions may be manifested at an early age (particularly dysmorphisms as well as neurological and ophthalmological conditions, whilst others (namely renal and cardiovascular events, evolve gradually and are manifested only years later. In a number of reports in literature it has been demonstrated how prematurity and consequent low weight at birth are risk factors for developing hypercholesterolemia, arterial hypertension, obesity, type 2 diabetes, QTc interval prolongation at basal electrocardiogram, early endothelial dysfunction, structural and functional cardiac modifications, and increased death rates from coronary heart disease. Even some drugs used in the neonatal management of preterm babies may have a detrimental effect on their future cardiac function. The aim of this narrative review was to overview the up to know few reports about metabolomics (a new and promising technique which allows the systematic study of the complete set of metabolites in a biological sample applied to the identification of a possible future cardiovascular system involvement in subjects born preterm. An outlook of the requirements for future researches has been also discussed.

  12. Novel bioinspired control approaches to increase the stiffness variability in multi-muscle driven joints

    International Nuclear Information System (INIS)

    Antagonistic muscle pairs pulling on a joint are in general able to modulate stiffness through co-activation. Closer analysis of the stiffness, however, shows that, depending on the muscle and joint parameters, domains might occur in joint angle space for which stiffness variation is limited (low stiffness variability) or even impossible (stiffness nodes). As a consequence, stiffness control utilizing pure co-activation might fail. This work presents novel strategies for simultaneous control of torque and stiffness in a hinge joint actuated by two antagonistic muscle pairs. One strategy handles stiffness nodes by shifting them away from the current joint position and thus regaining stiffness controllability. To prevent domains of low stiffness variation, an optimal muscle configuration is sought and finally defined which allows for a maximal stiffness variation across a wide joint angle range. Based on this optimal configuration, four additional control strategies are proposed and tested which deliver stiffnesses and torques comparable to those obtained in the optimal case. The strategies combine torque control and stiffness control by co-activation with novel ideas like activation overflow and an inverse model approach. All strategies are tested in simulation and the results are compared with those of the optimal setup.

  13. Increased co-operation between the IAEA and Euratom. The New Partnership Approach

    International Nuclear Information System (INIS)

    A New Partnership Approach (NPA) between the IAEA and Euratom has been founded to replace the 'observation' and 'Joint Team' regimes, which were found inefficient. The paper highlights the circumstances surrounding the birth of the NPA and the status of its implementation. Under the NPA the IAEA can be cost effective without delegating the inspection activities and the responsibilities essential to the fulfillment of the objectives of safeguards implementation. (The IAEA would perform all the required activities to meet the safeguards criteria and draw independent conclusions). The elements of the NPA are divided into inspection arrangements for various facility types and support activities, and the technical effectiveness of Euratom has enabled the translation of these elements into practical arrangements. Saving of more than 1000 person-days of inspection (PDIs) have been achieved. When fully implemented, the NPA will result in a much reduced inspection effort of about 1000 PDIs, compared to approximately 3100 PDIs which were expended in 1990-1991, in non-nuclear-weapon States of Euratom. The savings accrued are being used in other areas. (author). 4 figs, 1 tab

  14. Does Improved Water Access Increase Child School Attendance? A Quasi-Experimental Approach From Rural Ethiopia

    Science.gov (United States)

    Masuda, Y.; Cook, J.

    2012-12-01

    This paper analyzes the impact of improved water access on child school attendance using two years of primary panel data from a quasi-experimental study in Oromiya, Ethiopia. A predominant form of child labor in rural poor households in least developed countries is water collection. Girls are often the primary water collectors for households, and because of the time intensive nature of water collection improved water access may allow for time to be reallocated to schooling (Rosen and Vincent 1999; Nankhuni and Findeis 2004). Understanding how improved water access may increase schooling for girls has important development policy implications. Indeed, abundant research on returns to education suggests increased schooling for girls is tied to improved future child and maternal health, economic opportunities, and lower fertility rates (Handa 1996; Schultz 1998; Michaelowa 2000). The literature to date finds that improved water access leads to increased schooling; however, there still exists a clear gap in the literature for understanding this relationship for two reasons. First, only four studies have directly examined the relationship between improved water access and schooling in sub-Saharan Africa, and analyses have been limited due to the use of cross-sectional data and research designs (Nankhuni and Findeis 2004; Koolwal and Van de Walle 2010; Ndiritu and Nyangan 2011; Nauges and Strand 2011). Indeed, only two studies have attempted to control for the endogenous nature of water access. Second, all studies use a binary school enrollment indicator from household surveys, which may suffer from response bias and may be an imperfect measure for actual schooling. Respondents may feel pressured to report that their children are enrolled in school if, like in Ethiopia, there are compulsory education laws. This may result in an overestimation of school enrollment. In addition, most children from rural poor households combine work and school, and a binary indicator does

  15. A mathematical approach to increasing the long-term wealth of an agricultural enterprise

    Directory of Open Access Journals (Sweden)

    P. Theron

    2014-01-01

    Full Text Available This study focuses on developing an agricultural investment model based upon proven financial investment portfolio techniques. The model can be used as a tool to diversify agricultural risk over the long-term by optimising the proportion of land allocated to each of the agricultural products, resulting in increased value of the agricultural enterprise. Sensitivity analysis allows the strategist to understand the impact that future prices, gross margins and land availability may have on the long-term sustainability of the farming enterprise.

  16. Assessing the Economic Impact of Minimum Wage Increases on the Washington Economy: A General Equilibrium Approach

    OpenAIRE

    David Holland; Sanjoy Bhattacharjee; Leroy Stodick

    2006-01-01

    Washington voters passed Initiative Measure No. 688 on November 3, 1998. This bill increased Washington’s minimum wage to $5.70 on January 1, 1999.and to $6.50 on January 1, 2000. The Initiative required that future annual changes in Washington’s minimum wage be indexed to inflation in the BLS Consumer Price Index for Urban Wage Earners and Clerical Workers (CPI-W). As of 2005, Washington had the highest minimum wage in the nation at $7.35 per hour. Eleven other states have minimum wages abov...

  17. Economic expansion and increase in labout market formality: a poaching approach

    Directory of Open Access Journals (Sweden)

    Carlos Henrique L. Corseuil

    2012-06-01

    Full Text Available This paper investigates the relationship between economic expansion and the degree of formalization for the Brazilian labour market in the recent period. We present a theoretical framework that attempts to explain this relationship through the dynamics of firms hiring strategies. The main predictions are: the share of formal employment rises as the unemployment rate falls, and that the formal-informal wage gap increases, at least at the beginning of the economic expansion. In the empirical part, we use longitudinal microdata from a Brazilian household survey to check whether these two predictions are confirmed. To a large extent our results corroborate both predictions.

  18. Alpha hemolysin induces an increase of erythrocytes calcium: a FLIM 2-photon phasor analysis approach.

    Directory of Open Access Journals (Sweden)

    Susana Sanchez

    Full Text Available α-Hemolysin (HlyA from Escherichia coli is considered as the prototype of a family of toxins called RTX (repeat in toxin, a group of proteins that share genetic and structural features. HlyA is an important virulence factor in E. coli extraintestinal infections, such as meningitis, septicemia and urinary infections. High concentrations of the toxin cause the lysis of several cells such as erythrocytes, granulocytes, monocytes, endothelial and renal epithelial cells of different species. At low concentrations it induces the production of cytokines and apoptosis. Since many of the subcytolytic effects in other cells have been reported to be triggered by the increase of intracellular calcium, we followed the calcium concentration inside the erythrocytes while incubating with sublytic concentrations of HlyA. Calcium concentration was monitored using the calcium indicator Green 1, 2-photon excitation, and fluorescence lifetime imaging microscopy (FLIM. Data were analyzed using the phasor representation. In this report, we present evidence that, at sublytic concentrations, HlyA induces an increase of calcium concentration in rabbit erythrocytes in the first 10 s. Results are discussed in relation to the difficulties of measuring calcium concentrations in erythrocytes where hemoglobin is present, the contribution of the background and the heterogeneity of the response observed in individual cells.

  19. Uncovering steroidopathy in women with autism: a latent class analysis

    Science.gov (United States)

    2014-01-01

    Background Prenatal exposure to increased androgens has been implicated in both polycystic ovary syndrome (PCOS) and autism spectrum conditions (ASC), suggesting that PCOS may be increased among women with ASC. One study suggested elevated steroidopathic symptoms (‘steroidopathy’) in women with ASC. As the symptoms are not independent, we conducted a latent class analysis (LCA). The objectives of the current study are: (1) to test if these findings replicate in a larger sample; and (2) to use LCA to uncover affected clusters of women with ASC. Methods We tested two groups of women, screened using the Autism Spectrum Quotient - Group 1: n = 415 women with ASC (mean age 36.39 ± 11.98 years); and Group 2: n = 415 controls (mean age 39.96 ± 11.92 years). All participants completed the Testosterone-related Medical Questionnaire online. A multiple-group LCA was used to identify differences in latent class structure between women with ASC and controls. Results There were significant differences in frequency of steroid-related conditions and symptoms between women with ASC and controls. A two-class semi-constrained model best fit the data. Based on response patterns, we identified the classes as ‘Typical’ and ‘Steroidopathic’. The prevalence of the ‘Steroidopathic’ class was significantly increased within the ASC group (ΔG2 = 15, df =1, P = 0.0001). In particular, we confirmed higher frequencies of epilepsy, amenorrhea, dysmenorrhea, severe acne, gender dysphoria, and transsexualism, and differences in sexual preference in women with ASC. Conclusions Women with ASC are at increased risk for symptoms and conditions linked to steroids. LCA revealed this steroidopathy despite the apparent underdiagnosis of PCOS. PMID:24717046

  20. THEORETICAL APPROACH ON THE ROLE OF INNOVATION IN DEVELOPMENT AND INCREASING COMPETITIVENESS OF ENTERPRISES

    Directory of Open Access Journals (Sweden)

    Valentina Ofelia ROBESCU

    2014-06-01

    Full Text Available The intensity of the process of globalization and the new technological advances have resulted in changes in vision and behavior, so that the competitiveness and survival of European companies is linked increasingly more to IT processes efficiency and knowledge. In general, we consider innovation as a boosting factor of progress even in the period of economic and political crisis in which we find ourselves. The need for this research is the interest of companies from Romania towards innovation. In many industrial enterprises, or in the intermediate category of advice, and even among those in public services it has become necessary because of the innovation manager.. In this paper we dealt with the theoretical notion of innovation and impact on the development of enterprises.

  1. [Complication management after liver transplantation. Increasing patient safety by standardized approach and interdisciplinary cooperation].

    Science.gov (United States)

    Houben, P; Gotthardt, D N; Radeleff, B; Sauer, P; Büchler, M W; Schemmer, P

    2015-02-01

    The interdisciplinary management of postoperative complications in liver transplantation is of extreme importance. Due to organ shortage and prioritization of the most severely ill recipients in the model for end-stage liver disease (MELD)-based allocation, both donor and recipient associated morbidity are increasing. An interdisciplinary, structured monitoring concept is essential for the timely identification and specific treatment of postoperative complications. Interdisciplinary clinical rounds, laboratory testing and Doppler ultrasound monitoring of the graft perfusion are as important as comprehensive anti-infection prophylaxis and immunosuppression. Arterial perfusion disorders of any kind, biliary complications and postoperative fluid accumulation demand individualized therapeutic concepts. In summary, the success of liver transplantation depends on the communication and coordinated interdisciplinary cooperation of all disciplines involved. PMID:25604306

  2. Health newscasts for increasing influenza vaccination coverage: an inductive reasoning game approach.

    Directory of Open Access Journals (Sweden)

    Romulus Breban

    Full Text Available Both pandemic and seasonal influenza are receiving more attention from mass media than ever before. Topics such as epidemic severity and vaccination are changing the way in which we perceive the utility of disease prevention. Voluntary influenza vaccination has been recently modeled using inductive reasoning games. It has thus been found that severe epidemics may occur because individuals do not vaccinate and, instead, attempt to benefit from the immunity of their peers. Such epidemics could be prevented by voluntary vaccination if incentives were offered. However, a key assumption has been that individuals make vaccination decisions based on whether there was an epidemic each influenza season; no other epidemiological information is available to them. In this work, we relax this assumption and investigate the consequences of making more informed vaccination decisions while no incentives are offered. We obtain three major results. First, individuals will not cooperate enough to constantly prevent influenza epidemics through voluntary vaccination no matter how much they learned about influenza epidemiology. Second, broadcasting epidemiological information richer than whether an epidemic occurred may stabilize the vaccination coverage and suppress severe influenza epidemics. Third, the stable vaccination coverage follows the trend of the perceived benefit of vaccination. However, increasing the amount of epidemiological information released to the public may either increase or decrease the perceived benefit of vaccination. We discuss three scenarios where individuals know, in addition to whether there was an epidemic, (i the incidence, (ii the vaccination coverage and (iii both the incidence and the vaccination coverage, every influenza season. We show that broadcasting both the incidence and the vaccination coverage could yield either better or worse vaccination coverage than broadcasting each piece of information on its own.

  3. Projected increases in near-surface air temperature over Ontario, Canada: a regional climate modeling approach

    Science.gov (United States)

    Wang, Xiuquan; Huang, Guohe; Liu, Jinliang

    2015-09-01

    As the biggest economy in Canada, the Province of Ontario is now suffering many consequences caused by or associated with global warming, such as frequent and intense heat waves, floods, droughts, and wind gust. Planning of mitigation and adaptation strategies against the changing climate, which requires a better understanding of possible future climate outcomes over the Province in the context of global warming, is of great interest to local policy makers, stakeholders, and development practitioners. Therefore, in this study, high-resolution projections of near-surface air temperature outcomes including mean, maximum, and minimum daily temperature over Ontario are developed, aiming at investigating how the global warming would affect the local climatology of the major cities as well as the spatial patterns of air temperature over the entire Province. The PRECIS modeling system is employed to carry out regional climate ensemble simulations driven by the boundary conditions of a five-member HadCM3-based perturbed-physics ensemble (i.e., HadCM3Q0, Q3, Q10, Q13, and Q15). The ensemble simulations are then synthesized through a Bayesian hierarchical model to develop probabilistic projections of future temperature outcomes with consideration of some uncertain parameters involved in the regional climate modeling process. The results suggest that there would be a consistent increasing trend in the near-surface air temperature with time periods from 2030s to 2080s. The most likely mean temperature in next few decades (i.e., 2030s) would be [-2, 2] °C in northern Ontario, [2, 6] °C in the middle, and [6, 12] °C in the south, afterwards the mean temperature is likely to keep rising by ~ 2 °C per 30-years period. The continuous warming across the Province would drive the lowest mean temperature up to 2 °C in the north and the highest mean temperature up to 16 °C in the south. In addition, the spread of the most likely ranges of future outcomes shows a consistent

  4. Increasing behavioral flexibility? New archaeological and ecological approaches to understanding the Howieson's Poort in Southern Africa

    Science.gov (United States)

    Kandel, A. W.; Bolus, M.; Bruch, A. A.; Haidle, M. N.; Hertler, C.; Märker, M.

    2012-04-01

    The Howieson's Poort (HP) of Southern Africa peaked between 60 and 65 ka and represents a distinct phase of cultural innovation adopted by modern humans during the Middle Stone Age. While researchers generally attribute the rise and fall of the HP to social and environmental causes, neither provides a complete explanation. As patterns at the site level come into focus, large-scale trends explaining the HP expansion remain uncertain. Comparisons with earlier and later cultural phases may provide ways to view the HP phenomenon. The most notable artifacts of the HP lithic industry are standardized, crescent-shaped, backed stone tools called segments that were mounted on wooden shafts in several orientations using mixtures of ground pigment and plant resin to create composite tools such as stone-tipped arrows and spears. The use of ocher, often faceted or striated from grinding and sometimes engraved with geometric patterns, attests to functional and possibly symbolic behavior. Other attributes of the HP include the use of laminar lithic technology to produce blades and a preference for finer grained raw materials. While rare bone tools hint at advanced hunting strategies, other organic finds include geometrically engraved and perforated ostrich eggshell containers and perhaps shell beads, artifacts that serve as markers conveying individual and group status. Analyses of faunal remains supports the possible use of snares and traps, in addition to diverse hunting strategies. Even the sediments testify to changes in behavior that involved the increasing maintenance of living areas. Micromorphological evidence for the construction of bedding layers that were regularly cleaned by burning appears towards the end of the HP. While this combination of behaviors indicates a cultural complexity that did not exist before or after the HP, the reasons for its appearance and the causes of its demise remain unclear. To test the hypotheses of cultural and environmental causality and

  5. A New Approach for Increasing Ascorbyl Palmitate Stability by Addition of Non-irritant Co-antioxidant

    OpenAIRE

    Obreza, Aleš; Pečar, Slavko; Gosenca, Mirjam; GAŠPERLIN, MIRJANA

    2010-01-01

    The aim of this work was to test innovative approach for enhancing ascorbyl palmitate stability in microemulsions for topical application by addition of newly synthesized co-antioxidant 4-(tridecyloxy)benzaldehyde oxime (TDBO) and to investigate its antioxidant activity and finally to evaluate cytotoxicity of TDBO-loaded microemulsions on keratinocyte cells. TDBO significantly increased ascorbyl palmitate stability in oil-dispersed-in-water (o/w) microemulsions, most presumably due to reducti...

  6. Multi-frequency complex network from time series for uncovering oil-water flow structure

    Science.gov (United States)

    Gao, Zhong-Ke; Yang, Yu-Xuan; Fang, Peng-Cheng; Jin, Ning-De; Xia, Cheng-Yi; Hu, Li-Dan

    2015-02-01

    Uncovering complex oil-water flow structure represents a challenge in diverse scientific disciplines. This challenge stimulates us to develop a new distributed conductance sensor for measuring local flow signals at different positions and then propose a novel approach based on multi-frequency complex network to uncover the flow structures from experimental multivariate measurements. In particular, based on the Fast Fourier transform, we demonstrate how to derive multi-frequency complex network from multivariate time series. We construct complex networks at different frequencies and then detect community structures. Our results indicate that the community structures faithfully represent the structural features of oil-water flow patterns. Furthermore, we investigate the network statistic at different frequencies for each derived network and find that the frequency clustering coefficient enables to uncover the evolution of flow patterns and yield deep insights into the formation of flow structures. Current results present a first step towards a network visualization of complex flow patterns from a community structure perspective.

  7. Activation of futile cycles as an approach to increase ethanol yield during glucose fermentation in Saccharomyces cerevisiae.

    Science.gov (United States)

    Semkiv, Marta V; Dmytruk, Kostyantyn V; Abbas, Charles A; Sibirny, Andriy A

    2016-04-01

    An increase in ethanol yield by yeast from the fermentation of conventional sugars such as glucose and sucrose is possible by reducing the production of a key byproduct such as cellular biomass. Previously we have reported that overexpression of PHO8 gene encoding non-specific ATP-hydrolyzing alkaline phosphatase can lead to a decrease in cellular ATP content and to an increase in ethanol yield during glucose fermentation by Saccharomyces cerevisiae. In this work we further report on 2 new successful approaches to reduce cellular levels of ATP that increase ethanol yield and productivity. The first approach is based on the overexpression of the heterologous Escherichia coli apy gene encoding apyrase or SSB1 part of the chaperon that exhibit ATPase activity in yeast. In the second approach we constructed a futile cycle by the overexpression of S. cerevisiae genes encoding pyruvate carboxylase and phosphoenolpyruvate carboxykinase in S. cerevisiae. These genetically engineered strains accumulated more ethanol compared to the wild-type strain during alcoholic fermentation. PMID:26890808

  8. Uncovering the nutritional landscape of food

    CERN Document Server

    Kim, Seunghyeon; Foo, Mathias; Jin, Yong-Su; Kim, Pan-Jun

    2014-01-01

    The study of foods and nutrients is essential for designing healthy diets. This can be facilitated through quantitative, data-driven approaches that utilize massive nutritional information collected for many different foods. Using information from over 1,000 raw foods, we systematically evaluated the nutrient composition of each food in regards to satisfying daily nutritional requirements. Such nutrient balance within a food was quantified herein as nutritional fitness, using the food's frequency of occurrence in nutritionally-adequate food combinations. Nutritional fitness offers prioritization of recommendable foods within a food network, in which foods are connected based on similarities of nutrient compositions. We found a number of key nutrients, such as choline and \\alpha-linolenic acid, whose levels in foods can critically affect the foods' nutritional fitness. Analogously, pairs of nutrients can have the same effect. In fact, two nutrients can impact nutritional fitness synergistically, although the i...

  9. Uncovering Social Network Sybils in the Wild

    OpenAIRE

    Yang, Zhi; Wilson, Christo; Wang, Xiao; Gao, Tingting; Ben Y. Zhao; Dai, Yafei

    2011-01-01

    Sybil accounts are fake identities created to unfairly increase the power or resources of a single malicious user. Researchers have long known about the existence of Sybil accounts in online communities such as file-sharing systems, but have not been able to perform large scale measurements to detect them or measure their activities. In this paper, we describe our efforts to detect, characterize and understand Sybil account activity in the Renren online social network (OSN). We use ground tru...

  10. Uncovering the Hidden Costs of Offshoring

    DEFF Research Database (Denmark)

    Larsen, Marcus M.; Manning, Stephan; Pedersen, Torben

    2013-01-01

    This study investigates estimation errors due to hidden costs—the costs of implementation that are neglected in strategic decision-making processes—in the context of services offshoring. Based on data from the Offshoring Research Network, we find that decision makers are more likely to make cost-estimation...... errors given increasing configuration and task complexity in captive offshoring and offshore outsourcing, respectively. Moreover, we show that experience and a strong orientation toward organizational design in the offshoring strategy reduce the cost-estimation errors that follow from complexity. Our...

  11. The uncovered parity properties of the Czech Koruna

    Czech Academy of Sciences Publication Activity Database

    Derviz, Alexis

    2002-01-01

    Roč. 11, č. 1 (2002), s. 17-37. ISSN 1210-0455 R&D Projects: GA AV ČR KSK1019101 Institutional research plan: CEZ:AV0Z1075907 Keywords : uncovered parity * asset prices * international consumption-based capital asset pricing model Subject RIV: AH - Economics

  12. Uncovering key data points to improve OR profitability.

    Science.gov (United States)

    Stiefel, Robert A; Greenfield, Howard

    2014-03-01

    Using data analysis to target areas for performance improvement in the operating room (OR) involves: regularly monitoring key OR statistics, such as through use of a dashboard, determining the root causes of problems uncovered by the data analysis, making appropriate corrections and continuing to monitor performance. PMID:24701846

  13. Uncovering paradoxes from physicians' experiences of patient-centered ward-round.

    Science.gov (United States)

    Bååthe, Fredrik; Ahlborg, Gunnar; Edgren, Lars; Lagström, Annica; Nilsson, Kerstin

    2016-05-01

    Purpose The purpose of this paper is to uncover paradoxes emerging from physicians' experiences of a patient-centered and team-based ward round, in an internal medicine department. Design/methodology/approach Abductive reasoning relates empirical material to complex responsive processes theory in a dialectical process to further understandings. Findings This paper found the response from physicians, to a patient-centered and team-based ward round, related to whether the new demands challenged or confirmed individual physician's professional identity. Two empirically divergent perspectives on enacting the role of physician during ward round emerged: We-perspective and I-perspective, based on where the physician's professional identity was centered. Physicians with more of a We-perspective experienced challenges with the new round, while physicians with more of an I-perspective experienced alignment with their professional identity and embraced the new round. When identity is challenged, anxiety is aroused, and if anxiety is not catered to, then resistance is likely to follow and changes are likely to be hampered. Practical implications For change processes affecting physicians' professional identity, it is important for managers and change leaders to acknowledge paradox and find a balance between new knowledge that needs to be learnt and who the physician is becoming in this new procedure. Originality/value This paper provides increased understanding about how physicians' professional identity is interacting with a patient-centered ward round. It adds to the knowledge about developing health care in line with recent societal requests and with sustainable physician engagement. PMID:27198705

  14. Uncovering ecosystem service bundles through social preferences.

    Directory of Open Access Journals (Sweden)

    Berta Martín-López

    Full Text Available Ecosystem service assessments have increasingly been used to support environmental management policies, mainly based on biophysical and economic indicators. However, few studies have coped with the social-cultural dimension of ecosystem services, despite being considered a research priority. We examined how ecosystem service bundles and trade-offs emerge from diverging social preferences toward ecosystem services delivered by various types of ecosystems in Spain. We conducted 3,379 direct face-to-face questionnaires in eight different case study sites from 2007 to 2011. Overall, 90.5% of the sampled population recognized the ecosystem's capacity to deliver services. Formal studies, environmental behavior, and gender variables influenced the probability of people recognizing the ecosystem's capacity to provide services. The ecosystem services most frequently perceived by people were regulating services; of those, air purification held the greatest importance. However, statistical analysis showed that socio-cultural factors and the conservation management strategy of ecosystems (i.e., National Park, Natural Park, or a non-protected area have an effect on social preferences toward ecosystem services. Ecosystem service trade-offs and bundles were identified by analyzing social preferences through multivariate analysis (redundancy analysis and hierarchical cluster analysis. We found a clear trade-off among provisioning services (and recreational hunting versus regulating services and almost all cultural services. We identified three ecosystem service bundles associated with the conservation management strategy and the rural-urban gradient. We conclude that socio-cultural preferences toward ecosystem services can serve as a tool to identify relevant services for people, the factors underlying these social preferences, and emerging ecosystem service bundles and trade-offs.

  15. Approach to the evaluation of a patient with an increased serum osmolal gap and high-anion-gap metabolic acidosis.

    Science.gov (United States)

    Kraut, Jeffrey A; Xing, Shelly Xiaolei

    2011-09-01

    An increase in serum osmolality and serum osmolal gap with or without high-anion-gap metabolic acidosis is an important clue to exposure to one of the toxic alcohols, which include methanol, ethylene glycol, diethylene glycol, propylene glycol, or isopropanol. However, the increase in serum osmolal gap and metabolic acidosis can occur either together or alone depending on several factors, including baseline serum osmolal gap, molecular weight of the alcohol, and stage of metabolism of the alcohol. In addition, other disorders, including diabetic or alcoholic ketoacidosis, acute kidney injury, chronic kidney disease, and lactic acidosis, can cause high-anion-gap metabolic acidosis associated with an increased serum osmolal gap and therefore should be explored in the differential diagnosis. It is essential for clinicians to understand the value and limitations of osmolal gap to assist in reaching the correct diagnosis and initiating appropriate treatment. In this teaching case, we present a systematic approach to diagnosing high serum osmolality and increased serum osmolal gap with or without high-anion-gap metabolic acidosis. PMID:21794966

  16. A family group approach to increasing adherence to therapy in HIV-infected youths: results of a pilot project.

    Science.gov (United States)

    Lyon, Maureen E; Trexler, Connie; Akpan-Townsend, Carleen; Pao, Maryland; Selden, Keith; Fletcher, Jean; Addlestone, Irene C; D'Angelo, Lawrence J

    2003-06-01

    This paper describes the development of a novel, pilot program in which a combined family group and peer approach were used to increase adherence to antiretroviral therapy in HIV-infected youths. Twenty-three HIV-positive youths, 15-22 years of age and 23 family members or "treatment buddies" participated in one of three 12-week programs. The intervention had six biweekly family and youth education sessions and six biweekly youth-only education sessions. Devices to increase adherence to antiretroviral therapy such as pill boxes, calendars, and watch alarms were introduced at youth-only sessions. Eighteen of the 23 youths completed a group. Ninety-one percent of youths self-reported increased adherence to medications after completion of a group. Four participants experienced a one-log reduction in viral loads to undetectable levels during the intervention. Two participants continued to decline antiretroviral medications at the end of the intervention and demonstrated no decrease in viral load. Participants tested five devices and rated the multiple alarm watch as the best aid for improving adherence to medication. Family/treatment buddies rated the overall program as highly helpful, citing social support as most valuable. An unanticipated benefit was an increase in other health behaviors, including medical and dental appointments, hepatitis B and influenza immunizations, and referrals to mental health and substance abuse treatment. PMID:12880493

  17. The Tupange Project in Kenya: A Multifaceted Approach to Increasing Use of Long-Acting Reversible Contraceptives

    Science.gov (United States)

    Muthamia, Michael; Owino, Kenneth; Nyachae, Paul; Kilonzo, Margaret; Kamau, Mercy; Otai, Jane; Kabue, Mark; Keyonzo, Nelson

    2016-01-01

    ABSTRACT Background: Long-acting reversible contraceptives (LARCs) are safe and highly effective, and they have higher continuation rates than short-acting methods. Because only a small percentage of sexually active women in Kenya use LARCs, the Tupange project implemented a multifaceted approach to increase uptake of LARCs, particularly among the urban poor. The project included on-site mentoring, whole-site orientation, commodity security, quality improvement, and multiple demand-promotion and service-provision strategies, in the context of wide method choice. We report on activities in Nairobi between July 2011 and December 2014, the project implementation period. Methods: We used a household longitudinal survey of women of reproductive age to measure changes in the contraceptive prevalence rate (CPR) and other family planning-related variables. At baseline in July 2010, 2,676 women were interviewed; about 50% were successfully tracked and interviewed at endline in December 2014. A baseline service delivery point (SDP) survey of 112 health facilities and 303 service providers was conducted in July 2011, and an endline SDP survey was conducted in December 2014 to measure facility-based interventions. The SDP baseline survey was conducted after the household survey, as facilities were selected based on where clients said they obtained services. Results: The project led to significant increases in use of implants and intrauterine devices (IUDs). Uptake of implants increased by 6.5 percentage points, from 2.4% at baseline to 8.9% by endline, and uptake of IUDs increased by 2.1 percentage points, from 2.2% to 4.3%. By the endline survey, 37.7% of clients using pills and injectables at baseline had switched to LARCs. Contraceptive use among the poorest and poor wealth quintiles increased by 20.5 and 21.5 percentage points, respectively, from baseline to endline. Various myths and misconceptions reported about family planning methods declined significantly between

  18. Review on dry reforming of methane, a potentially more environmentally-friendly approach to the increasing natural gas exploitation.

    Science.gov (United States)

    Lavoie, Jean-Michel

    2014-01-01

    With the actual growth of the natural gas industry in the US as well as the potential and availability of this non-renewable carbon source worldwide, reforming of methane gas is getting increasing attention. Methane can be used for the production of heat or electricity, as well, it can be converted to syngas, a building block that could lead to the production of liquid fuels and chemicals, a very promising pathway in light of the increasing price of oil. Amongst the different reforming techniques, dry reforming could represent a very interesting approach both to valorize a cheap source or carbon (CO2) as well as to reduce the overall carbon footprint of the increasing worldwide fossil-based methane consumption. In this short review, attention will be given to the thermodynamics of dry reforming followed by an investigation on dry reforming using heterogeneous catalyst by focusing on the most popular elements used in literature for dry reforming. Attention will as well be given to other emerging techniques that may allow countering at one point the high thermodynamic penalties that accompanies conversion of methane using carbon dioxide. PMID:25426488

  19. Review on dry reforming of methane, a potentially more environmentally-friendly approach to the increasing natural gas exploitation

    Directory of Open Access Journals (Sweden)

    Jean-Michel eLavoie

    2014-11-01

    Full Text Available With the actual growth of the natural gas industry in the US as well as the potential and availability of this non-renewable carbon source worldwide, reforming of methane gas is getting increasing attention. Methane can be used for the production of heat or electricity, as well, it can be converted to syngas, a building block that could lead to the production of liquid fuels and chemical, a very promising pathway in light of the increasing price of oil. Amongst the different reforming techniques, dry reforming could represent a very interesting approach both to valorize a cheap source or carbon (CO2 as well as to reduce the overall carbon footprint of the increasing worldwide fossil-based methane consumption. In this short review, attention will be given on the thermodynamics of dry reforming followed by an investigation on dry reforming using heterogeneous catalyst by focusing on the mots popular elements used in literature for dry reforming. Attention will as well be given to different other emerging techniques that may allow countering at one point the high thermodynamic penalties that accompanies conversion of methane using carbon dioxide.

  20. Uncovering Student Ideas in Astronomy 45 Formative Assessment Probes

    CERN Document Server

    Keeley, Page

    2012-01-01

    What do your students know-or think they know-about what causes night and day, why days are shorter in winter, and how to tell a planet from a star? Find out with this book on astronomy, the latest in NSTA's popular Uncovering Student Ideas in Science series. The 45 astronomy probes provide situations that will pique your students' interest while helping you understand how your students think about key ideas related to the universe and how it operates.

  1. Conditional genome engineering in Toxoplasma gondii uncovers alternative invasion mechanisms

    OpenAIRE

    Andenmatten, Nicole; Egarter, Saskia; Jackson, Allison J.; JULLIEN, Nicolas; Herman, Jean-Paul; Meissner, Markus

    2012-01-01

    We established a conditional site–specific recombination system based on dimerizable Cre–mediated recombination in the apicomplexan parasite Toxoplasma gondii. Using a novel single vector strategy that allows ligand-dependent, efficient removal of a gene of interest, we generated three knockouts of apicomplexan genes considered essential for host-cell invasion. Our findings uncover the existence of an alternative invasion pathway in apicomplexan parasites.

  2. Uncovering the systemic issues that reside in home care

    OpenAIRE

    Giannasi, Wynona

    2012-01-01

    This video clip comprises the Keynote Address: “Uncovering the systemic issues that reside in home care” held at the 21st Annual John K. Friesen Conference, "Innovations in Home Care: A Public Policy Perspective," MAY 16-17, 2012, Vancouver, BC. Presented by Wynona Giannasi, Partner, Howegroup – Public Sector Consultants, Vancouver BC. It is well known that jurisdictions with more comprehensive and integrated home care delivery systems are able to extend independent living for older p...

  3. Malignant Gastroduodenal Obstruction: Treatment with Self-Expanding Uncovered Wallstent

    International Nuclear Information System (INIS)

    Purpose: To retrospectively evaluate the clinical effectiveness of a self-expanding uncovered Wallstent in patients with malignant gastroduodenal obstruction. Materials and Methods: Under combined endoscopic and fluoroscopic guidance, 29 patients with a malignant gastroduodenal stenosis were treated with a self-expanding uncovered metallic Wallstent. A dysphagia score was assessed before and after the intervention to measure the success of this palliative therapy. The dysphagia score ranged between grade 0 to grade 4: grade 0 = able to tolerate solid food, grade 1 = able to tolerate soft food, grade 2 = able to tolerate thick liquids, grade 3 = able to tolerate water or clear fluids, and grade 4 = unable to tolerate anything perorally. Stent patency and patients survival rates were calculated. Results: The insertion of the gastroduodenal stent was technically successful in 28 patients (96.5%). After stenting, 25 patients (86.2%) showed clinical improvement by at least one score point. During follow-up, 22 (78.5%) of 28 patients showed no stent occlusion until death and did not have to undergo any further intervention. In six patients (20.6%), all of whom were treated with secondary stent insertions, occlusion with tumor ingrowth and/or overgrowth was observed after the intervention. The median period of primary stent patency in our study was 240 days. Conclusion: Placement of an uncovered Wallstent is clinically effective in patients with malignant gastroduodenal obstruction. Stent placement is associated with high technical success, good palliation effect, and high durability of stent function.

  4. Increasing resource allocation and research into tobacco control activities: a comprehensive approach including primary prevention, treatment and brief intervention.

    Science.gov (United States)

    Richmond, R

    1993-01-01

    The range of tobacco control activities should be viewed as essential parts of a complex multi-component puzzle. Intervention strategies designed to address tobacco control should be comprehensive and include both primary and secondary prevention activities and be multi-faceted and capable of bringing about change at both the individual and broader social and cultural levels. In this paper I argue for a mutually inclusive framework in which the various components contribute in important and different ways. I examine the prevalence of smoking and identify the high risk groups, then I examine the range of available strategies and present the evidence for their success. I discuss the primary prevention approaches such as warning labels, taxes, price increases, workplace bans, education in schools, mass media and self-help materials, as well as brief interventions and treatment strategies which are conducted at the worksite, general practice and specialized cessation clinics. The areas for future research are delineated for increased resource allocation and include: the best ways to disseminate brief interventions to smokers, methods to motivate smokers; training of health professionals to deliver brief interventions; enhancing quitting and access to existing treatment resources among specific disadvantaged minority groups, e.g. migrants, unemployed youth, the effect on smoking prevalence of warning labels on cigarette packets and price rises on cigarettes. PMID:16818330

  5. Promoting Approaches For Increasing The Cost-Efficiency Of Energy Wood And Pulpwood Harvesting In Young Stands

    Energy Technology Data Exchange (ETDEWEB)

    Oikari, Markku; Palander, Teijo; Ovaskainen, Heikki (Univ. of Joensuu, Faculty of Forest Science FI-80101 Joensuu (Finland)); Kaerhae, Kalle (Metsaeteho Oy , FI-00171 Helsinki (Finland))

    2008-10-15

    Potential approaches for increasing the cost-efficiency of energy wood and industrial roundwood (i.e. pulpwood) harvesting from early thinnings in Finland were ranked in the survey carried out by Metsaeteho Oy and the University of Joensuu. The study was implemented by conducting personal interviews. Research data, based on a total of 40 interviews, were collected during January and February, 2008. In this study, employment, education, and operator issues proved to be of decisive importance for improving energy wood and industrial roundwood harvesting. In the opinion of the respondents, there is considerable potential for increasing the cost-efficiency of wood harvesting by improving harvesting conditions (i.e. effective tending of seedling stands, delaying harvesting operations, pre-clearance of undergrowth, and new wood production methods). The interviewees also stressed that harvesting methods can be rationalized, e.g. multiple-tree handling in industrial roundwood cuttings, integrated pulpwood and energy wood harvesting, and grapple scale measuring. If the most potential methods and techniques were utilized completely in wood harvesting, then there would be significant possibilities for cost savings in young stands. Based on the suggestions of this study, the most profitable guidelines should be utilized immediately

  6. Evaluation of Investment in Renovation to Increase the Quality of Buildings: A Specific Discounted Cash Flow (DCF Approach of Appraisal

    Directory of Open Access Journals (Sweden)

    Giuseppe Bonazzi

    2016-03-01

    Full Text Available The objective of this article is to develop and apply a specific discounting cash flow (DCF approach to evaluate investment in renovation to improve building quality, thus increasing energy efficiency. In this article, we develop and apply a specific net present value (NPV and an internal rate of return (IRR approach to quantify the value created for the owners of the building by the investment in renovation via energy-saving investments that produce positive externalities. The model has an applied interest because, in recent years, a lot of investments in real estate were made by owners in order to increase the green quality of the buildings, and several funds of public aid were provided by the government to stimulate these energy-saving investments. The model proposed here is applied to a case study of a 16-apartment building located in northern Italy considers the model attempts to quantify the initial investment value, the energy savings, the tax deduction of the initial investment and the terminal value of the investment as the increase in building value. The analysis shows that the model is consistent in evaluating investments to improve building quality, and investments within the context of the specific case study considered in the research have IRRs ranging from a minimum of 4.907% to a maximum of 12.980%. It could even be useful to consider a sample of cases to verify whether our results are representative of this specific case study. The model could represent a useful tool for consumers in evaluating their own investments in building renovation, from a stand-alone perspective and even by comparing them with other types of investment. The research could be developed in the future to quantify the social welfare generated by public spending via tax deductions to reduce the costs of investment in energy savings for buildings and could even be applied to new real estate projects in comparing different construction technologies and even

  7. A Markov chain approach to modelling charge exchange processes of an ion beam in monotonically increasing or decreasing potentials

    International Nuclear Information System (INIS)

    A Markov chain method is presented as an alternative approach to Monte Carlo simulations of charge exchange collisions by an energetic hydrogen ion beam with a cold background hydrogen gas. This method was used to determine the average energy of the resulting energetic neutrals along the path of the beam. A comparison with Monte Carlo modelling showed a good agreement but with the advantage that it required much less computing time and produced no numerical noise. In particular, the Markov chain method works well for monotonically increasing or decreasing electrostatic potentials. Finally, a good agreement is obtained with experimental results from Doppler shift spectroscopy on energetic beams from a hollow cathode discharge. In particular, the average energy of ions that undergo charge exchange reaches a plateau that can be well below the full energy that might be expected from the applied voltage bias, depending on the background gas pressure. For example, pressures of ∼20 mTorr limit the ion energy to ∼20% of the applied voltage

  8. Novel graphical approach as fouling pinch for increasing fouling formation period in heat exchanger network (HEN) state of the art

    International Nuclear Information System (INIS)

    In this paper a new graphical tool is proposed for investigation of fouling formation period in heat exchanger networks (HEN). The objective of this paper is increasing the time that HEN can perform its desirable heat transfer operation without required cleaning process. In a typical heat exchanger network, fouling formation rate of some streams is more than other ones. The method obtained in this work is based on given more opportunity for fouling formation for streams with high fouling formation rate. In fact high fouling formation rate streams are replaced with low fouling formation rate streams between different heat exchangers so that more fouling formation opportunity may be given for HEN. Therefore the HEN cleaning time decreases in fixed time period and the high fouling formation streams should pass from the path that the low fouling formation rate stream previously has passed, and inversely. As a result, secondly stream with high fouling formation rate mixes with residues of primary stream (low fouling formation rate stream). Therefore we should consider to adoption and conformability of streams structures (for prevention of streams destruction) and thermal considerations (for desirable heat transfer). Outlet temperatures of hot and cold streams should state in predefined temperatures. For satisfying thermal consideration after streams replacement this approach can be used in plants that cleanliness and its operational costs are most important problem.

  9. Animal models of Huntington's disease: implications in uncovering pathogenic mechanisms and developing therapies

    Institute of Scientific and Technical Information of China (English)

    Lin-hui WANG; Zheng-hong QIN

    2006-01-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder, which is caused by an abnormal expansion of Cytosine Adenine Guanine (CAG) trinucleotide repeat in the gene making huntingtin (Htt). Despite intensive research efforts devoted to investigate molecular mechanisms of pathogenesis, effective therapy for this devastating disease is still not available at present. The development of various animal models of HD has offered alternative approaches in the study of HD molecular pathology. Many HD models, including chemical-induced models and genetic models, mimic some aspects of HD symptoms and pathology. To date, however, there is no ideal model which replicates all of the essential features of neuropathology and progressive motor and cognitive impairments of human HD. As a result, our understanding of molecular mechanisms of pathogenesis in HD is still limited. A new model is needed in order to uncover the pathogenesis and to develop novel therapies for HD. In this review we discussed usefulness and limitations of various animal and cellular models of HD in uncovering molecular mechanisms of pathogenesis and developing novel therapies for HD.

  10. Image stacking approach to increase sensitivity of fluorescence detection using a low cost complementary metal-oxide-semiconductor (CMOS) webcam.

    Science.gov (United States)

    Balsam, Joshua; Bruck, Hugh Alan; Kostov, Yordan; Rasooly, Avraham

    2012-01-01

    Optical technologies are important for biological analysis. Current biomedical optical analyses rely on high-cost, high-sensitivity optical detectors such as photomultipliers, avalanched photodiodes or cooled CCD cameras. In contrast, Webcams, mobile phones and other popular consumer electronics use lower-sensitivity, lower-cost optical components such as photodiodes or CMOS sensors. In order for consumer electronics devices, such as webcams, to be useful for biomedical analysis, they must have increased sensitivity. We combined two strategies to increase the sensitivity of CMOS-based fluorescence detector. We captured hundreds of low sensitivity images using a Webcam in video mode, instead of a single image typically used in cooled CCD devices.We then used a computational approach consisting of an image stacking algorithm to remove the noise by combining all of the images into a single image. While video mode is widely used for dynamic scene imaging (e.g. movies or time-lapse photography), it is not used to capture a single static image, which removes noise and increases sensitivity by more than thirty fold. The portable, battery-operated Webcam-based fluorometer system developed here consists of five modules: (1) a low cost CMOS Webcam to monitor light emission, (2) a plate to perform assays, (3) filters and multi-wavelength LED illuminator for fluorophore excitation, (4) a portable computer to acquire and analyze images, and (5) image stacking software for image enhancement. The samples consisted of various concentrations of fluorescein, ranging from 30 μM to 1000 μM, in a 36-well miniature plate. In the single frame mode, the fluorometer's limit-of-detection (LOD) for fluorescein is ∼1000 μM, which is relatively insensitive. However, when used in video mode combined with image stacking enhancement, the LOD is dramatically reduced to 30 μM, sensitivity which is similar to that of state-of-the-art ELISA plate photomultiplier-based readers. Numerous medical

  11. Participatory approach: from problem identification to setting strategies for increased productivity and sustainability in small scale irrigated agriculture

    Science.gov (United States)

    Habtu, Solomon; Ludi, Eva; Jamin, Jean Yves; Oates, Naomi; Fissahaye Yohannes, Degol

    2014-05-01

    Practicing various innovations pertinent to irrigated farming at local field scale is instrumental to increase productivity and yield for small holder farmers in Africa. However the translation of innovations from local scale to the scale of a jointly operated irrigation scheme is far from trivial. It requires insight on the drivers for adoption of local innovations within the wider farmer communities. Participatory methods are expected to improve not only the acceptance of locally developed innovations within the wider farmer communities, but to allow also an estimation to which extend changes will occur within the entire irrigation scheme. On such a base, more realistic scenarios of future water productivity within an irrigation scheme, which is operated by small holder farmers, can be estimated. Initial participatory problem and innovation appraisal was conducted in Gumselassa small scale irrigation scheme, Ethiopia, from Feb 27 to March 3, 2012 as part of the EAU4FOOD project funded by EC. The objective was to identify and appraise problems which hinder sustainable water management to enhance production and productivity and to identify future research strategies. Workshops were conducted both at local (Community of Practices) and regional (Learning Practice Alliance) level. At local levels, intensive collaboration with farmers using participatory methods produced problem trees and a "Photo Safari" documented a range of problems that negatively impact on productive irrigated farming. A range of participatory methods were also used to identify local innovations. At regional level a Learning Platform was established that includes a wide range of stakeholders (technical experts from various government ministries, policy makers, farmers, extension agents, researchers). This stakeholder group did a range of exercise as well to identify major problems related to irrigated smallholder farming and already identified innovations. Both groups identified similar problems

  12. Indirect radio-chemo-beta therapy: a targeted approach to increase biological efficiency of x-rays based on energy

    Science.gov (United States)

    Oktaria, Sianne; Corde, Stéphanie; Lerch, Michael L. F.; Konstantinov, Konstantin; Rosenfeld, Anatoly B.; Tehei, Moeava

    2015-10-01

    Despite the use of multimodal treatments incorporating surgery, chemotherapy and radiotherapy, local control of gliomas remains a major challenge. The potential of a new treatment approach called indirect radio-chemo-beta therapy using the synergy created by combining methotrexate (MTX) with bromodeoxyuridine (BrUdR) under optimum energy x-ray irradiation is assessed. 9L rat gliosarcoma cells pre-treated with 0.01 μM MTX and/or 10 μM BrUdR were irradiated in vitro with 50 kVp, 125 kVp, 250 kVp, 6 MV and 10 MV x-rays. The cytotoxicity was assessed using clonogenic survival as the radiobiological endpoint. The photon energy with maximum effect was determined using radiation sensitization enhancement factors at 10% clonogenic survival (SER10%). The cell cycle distribution was investigated using flow cytometric analysis with propidium iodide staining. Incorporation of BrUdR in the DNA was detected by the fluorescence of labelled anti-BrUdR antibodies. The radiation sensitization enhancement exhibits energy dependence with a maximum of 2.3 at 125 kVp for the combined drug treated cells. At this energy, the shape of the clonogenic survival curve of the pharmacological agents treated cells changes substantially. This change is interpreted as an increased lethality of the local radiation environment and is attributed to supplemented inhibition of DNA repair. Radiation induced chemo-beta therapy was demonstrated in vitro by the targeted activation of combined pharmacological agents with optimized energy tuning of x-ray beams on 9 L cells. Our results show that this is a highly effective form of chemo-radiation therapy.

  13. Indirect radio-chemo-beta therapy: a targeted approach to increase biological efficiency of x-rays based on energy

    International Nuclear Information System (INIS)

    Despite the use of multimodal treatments incorporating surgery, chemotherapy and radiotherapy, local control of gliomas remains a major challenge. The potential of a new treatment approach called indirect radio-chemo-beta therapy using the synergy created by combining methotrexate (MTX) with bromodeoxyuridine (BrUdR) under optimum energy x-ray irradiation is assessed. 9L rat gliosarcoma cells pre-treated with 0.01 μM MTX and/or 10 μM BrUdR were irradiated in vitro with 50 kVp, 125 kVp, 250 kVp, 6 MV and 10 MV x-rays. The cytotoxicity was assessed using clonogenic survival as the radiobiological endpoint. The photon energy with maximum effect was determined using radiation sensitization enhancement factors at 10% clonogenic survival (SER10%). The cell cycle distribution was investigated using flow cytometric analysis with propidium iodide staining. Incorporation of BrUdR in the DNA was detected by the fluorescence of labelled anti-BrUdR antibodies. The radiation sensitization enhancement exhibits energy dependence with a maximum of 2.3 at 125 kVp for the combined drug treated cells. At this energy, the shape of the clonogenic survival curve of the pharmacological agents treated cells changes substantially. This change is interpreted as an increased lethality of the local radiation environment and is attributed to supplemented inhibition of DNA repair. Radiation induced chemo-beta therapy was demonstrated in vitro by the targeted activation of combined pharmacological agents with optimized energy tuning of x-ray beams on 9 L cells. Our results show that this is a highly effective form of chemo-radiation therapy. (paper)

  14. A new non-invasive approach based on polyhexamethylene biguanide increases the regression rate of HPV infection

    Directory of Open Access Journals (Sweden)

    Gentile Antonio

    2012-09-01

    Full Text Available Abstract Background HPV infection is a worldwide problem strictly linked to the development of cervical cancer. Persistence of the infection is one of the main factors responsible for the invasive progression and women diagnosed with intraepithelial squamous lesions are referred for further assessment and surgical treatments which are prone to complications. Despite this, there are several reports on the spontaneous regression of the infection. This study was carried out to evaluate the effectiveness of a long term polyhexamethylene biguanide (PHMB-based local treatment in improving the viral clearance, reducing the time exposure to the infection and avoiding the complications associated with the invasive treatments currently available. Method 100 women diagnosed with HPV infection were randomly assigned to receive six months of treatment with a PHMB-based gynecological solution (Monogin®, Lo.Li. Pharma, Rome - Italy or to remain untreated for the same period of time. Results A greater number of patients, who received the treatment were cleared of the infection at the two time points of the study (three and six months compared to that of the control group. A significant difference in the regression rate (90% Monogin group vs 70% control group was observed at the end of the study highlighting the time-dependent ability of PHMB to interact with the infection progression. Conclusions The topic treatment with PHMB is a preliminary safe and promising approach for patients with detected HPV infection increasing the chance of clearance and avoiding the use of invasive treatments when not strictly necessary. Trial registration ClinicalTrials.gov Identifier NCT01571141

  15. 3D geological mapping - uncovering the subsurface to increase environmental understanding

    OpenAIRE

    Kessler, Holger; Dearden, Rachel; Mathers, Steve; Peach, Denis

    2012-01-01

    Geological models provide geologists with a mechanism to express their geological knowledge and concepts in an explicit form. The construction of accurate and defensible 3D geological models requires therefore, not only high quality data such as geological maps and borehole records, but also an understanding of geological processes and features. This is a necessity, particularly in complex geological environments, where the data available is unlikely to be sufficient to describ...

  16. Uncovering the overlapping community structure of complex networks in nature and society

    CERN Document Server

    Pálla, G; Farkas, I; Vicsek, T; Palla, Gergely; Derenyi, Imre; Farkas, Illes; Vicsek, Tamas

    2005-01-01

    Many complex systems in nature and society can be described in terms of networks capturing the intricate web of connections among the units they are made of. A key question is how to interpret the global organization of such networks as the coexistence of their structural subunits (communities) associated with more highly interconnected parts. Identifying these a priori unknown building blocks (such as functionally related proteins, industrial sectors and groups of people) is crucial to the understanding of the structural and functional properties of networks. The existing deterministic methods used for large networks find separated communities, whereas most of the actual networks are made of highly overlapping cohesive groups of nodes. Here we introduce an approach to analysing the main statistical features of the interwoven sets of overlapping communities that makes a step towards uncovering the modular structure of complex systems. After defining a set of new characteristic quantities for the statistics of...

  17. Uncovering transcriptional regulation of metabolism by using metabolic network topology

    DEFF Research Database (Denmark)

    Patil, Kiran Raosaheb; Nielsen, Jens

    2005-01-01

    Cellular response to genetic and environmental perturbations is often reflected and/or mediated through changes in the metabolism, because the latter plays a key role in providing Gibbs free energy and precursors for biosynthesis. Such metabolic changes are often exerted through transcriptional...... changes induced by complex regulatory mechanisms coordinating the activity of different metabolic pathways. It is difficult to map such global transcriptional responses by using traditional methods, because many genes in the metabolic network have relatively small changes at their transcription level. We...... therefore developed an algorithm that is based on hypothesis-driven data analysis to uncover the transcriptional regulatory architecture of metabolic networks. By using information on the metabolic network topology from genome-scale metabolic reconstruction, we show that it is possible to reveal patterns in...

  18. DOES UNCOVERED INTEREST RATE PARITY HOLD IN TURKEY?

    Directory of Open Access Journals (Sweden)

    Ozcan Karahan

    2012-01-01

    Full Text Available Most of the earlier empirical studies focusing on developed countries failed to give evidence in favor of the Uncovered Interest Rate Parity (UIP. After intensive financial liberalization processes and mostly preferred free exchange rate regimes, a new area of research starts to involve the investigation whether UIP holds for developing economies differently. Accordingly, we tested the UIP for Turkey’s monthly interest rate and exchange rate data between 2002 and 2011. We run conventional regressions in the form of Ordinary Least Squares (OLS and used a simple Generalized Autoregressive Conditional Heteroskedasticity (GARCH analysis. The empirical results of both methods do not support the validity of UIP for Turkey. Thus, together with most of the earlier empirical studies focusing on developed countries and detecting the invalidity of UIP, we can argue that the experience of Turkey and developed economies are not different.

  19. Uncovering growth-suppressive MicroRNAs in lung cancer

    DEFF Research Database (Denmark)

    Liu, Xi; Sempere, Lorenzo F; Galimberti, Fabrizio;

    2009-01-01

    PURPOSE: MicroRNA (miRNA) expression profiles improve classification, diagnosis, and prognostic information of malignancies, including lung cancer. This study uncovered unique growth-suppressive miRNAs in lung cancer. EXPERIMENTAL DESIGN: miRNA arrays were done on normal lung tissues and...... adenocarcinomas from wild-type and proteasome degradation-resistant cyclin E transgenic mice to reveal repressed miRNAs in lung cancer. Real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays validated these findings. Lung cancer cell lines were derived from each......-malignant human lung tissue bank. RESULTS: miR-34c, miR-145, and miR-142-5p were repressed in transgenic lung cancers. Findings were confirmed by real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays. Similar miRNA profiles occurred in human normal versus malignant lung...

  20. Uncover the Ideology Behind News Reports Through Transitivity Analysis

    Institute of Scientific and Technical Information of China (English)

    董亚男

    2015-01-01

    When people read the reports relating to Occupy Central from different news papers, they get completely different feelings towards the event. To find out how this phenomenon happened, this paper is going to apply transitivity analysis to the news reports. The reports are selected from China Daily, CNN and BBC respectively. To have a deep application of this method, only verbal process wil be taken into consideration. This paper wil discuss the proportion of verbal process from the two sides (Occupy Central people as one side and people against them as the other), the message delivered by the verbal process, the sequence and the transformation of verbal process. The purpose is to uncover the ideology hidden behind the seemingly objective news reports through transitivity analysis.

  1. Online Course Increases Nutrition Professionals' Knowledge, Skills, and Self-Efficacy in Using an Ecological Approach to Prevent Childhood Obesity

    Science.gov (United States)

    Stark, Christina M.; Graham-Kiefer, Meredith L.; Devine, Carol M.; Dollahite, Jamie S.; Olson, Christine M.

    2011-01-01

    Objective: To assess the impact of an online continuing education course on the knowledge, skills, and self-efficacy of nutrition professionals to use an ecological approach to prevent childhood obesity. Design: Quasi-experimental design using intervention and delayed intervention comparison groups with pre/post-course assessments. Setting: Online…

  2. Does plasticity in plant physiological traits explain the rapid increase in water use efficiency? An ecohydrological modeling approach

    Science.gov (United States)

    Mastrotheodoros, Theodoros; Fatichi, Simone; Pappas, Christoforos; Molnar, Peter; Burlando, Paolo

    2016-04-01

    The rise of atmospheric CO2 concentration is expected to stimulate plant productivity by enhancing photosynthesis and reducing stomatal conductance and thus increasing plant water use efficiency (WUE) worldwide. An analysis of eddy covariance flux tower data from 21 forested ecosystems across the north hemisphere detected an unexpectedly large increase in WUE (Keenan et al, 2013), which was six times larger than the increase found by most previous studies based on controlled experiments (e.g., FACE), leaf-scale analyses, and numerical modelling. This increase could be solely attributed to the increase in atmospheric CO2 since other confounding factors were ruled out. Here, we investigate the potential contribution of plant plasticity, reflected in the temporal adjustment of major plant physiological traits, on changes in WUE using the ecohydrological model Tethys and Chloris (T&C). We hypothesize that the increase in WUE can be attributed to small variations in plant physiological traits, undetectable through observations, eventually triggered by the atmospheric CO2 increase. Data from the 21 sites in the above mentioned study are used to force the model. Simulation results with and without plasticity in the physiological traits (i.e., model parameters in our numerical experiments) are compared with the observed trends in WUE. We test several plant adaptation strategies in being effective in explaining the observed increase in WUE using a multifactorial numerical experiment in which we perturb in a systematic way selected plant parameters. Keenan, T. F., Hollinger, D. Y., Bohrer, G., Dragoni, D., Munger, J. W., Schmid, H. P., and Richardson, A. D. (2013). Increase in forest water-use efficiency as atmospheric carbon dioxide concentrations rise. Nature, 499(7458), 324-7.

  3. Real cost reduction and productivity increase in an individual industry: a price-accounting approach in theory and practice

    OpenAIRE

    Bisello, Martina; Opocher, Arrigo

    2013-01-01

    The inter-industry diversity in productivity increase stimulated many studies on the industrial sources of economic growth. Much less efforts have been devoted to the study of the industrial sources of real income increase. Albeit from the standpoint of the economic system these aspects are two sides of the same coin, one can consistently trace back an observable change in real wages (in terms of a certain output) and in capital compensation to its industrial sources only by using data on pri...

  4. Proceedings in uncovering the mechanism behind peroxisome proliferator-induced hepatocarcinogenesis

    International Nuclear Information System (INIS)

    The cancer risk assessment of peroxisome proliferators (PPs) has been a matter of debate for decades. PPs are non-genotoxic carcinogens that cause liver tumours in rodents. There is considerable evidence that humans are refractory to the carcinogenic effect of PPs. Still, some toxicologists argue that these chemicals should be considered carcinogenic until the opposite has been proven. To solve this matter, much work has been dedicated to uncovering the mode of action of PPs. The proceedings are reviewed and it is discussed whether these provide an explanation for the observed interspecies differences and shed a new light on human health risk assessment. The efforts in the past years have significantly increased our understanding of the pathways involved, but have also raised new questions. The question why humans seem to be refractory is yet to be answered. From this point of view, the safety assessment of PPs to humans therefore remains an issue of discussion

  5. Review on dry reforming of methane, a potentially more environmentally-friendly approach to the increasing natural gas exploitation

    OpenAIRE

    Lavoie, Jean-Michel

    2014-01-01

    With the actual growth of the natural gas industry in the US as well as the potential and availability of this non-renewable carbon source worldwide, reforming of methane gas is getting increasing attention. Methane can be used for the production of heat or electricity, as well, it can be converted to syngas, a building block that could lead to the production of liquid fuels and chemicals, a very promising pathway in light of the increasing price of oil. Amongst the different reforming techni...

  6. An input-output approach to analyze the ways to increase total output of energy sectors: The case of Japan

    International Nuclear Information System (INIS)

    The purpose of this study is to analyze the ways to increase total output of Japanese energy sectors in future time. In this study, Input-Output (IO) analysis is employed as a tool of analysis. This study focuses on petroleum refinery products and non-ferrous metals as analyzed sectors. The results show that positive impact observed in export and outside households consumption modifications while opposite impact is given by modification of import. The recommendations suggested based on these results are Japanese government should make breakthroughs so analyzed sector's export activities can increase and they have to careful in conducting import activities related to these sectors

  7. Review on dry reforming of methane, a potentially more environmentally-friendly approach to the increasing natural gas exploitation

    OpenAIRE

    Jean-Michel eLavoie

    2014-01-01

    With the actual growth of the natural gas industry in the US as well as the potential and availability of this non-renewable carbon source worldwide, reforming of methane gas is getting increasing attention. Methane can be used for the production of heat or electricity, as well, it can be converted to syngas, a building block that could lead to the production of liquid fuels and chemical, a very promising pathway in light of the increasing price of oil. Amongst the different reforming techniq...

  8. A microenvironment approach to reducing sedentary time and increasing physical activity of children and adults at a playground

    Science.gov (United States)

    Objective. Test whether a micro-environment park intervention in Grand Forks, ND, movement of seating away from a playground, would increase the physical activity and length of stay of park users. Method. STUDY 1, summer 2012: physical activity of children and adults was assessed during baseline (...

  9. Two Approaches for Using Web Sharing and Photography Assignments to Increase Critical Thinking in the Health Sciences

    Science.gov (United States)

    Walter, Katherine Ott; Baller, Stephanie L.; Kuntz, Aaron M.

    2012-01-01

    Increasing student critical thinking and active engagement with course content is an ongoing challenge in tertiary education. The present article explores the use of photography in two health sciences courses as a catalyst for the encouragement of critical thinking, creativity, engagement, and problem solving. The authors adapted photography…

  10. WWER-440 reactor thermal power increase. Up-to-date approaches to substantiation of the core heat-engineering reliability

    International Nuclear Information System (INIS)

    Increasing the Units power is an urgent problem for nuclear power plants with WWER-440 reactors. Improving the fuel assembly designs and calculated codes creates all prerequisites to fulfil this purpose. The decrease in the core power peaking is reached by using the profiled fuel assemblies, burnable absorber integrated into the fuel, the FA with the modernized interface attachment, modern calculated codes that allows to reduce conservatism of the RP safety substantiation. A wide spectrum of experimental study of behaviour of the fuel having reached burn-up (50-60) MW days / kg U under the transients and accident conditions was carried out, the post-irradiated examination of the fuel assemblies, fuel rods and fuel pellets with four and five annual operating fuel cycle were performed as well and confirmed the high reliability of the fuel, the presence of large margins of the fuel stack state that contributes to reactor operation at the increased power. The results of the carried out experiments on implementing the five and six annual fuel cycles show that the limiting fuel state as to its serviceability in the WWER-440 reactors is far from being reached. Presently there is an experience of the increased power operation of Kola NPP, Units 1, 2, 4 and Rovno NPP, Unit 2. The Loviisa NPP Units are operated at 109 % power. The Russian experts had gained an experience in substantiating the core operation at 108 % power for Paks NPP, Unit 4. In this paper the additional conditions for increasing the power of the Kola NPP, Units 1 and 2 and the main results of substantiation of increase in power of the Paks NPP, Unit 4 up to 1485 MW are presented in details

  11. 16 CFR 1610.34 - Only uncovered or exposed parts of wearing apparel to be tested.

    Science.gov (United States)

    2010-01-01

    ... apparel to be tested. 1610.34 Section 1610.34 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION... § 1610.34 Only uncovered or exposed parts of wearing apparel to be tested. (a) In determining whether an... uncovered or exposed part of such article of wearing apparel shall be tested according to the...

  12. 16 CFR 1611.34 - Only uncovered or exposed parts of wearing apparel to be tested.

    Science.gov (United States)

    2010-01-01

    ... apparel to be tested. 1611.34 Section 1611.34 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION... § 1611.34 Only uncovered or exposed parts of wearing apparel to be tested. In determining whether an... uncovered or exposed part of such article of wearing apparel shall be tested according to the...

  13. Increasing the effectiveness of instrumentation and control training programs using integrated training settings and a systematic approach to training

    International Nuclear Information System (INIS)

    The performance of plant maintenance-related tasks assigned to instrumentation and control (I ampersand C) technicians can be broken down into physical skills required to do the task; resident knowledge of how to do the task; effect of maintenance on plant operating conditions; interactions with other plant organizations such as operations, radiation protection, and quality control; and knowledge of consequences of miss-action. A technician who has learned about the task in formal classroom presentations has not had the advantage of integrating that knowledge with the requisite physical and communication skills; hence, the first time these distinct and vital parts of the task equation are put together is on the job, during initial task performance. On-the-job training provides for the integration of skills and knowledge; however, this form of training is limited by plant conditions, availability of supporting players, and training experience levels of the personnel conducting the exercise. For licensed operations personnel, most nuclear utilities use formal classroom and a full-scope control room simulator to achieve the integration of skills and knowledge in a controlled training environment. TU Electric has taken that same approach into maintenance areas by including identical plant equipment in a laboratory setting for the large portion of training received by maintenance personnel at its Comanche Peak steam electric station. The policy of determining training needs and defining the scope of training by using the systematic approach to training has been highly effective and provided training at a reasonable cost (approximately $18.00/student contact hour)

  14. Finasteride Does Not Increase the Risk of High-grade Prostate Cancer: A Bias-adjusted Modeling Approach

    OpenAIRE

    Redman, Mary W.; Tangen, Catherine M.; Goodman, Phyllis J.; Parnes, Howard; Ford, Leslie G.; Lucia, M. Scott; Coltman, Charles A.; Thompson, Ian M

    2008-01-01

    The Prostate Cancer Prevention Trial found that seven years of administration of finasteride reduced the risk of prostate cancer by 25% but with an apparent increased risk of high grade disease. Subsequent analyses found that finasteride affects cancer detection and improves accuracy of tumor grading at biopsy. We herein estimate the impact of finasteride on the risk of overall and high grade prostate cancer, accounting for these biases. Study endpoints (biopsy-proven cancer or a 7-year end-o...

  15. Assessing the Economic Impact of Energy Price Increases on Washington Agriculture and the Washington Economy: A General Equilibrium Approach

    OpenAIRE

    Holland, David W.; Leroy Stodick; Kathleen Painter

    2007-01-01

    A general equilibrium, multi-sector economic model of the Washington economy was developed to examine the economic impact on the Washington economy, especially the agricultural industries, from increasing energy prices experienced in 2005 and 2006. The energy group includes such fossil fuel-based commodities as gasoline and diesel fuel (refined petroleum products), natural gas, nitrogenous fertilizer, and petrochemical products. The economic model shows how the Washington economy adjusts to t...

  16. Eco-efficient approaches to land management: a case for increased integration of crop and animal production systems

    OpenAIRE

    Wilkins, R.J.

    2007-01-01

    Eco-efficiency is concerned with the efficient and sustainable use of resources in farm production and land management. It can be increased either by altering the management of individual crop and livestock enterprises or by altering the land-use system. This paper concentrates on the effects of crop sequence and rotation on soil fertility and nutrient use efficiency. The potential importance of mixed farming involving both crops and livestock is stressed, particularly when the systems incorp...

  17. Use of Insulin to Increase Epiblast Cell Number: Towards a New Approach for Improving ESC Isolation from Human Embryos

    Directory of Open Access Journals (Sweden)

    Jared M. Campbell

    2013-01-01

    Full Text Available Human embryos donated for embryonic stem cell (ESC derivation have often been cryopreserved for 5–10 years. As a consequence, many of these embryos have been cultured in media now known to affect embryo viability and the number of ESC progenitor epiblast cells. Historically, these conditions supported only low levels of blastocyst development necessitating their transfer or cryopreservation at the 4–8-cell stage. As such, these embryos are donated at the cleavage stage and require further culture to the blastocyst stage before hESC derivation can be attempted. These are generally of poor quality, and, consequently, the efficiency of hESC derivation is low. Recent work using a mouse model has shown that the culture of embryos from the cleavage stage with insulin to day 6 increases the blastocyst epiblast cell number, which in turn increases the number of pluripotent cells in outgrowths following plating, and results in an increased capacity to give rise to ESCs. These findings suggest that culture with insulin may provide a strategy to improve the efficiency with which hESCs are derived from embryos donated at the cleavage stage.

  18. Uncovering the mechanism(s) of deep brain stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Li Gang; Yu Chao; Lin Ling; Lu, Stephen C-Y [Inspiring Technical Laboratory, College of Precision Instruments and Opto-Electronics Engineering, Tianjin University, Tianjin 300072 (China)

    2005-01-01

    Deep brain stimulators, often called 'pacemakers for the brain', are implantable devices which continuously deliver impulse stimulation to specific targeted nuclei of deep brain structure, namely deep brain stimulation (DBS). To date, deep brain stimulation (DBS) is the most effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson's disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been put forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address our present knowledge of the effects of high-frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS.

  19. Uncovering the mechanism(s) of deep brain stimulation

    Science.gov (United States)

    Gang, Li; Chao, Yu; Ling, Lin; C-Y Lu, Stephen

    2005-01-01

    Deep brain stimulators, often called `pacemakers for the brain', are implantable devices which continuously deliver impulse stimulation to specific targeted nuclei of deep brain structure, namely deep brain stimulation (DBS). To date, deep brain stimulation (DBS) is the most effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson's disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been put forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address our present knowledge of the effects of high-frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS.

  20. Uncovering the mechanism(s) of deep brain stimulation

    International Nuclear Information System (INIS)

    Deep brain stimulators, often called 'pacemakers for the brain', are implantable devices which continuously deliver impulse stimulation to specific targeted nuclei of deep brain structure, namely deep brain stimulation (DBS). To date, deep brain stimulation (DBS) is the most effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson's disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been put forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address our present knowledge of the effects of high-frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS

  1. eHCM: Resources Reduction & Demand Increase, cover the gap by a managerial approach powered by an IT solutions.

    Science.gov (United States)

    Buccioli, Matteo; Agnoletti, Vanni; Padovani, Emanuele; Perger, Peter

    2014-01-01

    The economic and financial crisis has also had an important impact on the healthcare sector. Available resources have decreased, while at the same time costs as well as demand for healthcare services are on the rise. This coalescing negative impact on availability of healthcare resources is exacerbated even further by a widespread ignorance of management accounting matters. Little knowledge about costs is a strong source of costs augmentation. Although it is broadly recognized that cost accounting has a positive impact on healthcare organizations, it is not widespread adopted. Hospitals are essential components in providing overall healthcare. Operating rooms are critical hospital units not only in patient safety terms but also in expenditure terms. Understanding OR procedures in the hospital provides important information about how health care resources are used. There have been several scientific studies on management accounting in healthcare environments and more than ever there is a need for innovation, particularly by connecting business administration research findings to modern IT tools. IT adoption constitutes one of the most important innovation fields within the healthcare sector, with beneficial effects on the decision making processes. The e-HCM (e-Healthcare Cost Management) project consists of a cost calculation model which is applicable to Business Intelligence. The cost calculation approach comprises elements from both traditional cost accounting and activity-based costing. Direct costs for all surgical procedures can be calculated through a seven step implementation process. PMID:25160327

  2. Eco-efficient approaches to land management: a case for increased integration of crop and animal production systems.

    Science.gov (United States)

    Wilkins, R J

    2008-02-12

    Eco-efficiency is concerned with the efficient and sustainable use of resources in farm production and land management. It can be increased either by altering the management of individual crop and livestock enterprises or by altering the land-use system. This paper concentrates on the effects of crop sequence and rotation on soil fertility and nutrient use efficiency. The potential importance of mixed farming involving both crops and livestock is stressed, particularly when the systems incorporate biological nitrogen fixation and manure recycling. There is, however, little evidence that the trend in developed countries to farm-level specialization is being reduced. In some circumstances legislation to restrict diffuse pollution may provide incentives for more diverse eco-efficient farming and in other circumstances price premia for produce from eco-efficient systems, such as organic farming, and subsidies for the provision of environmental services may provide economic incentives for the adoption of such systems. However, change is likely to be most rapid where the present systems lead to obvious reductions in the productive potential of the land, such as in areas experiencing salinization. In other situations, there is promise that eco-efficiency could be increased on an area-wide basis by the establishment of linkages between farms of contrasting type, particularly between specialist crop and livestock farms, with contracts for the transfer of manures and, to a lesser extent, feeds. PMID:17652073

  3. Systematic Triple-Mutant Analysis Uncovers Functional Connectivity between Pathways Involved in Chromosome Regulation

    Directory of Open Access Journals (Sweden)

    James E. Haber

    2013-06-01

    Full Text Available Genetic interactions reveal the functional relationships between pairs of genes. In this study, we describe a method for the systematic generation and quantitation of triple mutants, termed triple-mutant analysis (TMA. We have used this approach to interrogate partially redundant pairs of genes in S. cerevisiae, including ASF1 and CAC1, two histone chaperones. After subjecting asf1Δ cac1Δ to TMA, we found that the Swi/Snf Rdh54 protein compensates for the absence of Asf1 and Cac1. Rdh54 more strongly associates with the chromatin apparatus and the pericentromeric region in the double mutant. Moreover, Asf1 is responsible for the synthetic lethality observed in cac1Δ strains lacking the HIRA-like proteins. A similar TMA was carried out after deleting both CLB5 and CLB6, cyclins that regulate DNA replication, revealing a strong functional connection to chromosome segregation. This approach can reveal functional redundancies that cannot be uncovered through traditional double-mutant analyses.

  4. Plant Phenotyping using Probabilistic Topic Models: Uncovering the Hyperspectral Language of Plants.

    Science.gov (United States)

    Wahabzada, Mirwaes; Mahlein, Anne-Katrin; Bauckhage, Christian; Steiner, Ulrike; Oerke, Erich-Christian; Kersting, Kristian

    2016-01-01

    Modern phenotyping and plant disease detection methods, based on optical sensors and information technology, provide promising approaches to plant research and precision farming. In particular, hyperspectral imaging have been found to reveal physiological and structural characteristics in plants and to allow for tracking physiological dynamics due to environmental effects. In this work, we present an approach to plant phenotyping that integrates non-invasive sensors, computer vision, as well as data mining techniques and allows for monitoring how plants respond to stress. To uncover latent hyperspectral characteristics of diseased plants reliably and in an easy-to-understand way, we "wordify" the hyperspectral images, i.e., we turn the images into a corpus of text documents. Then, we apply probabilistic topic models, a well-established natural language processing technique that identifies content and topics of documents. Based on recent regularized topic models, we demonstrate that one can track automatically the development of three foliar diseases of barley. We also present a visualization of the topics that provides plant scientists an intuitive tool for hyperspectral imaging. In short, our analysis and visualization of characteristic topics found during symptom development and disease progress reveal the hyperspectral language of plant diseases. PMID:26957018

  5. Multiple omics uncovers host-gut microbial mutualism during prebiotic fructooligosaccharide supplementation.

    Science.gov (United States)

    Kato, Tamotsu; Fukuda, Shinji; Fujiwara, Akemi; Suda, Wataru; Hattori, Masahira; Kikuchi, Jun; Ohno, Hiroshi

    2014-10-01

    Fructooligosaccharide (FOS), a prebiotic well known for its health-promoting properties, can improve the human gut ecosystem most likely through changes in its microbial composition. However, the detailed mechanism(s) of action of FOS in the modulation of the gut ecosystem remain(s) obscure. Traditional methods of profiling microbes and metabolites could barely show any significant features due to the existence of large interindividual differences, but our novel microbe-metabolite correlation approach, combined with faecal immunoglobulin A (IgA) measurements, has revealed that the induction of mucosal IgA by FOS supplementation correlated with the presence of specific bacteria. Furthermore, the metabolic dynamics of butyrate, L-phenylalanine, L-lysine and tyramine were positively correlated with that of these bacteria and IgA production, whereas p-cresol was negatively correlated. Taken together, our focused intraindividual analysis with omics approaches is a powerful strategy for uncovering the gut molecular network and could provide a new vista for understanding the human gut ecosystem. PMID:24848698

  6. Plant Phenotyping using Probabilistic Topic Models: Uncovering the Hyperspectral Language of Plants

    Science.gov (United States)

    Wahabzada, Mirwaes; Mahlein, Anne-Katrin; Bauckhage, Christian; Steiner, Ulrike; Oerke, Erich-Christian; Kersting, Kristian

    2016-01-01

    Modern phenotyping and plant disease detection methods, based on optical sensors and information technology, provide promising approaches to plant research and precision farming. In particular, hyperspectral imaging have been found to reveal physiological and structural characteristics in plants and to allow for tracking physiological dynamics due to environmental effects. In this work, we present an approach to plant phenotyping that integrates non-invasive sensors, computer vision, as well as data mining techniques and allows for monitoring how plants respond to stress. To uncover latent hyperspectral characteristics of diseased plants reliably and in an easy-to-understand way, we “wordify” the hyperspectral images, i.e., we turn the images into a corpus of text documents. Then, we apply probabilistic topic models, a well-established natural language processing technique that identifies content and topics of documents. Based on recent regularized topic models, we demonstrate that one can track automatically the development of three foliar diseases of barley. We also present a visualization of the topics that provides plant scientists an intuitive tool for hyperspectral imaging. In short, our analysis and visualization of characteristic topics found during symptom development and disease progress reveal the hyperspectral language of plant diseases. PMID:26957018

  7. Theoretical Explanations of Increasing Childlessness – Divergent Approaches and the Integrating Potential of the Frame Selection Theory

    Directory of Open Access Journals (Sweden)

    Dr. Jan Eckhard

    2014-02-01

    Full Text Available In order to explain the increasing childlessness in numerous European countries since the 1960s, research points to sociocultural changes on the one hand and rising costs of family formation on the other hand. Yet, there is no comprehensive theory capable of integrating both causes and their interaction. This paper discusses the possibilities of an integrative model which is based on frame selection theory. The model refers to decisions in relationships and discusses the interaction between sociocultural orientations and structural incentives. The resulting hypothesis that the effects of incentives on family formation depend on the situational compatibility of a family-framed relationship perception is subsequently empirically tested using the German family survey panel (Familiensurvey.

  8. Uncovering Multiple Populations in Globular Clusters with Washington Photometry

    Science.gov (United States)

    Geisler, Douglas; Cummings, Jeff; Villanova, Sandro; Carraro, Giovanni

    2015-01-01

    Globular Clusters (GCs), long considered as ideal Simple Stellar Populations, are now known to harbor a wide variety of chemical inhomogeneities. Multiple populations (MP) are being found in a growing number of Galactic globular clusters (GCs) via both photometric and spectroscopic techniques. Indeed, it has been suggested that a GC is an object that possesses MP. A definitive investigation of MP in GCs will undoubtedly provide a profound improvement in our understanding of their formation and evolution.However, most studies employ either high resolution VLT spectroscopy, HST photometry or inefficient filters from the ground. A ground-based photometric system which is both efficient and effective would be especially excellent for uncovering MP. We demonstrate that the Washington system meets these goals. The Washington C filter, in addition to being specifically designed for the purpose of detecting MPs, is both much broader and redder than competing UV filters, making it far more efficient at detecting MPs and much less sensitive to reddening and extinction.Our analysis of the well-studied GC NGC 1851 shows indeed that the C filter is both very efficient and effective at detecting its previously discovered MPs in the RGB and SGB, using relatively little telescope time on only a 1-meter telescope. Remarkably, we have also detected an intrinsically broad MS best characterized by two distinct but heavily overlapping populations that cannot be explained by binaries, field stars, or photometric errors. Detailed analysis shows that the MS distribution is in very good agreement with that seen on the RGB. This is the first time MPs in a MS have been discovered from the ground, and just as strikingly, using only a 1-meter telescope. The Washington system thus proves to be a very powerful tool for investigating MPs, and holds particular promise for extragalactic objects where photons are limited.

  9. The response of ecosystem carbon pools to management approaches that increase the growth of loblolly pine (Pinus taeda L.)

    Science.gov (United States)

    Vogel, J. G.; Bacon, A. R.; Bracho, R. G.; Grunwald, S.; Gonzalez-Benecke, C. A.; Jokela, E. J.; Markewitz, D.; Cucinella, J.; Akers, K.; Ross, C. W.; Peter, G. F.; Fox, T. D.; Martin, T.; Kane, M.

    2015-12-01

    Extending from Virginia to east Texas in the southeastern United States, managed pine forests are an important component of the region's carbon cycle. One objective of the Pine Integrated Network: Education, Mitigation, and Adaptation project (PINEMAP) is to improve estimates of how ecosystem carbon pools respond to the management strategies used to increase the growth of loblolly pine forests. Experimental studies (108 total) that had historically been used to understand forest productivity and stand dynamics by university-forest industry cooperatives have now been measured for the carbon stored in the trees, coarse-wood, forest floor, understory and soils to 1-meter (0-10 cm, 10-20 cm, 20-50 cm, and 50-100 cm). The age of the studied forests ranged from 4-26 years at the time of sampling, with 26 years very near the period when these forests are commonly harvested. The study sites encapsulated a wide regional range in precipitation (1080 mm -1780 mm) and potential evapotranspiration (716 mm - 1200 mm). The most prevalent three soil orders measured were Ultisols (62%), Alfisols (19%), and Spodosols (10%) with Entisols, Inceptisols and 1 Histosol making up the remainder (9%). Across all study sites, 455 experimental plots were measured. The plots had as a treatment either fertilization, competition control, and stand density control (thinning), including every possible combination of treatments and also 'no treatment'. The most common treatment regime, at 36% of the total number of plots, was the combination of competition control, fertilization, and thinning. The distribution of treatments relative to soils and climate prevented a simple analysis of single treatment effects and instead necessitated an examination how the carbon accumulation rate in wood, which is commonly measured and modeled in these forests, corresponded to the response of other C pools (e.g. forest floor and soil).

  10. Uncovering the interaction between empathetic pain and cognition.

    Science.gov (United States)

    Hu, Kesong; Fan, Zhiwei; He, Shuchang

    2015-11-01

    Recent studies have demonstrated that empathizing with pain involves both cognitive and affective components of pain. How does empathetic pain impact cognition? To investigate this question, in the present study, participants performed a classic color-word Stroop task that followed a pain portraying or a corresponding control image. We found that observing pain experience in another had a basic slowing down effect on Reaction times (RTs) during neutral Stroop trials. Further, it affected cognition in a way that it decreased interference and increased facilitation. Moreover, our findings revealed that RTs during the incongruent and congruent trials were essentially unchanged by pain observing (empathy vs. control). The data are best accounted by a two-opposing effect model that empathetic pain impacts cognition through two different ways: it slows down performance in general, and facilitates performance during incongruent and congruent trials in particular. In this way, the present study also lends support to an idea that all components of empathy should be understood from an integrative approach. PMID:25476997

  11. Acetabular Dysplasia and Surgical Approaches Other Than Direct Anterior Increases Risk for Malpositioning of the Acetabular Component in Total Hip Arthroplasty

    DEFF Research Database (Denmark)

    Gromov, Kirill; Greene, Meridith E; Huddleston, James I;

    2016-01-01

    BACKGROUND: Persistent acetabular dysplasia (AD) after periacetabular osteotomy has been hypothesized to increase the risk for malpositioning of the acetabular component. In this study, we investigate whether AD is an independent risk factor for cup malpositioning during primary total hip...... arthroplasty (THA). METHODS: Patient demographics, surgical approach, presence of AD assessed using the lateral center-edge angle, and acetabular cup positioning determined using Martell Hip Analysis Suite were investigated in 836 primary THA patients enrolled in a prospective multicenter study. RESULTS: We...

  12. Nordic Power market integration : a market based approach to the price effects of increased Nordic continental power trade in the Nordic market

    OpenAIRE

    Boge, Mathias Krogh

    2012-01-01

    Based on historical market data for 2011 this thesis models estimated effects that increased Nordic-Continental power trade potential would have had on trade and on Nordic prices during this year. The model used differs from most other models used to estimate trade effects as it focuses on realized market data contrasted to the more commonly used fundamental bottom up model of the power market. The approach used in this work suggests that one extra interconnector combined with ...

  13. Uncovering the genetic landscape for multiple sleep-wake traits.

    Directory of Open Access Journals (Sweden)

    Christopher J Winrow

    Full Text Available Despite decades of research in defining sleep-wake properties in mammals, little is known about the nature or identity of genes that regulate sleep, a fundamental behaviour that in humans occupies about one-third of the entire lifespan. While genome-wide association studies in humans and quantitative trait loci (QTL analyses in mice have identified candidate genes for an increasing number of complex traits and genetic diseases, the resources and time-consuming process necessary for obtaining detailed quantitative data have made sleep seemingly intractable to similar large-scale genomic approaches. Here we describe analysis of 20 sleep-wake traits from 269 mice from a genetically segregating population that reveals 52 significant QTL representing a minimum of 20 genomic loci. While many (28 QTL affected a particular sleep-wake trait (e.g., amount of wake across the full 24-hr day, other loci only affected a trait in the light or dark period while some loci had opposite effects on the trait during the light vs. dark. Analysis of a dataset for multiple sleep-wake traits led to previously undetected interactions (including the differential genetic control of number and duration of REM bouts, as well as possible shared genetic regulatory mechanisms for seemingly different unrelated sleep-wake traits (e.g., number of arousals and REM latency. Construction of a Bayesian network for sleep-wake traits and loci led to the identification of sub-networks of linkage not detectable in smaller data sets or limited single-trait analyses. For example, the network analyses revealed a novel chain of causal relationships between the chromosome 17@29cM QTL, total amount of wake, and duration of wake bouts in both light and dark periods that implies a mechanism whereby overall sleep need, mediated by this locus, in turn determines the length of each wake bout. Taken together, the present results reveal a complex genetic landscape underlying multiple sleep-wake traits

  14. 78 FR 65711 - Uncovered Innerspring Units From China, South Africa, and Vietnam Institution of Five-Year Reviews

    Science.gov (United States)

    2013-11-01

    ... orders on imports of uncovered innerspring units from South Africa and Vietnam (73 FR 75390 and 75391... uncovered innerspring units from China (74 FR 7661). The Commission is conducting reviews to determine... COMMISSION Uncovered Innerspring Units From China, South Africa, and Vietnam Institution of Five-Year...

  15. Uncovering molecular relaxation processes with nonlinear spectroscopies in the deep UV

    International Nuclear Information System (INIS)

    Highlights: • We discuss the outlook for multidimensional spectroscopies in the deep UV. • Photophysics are examined in small DNA components at cryogenic temperatures. • Wavepacket motions are detected in ring-opening systems with 2DUV spectroscopy. • Measurements of electronic wavepacket motions in molecules are proposed. - Abstract: Nonlinear laser spectroscopies in the deep UV spectral range are motivated by studies of biological systems and elementary processes in small molecules. This perspective article discusses recent technical advances in this area with a particular emphasis on diffractive optic based approaches to four-wave mixing spectroscopies. Applications to two classes of systems illustrate present experimental capabilities. First, experiments on DNA components at cryogenic temperatures are used to uncover features of excited state potential energy surfaces and vibrational cooling mechanisms. Second, sub-200 fs internal conversion processes and coherent wavepacket motions are investigated in cyclohexadiene and α-terpinene. Finally, we propose new experimental directions that combine methods for producing few-cycle UV laser pulses in noble gases with incoherent detection methods (e.g., photoionization) in experiments with time resolution near a singlefemtosecond. These measurements are motivated by knowledge of extremely fast non-adiabatic dynamics and the resolution of electronic wavepacket motions in molecules

  16. Uncovering Special Nuclear Materials by Low-energy Nuclear Reaction Imaging

    Science.gov (United States)

    Rose, P. B.; Erickson, A. S.; Mayer, M.; Nattress, J.; Jovanovic, I.

    2016-04-01

    Weapons-grade uranium and plutonium could be used as nuclear explosives with extreme destructive potential. The problem of their detection, especially in standard cargo containers during transit, has been described as “searching for a needle in a haystack” because of the inherently low rate of spontaneous emission of characteristic penetrating radiation and the ease of its shielding. Currently, the only practical approach for uncovering well-shielded special nuclear materials is by use of active interrogation using an external radiation source. However, the similarity of these materials to shielding and the required radiation doses that may exceed regulatory limits prevent this method from being widely used in practice. We introduce a low-dose active detection technique, referred to as low-energy nuclear reaction imaging, which exploits the physics of interactions of multi-MeV monoenergetic photons and neutrons to simultaneously measure the material’s areal density and effective atomic number, while confirming the presence of fissionable materials by observing the beta-delayed neutron emission. For the first time, we demonstrate identification and imaging of uranium with this novel technique using a simple yet robust source, setting the stage for its wide adoption in security applications.

  17. Uncovering Special Nuclear Materials by Low-energy Nuclear Reaction Imaging

    Science.gov (United States)

    Rose, P. B.; Erickson, A. S.; Mayer, M.; Nattress, J.; Jovanovic, I.

    2016-01-01

    Weapons-grade uranium and plutonium could be used as nuclear explosives with extreme destructive potential. The problem of their detection, especially in standard cargo containers during transit, has been described as “searching for a needle in a haystack” because of the inherently low rate of spontaneous emission of characteristic penetrating radiation and the ease of its shielding. Currently, the only practical approach for uncovering well-shielded special nuclear materials is by use of active interrogation using an external radiation source. However, the similarity of these materials to shielding and the required radiation doses that may exceed regulatory limits prevent this method from being widely used in practice. We introduce a low-dose active detection technique, referred to as low-energy nuclear reaction imaging, which exploits the physics of interactions of multi-MeV monoenergetic photons and neutrons to simultaneously measure the material’s areal density and effective atomic number, while confirming the presence of fissionable materials by observing the beta-delayed neutron emission. For the first time, we demonstrate identification and imaging of uranium with this novel technique using a simple yet robust source, setting the stage for its wide adoption in security applications. PMID:27087555

  18. Unexpected novel relational links uncovered by extensive developmental profiling of nuclear receptor expression.

    Directory of Open Access Journals (Sweden)

    Stéphanie Bertrand

    2007-11-01

    Full Text Available Nuclear receptors (NRs are transcription factors that are implicated in several biological processes such as embryonic development, homeostasis, and metabolic diseases. To study the role of NRs in development, it is critically important to know when and where individual genes are expressed. Although systematic expression studies using reverse transcriptase PCR and/or DNA microarrays have been performed in classical model systems such as Drosophila and mouse, no systematic atlas describing NR involvement during embryonic development on a global scale has been assembled. Adopting a systems biology approach, we conducted a systematic analysis of the dynamic spatiotemporal expression of all NR genes as well as their main transcriptional coregulators during zebrafish development (101 genes using whole-mount in situ hybridization. This extensive dataset establishes overlapping expression patterns among NRs and coregulators, indicating hierarchical transcriptional networks. This complete developmental profiling provides an unprecedented examination of expression of NRs during embryogenesis, uncovering their potential function during central nervous system and retina formation. Moreover, our study reveals that tissue specificity of hormone action is conferred more by the receptors than by their coregulators. Finally, further evolutionary analyses of this global resource led us to propose that neofunctionalization of duplicated genes occurs at the levels of both protein sequence and RNA expression patterns. Altogether, this expression database of NRs provides novel routes for leading investigation into the biological function of each individual NR as well as for the study of their combinatorial regulatory circuitry within the superfamily.

  19. Uncovering Special Nuclear Materials by Low-energy Nuclear Reaction Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Rose Jr., P.B.; Erickson, A. S.; Mayer, Michael F.; Nattress, J.; Jovanovic , I

    2016-04-18

    Weapons-grade uranium and plutonium could be used as nuclear explosives with extreme destructive potential. The problem of their detection, especially in standard cargo containers during transit, has been described as “searching for a needle in a haystack” because of the inherently low rate of spontaneous emission of characteristic penetrating radiation and the ease of its shielding. Currently, the only practical approach for uncovering well-shielded special nuclear materials is by use of active interrogation using an external radiation source. However, the similarity of these materials to shielding and the required radiation doses that may exceed regulatory limits prevent this method from being widely used in practice. We introduce a low-dose active detection technique, referred to as low-energy nuclear reaction imaging, which exploits the physics of interactions of multi-MeV monoenergetic photons and neutrons to simultaneously measure the material’s areal density and effective atomic number, while confirming the presence of fissionable materials by observing the beta-delayed neutron emission. For the first time, we demonstrate identification and imaging of uranium with this novel technique using a simple yet robust source, setting the stage for its wide adoption in security applications.

  20. 40 CFR 141.714 - Requirements for uncovered finished water storage facilities.

    Science.gov (United States)

    2010-07-01

    ... Treatment for Cryptosporidium Treatment Technique Requirements § 141.714 Requirements for uncovered finished... of at least 4-log virus, 3-log Giardia lamblia, and 2-log Cryptosporidium using a protocol approved... treatment technique requirement. Requirements for Microbial Toolbox Components...

  1. Novel resistance functions uncovered using functional metagenomic investigations of resistance reservoirs

    Directory of Open Access Journals (Sweden)

    Erica C. Pehrsson

    2013-06-01

    Full Text Available Rates of infection with antibiotic-resistant bacteria have increased precipitously over the past several decades, with far-reaching healthcare and societal costs. Recent evidence has established a link between antibiotic resistance genes in human pathogens and those found in non-pathogenic, commensal, and environmental organisms, prompting deeper investigation of natural and human-associated reservoirs of antibiotic resistance. Functional metagenomic selections, in which shotgun-cloned DNA fragments are selected for their ability to confer survival to an indicator host, have been increasingly applied to the characterization of many antibiotic resistance reservoirs. These experiments have demonstrated that antibiotic resistance genes are highly diverse and widely distributed, many times bearing little to no similarity to known sequences. Through unbiased selections for survival to antibiotic exposure, functional metagenomics can improve annotations by reducing the discovery of false-positive resistance and by allowing for the identification of previously unrecognizable resistance genes. In this review, we summarize the novel resistance functions uncovered using functional metagenomic investigations of natural and human-impacted resistance reservoirs. Examples of novel antibiotic resistance genes include those highly divergent from known sequences, those for which sequence is entirely unable to predict resistance function, bifunctional resistance genes, and those with unconventional, atypical resistance mechanisms. Overcoming antibiotic resistance in the clinic will require a better understanding of existing resistance reservoirs and the dissemination networks that govern horizontal gene exchange, informing best practices to limit the spread of resistance-conferring genes to human pathogens.

  2. Uncovering MIT wind myths through micro-climatological CFD analysis

    CERN Document Server

    Kalmikov, Alexander

    2013-01-01

    Popular campus myths of unusually strong pedestrian level winds are investigated with a Computational Fluid Dynamics (CFD) approach. The numerical simulations confirm the existence of the reported phenomena and provide a qualitative explanation of their physical mechanisms.

  3. Truth concealed behind "Zero Increase of Total Water Use" and coordination approach of socio-economic and eco-environmental water uses in the Weihe River Basin, China

    Science.gov (United States)

    Jia, Y.; Wei, N.; Hao, C.; You, J.; Niu, C.; Qiu, Y.

    2014-09-01

    The water resources situation in the water-stressed Weihe River Basin, China, is more serious now than ever before because of a decrease in water resources and socio-economic development. A "Zero increase of socio-economic water use" in recent years gives people a wrong understanding and conceals the water crisis in the basin because the socio-economic water consumption has actually increased. Water use for the hydro-ecological system has been greatly reduced by a decrease in water resources and socio-economic water consumption increase. New concepts of hierarchical water uses for every sector and water consumption control are suggested for coordinating water uses of the socio-economy and ecosystems in the water-stressed basin. The traditional water resources allocation and regulation in China usually set up a priority sequence for water use sectors. Generally speaking, domestic water use has the highest priority and a highest guarantee rate, followed by industrial water use, irrigation and lastly ecological water use. The concept of hierarchical water use for every sector is to distinguish the water use of every sector into minimum part, appropriate part, and expected extra part with different guarantee rates, and the minimum parts of all sectors should be first guaranteed. By applying a water allocation model, we compared the water allocation results of the traditional approach and the newly suggested approach. Although further study is desired, the results are believed to be of an important referential value to sustainable development in the basin.

  4. Step selection techniques uncover the environmental predictors of space use patterns in flocks of Amazonian birds.

    Science.gov (United States)

    Potts, Jonathan R; Mokross, Karl; Stouffer, Philip C; Lewis, Mark A

    2014-12-01

    Understanding the behavioral decisions behind animal movement and space use patterns is a key challenge for behavioral ecology. Tools to quantify these patterns from movement and animal-habitat interactions are vital for transforming ecology into a predictive science. This is particularly important in environments undergoing rapid anthropogenic changes, such as the Amazon rainforest, where animals face novel landscapes. Insectivorous bird flocks are key elements of avian biodiversity in the Amazonian ecosystem. Therefore, disentangling and quantifying the drivers behind their movement and space use patterns is of great importance for Amazonian conservation. We use a step selection function (SSF) approach to uncover environmental drivers behind movement choices. This is used to construct a mechanistic model, from which we derive predicted utilization distributions (home ranges) of flocks. We show that movement decisions are significantly influenced by canopy height and topography, but depletion and renewal of resources do not appear to affect movement significantly. We quantify the magnitude of these effects and demonstrate that they are helpful for understanding various heterogeneous aspects of space use. We compare our results to recent analytic derivations of space use, demonstrating that the analytic approximation is only accurate when assuming that there is no persistence in the animals' movement. Our model can be translated into other environments or hypothetical scenarios, such as those given by proposed future anthropogenic actions, to make predictions of spatial patterns in bird flocks. Furthermore, our approach is quite general, so could potentially be used to understand the drivers of movement and spatial patterns for a wide variety of animal communities. PMID:25558353

  5. An efficient approach for pixel decomposition to increase the spatial resolution of land surface temperature images from MODIS thermal infrared band data.

    Science.gov (United States)

    Wang, Fei; Qin, Zhihao; Li, Wenjuan; Song, Caiying; Karnieli, Arnon; Zhao, Shuhe

    2015-01-01

    Land surface temperature (LST) images retrieved from the thermal infrared (TIR) band data of Moderate Resolution Imaging Spectroradiometer (MODIS) have much lower spatial resolution than the MODIS visible and near-infrared (VNIR) band data. The coarse pixel scale of MODIS LST images (1000 m under nadir) have limited their capability in applying to many studies required high spatial resolution in comparison of the MODIS VNIR band data with pixel scale of 250-500 m. In this paper we intend to develop an efficient approach for pixel decomposition to increase the spatial resolution of MODIS LST image using the VNIR band data as assistance. The unique feature of this approach is to maintain the thermal radiance of parent pixels in the MODIS LST image unchanged after they are decomposed into the sub-pixels in the resulted image. There are two important steps in the decomposition: initial temperature estimation and final temperature determination. Therefore the approach can be termed double-step pixel decomposition (DSPD). Both steps involve a series of procedures to achieve the final result of decomposed LST image, including classification of the surface patterns, establishment of LST change with normalized difference of vegetation index (NDVI) and building index (NDBI), reversion of LST into thermal radiance through Planck equation, and computation of weights for the sub-pixels of the resulted image. Since the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) with much higher spatial resolution than MODIS data was on-board the same platform (Terra) as MODIS for Earth observation, an experiment had been done in the study to validate the accuracy and efficiency of our approach for pixel decomposition. The ASTER LST image was used as the reference to compare with the decomposed LST image. The result showed that the spatial distribution of the decomposed LST image was very similar to that of the ASTER LST image with a root mean square error (RMSE) of 2

  6. Uncovering homo-and hetero-interactions on the cell membrane using single particle tracking approaches

    Science.gov (United States)

    Torreno-Pina, Juan A.; Manzo, Carlo; Garcia-Parajo, Maria F.

    2016-03-01

    The plasma membrane of eukaryotic cells is responsible for a myriad of functions that regulate cell physiology and plays a crucial role in a multitude of processes that include adhesion, migration, signaling recognition and cell-cell communication. This is accomplished by specific interactions between different membrane components such as lipids and proteins on the lipid bilayer but also through interactions with the underlying cortical actin cytoskeleton on the intracellular side and the glycocalyx matrix in close proximity to the extracellular side. Advanced biophysical techniques, including single particle tracking (SPT) have revealed that the lateral diffusion of molecular components on the plasma membrane represents a landmark manifestation of such interactions. Indeed, by studying changes in the diffusivity of individual membrane molecules, including sub-diffusion, confined diffusion and/or transient arrest of molecules in membrane compartments, it has been possible to gain insight on the nature of molecular interactions and to infer on its functional role for cell response. In this review, we will revise some exciting results where SPT has been crucial to reveal homo- and hetero-interactions on the cell membrane.

  7. CNoA: Challenging Number Approach for uncovering TCP SYN flooding using SYN spoofing attack

    Directory of Open Access Journals (Sweden)

    L.Kavisankar

    2011-10-01

    Full Text Available The challenging number is used for the detection of Spoofing attack. The IP Spoofing is considered to beone of the potentially brutal attack which acts as a tool for the DDoS attack which is considered to be amajor threat among security problems in today’s internet. These kinds of attack are extremely severe.They bring down business of company drastically. DDoS attack can easily exhaust the computing andcommunication resources of its victim within a short period of time. There are attacks exploiting somevulnerability or implementation bug in the software implementation of a service to bring that down andsome attacks will use all the available resources at the target machine. This deals on attacks thatconsume all the bandwidth available to the victim machine. While concentrating on the bandwidth attackthe TCP SYN flood is the more prominent attack. TCP/IP protocol suite is the most widely used protocolsuite for data communication. The TCP SYN flood works by exhausting the TCP connection queue of thehost and thus denying legitimate connection request. There are various methods used to detect andprevent this attack, one of which is to block the packet based on SYN flag count from the same IP address.This kind of prevention methods becomes unsuitable when the attackers use the Spoofed IP address. TheSYN spoofing becomes a major tool the TCP SYN flooding. For the prevention of this kind of attacks, theTCP specific probing is used in the proposed scheme where the client is requested challenging numberwhile sending the ACK in the three way hand shake. This is very useful to find the Spoofed IPPackets/TCP SYN flood and preventing them.

  8. A dynamical network approach to uncovering hidden causality relationships in collective neuron firings

    CERN Document Server

    Ruszczycki, Bła\\ zej; Johnson, Neil F

    2009-01-01

    We analyze the synchronous firings of the salamander ganglion cells from the perspective of the complex network viewpoint where the network's links reflect the correlated behavior of firings. We study the time-aggregated properties of the resulting network focusing on its topological features. The behavior of pairwise correlations has been inspected in order to construct an appropriate measure that will serve as a weight of network connection.

  9. A Go/No-go approach to uncovering implicit attitudes towards safe and risky driving

    DEFF Research Database (Denmark)

    Martinussen, Laila Marianne; Sømhovd, Mikael J.; Møller, Mette; Siebler, Frank

    2015-01-01

    ' self-reports. Implicit attitudes towards safe and risky driving were measured in 53 Danish drivers (31 female, 22 male). Further, we explored the relationship between implicit attitudes towards risky and safe driving, and self-reported driving behaviour and skills. The results suggest that implicit...... attitudes were significantly related to self-reported driving behaviour and skills for male (but not female) drivers. Pending future research with larger sample sizes, the difference between implicit attitudes towards safe versus risky driving that we observed may contribute to a greater theoretical......Self-report measures of driving-related attitudes and beliefs miss potentially important precursors of driving behaviour, namely, automatic and implicit thought processes. The present study used an adapted Go/No-go Association Task to measure implicit thought without relying on the participants...

  10. SQUID–SIMS is a useful approach to uncover primary signals in the Archean sulfur cycle

    OpenAIRE

    Fischer, Woodward W.; Fike, David A; Johnson, Jena E; Raub, Timothy D; Guan, Yunbin; Kirschvink, Joseph L; Eiler, John M.

    2014-01-01

    The Agouron Institute and National Aeronautic and Space Administration Exobiology Award NNX09AM91G supported this work. Many aspects of Earth's early sulfur cycle, from the origin of mass-anomalous fractionations to the degree of biological participation, remain poorly understood-in part due to complications from postdepositional diagenetic and metamorphic processes. Using a combination of scanning high-resolution magnetic superconducting quantum interference device (SQUID) microscopy and ...

  11. An Integrative Approach Uncovers Biomarkers that Associate with Clinically Relevant Disease Outcomes in Vulvar Carcinoma

    DEFF Research Database (Denmark)

    Lavorato-Rocha, Andre M; Akagi, Erica M; de Melo Maia, Beatriz;

    2016-01-01

    was then analyzed by immunohistochemistry (IHC) in a large set of formalin-fixed paraffin-embedded (FFPE) specimens. This analyses, identified 47 putative drivers - 46 of which were characterized by copy number gains that were concomitant with overexpression and one with a copy number loss and...... downregulation. Two of these genes, PLXDC2 and GNB3, were selected for further validation: PLXDC2 was downregulated and GNB3 was overexpressed compared with non-neoplastic tissue. By IHC, both proteins were ubiquitously expressed throughout vulvar tissue. High expression of GNB3 and low PLXDC2 immunostaining in...

  12. HIV/AIDS orphans as farmers: uncovering pest knowledge differences through an ethnobiological approach in Benin

    NARCIS (Netherlands)

    Fagbémissi, R.C.; Price, L.L.

    2008-01-01

    The erosion of local/indigenous firming knowledge in the face of HIV/AIDS deaths in Africa has been noted as a point of concerti in the literature and by organizations such as the Food and Agriculture Organization of the United Nations. These concerns are about a break in the transmission of knowled

  13. Increasing the Efficiency of LiDAR Based Forest Inventories: A Novel Approach for Integrating Variable Radius Inventory Plots with LiDAR Data.

    Science.gov (United States)

    Falkowski, M. J.; Fekety, P.; Silva, C. A.; Hudak, A. T.

    2015-12-01

    LiDAR data are increasingly applied to support forest inventory and assessment across a variety of spatial scales. Typically this is achieved by integrating LiDAR data with forest inventory collected at fixed radius forest inventory plots. A well-designed forest inventory, one that covers the full range of structural and compositional variation across the forest of interest, is costly especially when collecting fixed radius plot data. Variable radius plots offer an alternative inventory protocol that is more efficient in terms of both time and money. However, integrating variable radius plot data with LiDAR data is problematic because the plots have unknown sizes that vary with variation in tree size. This leads to a spatial mismatch between LiDAR metrics (e.g., mean height, canopy cover, density, etc.) and plot data, which ultimately translates into errors in LiDAR derived forest inventory predictions. We propose and evaluate and novel approach for integrating variable radius plot data into a LiDAR based forest inventories in two different forest systems, one in the inland northwest and another in the northern lakes states of the USA. The novel approach calculates LiDAR metrics by weighting the point cloud proportional to return height, mimicking the way in which variable radius plot data weights tree measurements by tree size. This could increase inventory sampling efficiency, allowing for the collection of a greater number of inventory plots, and ultimately improve the performance of LiDAR based inventories.

  14. Surveying the experiences and perceptions of undergraduate nursing students of a flipped classroom approach to increase understanding of drug science and its application to clinical practice.

    Science.gov (United States)

    Hanson, Julie

    2016-01-01

    Patient harm from medication error is a significant issue. Individual failures by health professionals including knowledge deficits and poor communication have been identified as increasing the likelihood of medication administration errors. In Australia, the National Strategy for Quality Use of Medicines in 2002 compels health professionals to have the knowledge and skills to use medicines safely and effectively. This paper examines nursing students' perceptions of the effectiveness of a flipped classroom approach to increase understanding of pharmacology principles and the application of this knowledge to medication practice. An internet-based self-completion questionnaire was used in 2013 (n = 26) after the flipped classroom approach was implemented, and pre- (n = 6) and post-flipping (n = 25) in 2014. Students who engaged with digitally recorded lectures (eLectures) prior to face-to-face workshops stated that they had greater understanding of the subject and enhanced critical thinking skills. The replay function of the eLecture was perceived by some students as most beneficial to independent learning. However, for some students, time constraints meant that they relied on eLectures alone, while others preferred traditional teaching methods. Although limited by sample size and potential participant bias, the results provide insights about the flipped classroom experience from a student perspective. PMID:26494304

  15. Uncovering the Mechanism of Aggregation of Human Transthyretin*

    OpenAIRE

    Saelices, Lorena; Johnson, Lisa M.; Liang, Wilson Y.; Sawaya, Michael R.; Cascio, Duilio; Ruchala, Piotr; Whitelegge, Julian; Jiang, Lin; Riek, Roland; Eisenberg, David S.

    2015-01-01

    Background: Transthyretin (TTR) aggregation is associated with systemic amyloidosis. Results: Residue replacements on the F and H strands hinder TTR aggregation. Conclusion: The F and H strands are aggregation-driving segments of TTR. The binding of designed peptides inhibits protein aggregation. Significance: We point the way to new therapeutic approaches against TTR aggregation by using peptides to block amyloid segments.

  16. Adapting Evidence-Based Strategies to Increase Physical Activity Among African Americans, Hispanics, Hmong, and Native Hawaiians: A Social Marketing Approach

    Directory of Open Access Journals (Sweden)

    Mary Ann S. Van Duyn, PhD, MPH, RD

    2007-10-01

    Full Text Available IntroductionUsing a social marketing approach, we studied how best to adapt proven, evidence-based strategies to increase physical activity for use with underserved racial or ethnic groups.MethodsWe conducted focus groups with low-income Hispanic women in Texas, Hmong parents and their children in California, low-income African American women and men in the Mississippi Delta, and Native Hawaiian college students in Hawaii. We also interviewed key leaders of these communities. Topics of discussion were participants’ perceptions about 1 the benefits of engaging in physical activity, 2 the proposed evidence-based strategies for increasing each community’s level of physical activity, and 3 the benefits and barriers to following the proposed interventions for increasing physical activity. A total of 292 individuals participated in the study.ResultsAll groups considered that being physically active was part of their culture, and participants found culturally relevant suggestions for physical activities appealing. Overwhelmingly, strategies that aimed to create or improve social support and increase access to physical activity venues received the most positive feedback from all groups. Barriers to physical activity were not culturally specific; they are common to all underserved people (lack of time, transportation, access, neighborhood safety, or economic resources.ConclusionResults indicate that evidence-based strategies to increase physical activity need to be adapted for cultural relevance for each racial or ethnic group. Our research shows that members of four underserved populations are likely to respond to strategies that increase social support for physical activity and improve access to venues where they can be physically active. Further research is needed to test how to implement such strategies in ways that are embraced by community members.

  17. Regional Radiological Security Partnership in Southeast Asia - Increasing the Sustainability of Security Systems at the Site-Level by Using a Model Facility Approach

    International Nuclear Information System (INIS)

    In 2004, Australia, through the Australian Nuclear Science and Technology Organisation (ANSTO), created the Regional Security of Radioactive Sources (RSRS) project and partnered with the U.S. Department of Energy's Global Threat Reduction Initiative (GTRI) and the International Atomic Energy Agency (IAEA) to form the Southeast Asian Regional Radiological Security Partnership (RRSP). The intent of the RRSP is to cooperate with countries in Southeast Asia to improve the security of their radioactive sources. This Southeast Asian Partnership supports objectives to improve the security of high risk radioactive sources by raising awareness of the need and developing national programs to protect and control such materials, improve the security of such materials, and recover and condition the materials no longer in use. The RRSP has utilized many tools to meet those objectives including: provision of physical protection upgrades, awareness training, physical protection training, regulatory development, locating and recovering orphan sources, and most recently - development of model security procedures at a model facility. This paper discusses the benefits of establishing a model facility, the methods employed by the RRSP, and three of the expected outcomes of the Model Facility approach. The first expected outcome is to increase compliance with source security guidance materials and national regulations by adding context to those materials, and illustrating their impact on a facility. Second, the effectiveness of each of the tools above is increased by making them part of an integrated system. Third, the methods used to develop the model procedures establishes a sustainable process that can ultimately be transferred to all facilities beyond the model. Overall, the RRSP has utilized the Model Facility approach as an important tool to increase the security of radioactive sources, and to position facilities and countries for the long term secure management of those sources.

  18. Endoscopic removal of a spontaneously fractured biliary uncovered self-expandable metal stent.

    Science.gov (United States)

    Kawakubo, Kazumichi; Isayama, Hiroyuki; Tsujino, Takeshi; Nakai, Yousuke; Sasahira, Naoki; Kogure, Hirofumi; Hamada, Tsuyoshi; Nagano, Rie; Miyabayashi, Kouji; Yamamoto, Keisuke; Mohri, Dai; Sasaki, Takashi; Ito, Yukiko; Yamamoto, Natsuyo; Hirano, Kenji; Tada, Minoru; Koike, Kazuhiko

    2012-05-01

    Self-expandable metal stents (SEMS) are widely used for the palliative treatment of unresectable malignant biliary obstruction. However, the long-term durability of SEMSs in biliary strictures is not clear. We describe a case of endoscopic removal of spontaneously fractured uncovered biliary SEMS. A 59-year-old woman presented to our institution with a 1-year history of recurrent cholangitis. Her medical history included a proctectomy for rectal cancer and right hemihepatectomy for liver metastasis 10 years earlier. Five years after these operations, she developed a benign hilar stricture and had an uncovered SEMS placed in another hospital. Endoscopic retrograde cholangiopancreatography demonstrated that the SEMS was torn in half and the distal part of the stent was floating in the dilated common bile duct. The papillary orifice was dilated by endoscopic papillary large balloon dilation (EPLBD) using a 15-mm wire-guided balloon catheter. Subsequently, we inserted biopsy forceps into the bile duct and grasped the distal end of the broken SEMS under fluoroscopy. We successfully removed the fragment of the SEMS from the bile duct, along with the endoscope. The patient was discharged without complications. Placement of an uncovered biliary SEMS is not the preferred treatment for benign biliary strictures. Spontaneous fracture of an uncovered biliary SEMS is an extremely rare complication. We should be aware that stent fracture can occur when placing uncovered biliary SEMSs in patients with a long life expectancy. EPLBD is very useful for retrieving the fractured fragment of SEMS. PMID:22507093

  19. Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms

    OpenAIRE

    Nyström, Alexander; Thriene, Kerstin; Mittapalli, Venugopal; Kern, Johannes S; Kiritsi, Dimitra; Dengjel, Jörn; Bruckner-Tuderman, Leena

    2015-01-01

    Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB)—a severe skin fragility disorder associated with lifelong blistering and disabling progressive soft tissue fibrosis. Causative therapies for this complex disorder face major hurdles, and clinical implementation remains elusive. Here, we report an alternative evidence-based approach to ameliorate fibrosis and relieve symptoms in RDEB. Based on the findings that TGF-β activity is elevated in injured RDEB skin,...

  20. Uncovering steroidopathy in women with autism: a latent class analysis

    OpenAIRE

    Pohl, Alexa; Cassidy, Sarah; Auyeung, Bonnie; Baron-Cohen, Simon

    2014-01-01

    Background Prenatal exposure to increased androgens has been implicated in both polycystic ovary syndrome (PCOS) and autism spectrum conditions (ASC), suggesting that PCOS may be increased among women with ASC. One study suggested elevated steroidopathic symptoms (‘steroidopathy’) in women with ASC. As the symptoms are not independent, we conducted a latent class analysis (LCA). The objectives of the current study are: (1) to test if these findings replicate in a larger sample; and (2) to use...

  1. The Pro-children Project- a cross-national approach to increasing fruits and vegetables in the next generation and onwards

    Directory of Open Access Journals (Sweden)

    Anderson Annie S

    2006-09-01

    Full Text Available Abstract This editorial introduces the special series in the International Journal of Behavioral Nutrition and Physical Activity on the Pro Children study (Promoting and Sustaining Health through Increased vegetable and Fruit Consumption among European Schoolchildren. The Pro Children study is a new and innovative study that takes a cross -national approach to identifying the factors associated with fruit and vegetables consumption in European children (from nine countries and evaluating a multi-centre intervention programme. A full set of papers on many aspects of the study will appear as a series in the IJBPNA allowing a more detailed view of design, behavioural theoretical constructs, action, methods for implementation, assessment tools, impacts and outcomes to be reported. Areas for future work will also be identified and discussed in the context of the 21st century developed world environment which is superb at encouraging the promotion of energy dense foods and drinks.

  2. Uncovering China’s transport CO2 emission patterns at the regional level

    International Nuclear Information System (INIS)

    With China’s rapid economic development, its transport sector has experienced a dramatic growth, leading to a large amount of related CO2 emission. This paper aims to uncover China’s transport CO2 emission patterns at the regional and provincial level. We first present the CO2 emission features from transport sector in 30 Chinese provinces, including per capita emissions, emission intensities, and historical evolution of annual CO2 emission. We then quantify the related driving forces by adopting both period-wise and time-series LMDI analysis. Results indicate that significant regional CO2 emission disparities exist in China’s transport sector. The eastern region had higher total CO2 emissions and per capita CO2 emissions, but lower CO2 emission intensities in its transport sector. The western region had higher CO2 emission intensities and experienced a rapid CO2 emission increase. The CO2 emission increments in the eastern provinces were mainly contributed by both economic activity effect and population effect, while energy intensity partially offset the emission growth and energy structure had a marginal effect. However, in the central and western provinces, both economic activity effect and energy intensity effect induced the CO2 emission increases, while the effects from population and energy structure change were limited. - Highlights: • The CO2 emission features from transport sector in 30 Chinese provinces were presented. • The driving forces of CO2 emissions from transport sector were quantified. • Regional disparities on China’s transport sector CO2 emission exist. • Region-specific mitigation policies on transport sector CO2 emission are needed

  3. Otters Increasing - Threats Increasing

    OpenAIRE

    Andreas Kranz

    1994-01-01

    In some parts of Central Europe populations of otters are apparently increasing. Until recently, no research was being conducted on the ecology of otters in mainly artificial habitats like fish farms. Otters are not only a new source of conflict requiring species management, but appear once again threatened by illegal hunting. Austria is dealing with this problem using compensation for otter damage, electric fencing and translocation of problem otters. Despite a rise in illegal killing, Austr...

  4. Uncovering oral Neisseria tropism and persistence using metagenomic sequencing.

    Science.gov (United States)

    Donati, Claudio; Zolfo, Moreno; Albanese, Davide; Tin Truong, Duy; Asnicar, Francesco; Iebba, Valerio; Cavalieri, Duccio; Jousson, Olivier; De Filippo, Carlotta; Huttenhower, Curtis; Segata, Nicola

    2016-01-01

    Microbial epidemiology and population genomics have previously been carried out near-exclusively for organisms grown in vitro. Metagenomics helps to overcome this limitation, but it is still challenging to achieve strain-level characterization of microorganisms from culture-independent data with sufficient resolution for epidemiological modelling. Here, we have developed multiple complementary approaches that can be combined to profile and track individual microbial strains. To specifically profile highly recombinant neisseriae from oral metagenomes, we integrated four metagenomic analysis techniques: single nucleotide polymorphisms in the clade's core genome, DNA uptake sequence signatures, metagenomic multilocus sequence typing and strain-specific marker genes. We applied these tools to 520 oral metagenomes from the Human Microbiome Project, finding evidence of site tropism and temporal intra-subject strain retention. Although the opportunistic pathogen Neisseria meningitidis is enriched for colonization in the throat, N. flavescens and N. subflava populate the tongue dorsum, and N. sicca, N. mucosa and N. elongata the gingival plaque. The buccal mucosa appeared as an intermediate ecological niche between the plaque and the tongue. The resulting approaches to metagenomic strain profiling are generalizable and can be extended to other organisms and microbiomes across environments. PMID:27572971

  5. Uncovering the intrinsic variability of gamma-ray bursts

    Energy Technology Data Exchange (ETDEWEB)

    Golkhou, Vahid Z.; Butler, Nathaniel R., E-mail: vgolkhou@asu.edu, E-mail: natbutler@asu.edu [Cosmology Initiative, Arizona State University, Tempe, AZ 85287, USA. (United States)

    2014-05-20

    We develop a robust technique to determine the minimum variability timescale for gamma-ray burst (GRB) light curves, utilizing Haar wavelets. Our approach averages over the data for a given GRB, providing an aggregate measure of signal variation while also retaining sensitivity to narrow pulses within complicated time series. In contrast to previous studies using wavelets, which simply define the minimum timescale in reference to the measurement noise floor, our approach identifies the signature of temporally smooth features in the wavelet scaleogram and then additionally identifies a break in the scaleogram on longer timescales as a signature of a true, temporally unsmooth light curve feature or features. We apply our technique to the large sample of Swift GRB gamma-ray light curves and for the first time—due to the presence of a large number of GRBs with measured redshift—determine the distribution of minimum variability timescales in the source frame. We find a median minimum timescale for long-duration GRBs in the source frame of Δt {sub min} = 0.5 s, with the shortest timescale found being on the order of 10 ms. This short timescale suggests a compact central engine (3 × 10{sup 3} km). We discuss further implications for the GRB fireball model and present a tantalizing correlation between the minimum timescale and redshift, which may in part be due to cosmological time dilation.

  6. Hidden Stories: Uncovering the Visual Metaphor for Education and Communication

    Science.gov (United States)

    Hube, Amy M.; Tremblay, Kenneth R., Jr.; Leigh, Katharine E.

    2015-01-01

    Design solutions have become increasingly complex and based on a rapidly growing body of knowledge. In order to articulate a design solution to a client, the graphic use of the design narrative can effectively communicate complex ideas. Two case study interventions were conducted in an interior design program in which students were introduced to…

  7. A "one size fits all" approach to language fMRI: increasing specificity and applicability by adding a self-paced component.

    Science.gov (United States)

    Máté, Adrienn; Lidzba, Karen; Hauser, Till-Karsten; Staudt, Martin; Wilke, Marko

    2016-03-01

    We have previously established an fMRI task battery suitable for mapping the language processing network in children. Among the tasks used, the synonyms and the vowel identification task induced robust task-related activations in children with average language abilities; however, the fixed presentation time seems to be a drawback in participants with above- or below-average language abilities. This feasibility study in healthy adults (n = 20) was aimed at adapting these tasks to the individual level of each patient by implementing a self-paced stimulus presentation. The impact of using a block- versus an event-related statistical approach was also evaluated. The self-paced modification allowed our participants with above-average language abilities to process stimuli much faster than originally implemented, likely increasing task adherence. A higher specificity of the event-related analysis was confirmed by stronger left inferior frontal and crossed cerebellar activations. We suggest that self-paced paradigms and event-related analyses may both increase specificity and applicability. PMID:26514810

  8. Uncovering the Genetic Landscape for Multiple Sleep-Wake Traits

    OpenAIRE

    Winrow, Christopher J.; Deanna L Williams; Andrew Kasarskis; Joshua Millstein; Laposky, Aaron D.; Yang, He S.; Karrie Mrazek; Lili Zhou; Owens, Joseph R.; Daniel Radzicki; Fabian Preuss; Schadt, Eric E.; Kazuhiro Shimomura; Martha H Vitaterna; Chunsheng Zhang

    2009-01-01

    Despite decades of research in defining sleep-wake properties in mammals, little is known about the nature or identity of genes that regulate sleep, a fundamental behaviour that in humans occupies about one-third of the entire lifespan. While genome-wide association studies in humans and quantitative trait loci (QTL) analyses in mice have identified candidate genes for an increasing number of complex traits and genetic diseases, the resources and time-consuming process necessary for obtaining...

  9. Uncovering zoonoses awareness in an emerging disease ‘hotspot’

    OpenAIRE

    Paige, Sarah B.; Malave, Carly; Mbabazi, Edith; Mayer, Jonathan; Goldberg, Tony L.

    2014-01-01

    Emerging infectious diseases from animals pose significant and increasing threats to human health; places of risk are simultaneously viewed as conservation and emerging disease ‘hotspots’. The One World/One Health paradigm is an ‘assemblage’ discipline. Extensive research from the natural and social sciences, as well as public health have contributed to designing surveillance and response policy within the One World/One Health framework. However, little research has been undertaken that consi...

  10. Uncovering the multiple objectives behind national energy efficiency planning

    International Nuclear Information System (INIS)

    This work seeks to identify the fundamental objectives behind the development of energy efficiency (EE) plans for countries. It also presents a method to quantify the degree of achievement of each objective, through the identification and operationalization of attributes. This was achieved by applying Keeney's value-focused thinking approach. For that purpose, three key decision makers in EE planning were interviewed along with a bibliographic review on the subject. From this process six fundamental objectives were identified formalizing the problem as a multi-objective one: (i) to minimize the influence of energy use on climate change; (ii) to minimize the financial risk from the investment; (iii) to maximize the security of energy supply; (iv) to minimize investment costs; (v) to minimize the impacts of building new power plants and transmission infrastructures and (vi) to maximize the local air quality. The respective attributes were: (i) CO2 emissions savings; (ii) payback; (iii) imported energy savings; (iv) investment cost; (v) electricity savings; and (vi) total suspended particles savings. To show the usefulness of the work, the objectives and attributes identified were used to show the possible outcomes from five hypothetical EE plans for Portugal

  11. Uncovering phenotypes of poor-pitch singing: The Sung Performance Battery (SPB

    Directory of Open Access Journals (Sweden)

    Magdalena eBerkowska

    2013-10-01

    Full Text Available Singing is as natural as speaking for humans. Increasing evidence shows that the layman can carry a tune (e.g., when asked to sing a well-known song or to imitate single pitches, intervals and short melodies. Yet, important individual differences exist in the general population with regard to singing proficiency. Some individuals are particularly inaccurate or imprecise in producing or imitating pitch information (poor-pitch singers, thus showing a variety of singing phenotypes. Unfortunately, so far there is not a standard set of tasks for assessing singing proficiency in the general population, allowing to uncover and characterize individual profiles of poor-pitch singing. Different tasks and analysis methods are typically used in various experiments, making the comparison of the results across studies arduous. To fill this gap we propose here a new tool for assessing singing proficiency (the Sung Performance Battery, SPB. The SPB starts from the assessment of participants’ vocal range followed by five tasks: 1 single-pitch matching, 2 pitch-interval matching, 3 novel-melody matching, 4 singing from memory of familiar melodies (with lyrics and on a syllable, and 5 singing of familiar melodies (with lyrics and on a syllable at a slow tempo indicated by a metronome. Data analysis via acoustical methods provides objective measures of pitch accuracy and precision in terms of absolute and relative pitch. The SPB has been tested in a group of 50 occasional singers. The results indicate that the battery is useful for characterizing proficient singing and for detecting cases of inaccurate and/or imprecise singing.

  12. Quick determination of gas pressure before uncovering coal in cross-cuts and shafts

    Institute of Scientific and Technical Information of China (English)

    JIANG Cheng-lin; DENG Su-hua; ZHANG Chao-jie; CHENG Song-li; LV Shu-wen; WANG Chen; LI Xiao-wei; CHEN Yu-jia; XIE Qing-xue; LIU Ying; TANG Jun; YANG Fei-long; WANG Fa-kai

    2008-01-01

    The determination of gas pressure before uncovering coal in cross-cuts and in shafts is one of the important steps in predicting coal and gas outbursts. However, the time spent for testing gas pressure is, at present, very long, seriously affecting the application of outburst prediction techniques in opening coal seams in cross-cuts and shafts. In order to reduce the time needed in gas pressure tests and to improve the accuracy of tests, we analyzed the process of gas pressure tests and examined the effect of the length of boreholes in coal seams in tests. The result shows that 1) the shorter the borehole, the easier the real pressure value of gas can be obtained and 2) the main factors affecting the time spent in gas pressure tests are the length of the borehole in coal seams,the gas emission time after the borehole has been formed and the quality of the borehole-sealing. The longer the length of the borehole, the longer the gas emission time and the larger the pressure-relief circle formed around the borehole, the longer the time needed for pressure tests. By controlling the length of the borehole in a test case in the Huainan mining area, and adopting a quick sealing technique using a sticky liquid method, the sealing quality was clearly improved and the gas emission time as well as the amount of gas discharged greatly decreased. Before the method described, the time required for the gas pressure to increase during the pressure test process, was more than 10 days. With our new method the required time is only 5 hours. In addition, the accuracy of the gas pressure test is greatly improved.

  13. Interactome map uncovers phosphatidylserine transport by oxysterol-binding proteins.

    Science.gov (United States)

    Maeda, Kenji; Anand, Kanchan; Chiapparino, Antonella; Kumar, Arun; Poletto, Mattia; Kaksonen, Marko; Gavin, Anne-Claude

    2013-09-12

    The internal organization of eukaryotic cells into functionally specialized, membrane-delimited organelles of unique composition implies a need for active, regulated lipid transport. Phosphatidylserine (PS), for example, is synthesized in the endoplasmic reticulum and then preferentially associates--through mechanisms not fully elucidated--with the inner leaflet of the plasma membrane. Lipids can travel via transport vesicles. Alternatively, several protein families known as lipid-transfer proteins (LTPs) can extract a variety of specific lipids from biological membranes and transport them, within a hydrophobic pocket, through aqueous phases. Here we report the development of an integrated approach that combines protein fractionation and lipidomics to characterize the LTP-lipid complexes formed in vivo. We applied the procedure to 13 LTPs in the yeast Saccharomyces cerevisiae: the six Sec14 homology (Sfh) proteins and the seven oxysterol-binding homology (Osh) proteins. We found that Osh6 and Osh7 have an unexpected specificity for PS. In vivo, they participate in PS homeostasis and the transport of this lipid to the plasma membrane. The structure of Osh6 bound to PS reveals unique features that are conserved among other metazoan oxysterol-binding proteins (OSBPs) and are required for PS recognition. Our findings represent the first direct evidence, to our knowledge, for the non-vesicular transfer of PS from its site of biosynthesis (the endoplasmic reticulum) to its site of biological activity (the plasma membrane). We describe a new subfamily of OSBPs, including human ORP5 and ORP10, that transfer PS and propose new mechanisms of action for a protein family that is involved in several human pathologies such as cancer, dyslipidaemia and metabolic syndrome. PMID:23934110

  14. In the minds of OSCE examiners: uncovering hidden assumptions.

    Science.gov (United States)

    Chahine, Saad; Holmes, Bruce; Kowalewski, Zbigniew

    2016-08-01

    The Objective Structured Clinical Exam (OSCE) is a widely used method of assessment in medical education. Rater cognition has become an important area of inquiry in the medical education assessment literature generally, and in the OSCE literature specifically, because of concerns about potential compromises of validity. In this study, a novel approach to mixed methods that combined Ordinal Logistic Hierarchical Linear Modeling and cognitive interviews was used to gain insights about what examiners were thinking during an OSCE. This study is based on data from the 2010 to 2014 administrations of the Clinician Assessment for Practice Program OSCE for International Medical Graduates (IMGs) in Nova Scotia. An IMG is a physician trained outside of Canada who was a licensed practitioner in a different country. The quantitative data were examined alongside four follow-up cognitive interviews of examiners conducted after the 2014 administration. The quantitative results show that competencies of (1) Investigation and Management and (2) Counseling were highly predictive of the Overall Global score. These competencies were also described in the cognitive interviews as the most salient parts of OSCE. Examiners also found Communication Skills and Professional Behavior to be relevant but the quantitative results revealed these to be less predictive of the Overall Global score. The interviews also reveal that there is a tacit sequence by which IMGs are expected to proceed in an OSCE, starting with more basic competencies such as History Taking and building up to Investigation Management and Counseling. The combined results confirm that a hidden pattern exists with respect to how examiners rate candidates. This study has potential implications for research into rater cognition, and the design and scoring of practice-ready OSCEs. PMID:26661783

  15. Using Text Mining to Uncover Students' Technology-Related Problems in Live Video Streaming

    Science.gov (United States)

    Abdous, M'hammed; He, Wu

    2011-01-01

    Because of their capacity to sift through large amounts of data, text mining and data mining are enabling higher education institutions to reveal valuable patterns in students' learning behaviours without having to resort to traditional survey methods. In an effort to uncover live video streaming (LVS) students' technology related-problems and to…

  16. Community Mapping in Action: Uncovering Resources and Assets for Young Children and Their Families

    Science.gov (United States)

    Ordonez-Jasis, Rosario; Myck-Wayne, Janice

    2012-01-01

    Community mapping is a promising practice that can assist early intervention/early childhood special education (EI/ECSE) professionals uncover the depth and diversity of community needs, resources, and learning opportunities, in the neighborhoods surrounding their schools. Community mapping is an inquiry-based method that situates learning in the…

  17. Uncovering the Motivating Factors behind Writing in English in en EFL Context

    Science.gov (United States)

    Büyükyavuz, Oya; Çakir, Ismail

    2014-01-01

    Writing in a language, whether the target or native, is regarded as a complex activity operating on multiple cognitive levels. This study aimed to uncover the factors which motivate teacher trainees of English to write in English in an EFL context. The study also investigated the differences in the ways teacher trainees are motivated in terms of…

  18. Uncovering Influence through Social Network Analysis: The Role of Schools in Education for Sustainable Development

    Science.gov (United States)

    Kolleck, Nina

    2016-01-01

    This paper examines the implementation of Education for Sustainable Development (ESD) in Germany and explores the possibilities of Social Network Analysis (SNA) for uncovering influential actors in educational policy innovation processes. From the theoretical perspective, an actor's influence is inferred from its relative position within…

  19. Uncovering Pre-Service Music Teachers' Assumptions of Teaching, Learning, and Music

    Science.gov (United States)

    Bernard, Rhoda

    2009-01-01

    In this study, the author collected narratives from her students in a music teacher education programme. Using narrative analysis, students' assumptions and thoughts about music teaching, music learning and music making were uncovered. Through the presentation of a case study of one student, the author demonstrates some of the ways that the…

  20. Uncovering flux line correlations in superconductors by reverse monte carlo refinement of neutron scattering data

    OpenAIRE

    Laver, M.; Forgan, E. M.; Abrahamsen, Asger Bech; Bowell, C.; Geue, T.; Cubitt, R.

    2008-01-01

    We describe the use of reverse Monte Carlo refinement to extract structural information from angle-resolved data of a Bragg peak. Starting with small-angle neutron scattering data, the positional order of an ensemble of flux lines in superconducting Nb is revealed. We discuss the uncovered correlation functions in the light of topical theories, in particular, the "Bragg glass" paradigm.

  1. Uncovering flux line correlations in superconductors by reverse monte carlo refinement of neutron scattering data

    DEFF Research Database (Denmark)

    Laver, M.; Forgan, E.M.; Abrahamsen, Asger Bech;

    2008-01-01

    We describe the use of reverse Monte Carlo refinement to extract structural information from angle-resolved data of a Bragg peak. Starting with small-angle neutron scattering data, the positional order of an ensemble of flux lines in superconducting Nb is revealed. We discuss the uncovered...... correlation functions in the light of topical theories, in particular, the "Bragg glass" paradigm....

  2. Learning "through" Computers: Uncovering Students' Thought Processes while Solving Physics Problems

    Science.gov (United States)

    Soong, Benson

    2008-01-01

    This paper presents a study that illustrates how the author and an in service secondary school teacher used basic synchronous computer mediated communications (CMC) technology to help them uncover students' physics preconceptions and thought processes (including their misconceptions and misunderstandings) in a real class setting. In this paper, I…

  3. 77 FR 12227 - Long Term 2 Enhanced Surface Water Treatment Rule: Uncovered Finished Water Reservoirs; Public...

    Science.gov (United States)

    2012-02-29

    ... AGENCY 40 CFR Parts 141 and 142 Long Term 2 Enhanced Surface Water Treatment Rule: Uncovered Finished... requirement in the Long Term 2 Enhanced Surface Water Treatment Rule (LT2 rule). At this meeting, EPA will... information related to microbial occurrence of Cryptosporidium, Giardia, viruses, and other...

  4. Uncovering Mass Segregation with Galaxy Analogues in Dark Matter Simulations

    CERN Document Server

    Joshi, Gandhali D; Wadsley, James

    2016-01-01

    We investigate mass segregation in group and cluster environments by identifying galaxy analogues in high-resolution dark matter simulations. Subhalos identified by the AHF and ROCKSTAR halo finders have similar mass functions, independent of resolution, but different radial distributions due to significantly different subhalo hierarchies. We propose a simple way to classify subhalos as galaxy analogues. The radial distributions of galaxy analogues agree well at large halo-centric radii for both AHF and ROCKSTAR but disagree near parent halo centres where the phase-space information used by ROCKSTAR is essential. We see clear mass segregation at small radii (within $0.5\\,r_{vir}$) with average galaxy analogue mass decreasing with radius. Beyond the virial radius, we find a mild trend where the average galaxy analogue mass increases with radius. These mass segregation trends are strongest in small groups and dominated by the segregation of low mass analogues. The lack of mass segregation in massive galaxy anal...

  5. Vaporous Marketing: Uncovering Pervasive Electronic Cigarette Advertisements on Twitter.

    Directory of Open Access Journals (Sweden)

    Eric M Clark

    Full Text Available Twitter has become the "wild-west" of marketing and promotional strategies for advertisement agencies. Electronic cigarettes have been heavily marketed across Twitter feeds, offering discounts, "kid-friendly" flavors, algorithmically generated false testimonials, and free samples.All electronic cigarette keyword related tweets from a 10% sample of Twitter spanning January 2012 through December 2014 (approximately 850,000 total tweets were identified and categorized as Automated or Organic by combining a keyword classification and a machine trained Human Detection algorithm. A sentiment analysis using Hedonometrics was performed on Organic tweets to quantify the change in consumer sentiments over time. Commercialized tweets were topically categorized with key phrasal pattern matching.The overwhelming majority (80% of tweets were classified as automated or promotional in nature. The majority of these tweets were coded as commercialized (83.65% in 2013, up to 33% of which offered discounts or free samples and appeared on over a billion twitter feeds as impressions. The positivity of Organic (human classified tweets has decreased over time (5.84 in 2013 to 5.77 in 2014 due to a relative increase in the negative words 'ban', 'tobacco', 'doesn't', 'drug', 'against', 'poison', 'tax' and a relative decrease in the positive words like 'haha', 'good', 'cool'. Automated tweets are more positive than organic (6.17 versus 5.84 due to a relative increase in the marketing words like 'best', 'win', 'buy', 'sale', 'health', 'discount' and a relative decrease in negative words like 'bad', 'hate', 'stupid', 'don't'.Due to the youth presence on Twitter and the clinical uncertainty of the long term health complications of electronic cigarette consumption, the protection of public health warrants scrutiny and potential regulation of social media marketing.

  6. Alcohol consumption increases locomotion in an open field and induces Fos-immunoreactivity in reward and approach/withdrawal-related neurocircuitries.

    Science.gov (United States)

    Wscieklica, Tatiana; de Barros Viana, Milena; Le Sueur Maluf, Luciana; Pouza, Kathlein Cristiny Peres; Spadari, Regina Célia; Céspedes, Isabel Cristina

    2016-02-01

    Drug addiction is a chronically relapsing disorder characterized by compulsion to seek and take the drug, loss of control in limiting intake and, eventually, the emergence of a negative emotional state when access to the drug is prevented. Both dopamine and corticotropin-releasing factor (CRF)-mediated systems seem to play important roles in the modulation of alcohol abuse and dependence. The present study investigated the effects of alcohol consumption on anxiety and locomotor parameters and on the activation of dopamine and CRF-innervated brain regions. Male Wistar rats were given a choice of two bottles for 31 days, one containing water and the other a solution of saccharin + alcohol. Control animals only received water and a solution of 0.2% saccharin. On the 31st day, animals were tested in the elevated plus-maze and open field, and euthanized immediately after the behavioral tests. An independent group of animals was treated with ethanol and used to measure blood ethanol concentration. Results showed that alcohol intake did not alter behavioral measurements in the plus-maze, but increased the number of crossings in the open field, an index of locomotor activity. Additionally, alcohol intake increased Fos-immunoreactivity (Fos-ir) in the prefrontal cortex, in the shell region of the nucleus accumbens, in the medial and central amygdala, in the bed nucleus of the stria terminalis, in the septal region, and in the paraventricular and dorsomedial hypothalamus, structures that have been linked to reward and to approach/withdrawal behavior. These observations might be relevant to a better understanding of the behavioral and physiological alterations that follow alcohol consumption. PMID:26786746

  7. Functional gene pyrosequencing and network analysis: an approach to examine the response of denitrifying bacteria to increased nitrogen supply in salt marsh sediments

    Directory of Open Access Journals (Sweden)

    JenniferL.Bowen

    2013-11-01

    Full Text Available Functional gene pyrosequencing is emerging as a useful tool to examine the diversity and abundance of microbes that facilitate key biogeochemical processes. One such process, denitrification, is of particular importance because it converts fixed nitrate (NO3- to N2 gas, which returns to the atmosphere. In N limited salt marshes, removal of NO3- prior to entering adjacent waters helps prevent eutrophication. Understanding the dynamics of salt marsh microbial denitrification is thus imperative for the maintenance of healthy coastal ecosystems. We used pyrosequencing of the nirS gene to examine the denitrifying community response to fertilization in experimentally enriched marsh plots. A key challenge in the analysis of sequence data derived from pyrosequencing is understanding whether small differences in gene sequences are ecologically meaningful. We apply a novel approach from information theory that determined that the optimal similarity level for clustering DNA sequences into OTUs, while still capturing the ecological complexity of the system, was 88% similarity. With this clustering, phylogenetic analysis yielded 6 dominant clades of denitrifiers, the largest of which, accounting for more than half of all the sequences collected, had no close cultured representatives. Of the 638 OTUs identified, only 11 were present in all plots and no single OTU was dominant. We did, however, find a large number of specialist OTUs that were present only in a single plot. The high degree of endemic OTUs, while accounting for a large proportion of the nirS diversity in the plots, were found in lower abundance than the generalist taxa. The proportion of specialist taxa increased with increasing supply of nutrients, suggesting that addition of fertilizer may create conditions that expand the niche space for denitrifying organisms and may enhance the genetic capacity for denitrification.

  8. Unique small RNA signatures uncovered in the tammar wallaby genome

    Directory of Open Access Journals (Sweden)

    Lindsay James

    2012-10-01

    discovered crasiRNAs. These small RNAs are derived largely from centromere-enriched retroelements, including a novel SINE. Conclusions This study encompasses the first analyses of the major classes of small RNAs for the newly completed tammar genome, validates preliminary annotations using deep sequencing and computational approaches, and provides a foundation for future work on tammar-specific as well as conserved, but previously unknown small RNA progenitors and targets identified herein. The characterization of new miRNA target genes and a unique profile for crasiRNAs has allowed for insight into multiple RNA mediated processes in the tammar, including gene regulation, species incompatibilities, centromere and chromosome function.

  9. Uncovering Recovery: The Resistible Rise of Recovery and Resilience

    Directory of Open Access Journals (Sweden)

    David Harper

    2012-10-01

    Full Text Available Discourses of recovery and resilience have risen to positions of dominance in the mental health field. Models of recovery and resilience enjoy purchase, in both policy and practice, across a range of settings from self-described psychiatric survivors through to mental health charities through to statutory mental health service providers. Despite this ubiquity, there is confusion about what recovery means. In this article we problematize notions of recovery and resilience, and consider what, if anything, should be recovered from these concepts. We focus on three key issues, i individualization, ii the persistence of a deficit model, and iii collective approaches to recovery. Through documentary analysis we consider these issues across third sector organizations, and public and mental health policy. Firstly, definitional debates about recovery reflect wider ideological debates about the nature of mental health. The vagueness of these concepts and implicit assumptions inherent in dominant recovery and resilience discourses render them problematic because they individualize what are social problems. Secondly, these discourses, despite being seen as inherently liberatory are conceptually dependent on a notion of deficit in that talk of “positives” and “strengths” requires the existence of “negatives” and “weaknesses” for these concepts to make sense.  We argue that this does little to substantially transform dominant understandings of psychological distress. Thirdly, these issues combine to impact upon the progressive potential of recovery. It comes to be seen as an individualistic experiential narrative accompaniment to medical understandings where the structural causes of distress are obscured. This in turn impacts upon the potential for recovery to be used to explore more collective, political aspects of emotional distress. Drawing on the work of Fraser, we use this critique to characterize “recovery” as a “struggle for

  10. AB039. Novel Y-chromosomal microdeletions associated with non-obstructive azoospermia uncovered by high throughput sequencing of sequence-tagged sites (STSs)

    OpenAIRE

    Li, Zesong

    2016-01-01

    Y-chromosomal microdeletion (YCM) serves as an important genetic factor in non-obstructive azoospermia (NOA). Multiplex polymerase chain reaction (PCR) is routinely used to detect YCMs by tracing sequence-tagged sites (STSs) in the Y chromosome. Here we introduce a novel methodology in which we sequence 1,787 (post-filtering) STSs distributed across the entire male-specific Y chromosome (MSY) in parallel to uncover known and novel YCMs. We validated this approach with 766 Chinese men with NOA...

  11. RED for PMTCT: an adaptation of immunization's Reaching Every District approach increases coverage, access, and utilization of PMTCT care in Bondo District, Kenya.

    Science.gov (United States)

    Kanyuuru, Lynn; Kabue, Mark; Ashengo, Tigistu A; Ruparelia, Chandrakant; Mokaya, Evans; Malonza, Isaac

    2015-06-01

    Gaps exist in coverage, early access, and utilization of prevention of mother-to-child transmission of HIV (PMTCT) services in Kenya. The Maternal and Child Health Integrated Program, led by Jhpiego, piloted an adaptation of immunization's Reaching Every District (RED) approach in Bondo District as a way of improving PMTCT care. Routine district-level monthly summary service delivery pre- and post-implementation data were analyzed. Marked improvements resulted in the proportion of HIV-infected and non-infected pregnant women completing four focused prenatal care visits, from 25% to 41%, and the proportion of HIV-exposed infants (HEIs) tested at six weeks, from 27% to 78% (PHIV infection at 12months was 52%, while 77% of HEIs were issued antiretroviral prophylaxis by the end of the pilot. Implementation of RED for PMTCT demonstrated that PMTCT services can be delivered effectively in the context of the existing community strategy and resulted in increased coverage, access, and utilization of care for HIV-positive pregnant women and their children. PMID:26115861

  12. Vaporous Marketing: Uncovering Pervasive Electronic Cigarette Advertisements on Twitter

    Science.gov (United States)

    Jones, Chris A.; Williams, Jake Ryland; Kurti, Allison N.; Norotsky, Mitchell Craig; Danforth, Christopher M.; Dodds, Peter Sheridan

    2016-01-01

    Background Twitter has become the “wild-west” of marketing and promotional strategies for advertisement agencies. Electronic cigarettes have been heavily marketed across Twitter feeds, offering discounts, “kid-friendly” flavors, algorithmically generated false testimonials, and free samples. Methods All electronic cigarette keyword related tweets from a 10% sample of Twitter spanning January 2012 through December 2014 (approximately 850,000 total tweets) were identified and categorized as Automated or Organic by combining a keyword classification and a machine trained Human Detection algorithm. A sentiment analysis using Hedonometrics was performed on Organic tweets to quantify the change in consumer sentiments over time. Commercialized tweets were topically categorized with key phrasal pattern matching. Results The overwhelming majority (80%) of tweets were classified as automated or promotional in nature. The majority of these tweets were coded as commercialized (83.65% in 2013), up to 33% of which offered discounts or free samples and appeared on over a billion twitter feeds as impressions. The positivity of Organic (human) classified tweets has decreased over time (5.84 in 2013 to 5.77 in 2014) due to a relative increase in the negative words ‘ban’, ‘tobacco’, ‘doesn’t’, ‘drug’, ‘against’, ‘poison’, ‘tax’ and a relative decrease in the positive words like ‘haha’, ‘good’, ‘cool’. Automated tweets are more positive than organic (6.17 versus 5.84) due to a relative increase in the marketing words like ‘best’, ‘win’, ‘buy’, ‘sale’, ‘health’, ‘discount’ and a relative decrease in negative words like ‘bad’, ‘hate’, ‘stupid’, ‘don’t’. Conclusions Due to the youth presence on Twitter and the clinical uncertainty of the long term health complications of electronic cigarette consumption, the protection of public health warrants scrutiny and potential regulation of social media

  13. Uncovering the components of the Francisella tularensis Virulence stealth strategy

    Directory of Open Access Journals (Sweden)

    Bradley D Jones

    2014-03-01

    Full Text Available Over the last decade, studies on the virulence of the highly pathogenic intracellular bacterial pathogen Francisella tularensis have increased dramatically. The organism produces an inert LPS, a capsule, escapes the phagosome to grow in the cytosol (encoded by the FPI genes of a variety of host cell types that include epithelial, endothelial, dendritic, macrophage and neutrophil. This review focuses on the work that has identified and characterized individual virulence factors of this organism and we hope to highlight how these factors collectively function to produce the pathogenic strategy of this pathogen. In addition, several recent studies have been published characterizing F. tularensis mutants that induce host immune responses not observed in wild type F. tularensis strains that can induce protection against challenge with virulent F. tularensis. As more detailed studies with attenuated strains are performed, it will be possible to see how host models develop acquired immunity to Francisella. Collectively, detailed insights into the mechanisms of virulence of this pathogen are emerging that will allow the design of anti-infective strategies.

  14. Uncover the electroluminescence in wide band gap polymers

    Science.gov (United States)

    Qiao, B.; Teyssedre, G.; Laurent, C.

    2015-10-01

    Due to the rapidly increasing demand of electric power, insulating materials used in electrical components are pushed up to their limits, where their electronic properties are of fundamental importance. Electroluminescence provides an elegant way to investigate electronic properties, high field effects and electrical ageing of polymers although the emission spectrum is still poorly understood. Unlike in organic semi-conductors, electroluminescence spectra of large band gap polymers exhibit specific spectral features that cannot be interpreted on the basis of the photo-physical properties of the material. By irradiating polypropylene thin films with electrons up to a few keV and by analyzing the emitted light, we were able to isolate the elementary components of the emission and to reconstruct the electroluminescence spectrum. For the first time, a comprehensive study of electroluminescence in polymers is provided and the underlying mechanisms of the emission are discussed. The results herein provide an univocal demonstration that the electroluminescence from wide band gap polymers results in part from chemical reactions, opening the way to the diagnosis and prognosis of polymeric materials under electrical stress.

  15. Uncovering Spatial Variation in Acoustic Environments Using Sound Mapping.

    Science.gov (United States)

    Job, Jacob R; Myers, Kyle; Naghshineh, Koorosh; Gill, Sharon A

    2016-01-01

    Animals select and use habitats based on environmental features relevant to their ecology and behavior. For animals that use acoustic communication, the sound environment itself may be a critical feature, yet acoustic characteristics are not commonly measured when describing habitats and as a result, how habitats vary acoustically over space and time is poorly known. Such considerations are timely, given worldwide increases in anthropogenic noise combined with rapidly accumulating evidence that noise hampers the ability of animals to detect and interpret natural sounds. Here, we used microphone arrays to record the sound environment in three terrestrial habitats (forest, prairie, and urban) under ambient conditions and during experimental noise introductions. We mapped sound pressure levels (SPLs) over spatial scales relevant to diverse taxa to explore spatial variation in acoustic habitats and to evaluate the number of microphones needed within arrays to capture this variation under both ambient and noisy conditions. Even at small spatial scales and over relatively short time spans, SPLs varied considerably, especially in forest and urban habitats, suggesting that quantifying and mapping acoustic features could improve habitat descriptions. Subset maps based on input from 4, 8, 12 and 16 microphones differed slightly ( 4 dBA/pixel) from full maps than the remaining subset maps, but maps with input from eight microphones resulted in smaller differences. Thus, acoustic environments varied over small spatial scales and variation could be mapped with input from 4-8 microphones. Mapping sound in different environments will improve understanding of acoustic environments and allow us to explore the influence of spatial variation in sound on animal ecology and behavior. PMID:27467503

  16. Uncovering deep mysteries: the underwater life of an amphibious louse.

    Science.gov (United States)

    Leonardi, Maria Soledad; Aznar, F Javier; Crespo, Enrique A; Lazzari, Claudio R

    2014-12-01

    Despite the incredible success of insects in colonizing almost every habitat, they remain virtually absent in one major environment--the open sea. A variety of hypotheses have been raised to explain why just a few insect species are present in the ocean, but none of them appears to be fully explanatory. Lice belonging to the family Echinophthiriidae are ectoparasites on different species of pinnipeds and river otters, i.e. they have amphibious hosts, who regularly perform long excursions into the open sea reaching depths of hundreds of meters (thousands of feets). Consequently, lice must be able to support not only changes in their surrounding media, but also extreme variations in hydrostatic pressure as well as breathing in a low oxygen atmosphere. In order to shed some light on the way lice can survive during the diving excursions of their hosts, we have performed a series of experiments to test the survival capability of different instars of Antarctophthirus microchir (Phthiraptera: Anoplura) from South American sea lions Otaria flavescens, when submerged into seawater. These experiments were aimed at analyzing: (a) immersion tolerance along the louse life; (b) lice's ability to obtain oxygen from seawater; (c) physiological responses and mechanisms involved in survival underwater. Our experiments showed that the forms present in non-diving pups--i.e. eggs and first-instar nymphs--were unable to tolerate immersion in water, while following instars and adults, all usually found in diving hosts, supported it very well. Furthermore, as long as the level of oxygen dissolved in water was higher, the lice survival capability underwater increased, and the recovery period after returning to air declined. These results are discussed in relation to host ecology, host exploitation and lice functional morphology. PMID:25449903

  17. Mentoring, Task Sharing, and Community Outreach Through the TutoratPlus Approach: Increasing Use of Long-Acting Reversible Contraceptives in Senegal

    Science.gov (United States)

    Gueye, Babacar; Wesson, Jennifer; Koumtingue, Djimadoum; Stratton, Sara; Viadro, Claire; Talla, Hawa; Dioh, Etienne; Cissé, Carol; Sebikali, Boniface; Mamadou Daff, Bocar

    2016-01-01

    ABSTRACT Background: To broaden access to family planning in rural areas and improve contraceptive prevalence, Senegal, in the context of wide method choice, is promoting implants and the intrauterine device, currently used throughout the country by only 5.6% of women of reproductive age who are in union, primarily urban women. Methods: The TutoratPlus performance improvement approach strengthens family planning clinical skills, particularly for long-acting reversible contraceptives (LARCs), through mentoring, task sharing, and community outreach. Following a 2013 baseline situation analysis, 290 participating facilities in 12 of Senegal's 14 regions developed action plans to address gaps identified in 3 areas: provider performance, equipment, and infrastructure. Between 2013 and 2014, 85 trained mentors coached, demonstrated skills, and observed 857 providers, including nurses, nonclinical family planning counselors, and community health workers (CHWs), in LARC service provision through two 5-day visits per facility at 21-day intervals. We used routine service delivery data and TutoratPlus mentoring data to assess changes in contraceptive use, including LARCs, 6 months before and 6 months after the mentoring intervention among 100 of the facilities with complete data. Results: The baseline assessment of 290 facilities found that fewer than half (47%) had a provider who could offer at least 1 LARC method, and 64% to 69% lacked kits. Post-intervention, all 290 facilities were adequately equipped and clinically able to offer LARCs. Among the 552 clinical providers, the percentage with acceptable LARC performance (at least 80% of observation checklist items correct) doubled from 32% to 67% over the 2 mentoring visits. In the 100 facilities with available comparison data, the number of new LARC users rose from 1,552 to 2,879 in the 6 months pre- and post-intervention—an 86% increase. Conclusion: Success of the TutoratPlus approach in Senegal is likely in part

  18. From horizon to torus: Uncovering supermassive black hole systems

    Science.gov (United States)

    Murphy, Kendrah

    2009-06-01

    The complexity of the structure and behavior of AGNs is often imprinted in the Fe K line emission in their X-ray spectra. We present a study of the Seyfert galaxy NGC 2992 with RXTE and Suzaku , which highlights this complexity, as we find evidence of both persistent emission from the accretion disk and from matter more distant from the central black hole (i.e., the putative obscuring torus), as well as short-term flaring emission from the accretion disk. Future X-ray instrumentation is expected to allow us to significantly improve the constraints derived from the Fe K lines in AGN, such as the black-hole angular momentum (spin) and the inclination angle of the putative accretion disk. However, significant model-dependence and degeneracy will persist with radially-integrated Fe K line profiles, so we have investigated the feasibility of utilizing Fe K line emission from localized orbiting flares ("hotspots") to provide a more robust measure of black-hole spin. In addition to affecting the persistent and transient Fe K line emission, the physical structure, geometry, and orientation of the central engine harboring the black hole furthermore effect the observed continuum in specific ways. It is therefore necessary to self-consistently model the continuum and emission lines in order to derive constraints on the physical parameters of the system. Improved X-ray spectral data quality has facilitated the ability to disentangle some of the spectral components, but the increased spectral complexity creates a need for more sophisticated models. Such a need has arisen with respect to the X-ray spectra of obscured AGN. To that end, we describe a new X-ray spectral model, based on Monte-Carlo simulations of the toroidal reprocessor, that will allow one to self-consistently fit for the line emission from distant matter as well as the associated Compton-scattered continuum. The model is valid for arbitrary incident spectra and can therefore be combined with models of

  19. Using Consumer Preference Information to Increase the Reach and Impact of Media-Based Parenting Interventions in a Public Health Approach to Parenting Support

    Science.gov (United States)

    Metzler, Carol W.; Sanders, Matthew R.; Rusby, Julie C.; Crowley, Ryann N.

    2012-01-01

    Within a public health approach to improving parenting, the mass media offer a potentially more efficient and affordable format for directly reaching a large number of parents with evidence-based parenting information than do traditional approaches to parenting interventions that require delivery by a practitioner. Little is known, however, about…

  20. Chemical Analysis: An Indispensable Means for Uncovering Severe Cases of Fraud with Cosmetics and Tattoo Inks.

    Science.gov (United States)

    Hohl, Christopher; Hauri, Urs

    2016-01-01

    Three cases of fraud with commodities containing illegal stealth compounds are presented, which were uncovered by the State Laboratory Basel-City, Switzerland. All three commodities, grapefruit seed extracts, a phytocosmetical skin cream, and tattoo inks, were produced abroad, had forged declarations of ingredients and, in the case of the extracts and the cream, were marketed with far-reaching health claims. While inspections will identify suspicious products and would be able to eliminate health claims to some extent, only chemical analysis can uncover the illegal agents used and give law enforcement bodies the necessary evidence to immediately clamp down on those brands, where the stealth agent presents a serious health hazard to consumers. PMID:27198815

  1. Using Consumer Preference Information to Increase the Reach and Impact of Media-Based Parenting Interventions in a Public Health Approach to Parenting Support

    OpenAIRE

    Metzler, Carol W.; Sanders, Matthew R; Rusby, Julie C.; Crowley, Ryann

    2011-01-01

    Within a public health approach to improving parenting, the mass media offer a potentially more efficient and affordable format for directly reaching a large number of parents with evidence-based parenting information than do traditional approaches to parenting interventions that require delivery by a practitioner. Little is known, however, about factors associated with parents’ interest in and willingness to watch video messages about parenting. Knowledge of consumer preferences could inform...

  2. WeSME: Uncovering Mutual Exclusivity of Cancer Drivers and Beyond

    OpenAIRE

    Kim, Yoo-Ah; Madan, Sanna; Przytycka, Teresa M.

    2016-01-01

    Mutual exclusivity is a widely recognized property of many cancer drivers. Knowledge about these relationships can provide important insights into cancer drivers, cancer-driving pathways, and cancer subtypes. It can also be used to predict new functional interactions between cancer driving genes and uncover novel cancer drivers. Currently, most of mutual exclusivity analyses are preformed focusing on a limited set of genes in part due to the computational cost required to rigorously compute p...

  3. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

    OpenAIRE

    Kilpeläinen, Tuomas O; Carli, Jayne F Martin; Skowronski, Alicja A.; Sun, Qi; Kriebel, Jennifer; Feitosa, Mary F.; Hedman, Åsa K.; Drong, Alexander W.; Hayes, James E.; Zhao, Jinghua; Pers, Tune H; Schick, Ursula; Grarup, Niels; Kutalik, Zoltán; Trompet, Stella

    2016-01-01

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P

  4. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

    OpenAIRE

    Kilpeläinen, Tuomas O; Carli, Jayne F Martin; Skowronski, Alicja A.; Sun, Qi; Kriebel, Jennifer; Feitosa, Mary F.; Hedman, Åsa K.; Drong, Alexander W.; Hayes, James E.; Zhao, Jinghua; Pers, Tune H; Schick, Ursula; Grarup, Niels; Kutalik, Zoltán; Trompet, Stella

    2016-01-01

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P < 10(-6) in 19,979 additional individuals. We i...

  5. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

    OpenAIRE

    Kilpeläinen, Tuomas O; Carli, Jayne F Martin; Skowronski, Alicja A.; Sun, Qi; Kriebel, Jennifer; Feitosa, Mary F.; Hedman, Åsa K.; Drong, Alexander W.; Hayes, James E.; Zhao, Jinghua; Pers, Tune H; Schick, Ursula; Grarup, Niels; Kutalik, Zoltán; Trompet, Stella

    2016-01-01

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10−6 in 19,979 additional individuals. We ident...

  6. Genetic algorithms and Gaussian Bayesian networks to uncover the predictive core set of bibliometric indices

    OpenAIRE

    Ibáñez Martín, Alfonso; Armañanzas Arnedillo, Ruben; Bielza Lozoya, Maria Concepcion; Larrañaga Múgica, Pedro

    2015-01-01

    The diversity of bibliometric indices today poses the challenge of exploiting the relationships among them. Our research uncovers the best core set of relevant indices for predicting other bibliometric indices. An added difficulty is to select the role of each variable, that is, which bibliometric indices are predictive variables and which are response variables. This results in a novel multioutput regression problem where the role of each variable (predictor or respon...

  7. Endoscopic management of occluded biliary uncovered metal stents:A multicenter experience

    Institute of Scientific and Technical Information of China (English)

    Panagiotis Katsinelos; Kostas Fasoulas; Stefanos Atmatzidis; Christos Zavos; Jannis Kountouras; Athanasios Beltsis; Grigoris Chatzimavroudis; Dimitris Paikos; George Paroutoglou; Dimitris Kapetanos; Sotiris Terzoudis; Georgia Lazaraki; Ioannis Pilpilidis

    2011-01-01

    AIM:To compare diverse endoscopic interventions in the management of occluded uncovered self-expanding metal stents(SEMSs)that had been placed for palliative treatment of unresectable malignant biliary obstruction.METHODS:A retrospective review was undertaken in 4 tertiary endoscopic centers to determine optimal management of different types of occluded SEMSs.The technical success of performed treatment in occluded SEMSs,the patency of the stent,the need for re-intervention and the financial costs of each treatment were analyzed.RESULTS:Fifty four patients were included in the analysis;21 received Hanaro,19 Wallstent and 14 Flexus.For the relief of obstruction,a plastic stent was inserted in 24 patients,a second SEMS in 25 and mechanical cleaning was performed in 5 patients.The overall median second patency rates between second SEMSs and plastic stents did not differ(133 d for SEMSs vs 106 d for plastic stents;P = 0.856).Similarly,no difference was found between the overall survival of SEMS and plastic stent groups,and no procedure-related complications occurred.Incremental cost analysis showed that successive plastic stenting was a cost-saving strategy at least in Greece.CONCLUSION:Insertion of uncovered SEMSs or plastic stents is a safe and effective treatment for occluded uncovered SEMSs;insertion of plastic stents appears to be the most cost-effective strategy.

  8. Nanomedicine for therapeutic drug therapy: Approaches to increase the efficacy of drug therapy with nanoemulsion delivery and reduce the toxicity of quantum dots

    Science.gov (United States)

    Kambalapally, Swetha Reddy

    The advancement of nanotechnology has paved the way for novel nanoscale materials for use in a wide range of applications. The use of these nanomaterials in biomedicine facilitates the improvement of existing technologies for disease prevention and treatment through diagnostics, tumor detection, drug delivery, medical imaging and vaccine development. Nanotechnology delivery systems for therapeutic uses includes the formulation of nanoparticles in emulsions. These novel delivery systems can improve drug efficacy by their ability to enhance bioavailability, minimize drug side effects, decrease drug toxicity, provide targeted site delivery and increase circulation of the drug in the blood. Additionally, these delivery systems also improve the drug stability and encapsulation efficiency. In the Introduction, this thesis will describe a novel technique for the preparation of nanoemulsions which was utilized in drug delivery and diagnostic applications. This novel Phase Inversion Temperature (PIT) method is a solvent and polymer-free and low energy requiring emulsification method, typically utilizing oils stabilized by nonionic surfactants to prepare water in oil (W/O) emulsions. The correlation between the particle size, zeta potential and the emulsion stability is described. The use of this nanoemulsion delivery system for pharmaceuticals and nutraceuticals by utilizing in vitro systems was investigated. Using the PIT method, a self assembling nanoemulsion (SANE) of gamma Tocotrienols (gammaT3), a component of Vitamin E family has been demonstrated to reduce cholesterol accumulation in HepG-2 cells. The nanoemulsion is stable and the particle size is around 20 nm with a polydispersity index (PDI) of 0.065. The effect of the nano gammaT3 on the metabolism of cholesterol, HMG-CoA activity and Apo-B levels were evaluated in an in vitro system utilizing HepG2 cells. A new class of nanoparticles, Quantum dots (QDs) has shown immense potential as novel nanomaterials used as

  9. Benevolent Paradox: Integrating Community-Based Empowerment and Transdisciplinary Research Approaches into Traditional Frameworks to Increase Funding and Long-Term Sustainability of Chicano-Community Research Programs

    Science.gov (United States)

    de la Torre, Adela

    2014-01-01

    Niños Sanos, Familia Sana (NSFS) is a 5-year multi-intervention study aimed at preventing childhood obesity among Mexican-origin children in rural California. Using a transdisciplinary approach and community-based participatory research (CBPR) methodology, NSFS's development included a diversely trained team working in collaboration with…

  10. Flipped Classroom Modules for Large Enrollment General Chemistry Courses: A Low Barrier Approach to Increase Active Learning and Improve Student Grades

    Science.gov (United States)

    Eichler, Jack F.; Peeples, Junelyn

    2016-01-01

    In the face of mounting evidence revealing active learning approaches result in improved student learning outcomes compared to traditional passive lecturing, there is a growing need to change the way instructors teach large introductory science courses. However, a large proportion of STEM faculty continues to use traditional instructor-centered…

  11. Developing an analytical model to increase urban security from the Secured perspective by Designing (SBD Approach using fuzzy AHP method (case study: region 17 of Tehran

    Directory of Open Access Journals (Sweden)

    H. Zabihi

    2013-01-01

    to capture the vagueness of human thinking style and effectively solve multi-criteria decision making problems.Results of applying the model in studied area (region 3 of district 17 show that in order to achieve urban security, ‘physical security’ is the most important principle. In addition, the most significant sub-criteria determined to be ‘Good quality of public realm’, ‘Create defensible space’ with importance weights of 0.116 and 0.110, respectively. Finally, evaluating quadratic areas of the case study revealed that area 4 and area 1 with weights of 0.404 and 0.096 respectively are the best and worst areas in terms of urban security. 5– SuggestionsBased on analyzing the results, guidelines have been suggested in order to promote urban security level:-Protecting City equipments against vandalism and repairing or replacing them by municipality-Replacement of population absorber land use to the areas with low surveillance and control-Having coherent and continuous surveillance on entrances-Improving physical environment and safety through enhancing facilities and services-Increasing feeling of security among residents-Continuous space use by citizens through environmental design strategies-Defining special function to attract people and affect social activitiesKey words: Urban Security, Secured by Design (SBD approach, Region 17 of Tehran, Fuzzy Analytic Hierarchy Process (FAHP, Guidelines and Strategies.RefrencesArmitage, R. (2004. Secured by design-an investigation of its history, development and future role in crime reduction. Doctor of Philosophy thesis, The University of Huddersfield.Armitage, R., & Monchuk, L. (2009. Reconciling security with sustainability: the challenge for eco-homes. Built Environment, 35(3, 308-327.Atlas, R. Atlas safety and security design, INC, from http://www.cpted-security.comBrantingham, P. L., & Brantingham, P. J. (1993. Nodes, paths and edges: Considerations on the complexity of crime and the physical environment

  12. An increase of cereal intake as an approach to weight reduction in children is effective only when accompanied by nutrition education: a randomized controlled trial

    OpenAIRE

    García Olga P; Montemayor Karina; del R Arellano María; Rosado Jorge L.; Caamaño María del C

    2008-01-01

    Abstract Background The main emphasis of dietary advice for control of obesity has been on reducing dietary fat. Increasing ready to eat cereal (RTEC) consumption could be a strategy to reduce fat intake and increase carbohydrate intake resulting in a diet with lower energy density. Objectives 1. To determine if an increase in RTEC intake is an effective strategy to reduce excess body weight and blood lipids in overweight or at risk of overweight children. 2. To determine if a nutrition educa...

  13. An uncovered XIII century icon: Particular use of organic pigments and gilding techniques highlighted by analytical methods

    Science.gov (United States)

    Daveri, Alessia; Doherty, Brenda; Moretti, Patrizia; Grazia, Chiara; Romani, Aldo; Fiorin, Enrico; Brunetti, Brunetto Giovanni; Vagnini, Manuela

    2015-01-01

    The restoration of a panel painting depicting a Madonna and Child listed as an unknown Tuscan artist of the nineteenth century, permitted the hidden original version, a XIII century Medieval icon to be uncovered. It is discovery provided the opportunity for an extensive in situ campaign of non-invasive analytical investigations by portable imaging and spectroscopic techniques (infrared, X-ray fluorescence and diffraction, UV-Vis absorption and emission), followed by aimed micro-destructive investigations (Raman and SEM-EDS). This approach permitted characterization of the original ground and paint layers by complementary techniques. Furthermore, this protocol allowed supplementary particularities of great interest to be highlighted. Namely, numerous original gilding techniques have been accentuated in diverse areas and include the use of surrogate gold (disulphur tin), orpiment as a further false gold and an area with an original silver rich layer. Moreover, pigments including azurite mixed with indigo have been non-invasively identified. Micro-invasive analyses also allowed the diagnosis of organic colorants, namely, an animal anthraquinone lake, kermes and an unusual vegetal chalcone pigment, possibly safflower. The identification of the latter is extremely rare as a painting pigment and has been identified using an innovative adaption to surface enhanced Raman techniques on a cross-section. The resulting data contributes new hypotheses to the historic and artistic knowledge of materials and techniques utilized in XIII century icon paintings and ultimately provides scientific technical support of the recent restoration.

  14. X-ray Microscopy as an Approach to Increasing Accuracy and Efficiency of Serial Block-face Imaging for Correlated Light and Electron Microscopy of Biological Specimens

    OpenAIRE

    Bushong, Eric A; Johnson, Donald D.; Kim, Keun-Young; Terada, Masako; Hatori, Megumi; Peltier, Steven T.; Panda, Satchidananda; Merkle, Arno; Ellisman, Mark H.

    2014-01-01

    The recently developed three-dimensional electron microscopic (EM) method of serial block-face scanning electron microscopy (SBEM) has rapidly established itself as a powerful imaging approach. Volume EM imaging with this scanning electron microscopy (SEM) method requires intense staining of biological specimens with heavy metals to allow sufficient back-scatter electron signal and also to render specimens sufficiently conductive to control charging artifacts. These more extreme heavy metal s...

  15. The Impact of Increasing Stock Market Integration on Expected Gains from International Portfolio Diversification: Evidence from a Multivariate Approach with Time Varying Risk.

    OpenAIRE

    Arouri, Mohamed El Hedi

    2004-01-01

    This paper tests a conditional International Asset Pricing Model (ICAPM) using an asymmetric multivariate GARCH specification and investigates evolutions of ex ante benefits from world market diversification. The model is estimated simultaneously for 8 markets: the world market, 4 developed markets and 3 emerging markets. This approach allows to the price of market risk, betas and correlations to vary through time. The evidence supports the financial integration hypothesis and suggests that i...

  16. Increase in Thiol Oxidative Stress via Glutathione Reductase Inhibition as a Novel Approach to Enhance Cancer Sensitivity to X-Ray Irradiation

    OpenAIRE

    Zhao, Yong; Seefeldt, Teresa; Chen, Wei; Carlson, Laura; Stoebner, Adam; Hanson, Sarah; Foll, Ryan; Matthees, Duane P.; Palakurthi, Srinath; Guan, Xiangming

    2009-01-01

    Depletion of reduced form glutathione (GSH) has been extensively studied for its effect on sensitizing cancer to radiation. However, little is known about the effect of thiol oxidative stress created through an increase in glutathione disulfide (GSSG) on cancer sensitivity to radiation. In this study, an increase in GSSG was effectively created by 2-acetylamino-3-[4-(2-acetylamino-2-carboxyethylsulfanylthiocarbonylamino)phenylthiocarbamoylsulfanyl]propionic acid (2-AAPA), an irreversible glut...

  17. Increase in thiol oxidative stress via glutathione reductase inhibition as a novel approach to enhance cancer sensitivity to X-ray irradiation.

    Science.gov (United States)

    Zhao, Yong; Seefeldt, Teresa; Chen, Wei; Carlson, Laura; Stoebner, Adam; Hanson, Sarah; Foll, Ryan; Matthees, Duane P; Palakurthi, Srinath; Guan, Xiangming

    2009-07-15

    Depletion of the reduced form of glutathione (GSH) has been extensively studied for its effect on sensitizing cancer to radiation. However, little is known about the effects of thiol oxidative stress created through an increase in glutathione disulfide (GSSG) on cancer sensitivity to radiation. In this study, an increase in GSSG was effectively created using 2-acetylamino-3-[4-(2-acetylamino-2-carboxyethylsulfanylthiocarbonylamino)phenylthiocarbamoylsulfanyl]propionic acid (2-AAPA), an irreversible glutathione reductase (GR) inhibitor. Our results demonstrate that the GSSG increase significantly enhanced cancer sensitivity to X-ray irradiation in four human cancer cell lines (A431, MCF7, NCI-H226, and OVCAR-3). When cells were pretreated with 2-AAPA followed by X-ray irradiation, the IC(50) values for X-ray irradiation of A431, MCF7, NCI-H226, and OVCAR-3 cells were reduced, from 24.2 +/- 2.8, 42.5 +/- 3.0, 43.0 +/- 3.6, and 27.8+/-3.5 Gy to 6.75 +/- 0.9, 8.1 +/- 1.1, 6.75 +/- 1.0, and 12.1 +/- 1.7 Gy, respectively. The synergistic effects observed from the combination of X-rays plus 2-AAPA were comparable to those from the combination of X-rays plus buthionine sulfoximine, a reference compound known to increase cancer sensitivity to radiation. The synergistic effect was correlated with an increase in cell thiol oxidative stress, which was reflected by a five-to sixfold increase in GSSG and 25% increase in total disulfides. No change in GSH or total thiols was observed as a result of GR inhibition. PMID:19397999

  18. The invisible Web uncovering information sources search engines can't see

    CERN Document Server

    Sherman, Chris

    2001-01-01

    Enormous expanses of the Internet are unreachable with standard web search engines. This book provides the key to finding these hidden resources by identifying how to uncover and use invisible web resources. Mapping the invisible Web, when and how to use it, assessing the validity of the information, and the future of Web searching are topics covered in detail. Only 16 percent of Net-based information can be located using a general search engine. The other 84 percent is what is referred to as the invisible Web-made up of information stored in databases. Unlike pages on the visible Web, informa

  19. Genome engineering uncovers 54 evolutionarily conserved and testis-enriched genes that are not required for male fertility in mice.

    Science.gov (United States)

    Miyata, Haruhiko; Castaneda, Julio M; Fujihara, Yoshitaka; Yu, Zhifeng; Archambeault, Denise R; Isotani, Ayako; Kiyozumi, Daiji; Kriseman, Maya L; Mashiko, Daisuke; Matsumura, Takafumi; Matzuk, Ryan M; Mori, Masashi; Noda, Taichi; Oji, Asami; Okabe, Masaru; Prunskaite-Hyyrylainen, Renata; Ramirez-Solis, Ramiro; Satouh, Yuhkoh; Zhang, Qian; Ikawa, Masahito; Matzuk, Martin M

    2016-07-12

    Gene-expression analysis studies from Schultz et al. estimate that more than 2,300 genes in the mouse genome are expressed predominantly in the male germ line. As of their 2003 publication [Schultz N, Hamra FK, Garbers DL (2003) Proc Natl Acad Sci USA 100(21):12201-12206], the functions of the majority of these testis-enriched genes during spermatogenesis and fertilization were largely unknown. Since the study by Schultz et al., functional analysis of hundreds of reproductive-tract-enriched genes have been performed, but there remain many testis-enriched genes for which their relevance to reproduction remain unexplored or unreported. Historically, a gene knockout is the "gold standard" to determine whether a gene's function is essential in vivo. Although knockout mice without apparent phenotypes are rarely published, these knockout mouse lines and their phenotypic information need to be shared to prevent redundant experiments. Herein, we used bioinformatic and experimental approaches to uncover mouse testis-enriched genes that are evolutionarily conserved in humans. We then used gene-disruption approaches, including Knockout Mouse Project resources (targeting vectors and mice) and CRISPR/Cas9, to mutate and quickly analyze the fertility of these mutant mice. We discovered that 54 mutant mouse lines were fertile. Thus, despite evolutionary conservation of these genes in vertebrates and in some cases in all eukaryotes, our results indicate that these genes are not individually essential for male mouse fertility. Our phenotypic data are highly relevant in this fiscally tight funding period and postgenomic age when large numbers of genomes are being analyzed for disease association, and will prevent unnecessary expenditures and duplications of effort by others. PMID:27357688

  20. Genome engineering uncovers 54 evolutionarily conserved and testis-enriched genes that are not required for male fertility in mice

    Science.gov (United States)

    Miyata, Haruhiko; Castaneda, Julio M.; Fujihara, Yoshitaka; Yu, Zhifeng; Archambeault, Denise R.; Isotani, Ayako; Kiyozumi, Daiji; Kriseman, Maya L.; Mashiko, Daisuke; Matsumura, Takafumi; Matzuk, Ryan M.; Mori, Masashi; Noda, Taichi; Oji, Asami; Okabe, Masaru; Prunskaite-Hyyrylainen, Renata; Ramirez-Solis, Ramiro; Satouh, Yuhkoh; Zhang, Qian; Ikawa, Masahito; Matzuk, Martin M.

    2016-01-01

    Gene-expression analysis studies from Schultz et al. estimate that more than 2,300 genes in the mouse genome are expressed predominantly in the male germ line. As of their 2003 publication [Schultz N, Hamra FK, Garbers DL (2003) Proc Natl Acad Sci USA 100(21):12201–12206], the functions of the majority of these testis-enriched genes during spermatogenesis and fertilization were largely unknown. Since the study by Schultz et al., functional analysis of hundreds of reproductive-tract–enriched genes have been performed, but there remain many testis-enriched genes for which their relevance to reproduction remain unexplored or unreported. Historically, a gene knockout is the “gold standard” to determine whether a gene’s function is essential in vivo. Although knockout mice without apparent phenotypes are rarely published, these knockout mouse lines and their phenotypic information need to be shared to prevent redundant experiments. Herein, we used bioinformatic and experimental approaches to uncover mouse testis-enriched genes that are evolutionarily conserved in humans. We then used gene-disruption approaches, including Knockout Mouse Project resources (targeting vectors and mice) and CRISPR/Cas9, to mutate and quickly analyze the fertility of these mutant mice. We discovered that 54 mutant mouse lines were fertile. Thus, despite evolutionary conservation of these genes in vertebrates and in some cases in all eukaryotes, our results indicate that these genes are not individually essential for male mouse fertility. Our phenotypic data are highly relevant in this fiscally tight funding period and postgenomic age when large numbers of genomes are being analyzed for disease association, and will prevent unnecessary expenditures and duplications of effort by others. PMID:27357688

  1. PPARalpha siRNA-treated expression profiles uncover the causal sufficiency network for compound-induced liver hypertrophy.

    Directory of Open Access Journals (Sweden)

    Xudong Dai

    2007-03-01

    Full Text Available Uncovering pathways underlying drug-induced toxicity is a fundamental objective in the field of toxicogenomics. Developing mechanism-based toxicity biomarkers requires the identification of such novel pathways and the order of their sufficiency in causing a phenotypic response. Genome-wide RNA interference (RNAi phenotypic screening has emerged as an effective tool in unveiling the genes essential for specific cellular functions and biological activities. However, eliciting the relative contribution of and sufficiency relationships among the genes identified remains challenging. In the rodent, the most widely used animal model in preclinical studies, it is unrealistic to exhaustively examine all potential interactions by RNAi screening. Application of existing computational approaches to infer regulatory networks with biological outcomes in the rodent is limited by the requirements for a large number of targeted permutations. Therefore, we developed a two-step relay method that requires only one targeted perturbation for genome-wide de novo pathway discovery. Using expression profiles in response to small interfering RNAs (siRNAs against the gene for peroxisome proliferator-activated receptor alpha (Ppara, our method unveiled the potential causal sufficiency order network for liver hypertrophy in the rodent. The validity of the inferred 16 causal transcripts or 15 known genes for PPARalpha-induced liver hypertrophy is supported by their ability to predict non-PPARalpha-induced liver hypertrophy with 84% sensitivity and 76% specificity. Simulation shows that the probability of achieving such predictive accuracy without the inferred causal relationship is exceedingly small (p < 0.005. Five of the most sufficient causal genes have been previously disrupted in mouse models; the resulting phenotypic changes in the liver support the inferred causal roles in liver hypertrophy. Our results demonstrate the feasibility of defining pathways mediating drug

  2. Truth concealed behind "Zero Increase of Total Water Use" and coordination approach of socio-economic and eco-environmental water uses in the Weihe River Basin, China

    OpenAIRE

    Jia, Y.; Wei, N; Hao, C.; You, J.; Niu, C.; Qiu, Y

    2014-01-01

    The water resources situation in the water-stressed Weihe River Basin, China, is more serious now than ever before because of a decrease in water resources and socio-economic development. A "Zero increase of socio-economic water use" in recent years gives people a wrong understanding and conceals the water crisis in the basin because the socio-economic water consumption has actually increased. Water use for the hydro-ecological system has been greatly reduced by a decrease in water resources ...

  3. Man up Monday: An Integrated Public Health Approach to Increase Sexually Transmitted Infection Awareness and Testing among Male Students at a Midwest University

    Science.gov (United States)

    Anderson, Elizabeth A.; Eastman-Mueller, Heather P.; Henderson, Scott; Even, Susan

    2016-01-01

    Objective: This campaign sought to (a) increase awareness of sexual health and chlamydia testing; (b) motivate students, particularly sexually active men who do not pursue regular sexually transmitted infection (STI) testing, to get tested; and (c) improve the capacity of the student health center to provide free chlamydia testing and treatment…

  4. No Place to Hide: Missing Primitive Stars Outside Milky Way Uncovered

    Science.gov (United States)

    2010-02-01

    After years of successful concealment, the most primitive stars outside our Milky Way galaxy have finally been unmasked. New observations using ESO's Very Large Telescope have been used to solve an important astrophysical puzzle concerning the oldest stars in our galactic neighbourhood - which is crucial for our understanding of the earliest stars in the Universe. "We have, in effect, found a flaw in the forensic methods used until now," says Else Starkenburg, lead author of the paper reporting the study. "Our improved approach allows us to uncover the primitive stars hidden among all the other, more common stars." Primitive stars are thought to have formed from material forged shortly after the Big Bang, 13.7 billion years ago. They typically have less than one thousandth the amount of chemical elements heavier than hydrogen and helium found in the Sun and are called "extremely metal-poor stars" [1]. They belong to one of the first generations of stars in the nearby Universe. Such stars are extremely rare and mainly observed in the Milky Way. Cosmologists think that larger galaxies like the Milky Way formed from the merger of smaller galaxies. Our Milky Way's population of extremely metal-poor or "primitive" stars should already have been present in the dwarf galaxies from which it formed, and similar populations should be present in other dwarf galaxies. "So far, evidence for them has been scarce," says co-author Giuseppina Battaglia. "Large surveys conducted in the last few years kept showing that the most ancient populations of stars in the Milky Way and dwarf galaxies did not match, which was not at all expected from cosmological models." Element abundances are measured from spectra, which provide the chemical fingerprints of stars [2]. The Dwarf galaxies Abundances and Radial-velocities Team [3] used the FLAMES instrument on ESO's Very Large Telescope to measure the spectra of over 2000 individual giant stars in four of our galactic neighbours, the Fornax

  5. Detection of consensuses and treatment principles of diabetic nephropathy in traditional Chinese medicine: A new approach

    Directory of Open Access Journals (Sweden)

    Xu Tong

    2015-10-01

    Conclusion: The results suggest that the community detection-based approach is useful and feasible for uncovering consensuses and treatment principles of DN treatment in TCM, and could be used to address other similar problems in TCM.

  6. RESEARCH OF APPROACHES TO INCREASE THE EFFICIENCY OF FUNCTIONING OF RAILWAY TRANSPORT SUBDIVISIONS FROM THE POINT OF VIEW OF SUSTAINABLE DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    O. I. Kharchenko

    2014-07-01

    Full Text Available Purpose. Modern transport systems are not stable and can not stand up to the destabilizing factors. Global track record in the economic and commercial management systems is the use of the concept of sustainable development. It is necessary on the basis of analysis of literary sources to define the directions of efficiency increase of functioning of railway transport subdivisions from the point of view of sustainable development. Methodology. To achieve the purpose the features of the use of sustainable development conception and its realization were investigated at a management of the complex systems. The existent models were also analyzed in the field of efficiency increase of functioning of railway transport subdivisions. Findings. On the basis of literary sources analysis, keeping up the conceptual essence of the sustainable development, the main directions of efficiency increase of subdivisions functioning were selected. They take into account the basic requirements of steady development and should be considered as a complex. Originality. New directions to consider the efficiency increase issues from position of sustainable development were offered by the author. Three components of conceptions of sustainable development (economic, ecological and social should be examined in a balanced way. Thus, the above mentioned theoretical studies can promote the forming of new economy model corresponding to the purposes and principles of sustainable development. Practical value. The conducted analysis development confirms the necessity of researches on perspective directions of development of railway transport subdivisions, which are marked by the guidance of Ukrzaliznytsia. It enables to select basic directions for further research in the area of efficiency increase.

  7. Visual and quantitative approach to bone marrow foci of increased glucose uptake on PET/CT in a case of aplastic anaemia

    Energy Technology Data Exchange (ETDEWEB)

    Cicone, F. [Sant' Andrea Hospital, Univ. La Sapienza, Rome (Italy). Nuclear Medicine Dept.; Centre Hospitalier Univ. Vaudois (Switzerland). Nuclear Medicine; Lausanne Univ. (Switzerland); Stalder, M. [Institut Central des Hopitaux Valaisans, Sion (Switzerland). Service of Hematology; Cairoli, A. [Centre Hospitalier Univ. Vaudois (Switzerland). Service of Hematology; Lausanne Univ. (Switzerland); Bischof Delaloye, A.; Prior, J.O. [Centre Hospitalier Univ. Vaudois (Switzerland). Nuclear Medicine; Lausanne Univ. (Switzerland); Geiger, D.

    2010-07-01

    This case report shows the clinical impact of a FDG-PET/CT in the assessment of bone marrow (BM) of a patient with aplastic anemia. The feasibility of a quantitative approach to BM intensities on FDG-PET is also discussed. In the authors' opinion, a deeper understanding of the factors that might independently affect FDG uptake and the definition of normal ranges of BM SUV (standardized uptake value) might help to interpret PET/CT images. Further research is needed to understand the physio-pathological basis of FDG uptake in BM and the potential value of its quantification. The analysis of the bone marrow on PET/CT is an interesting field of research. A PET/CT scan contributed to differential diagnosis in a patient with suspected bone marrow aplasia for guiding bone marrow biopsies.

  8. Exploring the Life Expectancy Increase in Poland in the Context of CVD Mortality Fall: The Risk Assessment Bottom-Up Approach, From Health Outcome to Policies.

    Science.gov (United States)

    Kobza, Joanna; Geremek, Mariusz

    2015-01-01

    Life expectancy at birth is considered the best mortality-based summary indicator of the health status of the population and is useful for measuring long-term health changes. The objective of this article was to present the concept of the bottom-up policy risk assessment approach, developed to identify challenges involved in analyzing risk factor reduction policies and in assessing how the related health indicators have changed over time. This article focuses on the reasons of the significant life expectancy prolongation in Poland over the past 2 decades, thus includes policy context. The methodology details a bottom-up risk assessment approach, a chain of relations between the health outcome, risk factors, and health policy, based on Risk Assessment From Policy to Impact Dimension project guidance. A decline in cardiovascular disease mortality was a key factor that followed life expectancy prolongation. Among basic factors, tobacco and alcohol consumption, diet, physical activity, and new treatment technologies were identified. Poor health outcomes of the Polish population at the beginning of 1990s highlighted the need of the implementation of various health promotion programs, legal acts, and more effective public health policies. Evidence-based public health policy needs translating scientific research into policy and practice. The bottom-up case study template can be one of the focal tools in this process. Accountability for the health impact of policies and programs and legitimization of the decisions of policy makers has become one of the key questions nowadays in European countries' decision-making process and in EU public health strategy. PMID:26546595

  9. Uncovering the composition of microbial community structure and metagenomics among three gut locations in pigs with distinct fatness.

    Science.gov (United States)

    Yang, Hui; Huang, Xiaochang; Fang, Shaoming; Xin, Wenshui; Huang, Lusheng; Chen, Congying

    2016-01-01

    Uncovering the phylogenetic composition of microbial community and the potential functional capacity of microbiome in different gut locations is of great importance to pig production. Here we performed a comparative analysis of gut microbiota and metagenomics among jejunum, ileum and cecum in pigs with distinct fatness. 16S rRNA gene sequencing revealed dramatic differences of microbial composition, diversity and species abundance between small intestine and cecum. Clostridium and SMB53 were enriched in the small intestine, while Prevotella, Treponema, Ruminococcus and Faecalibacterium showed a higher abundance in the cecum. Functional capacity analysis of gut microbiome revealed that the microbiome of small intestine plays important roles in the metabolism of small molecule nutrients, while the microbiome of cecum has the stronger ability to degrade xylan, pectin and cellulose. We identified tens of fatness associated-bacterial species including Escherichia spp. that showed a notable increase of relative abundance in all three gut locations of high fatness pigs. We further suggested that the potential pathogens, inflammation process, and microbial metabolism and nutrient sensing are involved in the high fatness of pigs. These results improve our knowledge about microbiota compositions in different gut locations, and give an insight into the effect of gut microbiota on porcine fatness. PMID:27255518

  10. The 21st Century Graduate: Delivering a Tailored Approach to Social and Emotional Competency Training for Final Year Students to Enhance Graduate Attributes and Increase Employability

    OpenAIRE

    Jameson, Ailish; Carthy, Aiden; McGuinness, Colm; McSweeney, Fiona

    2015-01-01

    The Higher Education Authority recently reported an average drop-out rate of 16% for Irish third level students, which poses significant pedagogical and economic challenges across the educational sector and negatively impacts the Irish economy. With respect to tackling this issue, a considerable body of international research has identified a strong positive correlation between higher levels of emotional intelligence (EI) and increased levels of student engagement and academic attainment. A w...

  11. Results from an experimental trial at a Head Start center to evaluate two meal service approaches to increase fruit and vegetable intake of preschool aged children

    Directory of Open Access Journals (Sweden)

    Harnack Lisa J

    2012-04-01

    Full Text Available Abstract Background Strategies to increase fruit and vegetable consumption of preschool aged children are needed. Objectives Evaluate the independent effects of the following meal service strategies on intake of fruits and vegetables of preschool children: 1. Serving fruits and vegetables in advance of other menu items as part of traditional family style meal service; and 2. Serving meals portioned and plated by providers. Methods Fifty-three preschool aged children completed a randomized crossover experiment conducted at a Head Start center in Minneapolis, MN. Over a six week trial period each of the experimental meal service strategies (serving fruits and vegetable first and serving meals portioned by providers was implemented during lunch service for two one-week periods. Two one-week control periods (traditional family style meal service with all menu items served at once were also included over the six week trial period. Childrens lunch intake was observed as a measure of food and nutrient intake during each experimental condition. Results Fruit intake was significantly higher (p Conclusions Serving fruits in advance of other meal items may be a low cost easy to implement strategy for increasing fruit intake in young children. However, serving vegetables first does not appear to increase vegetable intake. Results provide support for current recommendations for traditional family style meal service in preschool settings.

  12. Uncovering Sundanese Values by Analyzing Symbolic Meaning of Ménak Priangan Clothing (1800-1942)

    Science.gov (United States)

    Karmila, M.; Suciati; Widiaty, I.

    2016-04-01

    This study investigates symbolic meanings found in the Sunda ethnic clothing, particularly the Menak Priangan clothing. This study aims to uncover and document those symbolic meanings found in the Menak Priangan clothing as an effort to develop Sunda cultural artefacts of West Java. This study on Menak Priangan clothing applies ethnography (visual) and aesthetic methods. The visual method is utilized in order to uncover local cultural (Sunda) values found in Menak Priangan clothing visualization, including: design, model, name, and representing colours, which then directed towards local Sundanese aesthetic concepts living within the Priangan community. Furthermore, aesthetic method is used to explore role of aesthetic values in empowering visual cultural values within certain community, particularly Sunda aesthetic values. The study results show that since the 19th century, Sunda ethnic clothing was limited to Priangan Sunda only, while traditional clothing wearing by Priangan people reflects their social strata, consisting of: a. Menak Gede (Menak pangluhurna: mayor), bearing raden title, b. Menak Leutik/Santana (mayor assistant), titles: asep, mas, agus, ujang, (Nyimas for woman), c. Somah/Cacah: ordinary people/lower class. Clothing is a cultural phenomenon within certain culture reflecting such society experiences. For Menak people, clothing and its accessories have important meanings. They wear such traditional clothing and accessories as a symbol of power they have within bureaucratic structure and as a symbol of social status they bear within traditional community structure.

  13. Uncovering diversity in the development of central noradrenergic neurons and their efferents.

    Science.gov (United States)

    Robertson, Sabrina D; Plummer, Nicholas W; Jensen, Patricia

    2016-06-15

    Uncovering the mechanisms that underlie central noradrenergic neuron heterogeneity is essential to understanding selective subtype vulnerability to disease and environmental insult. Using recombinase-based intersectional genetic fate mapping we have previously demonstrated that molecularly distinct progenitor populations give rise to mature noradrenergic neurons differing in their anatomical location, axon morphology and efferent projection pattern. Here we review the findings from our previous study and extend our analysis of the noradrenergic subpopulation defined by transient developmental expression of Hoxb1. Using a combination of intersectional genetic fate mapping and analysis of a targeted loss of function mutation in Hoxb1, we have now uncovered additional heterogeneity based on the requirement of some noradrenergic neurons for Hoxb1 expression. By comparing the distribution of noradrenergic neurons derived from the Hoxb1 expression domain in wild-type and mutant mice, we demonstrate that Hoxb1 expression is required by a subset of neurons in the pons. Additional fate mapping, using a Hoxb1 enhancer element that drives Cre recombinase expression exclusively in rhombomere 4 of the hindbrain, reveals the existence of a subpopulation of noradrenergic neurons in the pons with more restricted axonal targets than the full Hoxb1-derived subpopulation. The unique projection profile of this newly defined subpopulation suggests that it may be functionally distinct. These analyses shed new light on the molecular determinants of noradrenergic identity in the pons and the overall complexity of the central noradrenergic system. This article is part of a Special Issue entitled SI: Noradrenergic System. PMID:26612521

  14. From detecting astrocyte connectivity to uncovering drug effects in living tissues

    CERN Document Server

    Pires, Marcelo; Vaz, Sandra; Sebastião, Ana; Lind, Pedro G

    2013-01-01

    We introduce a simple procedure of multivariate signal analysis to uncover the connectivity structure among cells composing a living tissue and describe how to apply it for extracting insight on the effect of drugs in the tissue. The procedure is based in the covariance matrix of time resolved activity signals. By determining the time-lag that maximizes covariance one derives the weight of the corresponding connection between cells. Introducing simple constraints, it is possible to conclude if pairs of cells are connected or not and in which direction. After testing the method against synthetic data we apply it to study propagation of $Ca^{2+}$ waves in astrocytes, with the aim of uncovering the cell connectivity structure. Our method shows to be particularly suited for this type of networking signal propagation where signals are pulse-like and have short time-delays, and is shown to be superior to standard methods, namely a multivariate Granger algorithm. Finally, based the statistical analysis of the connec...

  15. A cheap and non-destructive approach to increase coverage/loading of hydrophilic hydroxide on hydrophobic carbon for lightweight and high-performance supercapacitors.

    Science.gov (United States)

    Zhang, Liuyang; Gong, Hao

    2015-01-01

    Carbon-based substrates offer unprecedented advantages in lightweight supercapacitors. However, it is still challenging to achieve high coverage or loading. Different from the traditional belief that a lack of defects or functional groups is the cause of poor growth on carbon-based substrates, we reckon that the major cause is the discrepancy between the hydrophilic nature of the metal oxide/hydroxide and the hydrophobic nature of carbon. To solve this incompatibility, we introduced ethanol into the precursor solution. The method to synthesize nickel copper hydroxide on carbon fiber paper employs only water and ethanol, in addition to nickel acetate and copper acetate. The results revealed good growth and tight adhesion of active materials on carbon fiber paper substrates. The specific capacitance and energy density per total weight of the active material plus substrate (carbon fiber paper, current collector) reached 770 F g(-1) and 33 Wh kg(-1) (1798 F g(-1) and 54 Wh kg(-1) per weight of the active materials), owing to the high loading of active material and the light weight of carbon fiber paper. These results signified the achievability of light, cheap and high-performance supercapacitors by an environmental-friendly approach. PMID:26643665

  16. Comparative Approach to Define Increased Regulatory T Cells in Different Cancer Subtypes by Combined Assessment of CD127 and FOXP3

    Directory of Open Access Journals (Sweden)

    Marc Beyer

    2011-01-01

    Full Text Available In recent years an increase of functional CD4+CD25+ regulatory T cells (Treg cells has been established for patients with solid tumors, acute leukemias, and lymphomas. We have reported an expanded pool of CD4+CD25high Treg cells in patients with chronic lymphatic leukemia (CLL, multiple myeloma (MM as well as its premalignant precursor monoclonal gammopathy of undetermined significance (MGUS. In healthy individuals, low-level expression of CD127 on T cells in addition to the expression of FOXP3 has been associated with Treg cells. Here, we demonstrate that the expanded FOXP3+ T-cell population in patients with colorectal cancer, CLL, MGUS, MM, follicular lymphoma, and Hodgkin's disease are exclusively CD127low Treg cells and were strongly suppressive. A significant portion of CD127lowFOXP3+ Treg cells expressed only low levels of CD25 suggesting that the previously reported expansion of CD25+ Treg cells underestimates the true expansion. The assessment of CCR7 and CD45RA expression on the expanded CD4+CD127lowFOXP3+ Treg cells revealed an increase of both naïve as well as central and effector memory Treg cells in peripheral blood. Our data strongly support superiority of combined CD127 and FOXP3 analysis in comparison to CD25 and FOXP3 assessment for further quantification of Treg cells in malignant diseases.

  17. The benchmark approach applied to a 28-day toxicity study with Rhodorsil Silane in rats. the impact of increasing the number of dose groups.

    Science.gov (United States)

    Woutersen, R A; Jonker, D; Stevenson, H; te Biesebeek, J D; Slob, W

    2001-07-01

    The OECD study design, aimed at obtaining a no-observed-adverse-effect level (NOAEL), may be suboptimal for deriving a benchmark dose. Therefore the present subacute (28-day) study was carried out to evaluate a multiple dose study design and to compare the results with the common OECD design. Seven groups of 10 female rats each were intragastrically administered corn oil without (controls) or with 50, 150, 300, 450, 600 or 750 mg Rhodorsil Silane/kg body weight/day, once daily (7 days/week) for 4 weeks. From the complete dataset, two subsets were selected, one representing a study design with seven dose groups of five animals (7 x 5 design), the other representing a study design with four dose groups of 10 animals (4 x 10 design). Under the conditions of the present study, the NOAEL for Rhodorsil Silane 198 was assessed at 50 mg/kg body weight/day, based on the data of the 4 x 10 design. The benchmark approach resulted in a benchmark dose of 19 mg/kg body weight/day, based on the data of the 7 x 5 design. Comparison of the results demonstrated that the multiple dose (7 x 5) design led to a more reliable result than the OECD (4 x 10) design, despite the smaller total number of animals. The dose-response analysis showed that at "the NOAEL" the effect on relative spleen weight was larger than 10%, illustrating that at the NOAEL, adverse effects may occur. PMID:11397516

  18. An Approach for Hydrogen Recycling in a Closed-loop Life Support Architecture to Increase Oxygen Recovery Beyond State-of-the-Art

    Science.gov (United States)

    Abney, Morgan B.; Miller, Lee; Greenwood, Zachary; Alvarez, Giraldo

    2014-01-01

    State-of-the-art atmosphere revitalization life support technology on the International Space Station is theoretically capable of recovering 50% of the oxygen from metabolic carbon dioxide via the Carbon Dioxide Reduction Assembly (CRA). When coupled with a Plasma Pyrolysis Assembly (PPA), oxygen recovery increases dramatically, thus drastically reducing the logistical challenges associated with oxygen resupply. The PPA decomposes methane to predominantly form hydrogen and acetylene. Because of the unstable nature of acetylene, a down-stream separation system is required to remove acetylene from the hydrogen stream before it is recycled to the CRA. A new closed-loop architecture that includes a PPA and downstream Hydrogen Purification Assembly (HyPA) is proposed and discussed. Additionally, initial results of separation material testing are reported.

  19. Collaborative Approaches to Increase the Utility of Spatial Data for the Wildfire Management Community Through NASA's Applied Remote Sensing Training Program

    Science.gov (United States)

    McCullum, A. J. K.; Schmidt, C.; Blevins, B.; Weber, K.; Schnase, J. L.; Carroll, M.; Prados, A. I.

    2015-12-01

    The utility of spatial data products and tools to assess risk and effectively manage wildfires has increased, highlighting the need for communicating information about these new capabilities to decision makers, resource managers, and community leaders. NASA's Applied Remote Sensing Training (ARSET) program works directly with agencies and policy makers to develop in-person and online training courses that teach end users how to access, visualize, and apply NASA Earth Science data in their profession. The expansion of ARSET into wildfire applications began in 2015 with a webinar and subsequent in-person training hosted in collaboration with Idaho State University's (ISU) GIS Training and Research Center (TReC). These trainings featured presentations from the USDA Forest Service's Remote Sensing Training and Applications Center, the Land Processes DAAC, Northwest Nazarene University, NASA Goddard Space Flight Center, and ISU's GIS TReC. The webinar focused on providing land managers, non-governmental organizations, and international management agencies with an overview of 1) remote sensing platforms for wildfire applications, 2) products for pre- and post-fire planning and assessment, 3) the use of terrain data, 4) new techniques and technologies such as Unmanned Aircraft Systems and the Soil Moisture Active Passive Mission (SMAP), and 5) the RECOVER Decision Support System. This training highlighted online tools that engage the wildfire community through collaborative monitoring and assessment efforts. Webinar attendance included 278 participants from 178 organizations in 42 countries and 33 US states. The majority of respondents (93%) from a post-webinar survey indicated they displayed improvement in their understanding of specific remote-sensing data products appropriate for their work needs. With collaborative efforts between federal, state, and local agencies and academic institutions, increased use of NASA Earth Observations may lead to improved near real

  20. Increased tumor necrosis factor alpha (TNF-alpha) and natural killer cell (NK) function using an integrative approach in late stage cancers.

    Science.gov (United States)

    See, Darryl; Mason, Stephanie; Roshan, Ramesh

    2002-05-01

    Natural products may increase cytotoxic activity of Natural Killer Cells (NK) Tumor Necrosis Factor alpha (TNF-alpha) while decreasing DNA damage in patients with late-stage cancer. Pilot studies have suggested that a combination of Nutraceuticals can raise NK cell function and TNF-alpha alpha activity and result in improved clinical outcomes in patients with late stage cancer. The objective of the study is to determine if Nutraceuticals can significantly raise NK function and TNF levels in patients with late stage cancer. After informed consent was obtained, 20 patients with stage IV, end-stage cancer were evaluated (one bladder, five breast, two prostate, one neuroblastoma, two non-small cell lung, three colon, 1 mesothelioma, two lymphoma, one ovarian, one gastric, one osteosarcoma). Transfer Factor Plus (TFP+, 3 tablets 3 times per day), IMUPlus (non denatured milk whey protein, 40 gm/day); Intravenous (50 to 100 gm/day) and oral (1-2 gm/day) ascorbic acid; Agaricus Blazeii Murill teas (10 gm/day); Immune Modulator Mix (a combination of vitamin, minerals, antioxidants and immune-enhancing natural products); nitrogenated soy extract (high levels of genistein and dadzein) and Andrographis Paniculata (500 mg twice, daily) were used. Baseline NK function by standard 4 h 51Cr release assay and TNF alpha and receptor levels were measured by ELISA from resting and phytohemagglutinin (PHA) stimulated adherent and non-adherent Peripheral Blood Mononuclear Cell (PBMC). Total mercaptans and glutathione in plasma were taken and compared to levels measured 6 months later. Complete blood counts and chemistry panels were routinely monitored. As of a mean of 6 months, 16/20 patients were still alive. The 16 survivors had significantly higher NK function than baseline (p < .01 for each) and TNF-alpha levels in all four cell populations studied (p < .01 for each). Total mercaptans (p < .01) and TNF-alpha receptor levels were significantly reduced (p < .01). It was also observed

  1. Transmission from theory to practice: Experiences using open-source code development and a virtual short course to increase the adoption of new theoretical approaches

    Science.gov (United States)

    Harman, C. J.

    2015-12-01

    Even amongst the academic community, new theoretical tools can remain underutilized due to the investment of time and resources required to understand and implement them. This surely limits the frequency that new theory is rigorously tested against data by scientists outside the group that developed it, and limits the impact that new tools could have on the advancement of science. Reducing the barriers to adoption through online education and open-source code can bridge the gap between theory and data, forging new collaborations, and advancing science. A pilot venture aimed at increasing the adoption of a new theory of time-variable transit time distributions was begun in July 2015 as a collaboration between Johns Hopkins University and The Consortium of Universities for the Advancement of Hydrologic Science (CUAHSI). There were four main components to the venture: a public online seminar covering the theory, an open source code repository, a virtual short course designed to help participants apply the theory to their data, and an online forum to maintain discussion and build a community of users. 18 participants were selected for the non-public components based on their responses in an application, and were asked to fill out a course evaluation at the end of the short course, and again several months later. These evaluations, along with participation in the forum and on-going contact with the organizer suggest strengths and weaknesses in this combination of components to assist participants in adopting new tools.

  2. FAMILIES’ FIRST IN EARLYCHILDHOOD INTERVENTION.A THEORETICAL APPROACH TOWARDS PARENT’S INVOLVEMENT AND INCREASE OF EFFICIENCY OF THE EARLY CHILDHOOD INTERVENTION

    Directory of Open Access Journals (Sweden)

    Manfred PRETIS

    2012-03-01

    Full Text Available Early Childhood Intervention (ECI for vulnerable children between the age of 0-3 and 6 can be seen as well established preventive service in Europe. Even though recent epidemiologic data indicate higher rates of vulnerability during childhood and adolescence, traditionally up to 6% of the children are eligible for the ECI treatment. Definitions describing the ECI include from stable or ad hoc trans-disciplinary teams helping the child, to specific professional profiles. There is a scientific consensus regarding the effects of the ECI upon the child’s development and the family dynamics. The ECI itself is responsible for more stable impact on the socio-emotional development of the child and the parent-child relationship. Specific focus in the research is given to the role of the parents as primary caregivers. Based on the importance of enhancing the interactions between the parents and the children, this paper discusses the strategies that help increase the efficiency of the ECI trough parental involvement. Special attention is dedicated to the mutual understanding, transparency and the use of common language such as the ICF.

  3. Uncovering brain-heart information through advanced signal and image processing.

    Science.gov (United States)

    Valenza, Gaetano; Toschi, Nicola; Barbieri, Riccardo

    2016-05-13

    Through their dynamical interplay, the brain and the heart ensure fundamental homeostasis and mediate a number of physiological functions as well as their disease-related aberrations. Although a vast number of ad hoc analytical and computational tools have been recently applied to the non-invasive characterization of brain and heart dynamic functioning, little attention has been devoted to combining information to unveil the interactions between these two physiological systems. This theme issue collects contributions from leading experts dealing with the development of advanced analytical and computational tools in the field of biomedical signal and image processing. It includes perspectives on recent advances in 7 T magnetic resonance imaging as well as electroencephalogram, electrocardiogram and cerebrovascular flow processing, with the specific aim of elucidating methods to uncover novel biological and physiological correlates of brain-heart physiology and physiopathology. PMID:27044995

  4. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

    DEFF Research Database (Denmark)

    Kilpeläinen, Tuomas O; Carli, Jayne F Martin; Skowronski, Alicja A;

    2016-01-01

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered....... Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO....... Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown...

  5. Uncovered Interest Parity in Central and Eastern Europe: Convergence and the Global Financial Crisis

    Directory of Open Access Journals (Sweden)

    Fabio Filipozzi

    2012-12-01

    Full Text Available This paper presents tests of uncovered interest parity in Croatia, the Czech Republic, Hungary, Poland and Romania; all countries in Central and Eastern Europe with floating exchange rates. Data are monthly and the trading horizon is three months. The estimations show that the UIP hypothesis is rejected for the full sample from 1999 to 2011 for all five countries. A number of reasons for the rejection were investigated. Rolling regressions show that standard versions of the UIP essentially lose all explanatory power in 2008-10, which was a period in which the global financial crisis led to instability in currency and interest markets in Central and Eastern Europe. Two indicators of global risk aversion were also found to enter significantly in the many UIP estimations. Finally, the size of the interest rates spread also seems to be of importance, at least for Poland and Romania

  6. Intraductal radiofrequency ablation of tumour ingrowth into an uncovered metal stent used for inoperable cholangiocarcinoma.

    Science.gov (United States)

    Lui, K L; Li, K K

    2013-12-01

    A 91-year-old woman diagnosed to have an inoperable cholangiocarcinoma had an uncovered metal stent inserted for palliative drainage. About 1.5 years later, tumour ingrowth into the metal stent caused cholangitis. Intraductal radiofrequency ablation was applied to create local coagulative tumour necrosis and the necrotic tissue was removed via a balloon catheter. A plastic stent was inserted to empirically treat any ensuing potential bile duct injury. The patient was discharged without complication with good palliative drainage. Intraductal radiofrequency ablation is a new technique for the treatment of metal stent occlusion due to tumour ingrowths. This is the first case report of this relatively safe and feasible new technique for the treatment of tumour ingrowth into a metal stent used as palliation for malignant biliary obstruction. PMID:24310661

  7. Lipidomics Analyses Reveal Temporal and Spatial Lipid Organization and Uncover Daily Oscillations in Intracellular Organelles.

    Science.gov (United States)

    Aviram, Rona; Manella, Gal; Kopelman, Naama; Neufeld-Cohen, Adi; Zwighaft, Ziv; Elimelech, Meytar; Adamovich, Yaarit; Golik, Marina; Wang, Chunyan; Han, Xianlin; Asher, Gad

    2016-05-19

    Cells have evolved mechanisms to handle incompatible processes through temporal organization by circadian clocks and by spatial compartmentalization within organelles defined by lipid bilayers. Recent advances in lipidomics have led to identification of plentiful lipid species, yet our knowledge regarding their spatiotemporal organization is lagging behind. In this study, we quantitatively characterized the nuclear and mitochondrial lipidome in mouse liver throughout the day, upon different feeding regimens, and in clock-disrupted mice. Our analyses revealed potential connections between lipid species within and between lipid classes. Remarkably, we uncovered diurnal oscillations in lipid accumulation in the nucleus and mitochondria. These oscillations exhibited opposite phases and readily responded to feeding time. Furthermore, we found that the circadian clock coordinates the phase relation between the organelles. In summary, our study provides temporal and spatial depiction of lipid organization and reveals the presence and coordination of diurnal rhythmicity in intracellular organelles. PMID:27161994

  8. Health Detectives: Uncovering the Mysteries of Disease (LBNL Science at the Theater)

    Energy Technology Data Exchange (ETDEWEB)

    Bissell, Mina; Canaria, Christie; Celnicker, Susan; Karpen, Gary

    2012-04-23

    In this April 23, 2012 Science at the Theater event, Berkeley Lab scientists discuss how they uncover the mysteries of disease in unlikely places. Speakers and topics include: World-renowned cancer researcher Mina Bissell's pioneering research on the role of the cellular microenvironment in breast cancer has changed the conversation about the disease. How does DNA instability cause disease? To find out, Christie Canaria images neural networks to study disorders such as Huntington's disease. Fruit flies can tell us a lot about ourselves. Susan Celniker explores the fruit fly genome to learn how our genome works. DNA is not destiny. Gary Karpen explores how environmental factors shape genome function and disease through epigenetics.

  9. Uncovering brain–heart information through advanced signal and image processing

    Science.gov (United States)

    Toschi, Nicola; Barbieri, Riccardo

    2016-01-01

    Through their dynamical interplay, the brain and the heart ensure fundamental homeostasis and mediate a number of physiological functions as well as their disease-related aberrations. Although a vast number of ad hoc analytical and computational tools have been recently applied to the non-invasive characterization of brain and heart dynamic functioning, little attention has been devoted to combining information to unveil the interactions between these two physiological systems. This theme issue collects contributions from leading experts dealing with the development of advanced analytical and computational tools in the field of biomedical signal and image processing. It includes perspectives on recent advances in 7 T magnetic resonance imaging as well as electroencephalogram, electrocardiogram and cerebrovascular flow processing, with the specific aim of elucidating methods to uncover novel biological and physiological correlates of brain–heart physiology and physiopathology. PMID:27044995

  10. Uncovering the role of p53 splice variants in human malignancy: a clinical perspective

    Directory of Open Access Journals (Sweden)

    Surget S

    2013-12-01

    Full Text Available Sylvanie Surget,1,2 Marie P Khoury,1,2 Jean-Christophe Bourdon1,21Dundee Cancer Centre, 2Jacqui Wood Cancer Centre, Ninewells Hospital, University of Dundee, Dundee, UKAbstract: Thirty-five years of research on p53 gave rise to more than 68,000 articles and reviews, but did not allow the uncovering of all the mysteries that this major tumor suppressor holds. How p53 handles the different signals to decide the appropriate cell fate in response to a stress and its implication in tumorigenesis and cancer progression remains unclear. Nevertheless, the uncovering of p53 isoforms has opened new perspectives in the cancer research field. Indeed, the human TP53 gene encodes not only one but at least twelve p53 protein isoforms, which are produced in normal tissues through alternative initiation of translation, usage of alternative promoters, and alternative splicing. In recent years, it became obvious that the different p53 isoforms play an important role in regulating cell fate in response to different stresses in normal cells by differentially regulating gene expression. In cancer cells, abnormal expression of p53 isoforms contributes actively to cancer formation and progression, regardless of TP53 mutation status. They can also be associated with response to treatment, depending on the cell context. The determination of p53 isoform expression and p53 mutation status helps to define different subtypes within a particular cancer type, which would have different responses to treatment. Thus, the understanding of the regulation of p53 isoform expression and their biological activities in relation to the cellular context would constitute an important step toward the improvement of the diagnostic, prognostic, and predictive values of p53 in cancer treatment. This review aims to summarize the involvement of p53 isoforms in cancer and to highlight novel potential therapeutic targets.Keywords: p53, isoforms, p63, p73, alternative splicing, cancer

  11. Metabolism of human insulin after subcutaneous administration: A possible means to uncover insulin misuse.

    Science.gov (United States)

    Thomas, Andreas; Brinkkötter, Paul; Schänzer, Wilhelm; Thevis, Mario

    2015-10-15

    The misuse of insulin for performance enhancement in sport or as toxic agent has frequently been reported in the past. In contrast to synthetic insulin analogues, the administration of recombinant human insulin is hardly recognized by mass spectrometry. The present study was designed to uncover the misuse of recombinant human insulin for doping control purposes as well as for forensic applications. It is hypothesized that an altered metabolite profile of circulating insulin prevails after subcutaneous administration due to exposure of insulin to epidermal proteases. In vitro experiments with skin tissue lysates (S9 fraction and microsomes), different biological fluids (urine, serum, plasma) and recombinant human insulin were performed and the deriving metabolites were characterized by liquid chromatography coupled to high resolution mass spectrometry (HRMS). Afterwards, authentic blood samples of patients suffering from diabetes mellitus and a control group of healthy humans were analysed. Therefore, a method using protein precipitation, ultrafiltration and antibody-coated magnetic beads for purification with subsequent separation by nano-scale liquid chromatography coupled a Q Exactive mass spectrometer was applied. Several metabolites of insulin with C-terminally truncated sequences of the B-chain (and A-chain in minor extent) were identified within this study. Here, the DesB30 human insulin represents the major metabolite in all experiments. This metabolite is frequently found in urine samples due to degradation processes and, thus, disqualifies this matrix for the intended purposes. In contrast, blood samples do commonly not contain DesB30 insulin, which was corroborated by data obtained from the control group. In post-administration blood samples, minute but distinct amounts (approx. 50 pg mL(-1)) of DesB30 insulin were found and suggest the use of this analyte as potential marker for subcutaneous human insulin administration, supporting the attempts to

  12. Uncovering beat deafness: detecting rhythm disorders with synchronized finger tapping and perceptual timing tasks.

    Science.gov (United States)

    Dalla Bella, Simone; Sowiński, Jakub

    2015-01-01

    A set of behavioral tasks for assessing perceptual and sensorimotor timing abilities in the general population (i.e., non-musicians) is presented here with the goal of uncovering rhythm disorders, such as beat deafness. Beat deafness is characterized by poor performance in perceiving durations in auditory rhythmic patterns or poor synchronization of movement with auditory rhythms (e.g., with musical beats). These tasks include the synchronization of finger tapping to the beat of simple and complex auditory stimuli and the detection of rhythmic irregularities (anisochrony detection task) embedded in the same stimuli. These tests, which are easy to administer, include an assessment of both perceptual and sensorimotor timing abilities under different conditions (e.g., beat rates and types of auditory material) and are based on the same auditory stimuli, ranging from a simple metronome to a complex musical excerpt. The analysis of synchronized tapping data is performed with circular statistics, which provide reliable measures of synchronization accuracy (e.g., the difference between the timing of the taps and the timing of the pacing stimuli) and consistency. Circular statistics on tapping data are particularly well-suited for detecting individual differences in the general population. Synchronized tapping and anisochrony detection are sensitive measures for identifying profiles of rhythm disorders and have been used with success to uncover cases of poor synchronization with spared perceptual timing. This systematic assessment of perceptual and sensorimotor timing can be extended to populations of patients with brain damage, neurodegenerative diseases (e.g., Parkinson's disease), and developmental disorders (e.g., Attention Deficit Hyperactivity Disorder). PMID:25867797

  13. Uncovering Time-Varying Parameters with the Kalman-Filter and the Flexible Least Squares: a Monte Carlo Study

    OpenAIRE

    Zsolt Darvas; Balázs Varga

    2012-01-01

    Using Monte Carlo methods, we compare the ability of the Kalman-filter, the Kalman-smoother and the flexible least squares (FLS) to uncover the parameters of an autoregression. We find that the ordinary least squares (OLS) estimator performs much better that the time-varying coefficient methods when the parameters are in fact constant, but the OLS does very poorly when parameters change. Neither the FLS, nor the Kalman-filter and Kalman-smoother can uncover sudden changes in parameters. But w...

  14. Price increase

    CERN Multimedia

    2005-01-01

    Please take note that after five years of stable prices at Restaurant No 1 a price increase will come into force on 1st January 2006. This increase has been agreed after discussions between the CSR (Comité de Surveillance des Restaurants) and the catering company Novae and will reflect the inflation rate of the last few years. In addition, a new children's menu will be introduced as well as 'Max Havelaar' fair-trade coffee at a price of 1.70 CHF.

  15. Price increase

    CERN Multimedia

    2006-01-01

    Please take note that after five years of stable prices at Restaurant No 1 a price increase will come into force on 1st January 2006. This increase has been agreed after discussions between the CSR (Comité de Surveillance des Restaurants) and the catering company Novae and will reflect the inflation rate of the last few years. In addition, a new children's menu will be introduced, as well as 'Max Havelaar' fair-trade coffee at a price of 1.70 CHF.

  16. Psychological Approach to Young Goodman Brown

    Institute of Scientific and Technical Information of China (English)

    杨秋仙

    2015-01-01

    <正>Compared with other literary approaches we have studied,I think the psychological approach is most suitable for analyzing Yong Goodman Brown written by American romanticism writer Hawthorne.Because psychoanalytical criticism,which is based on Sigmund Freud’s psychoanalysis mode,aims at uncovering the working of the human mind--especially the expression of the unconsciousness.Professor Jiang point out in his article Hawthorne’s Aesthetic Modernity

  17. Uncovering the Links between Prospective Teachers' Personal Responsibility, Academic Optimism, Hope, and Emotions about Teaching: A Mediation Analysis

    Science.gov (United States)

    Eren, Altay

    2014-01-01

    Prospective teachers' sense of personal responsibility has not been examined together with their academic optimism, hope, and emotions about teaching in a single study to date. However, to consider hope, academic optimism, and emotions about teaching together with personal responsibility is important to uncover the factors affecting…

  18. Uncovering the pKa dependent fluorescence quenching of carbon dots induced by chlorophenols

    Science.gov (United States)

    Zhang, Yu; Wang, Yu; Guan, Yafeng; Feng, Liang

    2015-03-01

    Fluorescence quenching induced by targets is always an alluring strategy to elucidate the possible photoluminescence origin of carbon dots. In this study, a new kind of N, S co-doped carbon dots (NSCDs) was synthesized and the fluorescence of NSCDs was surprisingly found to be quenched by chlorophenols (CPs) in a pKa dependent mode. Detailed investigation of this behavior demonstrated that phenolate was the responsible species and N and/or S dopants in NSCDs failed to play a role in the fluorescence quenching. Further evidence uncovered that the quenching was a static one, where a non-fluorescent intermediate was formed between electron-deficient C&z.dbd;O on the CDs surface and the electron-rich phenolic oxygen anion of chlorophenolate via nucleophilic addition. Moreover, one of the main photoluminescence origins of this kind of CDs was derived, namely surface emissive sites mostly attributed to carbonyl groups.Fluorescence quenching induced by targets is always an alluring strategy to elucidate the possible photoluminescence origin of carbon dots. In this study, a new kind of N, S co-doped carbon dots (NSCDs) was synthesized and the fluorescence of NSCDs was surprisingly found to be quenched by chlorophenols (CPs) in a pKa dependent mode. Detailed investigation of this behavior demonstrated that phenolate was the responsible species and N and/or S dopants in NSCDs failed to play a role in the fluorescence quenching. Further evidence uncovered that the quenching was a static one, where a non-fluorescent intermediate was formed between electron-deficient C&z.dbd;O on the CDs surface and the electron-rich phenolic oxygen anion of chlorophenolate via nucleophilic addition. Moreover, one of the main photoluminescence origins of this kind of CDs was derived, namely surface emissive sites mostly attributed to carbonyl groups. Electronic supplementary information (ESI) available: Texts, figures and tables giving partial experimental procedures, detailed characterizations

  19. The characteristic blue spectra of accretion disks in quasars as uncovered in the infrared.

    Science.gov (United States)

    Kishimoto, Makoto; Antonucci, Robert; Blaes, Omer; Lawrence, Andy; Boisson, Catherine; Albrecht, Marcus; Leipski, Christian

    2008-07-24

    Quasars are thought to be powered by supermassive black holes accreting surrounding gas. Central to this picture is a putative accretion disk which is believed to be the source of the majority of the radiative output. It is well known, however, that the most extensively studied disk model-an optically thick disk which is heated locally by the dissipation of gravitational binding energy-is apparently contradicted by observations in a few major respects. In particular, the model predicts a specific blue spectral shape asymptotically from the visible to the near-infrared, but this is not generally seen in the visible wavelength region where the disk spectrum is observable. A crucial difficulty has been that, towards the infrared, the disk spectrum starts to be hidden under strong, hot dust emission from much larger but hitherto unresolved scales, and thus has essentially been impossible to observe. Here we report observations of polarized light interior to the dust-emitting region that enable us to uncover this near-infrared disk spectrum in several quasars. The revealed spectra show that the near-infrared disk spectrum is indeed as blue as predicted. This indicates that, at least for the outer near-infrared-emitting radii, the standard picture of the locally heated disk is approximately correct. PMID:18650919

  20. Percutaneous Treatment of Malignant Jaundice Due to Extrahepatic Cholangiocarcinoma: Covered Viabil Stent Versus Uncovered Wallstents

    International Nuclear Information System (INIS)

    To compare clinical effectiveness of Viabil-covered stents versus uncovered metallic Wallstents, for palliation of malignant jaundice due to extrahepatic cholangiocarcinoma, 60 patients were enrolled in a prospective and randomized study. In half of the patients a bare Wallstent was used, and in the other half a Viabil biliary stent. Patients were followed up until death. Primary patency, survival, complication rates, and mean cost were calculated in both groups. Stent dysfunction occurred in 9 (30%) patients in the bare stent group after a mean period of 133.1 days and in 4 (13.3%) patients in the covered stent group after a mean of 179.5 days. The incidence of stent dysfunction was significantly lower in the covered stent group (P = 0.046). Tumor ingrowth occurred exclusively in the bare stent group (P = 0.007). Median survival was 180.5 days for the Wallstent and 243.5 days for the Viabil group (P = 0.039). Complications and mean cost were similar in the two groups. Viabil stent-grafts proved to be significantly superior to Wallstents for the palliation of malignant jaundice due to extrahepatic cholangiocarcinoma, with comparable cost and complication rates. Appropriate patient selection should be performed prior to stent placement.

  1. Percutaneous treatment of malignant jaundice due to extrahepatic cholangiocarcinoma: covered Viabil stent versus uncovered Wallstents.

    Science.gov (United States)

    Krokidis, Miltiadis; Fanelli, Fabrizio; Orgera, Gianluigi; Bezzi, Mario; Passariello, Roberto; Hatzidakis, Adam

    2010-02-01

    To compare clinical effectiveness of Viabil-covered stents versus uncovered metallic Wallstents, for palliation of malignant jaundice due to extrahepatic cholangiocarcinoma, 60 patients were enrolled in a prospective and randomized study. In half of the patients a bare Wallstent was used, and in the other half a Viabil biliary stent. Patients were followed up until death. Primary patency, survival, complication rates, and mean cost were calculated in both groups. Stent dysfunction occurred in 9 (30%) patients in the bare stent group after a mean period of 133.1 days and in 4 (13.3%) patients in the covered stent group after a mean of 179.5 days. The incidence of stent dysfunction was significantly lower in the covered stent group (P = 0.046). Tumor ingrowth occurred exclusively in the bare stent group (P = 0.007). Median survival was 180.5 days for the Wallstent and 243.5 days for the Viabil group (P = 0.039). Complications and mean cost were similar in the two groups. Viabil stent-grafts proved to be significantly superior to Wallstents for the palliation of malignant jaundice due to extrahepatic cholangiocarcinoma, with comparable cost and complication rates. Appropriate patient selection should be performed prior to stent placement. PMID:19495871

  2. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

    Science.gov (United States)

    Kilpeläinen, Tuomas O; Carli, Jayne F Martin; Skowronski, Alicja A; Sun, Qi; Kriebel, Jennifer; Feitosa, Mary F; Hedman, Åsa K; Drong, Alexander W; Hayes, James E; Zhao, Jinghua; Pers, Tune H; Schick, Ursula; Grarup, Niels; Kutalik, Zoltán; Trompet, Stella; Mangino, Massimo; Kristiansson, Kati; Beekman, Marian; Lyytikäinen, Leo-Pekka; Eriksson, Joel; Henneman, Peter; Lahti, Jari; Tanaka, Toshiko; Luan, Jian'an; Del Greco M, Fabiola; Pasko, Dorota; Renström, Frida; Willems, Sara M; Mahajan, Anubha; Rose, Lynda M; Guo, Xiuqing; Liu, Yongmei; Kleber, Marcus E; Pérusse, Louis; Gaunt, Tom; Ahluwalia, Tarunveer S; Ju Sung, Yun; Ramos, Yolande F; Amin, Najaf; Amuzu, Antoinette; Barroso, Inês; Bellis, Claire; Blangero, John; Buckley, Brendan M; Böhringer, Stefan; I Chen, Yii-Der; de Craen, Anton J N; Crosslin, David R; Dale, Caroline E; Dastani, Zari; Day, Felix R; Deelen, Joris; Delgado, Graciela E; Demirkan, Ayse; Finucane, Francis M; Ford, Ian; Garcia, Melissa E; Gieger, Christian; Gustafsson, Stefan; Hallmans, Göran; Hankinson, Susan E; Havulinna, Aki S; Herder, Christian; Hernandez, Dena; Hicks, Andrew A; Hunter, David J; Illig, Thomas; Ingelsson, Erik; Ioan-Facsinay, Andreea; Jansson, John-Olov; Jenny, Nancy S; Jørgensen, Marit E; Jørgensen, Torben; Karlsson, Magnus; Koenig, Wolfgang; Kraft, Peter; Kwekkeboom, Joanneke; Laatikainen, Tiina; Ladwig, Karl-Heinz; LeDuc, Charles A; Lowe, Gordon; Lu, Yingchang; Marques-Vidal, Pedro; Meisinger, Christa; Menni, Cristina; Morris, Andrew P; Myers, Richard H; Männistö, Satu; Nalls, Mike A; Paternoster, Lavinia; Peters, Annette; Pradhan, Aruna D; Rankinen, Tuomo; Rasmussen-Torvik, Laura J; Rathmann, Wolfgang; Rice, Treva K; Brent Richards, J; Ridker, Paul M; Sattar, Naveed; Savage, David B; Söderberg, Stefan; Timpson, Nicholas J; Vandenput, Liesbeth; van Heemst, Diana; Uh, Hae-Won; Vohl, Marie-Claude; Walker, Mark; Wichmann, Heinz-Erich; Widén, Elisabeth; Wood, Andrew R; Yao, Jie; Zeller, Tanja; Zhang, Yiying; Meulenbelt, Ingrid; Kloppenburg, Margreet; Astrup, Arne; Sørensen, Thorkild I A; Sarzynski, Mark A; Rao, D C; Jousilahti, Pekka; Vartiainen, Erkki; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G; Kajantie, Eero; Osmond, Clive; Palotie, Aarno; Eriksson, Johan G; Heliövaara, Markku; Knekt, Paul B; Koskinen, Seppo; Jula, Antti; Perola, Markus; Huupponen, Risto K; Viikari, Jorma S; Kähönen, Mika; Lehtimäki, Terho; Raitakari, Olli T; Mellström, Dan; Lorentzon, Mattias; Casas, Juan P; Bandinelli, Stefanie; März, Winfried; Isaacs, Aaron; van Dijk, Ko W; van Duijn, Cornelia M; Harris, Tamara B; Bouchard, Claude; Allison, Matthew A; Chasman, Daniel I; Ohlsson, Claes; Lind, Lars; Scott, Robert A; Langenberg, Claudia; Wareham, Nicholas J; Ferrucci, Luigi; Frayling, Timothy M; Pramstaller, Peter P; Borecki, Ingrid B; Waterworth, Dawn M; Bergmann, Sven; Waeber, Gérard; Vollenweider, Peter; Vestergaard, Henrik; Hansen, Torben; Pedersen, Oluf; Hu, Frank B; Eline Slagboom, P; Grallert, Harald; Spector, Tim D; Jukema, J W; Klein, Robert J; Schadt, Erik E; Franks, Paul W; Lindgren, Cecilia M; Leibel, Rudolph L; Loos, Ruth J F

    2016-01-01

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health. PMID:26833098

  3. Uncovering Multiple Populations with Washington Photometry: I. The Globular Cluster NGC 1851

    CERN Document Server

    Cummings, Jeffrey D; Villanova, S; Carraro, G

    2014-01-01

    The analysis of multiple populations (MPs) in globular clusters (GCs) has become a forefront area of research in astronomy. Multiple red giant branches (RGBs), subgiant branches (SGBs), and even main sequences (MSs) have now been observed photometrically in many GCs. UV photometry has been crucial in discovering and analyzing these MPs, but the Johnson U and the Stromgren and Sloan u filters that have generally been used are relatively inefficient and very sensitive to reddening and atmospheric extinction. In contrast, the Washington C filter is much broader and redder than these competing UV filters. Here we investigate the use of the Washington system to uncover MPs using only a 1-meter telescope. Our analysis of the well-studied GC NGC 1851 finds that the C filter is both very efficient and effective at detecting its previously discovered MPs in the RGB and SGB. Remarkably, we have also detected an intrinsically broad MS best characterized by two distinct but heavily overlapping populations that cannot be ...

  4. Flux Analysis Uncovers Key Role of Functional Redundancy in Formaldehyde Metabolism

    Directory of Open Access Journals (Sweden)

    Marx Christopher J

    2005-01-01

    Full Text Available Genome-scale analysis of predicted metabolic pathways has revealed the common occurrence of apparent redundancy for specific functional units, or metabolic modules. In many cases, mutation analysis does not resolve function, and instead, direct experimental analysis of metabolic flux under changing conditions is necessary. In order to use genome sequences to build models of cellular function, it is important to define function for such apparently redundant systems. Here we describe direct flux measurements to determine the role of redundancy in three modules involved in formaldehyde assimilation and dissimilation in a bacterium growing on methanol. A combination of deuterium and 14C labeling was used to measure the flux through each of the branches of metabolism for growth on methanol during transitions into and out of methylotrophy. The cells were found to differentially partition formaldehyde among the three modules depending on the flux of methanol into the cell. A dynamic mathematical model demonstrated that the kinetic constants of the enzymes involved are sufficient to account for this phenomenon. We demonstrate the role of redundancy in formaldehyde metabolism and have uncovered a new paradigm for coping with toxic, high-flux metabolic intermediates: a dynamic, interconnected metabolic loop.

  5. Gene Expression Deconvolution for Uncovering Molecular Signatures in Response to Therapy in Juvenile Idiopathic Arthritis

    Science.gov (United States)

    Rosenberg, Alan M.; Yeung, Rae S. M.; Morris, Quaid

    2016-01-01

    Gene expression-based signatures help identify pathways relevant to diseases and treatments, but are challenging to construct when there is a diversity of disease mechanisms and treatments in patients with complex diseases. To overcome this challenge, we present a new application of an in silico gene expression deconvolution method, ISOpure-S1, and apply it to identify a common gene expression signature corresponding to response to treatment in 33 juvenile idiopathic arthritis (JIA) patients. Using pre- and post-treatment gene expression profiles only, we found a gene expression signature that significantly correlated with a reduction in the number of joints with active arthritis, a measure of clinical outcome (Spearman rho = 0.44, p = 0.040, Bonferroni correction). This signature may be associated with a decrease in T-cells, monocytes, neutrophils and platelets. The products of most differentially expressed genes include known biomarkers for JIA such as major histocompatibility complexes and interleukins, as well as novel biomarkers including α-defensins. This method is readily applicable to expression datasets of other complex diseases to uncover shared mechanistic patterns in heterogeneous samples. PMID:27244050

  6. Proteomic Analysis of Cytokeratin Isoforms Uncovers Association with Survival in Lung Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Tarek G. Gharib

    2002-01-01

    Full Text Available Cytokeratins. (CK are intermediate filaments whose expression is often altered in epithelial cancer. Systematic identification of lung adenocarcinoma proteins using two-dimensional polyacrylamide gel electrophoresis and mass spectrometry has uncovered numerous CK isoforms. In this study, 93 lung adenocarcinomas. (64 stage I and 29 stage III and 10 uninvolved lung samples were quantitatively examined for protein expression. Fourteen of 21 isoforms of CK 7, 8, 18, 19 occurred at significantly higher levels. (P<.05 in tumors compared to uninvolved adjacent tissue. Specific isoforms of the four types of CK identified correlated with either clinical outcome or individual clinical-pathological parameters. All five of the CK7 isoforms associated with patient survival represented cleavage products. Two of five CK7 isoforms. (nos. 2165 and 2091, one of eight CK8 isoforms. (no. 439, one of three CK19 isoforms. (no. 1955 were associated with survival and significantly correlated to their mRNA levels, suggesting that transcription underlies overexpression of these CK isoforms. Our data indicate substantial heterogeneity among CK in lung adenocarcinomas resulting from posttranslational modifications, some of which correlated with patient survival and other clinical parameters. Therefore, specific isoforms of individual CK may have utility as diagnostic or predictive markers in lung adenocarcinomas.

  7. Gene Expression Deconvolution for Uncovering Molecular Signatures in Response to Therapy in Juvenile Idiopathic Arthritis.

    Directory of Open Access Journals (Sweden)

    Ang Cui

    Full Text Available Gene expression-based signatures help identify pathways relevant to diseases and treatments, but are challenging to construct when there is a diversity of disease mechanisms and treatments in patients with complex diseases. To overcome this challenge, we present a new application of an in silico gene expression deconvolution method, ISOpure-S1, and apply it to identify a common gene expression signature corresponding to response to treatment in 33 juvenile idiopathic arthritis (JIA patients. Using pre- and post-treatment gene expression profiles only, we found a gene expression signature that significantly correlated with a reduction in the number of joints with active arthritis, a measure of clinical outcome (Spearman rho = 0.44, p = 0.040, Bonferroni correction. This signature may be associated with a decrease in T-cells, monocytes, neutrophils and platelets. The products of most differentially expressed genes include known biomarkers for JIA such as major histocompatibility complexes and interleukins, as well as novel biomarkers including α-defensins. This method is readily applicable to expression datasets of other complex diseases to uncover shared mechanistic patterns in heterogeneous samples.

  8. UNCOVERING THE ORIGINS OF SPIRAL STRUCTURE BY MEASURING RADIAL VARIATION IN PATTERN SPEEDS

    International Nuclear Information System (INIS)

    Current theories of spiral and bar structure predict a variety of pattern speed behaviors, calling for detailed, direct measurement of the radial variation of pattern speeds. Our recently developed Radial Tremaine-Weinberg (TWR) method allows this goal to be achieved for the first time. Here, we present TWR spiral pattern speed estimates for M101, IC 342, NGC 3938, and NGC 3344 in order to investigate whether spiral structure is steady or winding, whether spirals are described by multiple pattern speeds, and the relation between bar and spiral speeds. Where possible, we interpret our pattern speeds estimates according to the resonance radii associated with each (established with the disk angular rotation), and compare these to previous determinations. By analyzing the high-quality H I and CO data cubes available for these galaxies, we show that it is possible to determine directly multiple pattern speeds within these systems, and hence identify the characteristic signatures of the processes that drive the spiral structure. Even this small sample of galaxies reveals a surprisingly complex taxonomy, with the first direct evidence for the presence of resonant coupling of multiple patterns found in some systems, and the measurement of a simple single-pattern speed in others. Overall, this study demonstrates that we are now in a position to uncover more of the apparently complex physics that lies behind spiral structure.

  9. MARS A Cosmic Stepping Stone Uncovering Humanity’s Cosmic Context

    CERN Document Server

    Nolan, Kevin

    2008-01-01

    The questions of our origin and cosmic abundance of life are among the most compelling facing humanity. We have determined much about the nature and origin of the Universe and our place in it, but with virtually all evidence of our origin long since gone from our world and an unimaginably vast Universe still to explore, defining answers are difficult to obtain. For all of the difficulties facing us however, the planet Mars may act as a ‘cosmic stepping stone’ in uncovering some of the answers. Although different today, the origin and early history of both Earth and Mars may have been similar enough to consider an origin to life on both. But because Mars’ planetary processes collapsed over three billion years ago – just as life was beginning to flourish on Earth – a significant and unique record of activity from that era perhaps relevant to the origin of life still resides there today. In recognition of this, both the US and Europe are currently engaged in one of the most ambitious programs of explor...

  10. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

    Science.gov (United States)

    Kilpeläinen, Tuomas O.; Carli, Jayne F. Martin; Skowronski, Alicja A.; Sun, Qi; Kriebel, Jennifer; Feitosa, Mary F; Hedman, Åsa K.; Drong, Alexander W.; Hayes, James E.; Zhao, Jinghua; Pers, Tune H.; Schick, Ursula; Grarup, Niels; Kutalik, Zoltán; Trompet, Stella; Mangino, Massimo; Kristiansson, Kati; Beekman, Marian; Lyytikäinen, Leo-Pekka; Eriksson, Joel; Henneman, Peter; Lahti, Jari; Tanaka, Toshiko; Luan, Jian'an; Greco M, Fabiola Del; Pasko, Dorota; Renström, Frida; Willems, Sara M.; Mahajan, Anubha; Rose, Lynda M.; Guo, Xiuqing; Liu, Yongmei; Kleber, Marcus E.; Pérusse, Louis; Gaunt, Tom; Ahluwalia, Tarunveer S.; Ju Sung, Yun; Ramos, Yolande F.; Amin, Najaf; Amuzu, Antoinette; Barroso, Inês; Bellis, Claire; Blangero, John; Buckley, Brendan M.; Böhringer, Stefan; I Chen, Yii-Der; de Craen, Anton J. N.; Crosslin, David R.; Dale, Caroline E.; Dastani, Zari; Day, Felix R.; Deelen, Joris; Delgado, Graciela E.; Demirkan, Ayse; Finucane, Francis M.; Ford, Ian; Garcia, Melissa E.; Gieger, Christian; Gustafsson, Stefan; Hallmans, Göran; Hankinson, Susan E.; Havulinna, Aki S; Herder, Christian; Hernandez, Dena; Hicks, Andrew A.; Hunter, David J.; Illig, Thomas; Ingelsson, Erik; Ioan-Facsinay, Andreea; Jansson, John-Olov; Jenny, Nancy S.; Jørgensen, Marit E.; Jørgensen, Torben; Karlsson, Magnus; Koenig, Wolfgang; Kraft, Peter; Kwekkeboom, Joanneke; Laatikainen, Tiina; Ladwig, Karl-Heinz; LeDuc, Charles A.; Lowe, Gordon; Lu, Yingchang; Marques-Vidal, Pedro; Meisinger, Christa; Menni, Cristina; Morris, Andrew P.; Myers, Richard H.; Männistö, Satu; Nalls, Mike A.; Paternoster, Lavinia; Peters, Annette; Pradhan, Aruna D.; Rankinen, Tuomo; Rasmussen-Torvik, Laura J.; Rathmann, Wolfgang; Rice, Treva K.; Brent Richards, J; Ridker, Paul M.; Sattar, Naveed; Savage, David B.; Söderberg, Stefan; Timpson, Nicholas J.; Vandenput, Liesbeth; van Heemst, Diana; Uh, Hae-Won; Vohl, Marie-Claude; Walker, Mark; Wichmann, Heinz-Erich; Widén, Elisabeth; Wood, Andrew R.; Yao, Jie; Zeller, Tanja; Zhang, Yiying; Meulenbelt, Ingrid; Kloppenburg, Margreet; Astrup, Arne; Sørensen, Thorkild I. A.; Sarzynski, Mark A.; Rao, D. C.; Jousilahti, Pekka; Vartiainen, Erkki; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G.; Kajantie, Eero; Osmond, Clive; Palotie, Aarno; Eriksson, Johan G.; Heliövaara, Markku; Knekt, Paul B.; Koskinen, Seppo; Jula, Antti; Perola, Markus; Huupponen, Risto K.; Viikari, Jorma S.; Kähönen, Mika; Lehtimäki, Terho; Raitakari, Olli T.; Mellström, Dan; Lorentzon, Mattias; Casas, Juan P.; Bandinelli, Stefanie; März, Winfried; Isaacs, Aaron; van Dijk, Ko W.; van Duijn, Cornelia M.; Harris, Tamara B.; Bouchard, Claude; Allison, Matthew A.; Chasman, Daniel I.; Ohlsson, Claes; Lind, Lars; Scott, Robert A.; Langenberg, Claudia; Wareham, Nicholas J.; Ferrucci, Luigi; Frayling, Timothy M.; Pramstaller, Peter P.; Borecki, Ingrid B.; Waterworth, Dawn M.; Bergmann, Sven; Waeber, Gérard; Vollenweider, Peter; Vestergaard, Henrik; Hansen, Torben; Pedersen, Oluf; Hu, Frank B.; Eline Slagboom, P; Grallert, Harald; Spector, Tim D.; Jukema, J.W.; Klein, Robert J.; Schadt, Erik E; Franks, Paul W.; Lindgren, Cecilia M.; Leibel, Rudolph L.; Loos, Ruth J. F.

    2016-01-01

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10−6 in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10−8) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health. PMID:26833098

  11. Conched out: Total reconstructed fisheries catches for the Turks and Caicos Islands uncover unsustainable resource usage

    Directory of Open Access Journals (Sweden)

    Aylin eUlman

    2016-05-01

    Full Text Available The Turks and Caicos Islands’ total marine fisheries catches were estimated for 1950-2012 using a catch reconstruction approach, estimating all removals, including reported catch destined for export, and unreported domestic artisanal and subsistence catches. Total reconstructed catch for the period is approximately 2.8 times that reported by Turks and Caicos to the FAO, and 86% higher than the export-adjusted national reported baseline. The pattern of total catches (strong decline to 1970, followed by gradual increase differs distinctly from that shown by data reported to FAO. Reported landings show a steady increase from less than 1,000 t∙year-1 in the 1950s to around 6,000 t∙year-1 in the 2000s. In contrast, the total reconstructed catches suggest declines in total catches from around 20,000 t in 1950 to a low of about 5,000 t in 1970, before gradual increases to about 12 500 t·year-1 in the late 2000s. Major discrepancies between reported and reconstructed data are under-reported artisanal catches in the early decades (accounting for 86% of total catches, and the absence of subsistence catches (14% of total catches in reported data. Queen conch (Strombus gigas and Caribbean spiny lobster (Panulirus argus dominate reconstructed catches. No discards were estimated as fishing has been highly selective, carried out by hand collection (conch, trap or hook (lobster, or hook and line (finfish. New data published here from local seafood consumption surveys demonstrates that the total local consumption of conch equates to almost the entire total allowable catch, before exported amounts are even factored. Policy-makers in the Turks and Caicos need to act if the sustainability of the fisheries stock and fishing industry is to be ensured.

  12. Where we stand, where we are moving: Surveying computational techniques for identifying miRNA genes and uncovering their regulatory role

    KAUST Repository

    Kleftogiannis, Dimitrios A.

    2013-06-01

    Traditional biology was forced to restate some of its principles when the microRNA (miRNA) genes and their regulatory role were firstly discovered. Typically, miRNAs are small non-coding RNA molecules which have the ability to bind to the 3\\'untraslated region (UTR) of their mRNA target genes for cleavage or translational repression. Existing experimental techniques for their identification and the prediction of the target genes share some important limitations such as low coverage, time consuming experiments and high cost reagents. Hence, many computational methods have been proposed for these tasks to overcome these limitations. Recently, many researchers emphasized on the development of computational approaches to predict the participation of miRNA genes in regulatory networks and to analyze their transcription mechanisms. All these approaches have certain advantages and disadvantages which are going to be described in the present survey. Our work is differentiated from existing review papers by updating the methodologies list and emphasizing on the computational issues that arise from the miRNA data analysis. Furthermore, in the present survey, the various miRNA data analysis steps are treated as an integrated procedure whose aims and scope is to uncover the regulatory role and mechanisms of the miRNA genes. This integrated view of the miRNA data analysis steps may be extremely useful for all researchers even if they work on just a single step. © 2013 Elsevier Inc.

  13. Uncovering Tacit Knowledge: A Pilot Study to Broaden the Concept of Knowledge in Knowledge Translation

    Directory of Open Access Journals (Sweden)

    Edwards Nancy

    2011-08-01

    Full Text Available Abstract Background All sectors in health care are being asked to focus on the knowledge-to-practice gap, or knowledge translation, to increase service effectiveness. A social interaction approach to knowledge translation assumes that research evidence becomes integrated with previously held knowledge, and practitioners build on and co-create knowledge through mutual interactions. Knowledge translation strategies for public health have not provided anticipated positive changes in evidence-based practice, possibly due in part to a narrow conceptualization of knowledge. More work is needed to understand the role of tacit knowledge in decision-making and practice. This pilot study examined how health practitioners applied tacit knowledge in public health program planning and implementation. Methods This study used a narrative approach, where teams from two public health units in Ontario, Canada were conveniently selected. Respondents participated in individual interviews and focus groups at each site. Questions were designed to understand the role of tacit knowledge as it related to the program planning process. Data were analyzed through a combination of content analysis and thematic comparison. Results The findings highlighted two major aspects of knowledge that arose: the use of tacit knowledge and the integration of tacit and explicit knowledge. Tacit knowledge included: past experiences, organization-specific knowledge, community contextual knowledge, and the recognition of the tacit knowledge of others. Explicit knowledge included: research literature, the Internet, popular magazines, formal assessments (surveys and interviews, legislation and regulations. Participants sometimes deliberately combined tacit and explicit knowledge sources in planning. Conclusions This pilot demonstrated that front-line public health workers draw upon both tacit knowledge and explicit knowledge in their everyday lived reality. Further, tacit knowledge plays an

  14. Tumour-specific proline vulnerability uncovered by differential ribosome codon reading.

    Science.gov (United States)

    Loayza-Puch, Fabricio; Rooijers, Koos; Buil, Levi C M; Zijlstra, Jelle; Oude Vrielink, Joachim F; Lopes, Rui; Ugalde, Alejandro Pineiro; van Breugel, Pieter; Hofland, Ingrid; Wesseling, Jelle; van Tellingen, Olaf; Bex, Axel; Agami, Reuven

    2016-02-25

    Tumour growth and metabolic adaptation may restrict the availability of certain amino acids for protein synthesis. It has recently been shown that certain types of cancer cells depend on glycine, glutamine, leucine and serine metabolism to proliferate and survive. In addition, successful therapies using L-asparaginase-induced asparagine deprivation have been developed for acute lymphoblastic leukaemia. However, a tailored detection system for measuring restrictive amino acids in each tumour is currently not available. Here we harness ribosome profiling for sensing restrictive amino acids, and develop diricore, a procedure for differential ribosome measurements of codon reading. We first demonstrate the functionality and constraints of diricore using metabolic inhibitors and nutrient deprivation assays. Notably, treatment with L-asparaginase elicited both specific diricore signals at asparagine codons and high levels of asparagine synthetase (ASNS). We then applied diricore to kidney cancer and discover signals indicating restrictive proline. As for asparagine, this observation was linked to high levels of PYCR1, a key enzyme in proline production, suggesting a compensatory mechanism allowing tumour expansion. Indeed, PYCR1 is induced by shortage of proline precursors, and its suppression attenuated kidney cancer cell proliferation when proline was limiting. High PYCR1 is frequently observed in invasive breast carcinoma. In an in vivo model system of this tumour, we also uncover signals indicating restrictive proline. We further show that CRISPR-mediated knockout of PYCR1 impedes tumorigenic growth in this system. Thus, diricore has the potential to reveal unknown amino acid deficiencies, vulnerabilities that can be used to target key metabolic pathways for cancer treatment. PMID:26878238

  15. The proteome and phosphoproteome of maize pollen uncovers fertility candidate proteins.

    Science.gov (United States)

    Chao, Qing; Gao, Zhi-Fang; Wang, Yue-Feng; Li, Zhe; Huang, Xia-He; Wang, Ying-Chun; Mei, Ying-Chang; Zhao, Biligen-Gaowa; Li, Liang; Jiang, Yu-Bo; Wang, Bai-Chen

    2016-06-01

    Maize is unique since it is both monoecious and diclinous (separate male and female flowers on the same plant). We investigated the proteome and phosphoproteome of maize pollen containing modified proteins and here we provide a comprehensive pollen proteome and phosphoproteome which contain 100,990 peptides from 6750 proteins and 5292 phosphorylated sites corresponding to 2257 maize phosphoproteins, respectively. Interestingly, among the total 27 overrepresented phosphosite motifs we identified here, 11 were novel motifs, which suggested different modification mechanisms in plants compared to those of animals. Enrichment analysis of pollen phosphoproteins showed that pathways including DNA synthesis/chromatin structure, regulation of RNA transcription, protein modification, cell organization, signal transduction, cell cycle, vesicle transport, transport of ions and metabolisms, which were involved in pollen development, the following germination and pollen tube growth, were regulated by phosphorylation. In this study, we also found 430 kinases and 105 phosphatases in the maize pollen phosphoproteome, among which calcium dependent protein kinases (CDPKs), leucine rich repeat kinase, SNF1 related protein kinases and MAPK family proteins were heavily enriched and further analyzed. From our research, we also uncovered hundreds of male sterility-associated proteins and phosphoproteins that might influence maize productivity and serve as targets for hybrid maize seed production. At last, a putative complex signaling pathway involving CDPKs, MAPKs, ubiquitin ligases and multiple fertility proteins was constructed. Overall, our data provides new insight for further investigation of protein phosphorylation status in mature maize pollen and construction of maize male sterile mutants in the future. PMID:26969016

  16. Multivariate weighted recurrence network inference for uncovering oil-water transitional flow behavior in a vertical pipe.

    Science.gov (United States)

    Gao, Zhong-Ke; Yang, Yu-Xuan; Cai, Qing; Zhang, Shan-Shan; Jin, Ning-De

    2016-06-01

    Exploring the dynamical behaviors of high water cut and low velocity oil-water flows remains a contemporary and challenging problem of significant importance. This challenge stimulates us to design a high-speed cycle motivation conductance sensor to capture spatial local flow information. We systematically carry out experiments and acquire the multi-channel measurements from different oil-water flow patterns. Then we develop a novel multivariate weighted recurrence network for uncovering the flow behaviors from multi-channel measurements. In particular, we exploit graph energy and weighted clustering coefficient in combination with multivariate time-frequency analysis to characterize the derived complex networks. The results indicate that the network measures are very sensitive to the flow transitions and allow uncovering local dynamical behaviors associated with water cut and flow velocity. These properties render our method particularly useful for quantitatively characterizing dynamical behaviors governing the transition and evolution of different oil-water flow patterns. PMID:27368782

  17. Mechanisms of heat transfer in the uncovered region of a bundle during the boil-off transient

    International Nuclear Information System (INIS)

    The small break accident which occurred at the TMI-2 plant resulted in partial uncovery of the core. To study the thermal-hydraulic phenomena in the uncovered portion of the core, tests were conducted from the EPRI/SUNY Buffalo 3 x 3 rod bundle. Observations from motion pictures and test data show that liquid entrainment and liquid fallback occur in the upper rod bundle region during the early stage of the boiling dry transient. The liquid entrainment and liquid fallback are the results of flow restrictions in the upper bundle tie-plate and spacer grids. The presence of liquid droplets during the entrainment and the fallback greatly influenced the heat transfer in the uncovered portion of the bundle

  18. Uncovering the Essence of What Animates Us Beneath The Dance: Investigating the Lived Experiences of Bodily Perceptions Generated While Dancing

    OpenAIRE

    Kurnaedy, Karen McKinlay

    2013-01-01

    This dissertation is a phenomenological study in which I endeavour to uncover the essence of what animates us beneath the dance by investigating the lived experiences of bodily perceptions generated while dancing. I present four perspectives to illuminate this essence. In my first perspective, I offer literature from a variety of phenomenologists, dancers and choreographers which substantiate vital and spiritual perceptions generated while dancing. In my second perspective, I conduct an autob...

  19. Sociocultural Theory as an Approach to Aid EFL Learners

    Science.gov (United States)

    Behroozizad, Sorayya; Nambiar, Radha M. K.; Amir, Zaini

    2014-01-01

    Learning English as a foreign language (EFL) has long been regarded a challenging task. Said challenge is clearly evident in the many studies attempting to delineate some of the major problems faced by EFL learners while trying to uncover both the sources and the solutions. This paper turns to the Vygotskian approach to language learning, in…

  20. Novel Y-chromosomal microdeletions associated with non-obstructive azoospermia uncovered by high throughput sequencing of sequence-tagged sites (STSs).

    Science.gov (United States)

    Liu, Xiao; Li, Zesong; Su, Zheng; Zhang, Junjie; Li, Honggang; Xie, Jun; Xu, Hanshi; Jiang, Tao; Luo, Liya; Zhang, Ruifang; Zeng, Xiaojing; Xu, Huaiqian; Huang, Yi; Mou, Lisha; Hu, Jingchu; Qian, Weiping; Zeng, Yong; Zhang, Xiuqing; Xiong, Chengliang; Yang, Huanming; Kristiansen, Karsten; Cai, Zhiming; Wang, Jun; Gui, Yaoting

    2016-01-01

    Y-chromosomal microdeletion (YCM) serves as an important genetic factor in non-obstructive azoospermia (NOA). Multiplex polymerase chain reaction (PCR) is routinely used to detect YCMs by tracing sequence-tagged sites (STSs) in the Y chromosome. Here we introduce a novel methodology in which we sequence 1,787 (post-filtering) STSs distributed across the entire male-specific Y chromosome (MSY) in parallel to uncover known and novel YCMs. We validated this approach with 766 Chinese men with NOA and 683 ethnically matched healthy individuals and detected 481 and 98 STSs that were deleted in the NOA and control group, representing a substantial portion of novel YCMs which significantly influenced the functions of spermatogenic genes. The NOA patients tended to carry more and rarer deletions that were enriched in nearby intragenic regions. Haplogroup O2* was revealed to be a protective lineage for NOA, in which the enrichment of b1/b3 deletion in haplogroup C was also observed. In summary, our work provides a new high-resolution portrait of deletions in the Y chromosome. PMID:26907467

  1. AB039. Novel Y-chromosomal microdeletions associated with non-obstructive azoospermia uncovered by high throughput sequencing of sequence-tagged sites (STSs)

    Science.gov (United States)

    Li, Zesong

    2016-01-01

    Y-chromosomal microdeletion (YCM) serves as an important genetic factor in non-obstructive azoospermia (NOA). Multiplex polymerase chain reaction (PCR) is routinely used to detect YCMs by tracing sequence-tagged sites (STSs) in the Y chromosome. Here we introduce a novel methodology in which we sequence 1,787 (post-filtering) STSs distributed across the entire male-specific Y chromosome (MSY) in parallel to uncover known and novel YCMs. We validated this approach with 766 Chinese men with NOA and 683 ethnically matched healthy individuals and detected 481 and 98 STSs that were deleted in the NOA and control group, representing a substantial portion of novel YCMs which significantly influenced the functions of spermatogenic genes. The NOA patients tended to carry more and rarer deletions that were enriched in nearby intragenic regions. Haplogroup O2* was revealed to be a protective lineage for NOA, in which the enrichment of b1/b3 deletion in haplogroup C was also observed. In summary, our work provides a new high-resolution portrait of deletions in the Y chromosome.

  2. Multivariate approaches in plant science

    DEFF Research Database (Denmark)

    Gottlieb, D.M.; Schultz, j.; Bruun, Susanne Wrang;

    2004-01-01

    amount of data. We present a multivariate approach to the handling of data in proteomics with the advantage that protein patterns can be spotted at an early stage and consequently the proteins selected for sequencing can be selected intelligently. These methods can also be applied to other data....... Traditionally statistical methods are not suitable for analysis of the huge amounts of data, where the number of variables exceed the number of objects. Multivariate data analysis, on the other hand, may uncover the hidden structures present in these data. This study takes its starting point in the field...

  3. Uncovering protein interaction in abstracts and text using a novel linear model and word proximity networks

    CERN Document Server

    Abi-Haidar, Alaa; Maguitman, Ana G; Radivojac, Predrag; Retchsteiner, Andreas; Verspoor, Karin; Wang, Zhiping; Rocha, Luis M; 10.1186/gb-2008-9-s2-s11

    2008-01-01

    We participated in three of the protein-protein interaction subtasks of the Second BioCreative Challenge: classification of abstracts relevant for protein-protein interaction (IAS), discovery of protein pairs (IPS) and text passages characterizing protein interaction (ISS) in full text documents. We approached the abstract classification task with a novel, lightweight linear model inspired by spam-detection techniques, as well as an uncertainty-based integration scheme. We also used a Support Vector Machine and the Singular Value Decomposition on the same features for comparison purposes. Our approach to the full text subtasks (protein pair and passage identification) includes a feature expansion method based on word-proximity networks. Our approach to the abstract classification task (IAS) was among the top submissions for this task in terms of the measures of performance used in the challenge evaluation (accuracy, F-score and AUC). We also report on a web-tool we produced using our approach: the Protein Int...

  4. Hope for GWAS: Relevant Risk Genes Uncovered from GWAS Statistical Noise

    OpenAIRE

    Catarina Correia; Yoan Diekmann; Vicente, Astrid M; Pereira-Leal, José B.

    2014-01-01

    Hundreds of genetic variants have been associated to common diseases through genome-wide association studies (GWAS), yet there are limits to current approaches in detecting true small effect risk variants against a background of false positive findings. Here we addressed the missing heritability problem, aiming to test whether there are indeed risk variants within GWAS statistical noise and to develop a systematic strategy to retrieve these hidden variants. Employing an integrative approach,...

  5. Ethical Considerations in a Three-Tiered Approach to School Discipline Policy and Practice

    Science.gov (United States)

    Mayworm, Ashley M.; Sharkey, Jill D.

    2014-01-01

    Research indicates that school discipline policies and practices have a significant influence on both student and school functioning. The purpose of this article is to uncover how the ethical standards guiding the field of school psychology inform school decisions about discipline in a three-tiered approach. Various discipline approaches,…

  6. A Bayesian Approach to Multifractal Extremes

    Science.gov (United States)

    Tchiguirinskaia, Ioulia; Schertzer, Daniel; Lovejoy, Shaun

    2013-04-01

    Drivers such as climate change and rapid urbanisation will result in increasing flood problems in urban environments through this century. Problems encountered in existing flood defence strategies are often related to the data non-stationary, long range dependencies and the clustering of extremes often resulting in fat tailed (i.e., a power-law tail) probability distributions. We discuss how to better predict the floods by using a physically based approach established on systems that respect a scale symmetry over a wide range of space-time scales to determine the relationship between flood magnitude and return period for a wide range of aggregation periods. The classical quantile distributions unfortunately rely on two hypotheses that are questionable: stationarity and independency of the components of the time series. We pointed out that beyond the classical sampling of the extremes and its limitations, there is the possibility to eliminate long-range dependency by uncovering a white-noise process whose fractional integration generates the observed long-range dependent process. The results were obtained during the CEATI Project "Multifractals and physically based estimates of extreme floods". The ambition of this project was to investigate very large data sets of reasonable quality (e.g., daily stream flow data recorded for at least 20 years for several thousands of gages distributed all over Canada and the USA). The multifractal parameters such as the mean intermittency parameter and the multifractality index were estimated on 8332 time series. The results confirm the dependence of multifractal parameter estimates on the length of available data. Then developing a metric for parameter estimation error became a principal step in uncertainty evaluation with respect to the multifractal estimates. A technique for estimating confidence intervals with the help of a Bayesian approach was developed. A detailed comparison of multifractal quantile plots and paleoflood data

  7. Corpus-Based Approaches to Semantic Interpretation in NLP

    OpenAIRE

    Ng, Hwee Tou; Zelle, John

    1997-01-01

    In recent years, there has been a flurry of research into empirical, corpus-based learning approaches to natural language processing (NLP). Most empirical NLP work to date has focused on relatively low-level language processing such as part-of-speech tagging, text segmentation, and syntactic parsing. The success of these approaches has stimulated research in using empirical learning techniques in other facets of NLP, including semantic analysis -- uncovering the meaning of an utterance. This ...

  8. Realizing full coverage of perovskite film on substrate surface during solution processing: Characterization and elimination of uncovered surface

    Science.gov (United States)

    Li, Yan; He, Xue-Long; Ding, Bin; Gao, Li-Li; Yang, Guan-Jun; Li, Cheng-Xin; Li, Chang-Jiu

    2016-07-01

    The full coverage of the perovskite film on the substrate surface is of significant importance for the high performance perovskite solar cells. In order to obtain full coverage perovskite films by one-step deposition method, the microstructures of both uncovered areas and covered areas of the CH3NH3PbI3 film are comparatively investigated. Results show that the uncovered area indeed has an ultra-thin layer of CH3NH3PbI3 film which is too thin to cover the rough surface morphology of the substrate, and the localized solute accumulation due to long crystal growth time is responsible for the non-full coverage of the perovskite film. Then by decreasing the crystal growth time, the localized solute accumulation is eliminated gradually and subsequently a full coverage of perovskite film on substrate surface is realized. As a result, the perovskite solar cells show a conversion efficiency of ∼13% with the uniform and full coverage perovskite film.

  9. A distinctive avian assemblage (Aves: Passeriformes) in Western Darién, Panama is uncovered through a disease surveillance program.

    Science.gov (United States)

    Miller, Matthew J

    2014-06-01

    Basic knowledge about the distribution of flora and fauna is lacking for most tropical areas. Improving our knowledge of the tropical biota will help address contemporary global problems, including emerging tropical diseases. Less appreciated is the role that applied studies can have in improving our understanding of basic biological patterns and processes in the tropics. Here, I describe a novel avifauna assemblage uncovered in Western Darién province in the Republic of Panama that was uncovered during a vector-borne disease surveillance program. I compared the passerine bird species composition at 16 sites using records from recent ornithological expeditions sponsored by the Smithsonian Tropical Research Institute in Central and Eastern Panama. Based on the results of a Mantel test, geographic distance did not correlate with pairwise distinctiveness of sites. instead, based on an index of distinctiveness modified from the Chao-Jaccard index, most sites were more or less similarly distinctive, with one site, Aruza Abajo, significantly more distinctive than the rest. I found that the distinctiveness of this site was due not only to the presence of several rare and range-restricted taxa, but also to the absence of taxa that are common elsewhere. This finding provides more evidence of high species composition turnover (beta-diversity) in the Panamanian biota, which appears to be driven by a combination of soil and climate differences over narrow distances. PMID:25102652

  10. The fallacy of coverage: uncovering disparities to improve immunization rates through evidence. Results from the Canadian International Immunization Initiative Phase 2 - Operational Research Grants.

    Science.gov (United States)

    Mhatre, Sharmila L; Schryer-Roy, Anne-Marie

    2009-01-01

    Immunization can and does save lives. However, the presence of vaccines does not easily translate into every child being vaccinated, and this is what the studies in this journal supplement reveal. From South Asia to West Africa,the evidence presented here reveals what we are calling the fallacy of coverage, going beyond uncovering the real vaccination rates to providing evidence on the reasons for the lack of effective coverage.The evidence for the fallacy of coverage is part of an operational research program entitled the Canadian International Immunization Initiative Phase 2 (CIII2). Through a competitive peer review process, six research grants were awarded to increase access to and enhance immunization services. This journal supplement provides a forum for the presentation of the results of five of the six studies.The story of the fallacy of coverage is made up of five theme areas of evidence - timeliness of immunization, social and gender inequities, vaccine efficacy, understanding demand side issues to tailor interventions, and national data sets masking actual district level coverage rates - that reveal the discrepancies in immunization coverage rates and the reasons behind these discrepancies. As part of the story, and to turn around the fallacy of coverage, the studies also provide proof of effective and locally relevant solutions.Policies and funding, while keeping an eye on future diseases, clearly need to maintain and increase support to address existing vaccine-preventable diseases to increase coverage such that by 2015 we can achieve 90% national vaccination coverage and reach the MDG of reducing mortality rates among children under five by two-thirds.The results from the operational research grants of the CIII2 offer some answers on how to reach this goal by demonstrating how locally generated evidence can inform immunization strategies to ensure that children who need to get vaccinated will get vaccinated, and vaccinated on time. PMID:19828053

  11. Uncovering biologically significant lipid isomers with liquid chromatography, ion mobility spectrometry and mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Kyle, Jennifer E.; Zhang, Xing; Weitz, Karl K.; Monroe, Matthew E.; Ibrahim, Yehia M.; Moore, Ronald J.; Cha, Jeeyeon; Sun, Xiaofei; Lovelace, Erica S.; Wagoner, Jessica; Polyak, Stephen J.; Metz, Thomas O.; Dey, Sudhansu K.; Smith, Richard D.; Burnum-Johnson, Kristin E.; Baker, Erin S.

    2016-01-01

    Understanding how biological molecules are generated, metabolized and eliminated in living systems is important for interpreting processes such as immune response and disease pathology. While genomic and proteomic studies have provided vast amounts of information over the last several decades, interest in lipidomics has also grown due to improved analytical technologies revealing altered lipid metabolism in type 2 diabetes, cancer, and lipid storage disease. Liquid chromatography and mass spectrometry (LC-MS) measurements are currently the dominant approach for characterizing the lipidome by providing detailed information on the spatial and temporal composition of lipids. However, interpreting lipids’ biological roles is challenging due to the existence of numerous structural and stereoisomers (i.e. distinct acyl chain and double-bond positions), which are unresolvable using present LC-MS approaches. Here we show that combining structurally-based ion mobility spectrometry (IMS) with LC-MS measurements distinguishes lipid isomers and allows insight into biological and disease processes.

  12. Cryptic Speciation Patterns in Iranian Rock Lizards Uncovered by Integrative Taxonomy

    OpenAIRE

    Ahmadzadeh, Faraham; Flecks, Morris; Miguel A. Carretero; Mozaffari, Omid; Böhme, Wolfgang; Harris, D. James; Freitas, Susana; Rödder, Dennis

    2013-01-01

    While traditionally species recognition has been based solely on morphological differences either typological or quantitative, several newly developed methods can be used for a more objective and integrative approach on species delimitation. This may be especially relevant when dealing with cryptic species or species complexes, where high overall resemblance between species is coupled with comparatively high morphological variation within populations. Rock lizards, genus Darevskia, are such a...

  13. A metagenomic β-glucuronidase uncovers a core adaptive function of the human intestinal microbiome

    OpenAIRE

    Gloux, Karine; Berteau, Olivier; El oumami, Hanane; Béguet, Fabienne; Leclerc, Marion; Doré, Joël

    2010-01-01

    In the human gastrointestinal tract, bacterial β-D-glucuronidases (BG; E.C. 3.2.1.31) are involved both in xenobiotic metabolism and in some of the beneficial effects of dietary compounds. Despite their biological significance, investigations are hampered by the fact that only a few BGs have so far been studied. A functional metagenomic approach was therefore performed on intestinal metagenomic libraries using chromogenic glucuronides as probes. Using this strategy, 19 positive metagenomic cl...

  14. Uncovering University Students’ Readiness through Their Assessment of Workplace Communication Skills

    OpenAIRE

    Joel M. Magogwe; Leonard B. M. Nkosana; Beauty B. Ntereke

    2014-01-01

    Employers in today’s competitive and challenging global world prefer employees who possess “soft skills” inaddition to “hard skills” because they make an impact and create a good impression in the workplace. This studyexamined employment readiness of the University of Botswana (UB) students who took the AdvancedCommunication Skills (GEC 213) course in 2013. It also explored their perceptions on the importance of these skills.A triangulation approach was used involving a survey and interview t...

  15. Health Econometric: Uncovering the Anthropometric Behavior on the Women's Labor Market

    OpenAIRE

    Lopez-Pablos, Rodrigo A.

    2007-01-01

    Exploring current literature which assess relations between cognitive ability and height, obesity, and its productivity-employability effect on women's labor market, we appraised the Argentine case to quantify for social-physical interactions which involve anthropometric and traditional economic variables. Hence, an anthropometric Mincer approach has been adapted by using probabilistic and censured econometric models which were developed for it. There has been found evidence that could be ...

  16. Directed Evolution of an Enantioselective Epoxide Hydrolase : Uncovering the Source of Enantioselectivity at Each Evolutionary Stage

    OpenAIRE

    Reetz, Manfred T.; Bocola, Marco; Wang, Li-Wen; Sanchis, Joaquin; Cronin, Annette; Arand, Michael; Zou, Jinyu; Archelas, Alain; Bottalla, Anne-Lise; Naworyta, Agata; Mowbray, Sherry L.

    2009-01-01

    Directed evolution of enzymes as enantioselective catalysts in organic chemistry is an alternative to traditional asymmetric catalysis using chiral transition-metal complexes or organocatalysts, the different approaches often being complementary. Moreover, directed evolution studies allow us to learn more about how enzymes perform mechanistically. The present study concerns a previously evolved highly enantioselective mutant of the epoxide hydrolase from Aspergillus niger in the hydrolytic ki...

  17. Genetic Architecture of Vitamin B12 and Folate Levels Uncovered Applying Deeply Sequenced Large Datasets

    OpenAIRE

    Niels Grarup; Patrick Sulem; Sandholt, Camilla H.; Gudmar Thorleifsson; Ahluwalia, Tarunveer S.; Valgerdur Steinthorsdottir; Helgi Bjarnason; Gudbjartsson, Daniel F.; Magnusson, Olafur T.; Thomas Sparsø; Anders Albrechtsen; Augustine Kong; Gisli Masson; Geng Tian; Hongzhi Cao

    2013-01-01

    Genome-wide association studies have mainly relied on common HapMap sequence variations. Recently, sequencing approaches have allowed analysis of low frequency and rare variants in conjunction with common variants, thereby improving the search for functional variants and thus the understanding of the underlying biology of human traits and diseases. Here, we used a large Icelandic whole genome sequence dataset combined with Danish exome sequence data to gain insight into the genetic architectu...

  18. Uncovering the Protein Lysine and Arginine Methylation Network in Arabidopsis Chloroplasts

    OpenAIRE

    Alban, Claude; Tardif, Marianne; Mininno, Morgane; Brugiere, Sabine; Gilgen, Annabelle; Ma, Sheng; Mazzoleni, Meryl; Gigarel, Oceane; Martin-Laffon, Jacqueline; Ferro, Myriam

    2014-01-01

    Post-translational modification of proteins by the addition of methyl groups to the side chains of Lys and Arg residues is proposed to play important roles in many cellular processes. In plants, identification of non-histone methylproteins at a cellular or subcellular scale is still missing. To gain insights into the extent of this modification in chloroplasts we used a bioinformatics approach to identify protein methyltransferases targeted to plastids and set up a workflow to specifically id...

  19. Uncovering Local Trends in Genetic Effects of Multiple Phenotypes via Functional Linear Models.

    Science.gov (United States)

    Vsevolozhskaya, Olga A; Zaykin, Dmitri V; Barondess, David A; Tong, Xiaoren; Jadhav, Sneha; Lu, Qing

    2016-04-01

    Recent technological advances equipped researchers with capabilities that go beyond traditional genotyping of loci known to be polymorphic in a general population. Genetic sequences of study participants can now be assessed directly. This capability removed technology-driven bias toward scoring predominantly common polymorphisms and let researchers reveal a wealth of rare and sample-specific variants. Although the relative contributions of rare and common polymorphisms to trait variation are being debated, researchers are faced with the need for new statistical tools for simultaneous evaluation of all variants within a region. Several research groups demonstrated flexibility and good statistical power of the functional linear model approach. In this work we extend previous developments to allow inclusion of multiple traits and adjustment for additional covariates. Our functional approach is unique in that it provides a nuanced depiction of effects and interactions for the variables in the model by representing them as curves varying over a genetic region. We demonstrate flexibility and competitive power of our approach by contrasting its performance with commonly used statistical tools and illustrate its potential for discovery and characterization of genetic architecture of complex traits using sequencing data from the Dallas Heart Study. PMID:27027515

  20. Hope for GWAS: Relevant Risk Genes Uncovered from GWAS Statistical Noise

    Directory of Open Access Journals (Sweden)

    Catarina Correia

    2014-09-01

    Full Text Available Hundreds of genetic variants have been associated to common diseases through genome-wide association studies (GWAS, yet there are limits to current approaches in detecting true small effect risk variants against a background of false positive findings. Here we addressed the missing heritability problem, aiming to test whether there are indeed risk variants within GWAS statistical noise and to develop a systematic strategy to retrieve these hidden variants. Employing an integrative approach, which combines protein-protein interactions with association data from GWAS for 6 common diseases, we found that associated-genes at less stringent significance levels (p < 0.1 with any of these diseases are functionally connected beyond noise expectation. This functional coherence was used to identify disease-relevant subnetworks, which were shown to be enriched in known genes, outperforming the selection of top GWAS genes. As a proof of principle, we applied this approach to breast cancer, supporting well-known breast cancer genes, while pinpointing novel susceptibility genes for experimental validation. This study reinforces the idea that GWAS are under-analyzed and that missing heritability is rather hidden. It extends the use of protein networks to reveal this missing heritability, thus leveraging the large investment in GWAS that produced so far little tangible gain.

  1. Comparative phylogenomics uncovers the impact of symbiotic associations on host genome evolution.

    Directory of Open Access Journals (Sweden)

    Pierre-Marc Delaux

    2014-07-01

    Full Text Available Mutualistic symbioses between eukaryotes and beneficial microorganisms of their microbiome play an essential role in nutrition, protection against disease, and development of the host. However, the impact of beneficial symbionts on the evolution of host genomes remains poorly characterized. Here we used the independent loss of the most widespread plant-microbe symbiosis, arbuscular mycorrhization (AM, as a model to address this question. Using a large phenotypic approach and phylogenetic analyses, we present evidence that loss of AM symbiosis correlates with the loss of many symbiotic genes in the Arabidopsis lineage (Brassicales. Then, by analyzing the genome and/or transcriptomes of nine other phylogenetically divergent non-host plants, we show that this correlation occurred in a convergent manner in four additional plant lineages, demonstrating the existence of an evolutionary pattern specific to symbiotic genes. Finally, we use a global comparative phylogenomic approach to track this evolutionary pattern among land plants. Based on this approach, we identify a set of 174 highly conserved genes and demonstrate enrichment in symbiosis-related genes. Our findings are consistent with the hypothesis that beneficial symbionts maintain purifying selection on host gene networks during the evolution of entire lineages.

  2. Patterns and Correlations in Economic Phenomena Uncovered Using Concepts of Statistical Physics

    Science.gov (United States)

    Stanley, H.E.; Gopikrishnan, P.; Plerou, H.V.; Salinger, M.A.

    This paper discusses some of the similarities between work being done by economists and by physicists seeking to find "patterns" in economics. We also mention some of the differences in the approaches taken and seek to justify these different approaches by developing the argument that by approaching the same problem from different points of view, new results might emerge. In particular, we review two such new results. Specifically, we discuss the two newly-discovered scaling results that appear to be "universal", in the sense that they hold for widely different economies as well as for different time periods: (i) the fluctuation of price changes of any stock market is characterized by a probability density function (PDF), which is a simple power law with exponent alpha + 1 = 4 extending over 102 standard deviations (a factor of 108 on the y-axis); this result is analogous to the Gutenberg-Richter power law describing the histogram of earthquakes of a given strength; (ii) for a wide range of economic organizations, the histogram that shows how size of organization is inversely correlated to fluctuations in size with an exponent approx 0.2. Neither of these two new empirical laws has a firm theoretical foundation. We also discuss results that are reminiscent of phase transitions in spin systems, where the divergent behavior of the response function at the critical point (zero magnetic field) leads to large fluctuations. We discuss a curious "symmetry breaking" for values of Sigma above a certain threshold value Σ_c; here Σ is defined to be the local first moment of the probability distribution of demand Ω - the difference between the number of shares traded in buyer-initiated and seller-initiated trades. This feature is qualitatively identical to the behavior of the probability density of the magnetization for fixed values of the inverse temperature.

  3. Uncovering dispersion properties in semiconductor waveguides to study photon-pair generation

    CERN Document Server

    Laiho, K; Schlager, A; Suchomel, H; Höfling, S; Kamp, M; Schneider, C; Weihs, G

    2016-01-01

    We investigate the dispersion properties of ridge Bragg-reflection waveguides to deduce their phasematching characteristics. These are crucial for exploiting them as sources of parametric down-conversion (PDC). In order to estimate the phasematching bandwidth we first determine the group refractive indices of the interacting modes via Fabry-Perot experiments in two distant wavelength regions. Second, by measuring the spectra of the emitted PDC photons we gain access to their group index dispersion. Our results offer a simple approach for determining the PDC process parameters in the spectral domain and provide an important feedback for designing such sources, especially in the broadband case.

  4. Uncovering the underlying physical mechanisms of biological systems via quantification of landscape and flux

    Science.gov (United States)

    Li, Xu; Xiakun, Chu; Zhiqiang, Yan; Xiliang, Zheng; Kun, Zhang; Feng, Zhang; Han, Yan; Wei, Wu; Jin, Wang

    2016-01-01

    In this review, we explore the physical mechanisms of biological processes such as protein folding and recognition, ligand binding, and systems biology, including cell cycle, stem cell, cancer, evolution, ecology, and neural networks. Our approach is based on the landscape and flux theory for nonequilibrium dynamical systems. This theory provides a unifying principle and foundation for investigating the underlying mechanisms and physical quantification of biological systems. Project supported by the Natural Science Foundation of China (Grant Nos. 21190040, 11174105, 91225114, 91430217, and 11305176) and Jilin Province Youth Foundation, China (Grant No. 20150520082JH).

  5. An Optimization-Driven Analysis Pipeline to Uncover Biomarkers and Signaling Paths: Cervix Cancer

    Directory of Open Access Journals (Sweden)

    Enery Lorenzo

    2015-05-01

    Full Text Available Establishing how a series of potentially important genes might relate to each other is relevant to understand the origin and evolution of illnesses, such as cancer. High‑throughput biological experiments have played a critical role in providing information in this regard. A special challenge, however, is that of trying to conciliate information from separate microarray experiments to build a potential genetic signaling path. This work proposes a two-step analysis pipeline, based on optimization, to approach meta-analysis aiming to build a proxy for a genetic signaling path.

  6. An Integrated Metabolomic and Genomic Mining Workflow to Uncover the Biosynthetic Potential of Bacteria

    DEFF Research Database (Denmark)

    Månsson, Maria; Vynne, Nikolaj Grønnegaard; Klitgaard, Andreas;

    2016-01-01

    Microorganisms are a rich source of bioactives; however, chemical identification is a major bottleneck. Strategies that can prioritize the most prolific microbial strains and novel compounds are of great interest. Here, we present an integrated approach to evaluate the biosynthetic richness in...... bacteria and mine the associated chemical diversity. Thirteen strains closely related to Pseudoalteromonas luteoviolacea isolated from all over the Earth were analyzed using an untargeted metabolomics strategy, and metabolomic profiles were correlated with whole-genome sequences of the strains. We found......, integrative strategy for elucidating the chemical richness of a given set of bacteria and link the chemistry to biosynthetic genes....

  7. Assessing and Increasing Physical Activity

    Science.gov (United States)

    Van Camp, Carole M.; Hayes, Lynda B.

    2012-01-01

    Increasing physical activity is a crucial component of any comprehensive approach to combat the growing obesity epidemic. This review summarizes recent behavioral research on the measurement of physical activity and interventions aimed at increasing physical activity and provides directions for future research.

  8. Moderate acute malnutrition: uncovering the known and unknown for more effective prevention and treatment.

    Science.gov (United States)

    Wegner, Christopher William; Loechl, Cornelia; Mokhtar, Najat

    2015-03-01

    With a fast-approaching post-Millennium Development Goal era, there is an urgent need to boost global investment in efforts to reduce child malnutrition. Critical to the management of moderate malnutrition, and therefore to the new Sustainable Development Goals, is addressing severe acute malnutrition (SAM) and moderate acute malnutrition (MAM). Despite the considerable difference in the approximate number of children affected by MAM (33 million) compared with SAM (19 million), there is currently no standardized approach to the management of MAM. In partnership with Valid International, the World Food Programme, and the Micronutrient Initiative, the International Atomic Energy Agency hosted the International Symposium on Understanding Moderate Malnutrition in Children for Effective Interventions in Vienna, Austria, 26-29 May 2014. This symposium focused on the management (prevention and treatment) of MAM in children. The symposium convened over 350 participants from 63 countries, the majority of whom represented governments responding to moderate malnutrition in their populations, nearly 70 national and international organizations from the United Nations and nongovernmental sectors, and universities from around the world, as well as donor governments and private-sector entities. The symposium was structured around nine sessions over a 3-day period, progressing from a global analysis of the scale of the problem to recent research findings relevant to designing effective interventions. This Supplement contains a series of papers that summarize the symposium sessions and other fundamental aspects important to improving the management of moderate malnutrition in children. PMID:25902608

  9. Chemical Genetics Uncovers Novel Inhibitors of Lignification, Including p-Iodobenzoic Acid Targeting CINNAMATE-4-HYDROXYLASE.

    Science.gov (United States)

    Van de Wouwer, Dorien; Vanholme, Ruben; Decou, Raphaël; Goeminne, Geert; Audenaert, Dominique; Nguyen, Long; Höfer, René; Pesquet, Edouard; Vanholme, Bartel; Boerjan, Wout

    2016-09-01

    Plant secondary-thickened cell walls are characterized by the presence of lignin, a recalcitrant and hydrophobic polymer that provides mechanical strength and ensures long-distance water transport. Exactly the recalcitrance and hydrophobicity of lignin put a burden on the industrial processing efficiency of lignocellulosic biomass. Both forward and reverse genetic strategies have been used intensively to unravel the molecular mechanism of lignin deposition. As an alternative strategy, we introduce here a forward chemical genetic approach to find candidate inhibitors of lignification. A high-throughput assay to assess lignification in Arabidopsis (Arabidopsis thaliana) seedlings was developed and used to screen a 10-k library of structurally diverse, synthetic molecules. Of the 73 compounds that reduced lignin deposition, 39 that had a major impact were retained and classified into five clusters based on the shift they induced in the phenolic profile of Arabidopsis seedlings. One representative compound of each cluster was selected for further lignin-specific assays, leading to the identification of an aromatic compound that is processed in the plant into two fragments, both having inhibitory activity against lignification. One fragment, p-iodobenzoic acid, was further characterized as a new inhibitor of CINNAMATE 4-HYDROXYLASE, a key enzyme of the phenylpropanoid pathway synthesizing the building blocks of the lignin polymer. As such, we provide proof of concept of this chemical biology approach to screen for inhibitors of lignification and present a broad array of putative inhibitors of lignin deposition for further characterization. PMID:27485881

  10. The taxonomy statistic uncovers novel clinical patterns in a population of ischemic stroke patients.

    Directory of Open Access Journals (Sweden)

    Andrzej Tukiendorf

    Full Text Available In this paper, we describe a simple taxonomic approach for clinical data mining elaborated by Marczewski and Steinhaus (M-S, whose performance equals the advanced statistical methodology known as the expectation-maximization (E-M algorithm. We tested these two methods on a cohort of ischemic stroke patients. The comparison of both methods revealed strong agreement. Direct agreement between M-S and E-M classifications reached 83%, while Cohen's coefficient of agreement was κ = 0.766(P < 0.0001. The statistical analysis conducted and the outcomes obtained in this paper revealed novel clinical patterns in ischemic stroke patients. The aim of the study was to evaluate the clinical usefulness of Marczewski-Steinhaus' taxonomic approach as a tool for the detection of novel patterns of data in ischemic stroke patients and the prediction of disease outcome. In terms of the identification of fairly frequent types of stroke patients using their age, National Institutes of Health Stroke Scale (NIHSS, and diabetes mellitus (DM status, when dealing with rough characteristics of patients, four particular types of patients are recognized, which cannot be identified by means of routine clinical methods. Following the obtained taxonomical outcomes, the strong correlation between the health status at moment of admission to emergency department (ED and the subsequent recovery of patients is established. Moreover, popularization and simplification of the ideas of advanced mathematicians may provide an unconventional explorative platform for clinical problems.

  11. Standing of nucleic acid testing strategies in veterinary diagnosis laboratories to uncover Mycobacterium tuberculosis complex members.

    Science.gov (United States)

    Costa, Pedro; Botelho, Ana; Couto, Isabel; Viveiros, Miguel; Inácio, João

    2014-01-01

    Nucleic acid testing (NAT) designate any molecular approach used for the detection, identification, and characterization of pathogenic microorganisms, enabling the rapid, specific, and sensitive diagnostic of infectious diseases, such as tuberculosis. These assays have been widely used since the 90s of the last century in human clinical laboratories and, subsequently, also in veterinary diagnostics. Most NAT strategies are based in the polymerase chain reaction (PCR) and its several enhancements and variations. From the conventional PCR, real-time PCR and its combinations, isothermal DNA amplification, to the nanotechnologies, here we review how the NAT assays have been applied to decipher if and which member of the Mycobacterium tuberculosis complex is present in a clinical sample. Recent advances in DNA sequencing also brought new challenges and have made possible to generate rapidly and at a low cost, large amounts of sequence data. This revolution with the high-throughput sequencing (HTS) technologies makes whole genome sequencing (WGS) and metagenomics the trendiest NAT strategies, today. The ranking of NAT techniques in the field of clinical diagnostics is rising, and we provide a SWOT (Strengths, Weaknesses, Opportunities, and Threats) analysis with our view of the use of molecular diagnostics for detecting tuberculosis in veterinary laboratories, notwithstanding the gold standard being still the classical culture of the agent. The complementary use of both classical and molecular diagnostics approaches is recommended to speed the diagnostic, enabling a fast decision by competent authorities and rapid tackling of the disease. PMID:25988157

  12. Simultaneously uncovering the patterns of brain regions involved in different story reading subprocesses.

    Directory of Open Access Journals (Sweden)

    Leila Wehbe

    Full Text Available Story understanding involves many perceptual and cognitive subprocesses, from perceiving individual words, to parsing sentences, to understanding the relationships among the story characters. We present an integrated computational model of reading that incorporates these and additional subprocesses, simultaneously discovering their fMRI signatures. Our model predicts the fMRI activity associated with reading arbitrary text passages, well enough to distinguish which of two story segments is being read with 74% accuracy. This approach is the first to simultaneously track diverse reading subprocesses during complex story processing and predict the detailed neural representation of diverse story features, ranging from visual word properties to the mention of different story characters and different actions they perform. We construct brain representation maps that replicate many results from a wide range of classical studies that focus each on one aspect of language processing and offer new insights on which type of information is processed by different areas involved in language processing. Additionally, this approach is promising for studying individual differences: it can be used to create single subject maps that may potentially be used to measure reading comprehension and diagnose reading disorders.

  13. Increasing instruction time in school does increase learning

    DEFF Research Database (Denmark)

    Humlum, Maria; Nandrup, Anne Brink; Andersen, Simon Calmar

    2016-01-01

    Increasing instruction time in school is a central element in the attempts of many governments to improve student learning, but prior research—mainly based on observational data—disputes the effect of this approach and points out the potential negative effects on student behavior. Based on a large......-scale, cluster-randomized trial, we find that increasing instruction time increases student learning and that a general increase in instruction time is at least as efficient as an expert-developed, detailed teaching program that increases instruction with the same amount of time. These findings support the value...

  14. Learning with and from Facebook: Uncovering Power Asymmetries in Educational Interactions

    Science.gov (United States)

    Rambe, Patient; Ng'ambi, Dick

    2014-01-01

    Although social networking sites (SNS) are increasingly popular among students, their academic application is unfolding on trial basis and best practices for integration into mainstream teaching are yet to be fully realised. More importantly, is the need to understand how these sites shape academic relations and participation of heterogeneous…

  15. APC mutant zebrafish uncover a changing temporal requirement for wnt signaling in liver development.

    NARCIS (Netherlands)

    Goessling, W.; North, T.E.; Lord, A.M.; Ceol, C.; Lee, S.; Weidinger, G.; Bourque, C.; Strijbosch, R.; Haramis, A.P.; Puder, M.; Clevers, H.; Moon, R.T.; Zon, L.I.

    2008-01-01

    Developmental signaling pathways hold the keys to unlocking the promise of adult tissue regeneration, and to inhibiting carcinogenesis. Patients with mutations in the Adenomatous Polyposis Coli (APC) gene are at increased risk of developing hepatoblastoma, an embryonal form of liver cancer, suggesti

  16. The relationship between DTCA, drug requests, and prescriptions: Uncovering variation in specialty and space

    NARCIS (Netherlands)

    S. Stremersch (Stefan); V. Schwartz-Landsman (Vardit); S. Venkataraman (Sriram)

    2013-01-01

    textabstractPatients increasingly request their physicians to prescribe specific brands of pharmaceutical drugs. A popular belief is that requests are triggered by direct-to-consumer advertising (DTCA). We examine the relationship between DTCA, patient requests, and prescriptions for statins. We fin

  17. Arcaine uncovers dual interactions of polyamines with the N-methyl-D-aspartate receptor

    International Nuclear Information System (INIS)

    This study investigated the interaction between the polyamines spermine and spermidine and the N-methyl-D-aspartate (NMDA) receptor by using (+)-[3H]-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-im ine maleate ([3H]MK801) binding to well washed rat brain membranes. The actions of arcaine, agmatine, diethylenetriamine and 1,8-octanediamine as polyamine antagonists were compared to use as tools in this study. Arcaine was found to be the antagonist of choice due to its greater potency. Several divalent cations, including Ba++, Ca++ and Sr++, but not Zn++, decreased the apparent potency of arcaine. These cations enhance [3H]MK801 binding in a similar fashion to spermidine and spermine suggesting that they may share a common site and mechanism of action. Moreover, arcaine competitively reduced the enhancement of [3H]MK801 binding produced by Sr++ did not alter the inhibition produced by higher concentrations of this cation, a phenomenon that also occurs with spermidine. The distinct arcaine sensitivity of the two separate phases of the concentration-response curves of both spermidine and Sr++ suggests two separate mechanisms underlying the action of spermidine-like drugs on the NMDA receptor. Further investigation of the increase in [3H]MK801 binding produced by spermidine revealed that spermidine increased the equilibrium affinity of this ligand by 2-fold without significantly altering the density of binding sites. In contrast, polyamine induced increases in the dissociation of [3H]MK801 required higher polyamine concentrations than necessary to increase ligand binding and were relatively insensitive to arcaine. These findings suggest that polyamines do not activate or promote the activation of the NMDA receptor, but instead enhance [3H]MK801 binding by allosterically increasing ligand affinity

  18. Transplant experiments uncover Baltic Sea basin-specific responses in bacterioplankton community composition and metabolic activities.

    Science.gov (United States)

    Lindh, Markus V; Figueroa, Daniela; Sjöstedt, Johanna; Baltar, Federico; Lundin, Daniel; Andersson, Agneta; Legrand, Catherine; Pinhassi, Jarone

    2015-01-01

    Anthropogenically induced changes in precipitation are projected to generate increased river runoff to semi-enclosed seas, increasing loads of terrestrial dissolved organic matter and decreasing salinity. To determine how bacterial community structure and functioning adjust to such changes, we designed microcosm transplant experiments with Baltic Proper (salinity 7.2) and Bothnian Sea (salinity 3.6) water. Baltic Proper bacteria generally reached higher abundances than Bothnian Sea bacteria in both Baltic Proper and Bothnian Sea water, indicating higher adaptability. Moreover, Baltic Proper bacteria growing in Bothnian Sea water consistently showed highest bacterial production and beta-glucosidase activity. These metabolic responses were accompanied by basin-specific changes in bacterial community structure. For example, Baltic Proper Pseudomonas and Limnobacter populations increased markedly in relative abundance in Bothnian Sea water, indicating a replacement effect. In contrast, Roseobacter and Rheinheimera populations were stable or increased in abundance when challenged by either of the waters, indicating an adjustment effect. Transplants to Bothnian Sea water triggered the initial emergence of particular Burkholderiaceae populations, and transplants to Baltic Proper water triggered Alteromonadaceae populations. Notably, in the subsequent re-transplant experiment, a priming effect resulted in further increases to dominance of these populations. Correlated changes in community composition and metabolic activity were observed only in the transplant experiment and only at relatively high phylogenetic resolution. This suggested an importance of successional progression for interpreting relationships between bacterial community composition and functioning. We infer that priming effects on bacterial community structure by natural episodic events or climate change induced forcing could translate into long-term changes in bacterial ecosystem process rates. PMID

  19. Transcriptome atlas of eight liver cell types uncovers effects of histidine catabolites on rat liver regeneration

    Indian Academy of Sciences (India)

    C. F. Chang; J. Y. Fan; F. C. Zhang; J. Ma; C. S. Xu

    2010-12-01

    Eight liver cell types were isolated using the methods of Percoll density gradient centrifugation and immunomagnetic beads to explore effects of histidine catabolites on rat liver regeneration. Rat Genome 230 2.0 Array was used to detect the expression profiles of genes associated with metabolism of histidine and its catabolites for the above-mentioned eight liver cell types, and bioinformatic and systems biology approaches were employed to analyse the relationship between above genes and rat liver regeneration. The results showed that the urocanic acid (UA) was degraded from histidine in Kupffer cells, acts on Kupffer cells itself and dendritic cells to generate immune suppression by autocrine and paracrine modes. Hepatocytes, biliary epithelia cells, oval cells and dendritic cells can convert histidine to histamine, which can promote sinusoidal endothelial cells proliferation by GsM pathway, and promote the proliferation of hepatocytes and biliary epithelia cells by GqM pathway.

  20. A perspective on terra incognita: uncovering the neuroanatomy of the human subcortex

    Directory of Open Access Journals (Sweden)

    Anneke eAlkemade

    2013-12-01

    Full Text Available Recent exciting advancements in the field of in-vivo neuroimaging allow for visualization of the living human brain with unprecedented anatomical detail. Large consortium studies will provide us with novel insights in the function and connectivity of the human brain. However, it is unlikely that the spatial resolution obtained using in-vivo imaging will, in the near future, approximate the level of detail obtained in post-mortem anatomical studies. Initiatives such as the recently published Big Brain project (Amunts et al., 2013 herald a novel approach in post-mortem brain research. We feel that linking data from histological observations with in-vivo imaging studies will greatly advance our understanding of the functional neuroanatomy of the human brain.

  1. An integrative genomics screen uncovers ncRNA T-UCR functions in neuroblastoma tumours.

    Science.gov (United States)

    Mestdagh, P; Fredlund, E; Pattyn, F; Rihani, A; Van Maerken, T; Vermeulen, J; Kumps, C; Menten, B; De Preter, K; Schramm, A; Schulte, J; Noguera, R; Schleiermacher, G; Janoueix-Lerosey, I; Laureys, G; Powel, R; Nittner, D; Marine, J-C; Ringnér, M; Speleman, F; Vandesompele, J

    2010-06-17

    Different classes of non-coding RNAs, including microRNAs, have recently been implicated in the process of tumourigenesis. In this study, we examined the expression and putative functions of a novel class of non-coding RNAs known as transcribed ultraconserved regions (T-UCRs) in neuroblastoma. Genome-wide expression profiling revealed correlations between specific T-UCR expression levels and important clinicogenetic parameters such as MYCN amplification status. A functional genomics approach based on the integration of multi-level transcriptome data was adapted to gain insights into T-UCR functions. Assignments of T-UCRs to cellular processes such as TP53 response, differentiation and proliferation were verified using various cellular model systems. For the first time, our results define a T-UCR expression landscape in neuroblastoma and suggest widespread T-UCR involvement in diverse cellular processes that are deregulated in the process of tumourigenesis. PMID:20383195

  2. Genetic architecture of vitamin B12 and folate levels uncovered applying deeply sequenced large datasets.

    Science.gov (United States)

    Grarup, Niels; Sulem, Patrick; Sandholt, Camilla H; Thorleifsson, Gudmar; Ahluwalia, Tarunveer S; Steinthorsdottir, Valgerdur; Bjarnason, Helgi; Gudbjartsson, Daniel F; Magnusson, Olafur T; Sparsø, Thomas; Albrechtsen, Anders; Kong, Augustine; Masson, Gisli; Tian, Geng; Cao, Hongzhi; Nie, Chao; Kristiansen, Karsten; Husemoen, Lise Lotte; Thuesen, Betina; Li, Yingrui; Nielsen, Rasmus; Linneberg, Allan; Olafsson, Isleifur; Eyjolfsson, Gudmundur I; Jørgensen, Torben; Wang, Jun; Hansen, Torben; Thorsteinsdottir, Unnur; Stefánsson, Kari; Pedersen, Oluf

    2013-06-01

    Genome-wide association studies have mainly relied on common HapMap sequence variations. Recently, sequencing approaches have allowed analysis of low frequency and rare variants in conjunction with common variants, thereby improving the search for functional variants and thus the understanding of the underlying biology of human traits and diseases. Here, we used a large Icelandic whole genome sequence dataset combined with Danish exome sequence data to gain insight into the genetic architecture of serum levels of vitamin B(12) (B12) and folate. Up to 22.9 million sequence variants were analyzed in combined samples of 45,576 and 37,341 individuals with serum B(12) and folate measurements, respectively. We found six novel loci associating with serum B(12) (CD320, TCN2, ABCD4, MMAA, MMACHC) or folate levels (FOLR3) and confirmed seven loci for these traits (TCN1, FUT6, FUT2, CUBN, CLYBL, MUT, MTHFR). Conditional analyses established that four loci contain additional independent signals. Interestingly, 13 of the 18 identified variants were coding and 11 of the 13 target genes have known functions related to B(12) and folate pathways. Contrary to epidemiological studies we did not find consistent association of the variants with cardiovascular diseases, cancers or Alzheimer's disease although some variants demonstrated pleiotropic effects. Although to some degree impeded by low statistical power for some of these conditions, these data suggest that sequence variants that contribute to the population diversity in serum B(12) or folate levels do not modify the risk of developing these conditions. Yet, the study demonstrates the value of combining whole genome and exome sequencing approaches to ascertain the genetic and molecular architectures underlying quantitative trait associations. PMID:23754956

  3. Cryptic speciation patterns in Iranian rock lizards uncovered by integrative taxonomy.

    Directory of Open Access Journals (Sweden)

    Faraham Ahmadzadeh

    Full Text Available While traditionally species recognition has been based solely on morphological differences either typological or quantitative, several newly developed methods can be used for a more objective and integrative approach on species delimitation. This may be especially relevant when dealing with cryptic species or species complexes, where high overall resemblance between species is coupled with comparatively high morphological variation within populations. Rock lizards, genus Darevskia, are such an example, as many of its members offer few diagnostic morphological features. Herein, we use a combination of genetic, morphological and ecological criteria to delimit cryptic species within two species complexes, D. chlorogaster and D. defilippii, both distributed in northern Iran. Our analyses are based on molecular information from two nuclear and two mitochondrial genes, morphological data (15 morphometric, 16 meristic and four categorical characters and eleven newly calculated spatial environmental predictors. The phylogeny inferred for Darevskia confirmed monophyly of each species complex, with each of them comprising several highly divergent clades, especially when compared to other congeners. We identified seven candidate species within each complex, of which three and four species were supported by Bayesian species delimitation within D. chlorogaster and D. defilippii, respectively. Trained with genetically determined clades, Ecological Niche Modeling provided additional support for these cryptic species. Especially those within the D. defilippii-complex exhibit well-differentiated niches. Due to overall morphological resemblance, in a first approach PCA with mixed variables only showed the separation between the two complexes. However, MANCOVA and subsequent Discriminant Analysis performed separately for both complexes allowed for distinction of the species when sample size was large enough, namely within the D. chlorogaster-complex. In conclusion

  4. Uncovering the protein lysine and arginine methylation network in Arabidopsis chloroplasts.

    Science.gov (United States)

    Alban, Claude; Tardif, Marianne; Mininno, Morgane; Brugière, Sabine; Gilgen, Annabelle; Ma, Sheng; Mazzoleni, Meryl; Gigarel, Océane; Martin-Laffon, Jacqueline; Ferro, Myriam; Ravanel, Stéphane

    2014-01-01

    Post-translational modification of proteins by the addition of methyl groups to the side chains of Lys and Arg residues is proposed to play important roles in many cellular processes. In plants, identification of non-histone methylproteins at a cellular or subcellular scale is still missing. To gain insights into the extent of this modification in chloroplasts we used a bioinformatics approach to identify protein methyltransferases targeted to plastids and set up a workflow to specifically identify Lys and Arg methylated proteins from proteomic data used to produce the Arabidopsis chloroplast proteome. With this approach we could identify 31 high-confidence Lys and Arg methylation sites from 23 chloroplastic proteins, of which only two were previously known to be methylated. These methylproteins are split between the stroma, thylakoids and envelope sub-compartments. They belong to essential metabolic processes, including photosynthesis, and to the chloroplast biogenesis and maintenance machinery (translation, protein import, division). Also, the in silico identification of nine protein methyltransferases that are known or predicted to be targeted to plastids provided a foundation to build the enzymes/substrates relationships that govern methylation in chloroplasts. Thereby, using in vitro methylation assays with chloroplast stroma as a source of methyltransferases we confirmed the methylation sites of two targets, plastid ribosomal protein L11 and the β-subunit of ATP synthase. Furthermore, a biochemical screening of recombinant chloroplastic protein Lys methyltransferases allowed us to identify the enzymes involved in the modification of these substrates. The present study provides a useful resource to build the methyltransferases/methylproteins network and to elucidate the role of protein methylation in chloroplast biology. PMID:24748391

  5. Medicare Home Visit Program Associated With Fewer Hospital And Nursing Home Admissions, Increased Office Visits.

    Science.gov (United States)

    Mattke, Soeren; Han, Dan; Wilks, Asa; Sloss, Elizabeth

    2015-12-01

    Clinical home visit programs for Medicare beneficiaries are a promising approach to supporting aging in place and avoiding high-cost institutional care. Such programs combine a comprehensive geriatric assessment by a clinician during a home visit with referrals to community providers and health plan resources to address uncovered issues. We evaluated UnitedHealth Group's HouseCalls program, which has been offered to Medicare Advantage plan members in Arkansas, Georgia, Missouri, South Carolina, and Texas since January 2008. We found that, compared to non-HouseCalls Medicare Advantage plan members and fee-for-service beneficiaries, HouseCalls participants had reductions in admissions to hospitals (1 percent and 14 percent, respectively) and lower risk of nursing home admission (0.67 percent and 1.3 percent, respectively). In addition, participants' numbers of office visits--chiefly to specialists--increased 2-6 percent (depending on the comparison group). The program's effects on emergency department use were mixed. These results indicate that a thorough home-based clinical assessment of a member's health and home environment combined with referral services can support aging in place, promote physician office visits, and preempt costly institutional care. PMID:26643635

  6. Distilling a Visual Network of Retinitis Pigmentosa Gene-Protein Interactions to Uncover New Disease Candidates

    OpenAIRE

    Daniel Boloc; Sergio Castillo-Lara; Gemma Marfany; Roser Gonzàlez-Duarte; Abril, Josep F

    2015-01-01

    BACKGROUND: Retinitis pigmentosa (RP) is a highly heterogeneous genetic visual disorder with more than 70 known causative genes, some of them shared with other non-syndromic retinal dystrophies (e.g. Leber congenital amaurosis, LCA). The identification of RP genes has increased steadily during the last decade, and the 30% of the cases that still remain unassigned will soon decrease after the advent of exome/genome sequencing. A considerable amount of genetic and functional data on single RD g...

  7. SNP and Mutation Data on the Web – Hidden Treasures for Uncovering

    OpenAIRE

    Barnes, Michael R.

    2002-01-01

    SNP data has grown exponentially over the last two years, SNP database evolution has matched this growth, as initial development of several independent SNP databases has given way to one central SNP database, dbSNP. Other SNP databases have instead evolved to complement this central database by providing gene specific focus and an increased level of curation and analysis on subsets of data, derived from the central data set. By contrast, human mutation data, which has been collected over many...

  8. Battling Barrett's esophagus: uncovering the genetics and epigenetics of Barrrett's esophagus and esophageal adenocarcinoma

    OpenAIRE

    Streppel, M.M.

    2014-01-01

    Barrett’s esophagus (BE) is a common premalignant condition of the distal esophagus with a high incidence among Caucasian males. It is an important risk factor for the development of esophageal adenocarcinoma (EAC). EACs arise in BE following a multistep sequence through low- and high-grade dysplasia, finally culminating in an invasive adenocarcinoma. Because of this increased risk of developing an EAC and poor prognosis of EAC patients, BE patients are offered endoscopic surveillance in orde...

  9. Uncovering the role of human resources in corporate social responsibility: case evidence from Lebanon

    OpenAIRE

    Dirani, Ali El

    2012-01-01

    Over the past two decades, the interest in the concept of Corporate Social Responsibility (CSR) within both the academic and practitioner discourse has been rapidly increasing. CSR has developed to become a strategic objective for many organizations, with the credibility of CSR hinging on implementation as statements. This thesis aims to explore the role that Human Resources (HR) can play in CSR strategy development and implementation. Through a systematic review of relevant literatures on CS...

  10. Proteomic Analysis Uncovers Novel Actions of the Neurosecretory Protein VGF in Nociceptive Processing

    OpenAIRE

    Riedl, Maureen S; Braun, Patrick D.; Kitto, Kelley F.; Roiko, Samuel A.; Anderson, Lorraine B.; Honda, Christopher N.; Fairbanks, Carolyn A.; Vulchanova, Lucy

    2009-01-01

    Peripheral tissue injury is associated with changes in protein expression in sensory neurons that may contribute to abnormal nociceptive processing. We used cultured dorsal root ganglion (DRG) neurons as a model of axotomized neurons to investigate early changes in protein expression following nerve injury. Comparing protein levels immediately after DRG dissociation and 24 h later by proteomic differential expression analysis, we found a substantial increase in the levels of the neurotrophin-...

  11. Highly Multiplexed Imaging Uncovers Changes in Compositional Noise within Assembling Focal Adhesions.

    Science.gov (United States)

    Harizanova, Jana; Fermin, Yessica; Malik-Sheriff, Rahuman S; Wieczorek, Jakob; Ickstadt, Katja; Grecco, Hernán E; Zamir, Eli

    2016-01-01

    Integrin adhesome proteins bind each other in alternative manners, forming within the cell diverse cell-matrix adhesion sites with distinct properties. An intriguing question is how such modular assembly of adhesion sites is achieved correctly solely by self-organization of their components. Here we address this question using high-throughput multiplexed imaging of eight proteins and two phosphorylation sites in a large number of single focal adhesions. We found that during the assembly of focal adhesions the variances of protein densities decrease while the correlations between them increase, suggesting reduction in the noise levels within these structures. These changes correlate independently with the area and internal density of focal adhesions, but not with their age or shape. Artificial neural network analysis indicates that a joint consideration of multiple components improves the predictability of paxillin and zyxin levels in internally dense focal adhesions. This suggests that paxillin and zyxin densities in focal adhesions are fine-tuned by integrating the levels of multiple other components, thus averaging-out stochastic fluctuations. Based on these results we propose that increase in internal protein densities facilitates noise suppression in focal adhesions, while noise suppression enables their stable growth and further density increase-hence forming a feedback loop giving rise to a quality-controlled assembly. PMID:27519053

  12. Proteomic analysis uncovers novel actions of the neurosecretory protein VGF in nociceptive processing.

    Science.gov (United States)

    Riedl, Maureen S; Braun, Patrick D; Kitto, Kelley F; Roiko, Samuel A; Anderson, Lorraine B; Honda, Christopher N; Fairbanks, Carolyn A; Vulchanova, Lucy

    2009-10-21

    Peripheral tissue injury is associated with changes in protein expression in sensory neurons that may contribute to abnormal nociceptive processing. We used cultured dorsal root ganglion (DRG) neurons as a model of axotomized neurons to investigate early changes in protein expression after nerve injury. Comparing protein levels immediately after DRG dissociation and 24 h later by proteomic differential expression analysis, we found a substantial increase in the levels of the neurotrophin-inducible protein VGF (nonacronymic), a putative neuropeptide precursor. In a rodent model of nerve injury, VGF levels were increased within 24 h in both injured and uninjured DRG neurons, and the increase persisted for at least 7 d. VGF was also upregulated 24 h after hindpaw inflammation. To determine whether peptides derived from proteolytic processing of VGF participate in nociceptive signaling, we examined the spinal effects of AQEE-30 and LQEQ-19, potential proteolytic products shown previously to be bioactive. Each peptide evoked dose-dependent thermal hyperalgesia that required activation of the mitogen-activated protein kinase p38. In addition, LQEQ-19 induced p38 phosphorylation in spinal microglia when injected intrathecally and in the BV-2 microglial cell line when applied in vitro. In summary, our results demonstrate rapid upregulation of VGF in sensory neurons after nerve injury and inflammation and activation of microglial p38 by VGF peptides. Therefore, VGF peptides released from sensory neurons may participate in activation of spinal microglia after peripheral tissue injury. PMID:19846725

  13. Increasing Responsibility towards Environment

    Directory of Open Access Journals (Sweden)

    Mihaela Comanescu

    2009-11-01

    Full Text Available In the international climate of the early millennium, the need for reconciliation between economic and social development, on one hand, and the environment, on the other hand, is essential. Therefore, sustainable development must be promoted, because it integrates economic growth, improved quality of life, health, education, social development and environmental protection.Environmental issues are particularly complex as their causes are interdependent. This requires actions at all levels: local, national, regional as well as at the European Union level, each with its own role in increasing responsibility for the environmental protection.It is widely recognized that to obtain successful results an integrated approach has to be used to manage the environment, by adopting long-term strategies and action plans. It requires a detailed analysis of the links between different policies and responsibilities, including the links between different administrative levels.

  14. Increasing Responsibility towards Environment

    Directory of Open Access Journals (Sweden)

    Mihaela COMĂNESCU

    2010-05-01

    Full Text Available In the international climate of the early millennium, the need for reconciliation between economic and social development, on one hand, and the environment, on the other hand, is essential. Therefore, sustainable development must be promoted, because it integrates economic growth, improves quality of life, health, education, social development and environmental protection. Environmental issues are particularly complex as their causes are interdependent. This requires actions at all levels: local, national, regional as well as at the European Union level, each with its own role in increasing responsibility for the environmental protection. It is widely recognized that to obtain successful results an integrated approach has to be used to manage the environment, by adopting long-term strategies and action plans. It requires a detailed analysis of the links between different policies and responsibilities, including the links between different administrative levels.

  15. Uncovering a Latent Multinomial: Analysis of Mark-Recapture Data with Misidentification

    Science.gov (United States)

    Link, W.A.; Yoshizaki, J.; Bailey, L.L.; Pollock, K.H.

    2009-01-01

    Natural tags based on DNA fingerprints or natural features of animals are now becoming very widely used in wildlife population biology. However, classic capture-recapture models do not allow for misidentification of animals which is a potentially very serious problem with natural tags. Statistical analysis of misidentification processes is extremely difficult using traditional likelihood methods but is easily handled using Bayesian methods. We present a general framework for Bayesian analysis of categorical data arising from a latent multinomial distribution. Although our work is motivated by a specific model for misidentification in closed population capture-recapture analyses, with crucial assumptions which may not always be appropriate, the methods we develop extend naturally to a variety of other models with similar structure. Suppose that observed frequencies f are a known linear transformation f=A'x of a latent multinomial variable x with cell probability vector pi= pi(theta). Given that full conditional distributions [theta | x] can be sampled, implementation of Gibbs sampling requires only that we can sample from the full conditional distribution [x | f, theta], which is made possible by knowledge of the null space of A'. We illustrate the approach using two data sets with individual misidentification, one simulated, the other summarizing recapture data for salamanders based on natural marks.

  16. Uncovering molecular processes in crystal nucleation and growth by using molecular simulation.

    Science.gov (United States)

    Anwar, Jamshed; Zahn, Dirk

    2011-02-25

    Exploring nucleation processes by molecular simulation provides a mechanistic understanding at the atomic level and also enables kinetic and thermodynamic quantities to be estimated. However, whilst the potential for modeling crystal nucleation and growth processes is immense, there are specific technical challenges to modeling. In general, rare events, such as nucleation cannot be simulated using a direct "brute force" molecular dynamics approach. The limited time and length scales that are accessible by conventional molecular dynamics simulations have inspired a number of advances to tackle problems that were considered outside the scope of molecular simulation. While general insights and features could be explored from efficient generic models, new methods paved the way to realistic crystal nucleation scenarios. The association of single ions in solvent environments, the mechanisms of motif formation, ripening reactions, and the self-organization of nanocrystals can now be investigated at the molecular level. The analysis of interactions with growth-controlling additives gives a new understanding of functionalized nanocrystals and the precipitation of composite materials. PMID:21271625

  17. Using giant scarlet runner bean embryos to uncover regulatory networks controlling suspensor gene activity

    Directory of Open Access Journals (Sweden)

    Kelli F. Henry

    2015-02-01

    Full Text Available One of the major unsolved issues in plant development is understanding the regulatory networks that control the differential gene activity that is required for the specification and development of the two major embryonic regions, the embryo proper and suspensor. Historically, the giant embryo of scarlet runner bean (SRB, Phaseolus coccineus, has been used as a model system to investigate the physiological events that occur early in embryogenesis – focusing on the question of what role the suspensor region plays. A major feature distinguishing SRB embryos from those of other plants is a highly enlarged suspensor containing at least 200 cells that synthesize growth regulators required for subsequent embryonic development. Recent studies have exploited the giant size of the SRB embryo to micro-dissect the embryo proper and suspensor regions in order to use genomics-based approaches to identify regulatory genes that may be involved in controlling suspensor and embryo proper differentiation, as well as the cellular processes that may be unique to each embryonic region. Here we review the current genomics resources that make SRB embryos a compelling model system for studying the early events required to program embryo development.

  18. Using Caenorhabditis elegans to Uncover Conserved Functions of Omega-3 and Omega-6 Fatty Acids

    Directory of Open Access Journals (Sweden)

    Jennifer L. Watts

    2016-02-01

    Full Text Available The nematode Caenorhabditis elegans is a powerful model organism to study functions of polyunsaturated fatty acids. The ability to alter fatty acid composition with genetic manipulation and dietary supplementation permits the dissection of the roles of omega-3 and omega-6 fatty acids in many biological process including reproduction, aging and neurobiology. Studies in C. elegans to date have mostly identified overlapping functions of 20-carbon omega-6 and omega-3 fatty acids in reproduction and in neurons, however, specific roles for either omega-3 or omega-6 fatty acids are beginning to emerge. Recent findings with importance to human health include the identification of a conserved Cox-independent prostaglandin synthesis pathway, critical functions for cytochrome P450 derivatives of polyunsaturated fatty acids, the requirements for omega-6 and omega-3 fatty acids in sensory neurons, and the importance of fatty acid desaturation for long lifespan. Furthermore, the ability of C. elegans to interconvert omega-6 to omega-3 fatty acids using the FAT-1 omega-3 desaturase has been exploited in mammalian studies and biotechnology approaches to generate mammals capable of exogenous generation of omega-3 fatty acids.

  19. Network-Based Analysis on Orthogonal Separation of Human Plasma Uncovers Distinct High Density Lipoprotein Complexes.

    Science.gov (United States)

    Li, Hailong; Gordon, Scott M; Zhu, Xiaoting; Deng, Jingyuan; Swertfeger, Debi K; Davidson, W Sean; Lu, L Jason

    2015-08-01

    High density lipoprotein (HDL) particles are blood-borne complexes whose plasma levels have been associated with protection from cardiovascular disease (CVD). Recent studies have demonstrated the existence of distinct HDL subspecies; however, these have been difficult to isolate and characterize biochemically. Here, we present the first report that employs a network-based approach to systematically infer HDL subspecies. Healthy human plasma was separated into 58 fractions using our previously published three orthogonal chromatography techniques. Similar local migration patterns among HDL proteins were captured with a novel similarity score, and individual comigration networks were constructed for each fraction. By employing a graph mining algorithm, we identified 183 overlapped cliques, among which 38 were further selected as candidate HDL subparticles. Each of these 38 subparticles had at least two literature supports. In addition, GO function enrichment analysis showed that they were enriched with fundamental biological and CVD protective functions. Furthermore, gene knockout experiments in mouse model supported the validity of these subparticles related to three apolipoproteins. Finally, analysis of an apoA-I deficient human patient's plasma provided additional support for apoA-I related complexes. Further biochemical characterization of these putative subspecies may facilitate the mechanistic research of CVD and guide targeted therapeutics aimed at its mitigation. PMID:26057100

  20. Site-specific Interaction Mapping of Phosphorylated Ubiquitin to Uncover Parkin Activation.

    Science.gov (United States)

    Yamano, Koji; Queliconi, Bruno B; Koyano, Fumika; Saeki, Yasushi; Hirokawa, Takatsugu; Tanaka, Keiji; Matsuda, Noriyuki

    2015-10-16

    Damaged mitochondria are eliminated through autophagy machinery. A cytosolic E3 ubiquitin ligase Parkin, a gene product mutated in familial Parkinsonism, is essential for this pathway. Recent progress has revealed that phosphorylation of both Parkin and ubiquitin at Ser(65) by PINK1 are crucial for activation and recruitment of Parkin to the damaged mitochondria. However, the mechanism by which phosphorylated ubiquitin associates with and activates phosphorylated Parkin E3 ligase activity remains largely unknown. Here, we analyze interactions between phosphorylated forms of both Parkin and ubiquitin at a spatial resolution of the amino acid residue by site-specific photo-crosslinking. We reveal that the in-between-RING (IBR) domain along with RING1 domain of Parkin preferentially binds to ubiquitin in a phosphorylation-dependent manner. Furthermore, another approach, the Fluoppi (fluorescent-based technology detecting protein-protein interaction) assay, also showed that pathogenic mutations in these domains blocked interactions with phosphomimetic ubiquitin in mammalian cells. Molecular modeling based on the site-specific photo-crosslinking interaction map combined with mass spectrometry strongly suggests that a novel binding mechanism between Parkin and ubiquitin leads to a Parkin conformational change with subsequent activation of Parkin E3 ligase activity. PMID:26260794

  1. Networks uncover hidden lexical borrowing in Indo-European language evolution.

    Science.gov (United States)

    Nelson-Sathi, Shijulal; List, Johann-Mattis; Geisler, Hans; Fangerau, Heiner; Gray, Russell D; Martin, William; Dagan, Tal

    2011-06-22

    Language evolution is traditionally described in terms of family trees with ancestral languages splitting into descendent languages. However, it has long been recognized that language evolution also entails horizontal components, most commonly through lexical borrowing. For example, the English language was heavily influenced by Old Norse and Old French; eight per cent of its basic vocabulary is borrowed. Borrowing is a distinctly non-tree-like process--akin to horizontal gene transfer in genome evolution--that cannot be recovered by phylogenetic trees. Here, we infer the frequency of hidden borrowing among 2346 cognates (etymologically related words) of basic vocabulary distributed across 84 Indo-European languages. The dataset includes 124 (5%) known borrowings. Applying the uniformitarian principle to inventory dynamics in past and present basic vocabularies, we find that 1373 (61%) of the cognates have been affected by borrowing during their history. Our approach correctly identified 117 (94%) known borrowings. Reconstructed phylogenetic networks that capture both vertical and horizontal components of evolutionary history reveal that, on average, eight per cent of the words of basic vocabulary in each Indo-European language were involved in borrowing during evolution. Basic vocabulary is often assumed to be relatively resistant to borrowing. Our results indicate that the impact of borrowing is far more widespread than previously thought. PMID:21106583

  2. Breakpoint analysis of transcriptional and genomic profiles uncovers novel gene fusions spanning multiple human cancer types.

    Directory of Open Access Journals (Sweden)

    Craig P Giacomini

    2013-04-01

    Full Text Available Gene fusions, like BCR/ABL1 in chronic myelogenous leukemia, have long been recognized in hematologic and mesenchymal malignancies. The recent finding of gene fusions in prostate and lung cancers has motivated the search for pathogenic gene fusions in other malignancies. Here, we developed a "breakpoint analysis" pipeline to discover candidate gene fusions by tell-tale transcript level or genomic DNA copy number transitions occurring within genes. Mining data from 974 diverse cancer samples, we identified 198 candidate fusions involving annotated cancer genes. From these, we validated and further characterized novel gene fusions involving ROS1 tyrosine kinase in angiosarcoma (CEP85L/ROS1, SLC1A2 glutamate transporter in colon cancer (APIP/SLC1A2, RAF1 kinase in pancreatic cancer (ATG7/RAF1 and anaplastic astrocytoma (BCL6/RAF1, EWSR1 in melanoma (EWSR1/CREM, CDK6 kinase in T-cell acute lymphoblastic leukemia (FAM133B/CDK6, and CLTC in breast cancer (CLTC/VMP1. Notably, while these fusions involved known cancer genes, all occurred with novel fusion partners and in previously unreported cancer types. Moreover, several constituted druggable targets (including kinases, with therapeutic implications for their respective malignancies. Lastly, breakpoint analysis identified new cell line models for known rearrangements, including EGFRvIII and FIP1L1/PDGFRA. Taken together, we provide a robust approach for gene fusion discovery, and our results highlight a more widespread role of fusion genes in cancer pathogenesis.

  3. Uncovering Implicit Assumptions: a Large-Scale Study on Students' Mental Models of Diffusion

    Science.gov (United States)

    Stains, Marilyne; Sevian, Hannah

    2015-12-01

    Students' mental models of diffusion in a gas phase solution were studied through the use of the Structure and Motion of Matter (SAMM) survey. This survey permits identification of categories of ways students think about the structure of the gaseous solute and solvent, the origin of motion of gas particles, and trajectories of solute particles in the gaseous medium. A large sample of data ( N = 423) from students across grade 8 (age 13) through upper-level undergraduate was subjected to a cluster analysis to determine the main mental models present. The cluster analysis resulted in a reduced data set ( N = 308), and then, mental models were ascertained from robust clusters. The mental models that emerged from analysis were triangulated through interview data and characterised according to underlying implicit assumptions that guide and constrain thinking about diffusion of a solute in a gaseous medium. Impacts of students' level of preparation in science and relationships of mental models to science disciplines studied by students were examined. Implications are discussed for the value of this approach to identify typical mental models and the sets of implicit assumptions that constrain them.

  4. Uncovering High Thermoelectric Figure of Merit in (Hf,Zr)NiSn Half-Heusler Alloys

    OpenAIRE

    Chen, L.; Gao, S; Zeng, X; Dehkordi, A. M.; Tritt, T. M; Poon, S. J.

    2015-01-01

    Half-Heusler alloys (MgAgSb structure) are promising thermoelectric materials. RNiSn half-Heusler phases (R=Hf, Zr, Ti) are the most studied in view of their thermal stability. The highest dimensionless figure of merit (ZT) obtained is ~1 in the temperature range ~450-900oC, primarily achieved in nanostructured alloys. Through proper annealing, ZT~1.2 has been obtained in a previous ZT~1 n-type (Hf,Zr)NiSn phase without the nanostructure. There is an appreciable increase in the power factor, ...

  5. Uncovering a context-specific connectional fingerprint of human dorsal premotor cortex

    DEFF Research Database (Denmark)

    Moisa, Marius; Siebner, Hartwig R; Pohmann, Rolf;

    2012-01-01

    -handed individuals performed externally paced sequential key presses with their left hand. Movements were cued by abstract visual stimuli, and subjects either freely selected a key press or responded according to a prelearned visuomotor mapping rule. Continuous arterial spin labeling was interleaved with TMS to...... directly assess how stimulation of left PMd modulates task-related brain activity depending on the mode of movement selection. Relative to passive viewing, both tasks activated a frontoparietal motor network. Compared with low-intensity TMS, high-intensity TMS of left PMd was associated with an increase in...

  6. Induced Pluripotent Stem Cell Models of Progranulin-Deficient Frontotemporal Dementia Uncover Specific Reversible Neuronal Defects

    Directory of Open Access Journals (Sweden)

    Sandra Almeida

    2012-10-01

    Full Text Available The pathogenic mechanisms of frontotemporal dementia (FTD remain poorly understood. Here we generated multiple induced pluripotent stem cell lines from a control subject, a patient with sporadic FTD, and an FTD patient with a novel heterozygous GRN mutation (progranulin [PGRN] S116X. In neurons and microglia differentiated from PGRN S116X induced pluripotent stem cells, the levels of intracellular and secreted PGRN were reduced, establishing patient-specific cellular models of PGRN haploinsufficiency. Through a systematic screen of inducers of cellular stress, we found that PGRN S116X neurons, but not sporadic FTD neurons, exhibited increased sensitivity to staurosporine and other kinase inhibitors. Moreover, the serine/threonine kinase S6K2, a component of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways, was specifically downregulated in PGRN S116X neurons. Both increased sensitivity to kinase inhibitors and reduced S6K2 were rescued by PGRN expression. Our findings identify cell-autonomous, reversible defects in patient neurons with PGRN deficiency, and provide a compelling model for studying PGRN-dependent pathogenic mechanisms and testing potential therapies.

  7. Metabolic profiling uncovers a phenotypic signature of small for gestational age in early pregnancy.

    LENUS (Irish Health Repository)

    Horgan, Richard P

    2012-01-31

    Being born small for gestational age (SGA) confers increased risks of perinatal morbidity and mortality and increases the risk of cardiovascular complications and diabetes in later life. Accumulating evidence suggests that the etiology of SGA is usually associated with poor placental vascular development in early pregnancy. We examined metabolomic profiles using ultra performance liquid chromatography-mass spectrometry (UPLC-MS) in three independent studies: (a) venous cord plasma from normal and SGA babies, (b) plasma from a rat model of placental insufficiency and controls, and (c) early pregnancy peripheral plasma samples from women who subsequently delivered a SGA baby and controls. Multivariate analysis by cross-validated Partial Least Squares Discriminant Analysis (PLS-DA) of all 3 studies showed a comprehensive and similar disruption of plasma metabolism. A multivariate predictive model combining 19 metabolites produced by a Genetic Algorithm-based search program gave an Odds Ratio for developing SGA of 44, with an area under the Receiver Operator Characteristic curve of 0.9. Sphingolipids, phospholipids, carnitines, and fatty acids were among this panel of metabolites. The finding of a consistent discriminatory metabolite signature in early pregnancy plasma preceding the onset of SGA offers insight into disease pathogenesis and offers the promise of a robust presymptomatic screening test.

  8. Integrating landscape genomics and spatially explicit approaches to detect loci under selection in clinal populations

    OpenAIRE

    Jones, Matthew R.; Forester, Brenna R.; Teufel, Ashley I.; Adams, Rachael V.; Anstett, Daniel N.; Goodrich, Betsy A.; Erin L. Landguth; Joost, Stéphane; Manel, Stéphanie

    2013-01-01

    Uncovering the genetic basis of adaptation hinges on the ability to detect loci under selection. However, population genomics outlier approaches to detect selected loci may be inappropriate for clinal populations or those with unclear population structure because they require that individuals be clustered into populations. An alternate approach, landscape genomics, uses individual-based approaches to detect loci under selection and reveal potential environmental drivers of selection. We teste...

  9. Uncovering category specificity of genital sexual arousal in women: The critical role of analytic technique.

    Science.gov (United States)

    Pulverman, Carey S; Hixon, J Gregory; Meston, Cindy M

    2015-10-01

    Based on analytic techniques that collapse data into a single average value, it has been reported that women lack category specificity and show genital sexual arousal to a large range of sexual stimuli including those that both match and do not match their self-reported sexual interests. These findings may be a methodological artifact of the way in which data are analyzed. This study examined whether using an analytic technique that models data over time would yield different results. Across two studies, heterosexual (N = 19) and lesbian (N = 14) women viewed erotic films featuring heterosexual, lesbian, and gay male couples, respectively, as their physiological sexual arousal was assessed with vaginal photoplethysmography. Data analysis with traditional methods comparing average genital arousal between films failed to detect specificity of genital arousal for either group. When data were analyzed with smoothing regression splines and a within-subjects approach, both heterosexual and lesbian women demonstrated different patterns of genital sexual arousal to the different types of erotic films, suggesting that sophisticated statistical techniques may be necessary to more fully understand women's genital sexual arousal response. Heterosexual women showed category-specific genital sexual arousal. Lesbian women showed higher arousal to the heterosexual film than the other films. However, within subjects, lesbian women showed significantly different arousal responses suggesting that lesbian women's genital arousal discriminates between different categories of stimuli at the individual level. Implications for the future use of vaginal photoplethysmography as a diagnostic tool of sexual preferences in clinical and forensic settings are discussed. PMID:26118962

  10. Uncovering the Stabilization Mechanism in Bimetallic Ruthenium-Iridium Anodes for Proton Exchange Membrane Electrolyzers.

    Science.gov (United States)

    Saveleva, Viktoriia A; Wang, Li; Luo, Wen; Zafeiratos, Spyridon; Ulhaq-Bouillet, Corinne; Gago, Aldo S; Friedrich, K Andreas; Savinova, Elena R

    2016-08-18

    Proton exchange membrane (PEM) electrolyzers are attracting an increasing attention as a promising technology for the renewable electricity storage. In this work, near ambient pressure X-ray photoelectron spectroscopy (NAP-XPS) is applied for in situ monitoring of the surface state of membrane electrode assemblies with RuO2 and bimetallic Ir0.7Ru0.3O2 anodes during water splitting. We demonstrate that Ir protects Ru from the formation of an unstable hydrous Ru(IV) oxide thereby rendering bimetallic Ru-Ir oxide electrodes with higher corrosion resistance. We further show that the water splitting occurs through a surface Ru(VIII) intermediate, and, contrary to common opinion, the presence of Ir does not hinder its formation. PMID:27477824

  11. Seeking knowledge, discovering learning: uncovering the impetus for baccalaureate nursing studies in Malaysian Borneo.

    Science.gov (United States)

    Birks, Melanie; Francis, Karen; Chapman, Ysanne

    2009-06-01

    Changes to the nursing profession over recent decades have provoked an increasing migration of nursing education into the tertiary sector. For nurses who live and work in developing nations, such as Malaysia, opportunities for further study might be limited, particularly for those located in more remote regions. This paper reports on a research study of registered nurses who undertook baccalaureate degree studies in off-campus mode in Malaysian Borneo. A grounded theory methodology was employed in this research, which is part of a larger study into the nature and outcomes of change experienced as a result of postregistration degree studies. This paper explores the reasons why nurses in this location enrolled in one such course and the extent to which completion of their studies addressed their motivational goals. The findings indicate that the experience of learning and acquisition of knowledge was well beyond what was expected, resulting in a sense of achievement that was similarly unanticipated. PMID:19531074

  12. World citation and collaboration networks: uncovering the role of geography in science

    CERN Document Server

    Pan, Raj Kumar; Fortunato, Santo

    2012-01-01

    Modern information and communication technologies, especially the Internet, have diminished the role of spatial distances and territorial boundaries. This has enabled scientists for closer collaboration and internationalization. Nevertheless, geography remains an important factor affecting the dynamics of science. Hence, assessing the influence of spatial proximity between scientists is crucial to promote efficient collaboration strategies and, ultimately, to improve the quality of science. Here we present a systematic analysis of citation and collaboration streams between cities and countries. By assigning papers to the geographic locations of their authors' affiliations, we construct weighted networks of citations and collaborations. The citation flows as well as the collaboration strengths between cities decrease with the distance between them and follow gravity laws with exponents close to 1. Moreover, for a given number of authors, the diversity of affiliations increases the number of citations, especial...

  13. Tissue-Specific Gain of RTK Signalling Uncovers Selective Cell Vulnerability during Embryogenesis.

    Directory of Open Access Journals (Sweden)

    Yannan Fan

    Full Text Available The successive events that cells experience throughout development shape their intrinsic capacity to respond and integrate RTK inputs. Cellular responses to RTKs rely on different mechanisms of regulation that establish proper levels of RTK activation, define duration of RTK action, and exert quantitative/qualitative signalling outcomes. The extent to which cells are competent to deal with fluctuations in RTK signalling is incompletely understood. Here, we employ a genetic system to enhance RTK signalling in a tissue-specific manner. The chosen RTK is the hepatocyte growth factor (HGF receptor Met, an appropriate model due to its pleiotropic requirement in distinct developmental events. Ubiquitously enhanced Met in Cre/loxP-based Rosa26(stopMet knock-in context (Del-R26(Met reveals that most tissues are capable of buffering enhanced Met-RTK signalling thus avoiding perturbation of developmental programs. Nevertheless, this ubiquitous increase of Met does compromise selected programs such as myoblast migration. Using cell-type specific Cre drivers, we genetically showed that altered myoblast migration results from ectopic Met expression in limb mesenchyme rather than in migrating myoblasts themselves. qRT-PCR analyses show that ectopic Met in limbs causes molecular changes such as downregulation in the expression levels of Notum and Syndecan4, two known regulators of morphogen gradients. Molecular and functional studies revealed that ectopic Met expression in limb mesenchyme does not alter HGF expression patterns and levels, but impairs HGF bioavailability. Together, our findings show that myoblasts, in which Met is endogenously expressed, are capable of buffering increased RTK levels, and identify mesenchymal cells as a cell type vulnerable to ectopic Met-RTK signalling. These results illustrate that embryonic cells are sensitive to alterations in the spatial distribution of RTK action, yet resilient to fluctuations in signalling levels of an

  14. Uncovering latent deficits due to mild traumatic brain injury by using normobaric hypoxia stress.

    Science.gov (United States)

    Temme, Leonard; Bleiberg, Joseph; Reeves, Dennis; Still, David L; Levinson, Dan; Browning, Rebecca

    2013-01-01

    Memory deficits and other cognitive symptoms frequently associated with mTBI are commonly thought to resolve within 7-10 days. This generalization is based principally on observations made in individuals who are in the unstressed environmental conditions typical of a clinic and so does not consider the impact of physiologic, environmental, or psychological stress. Normobaric hypoxic stress can be generated with normal mean sea level (MSL) air, which is about 21% oxygen (O2) and 78% nitrogen (N), by reducing the percentage of O2 and increasing the percentage of N so that the resultant mixed-gas has a partial pressure of O2 approximating that of specified altitudes. This technique was used to generate normobaric hypoxic equivalents of 8,000, 12,000, and 14,000 feet above MSL in a group of 36 volunteers with a mTBI history and an equal number of controls matched on the basis of age, gender, tobacco smoking consumption, weight, height, and body mass index. Short-term visual memory was tested using the Matching to Sample (M2S) subtest of the BrainCheckers analog of the Automated Neuropsychological Assessment Metrics. Although there were no significant differences in M2S performance between the two groups of subjects at MSL, with increased altitude, the mTBI group performance was significantly worse than that of the control group. When the subjects were returned to MSL, the difference disappeared. This finding suggests that the "hypoxic challenge" paradigm developed here has potential clinical utility for assessing the effects of mTBI in individuals who appear asymptomatic under normal conditions. PMID:23641232

  15. Yeast Model Uncovers Dual Roles of Mitochondria in the Action of Artemisinin.

    Directory of Open Access Journals (Sweden)

    2005-09-01

    Full Text Available Artemisinins, derived from the wormwood herb Artemisia annua, are the most potent antimalarial drugs currently available. Despite extensive research, the exact mode of action of artemisinins has not been established. Here we use yeast, Saccharamyces cerevisiae, to probe the core working mechanism of this class of antimalarial agents. We demonstrate that artemisinin's inhibitory effect is mediated by disrupting the normal function of mitochondria through depolarizing their membrane potential. Moreover, in a genetic study, we identify the electron transport chain as an important player in artemisinin's action: Deletion of NDE1 or NDI1, which encode mitochondrial NADH dehydrogenases, confers resistance to artemisinin, whereas overexpression of NDE1 or NDI1 dramatically increases sensitivity to artemisinin. Mutations or environmental conditions that affect electron transport also alter host's sensitivity to artemisinin. Sensitivity is partially restored when the Plasmodium falciparum NDI1 ortholog is expressed in yeast ndi1 strain. Finally, we showed that artemisinin's inhibitory effect is mediated by reactive oxygen species. Our results demonstrate that artemisinin's effect is primarily mediated through disruption of membrane potential by its interaction with the electron transport chain, resulting in dysfunctional mitochondria. We propose a dual role of mitochondria played during the action of artemisinin: the electron transport chain stimulates artemisinin's effect, most likely by activating it, and the mitochondria are subsequently damaged by the locally generated free radicals.

  16. Thyroid-Specific Genes Expression Uncovered Age-Related Differences in Pediatric Thyroid Carcinomas

    Directory of Open Access Journals (Sweden)

    Maria Isabel Cunha Vieira Cordioli

    2016-01-01

    Full Text Available Despite a more advanced stage of disease at presentation, a better response to radioiodine (RAI therapy and a reduced overall mortality have been reported in pediatric differentiated thyroid cancer (DTC in comparison to adult DTC. Few studies suggested that the better response to RAI therapy in pediatric patients might be associated with an increased expression of NIS. However, a marked heterogeneity within the pediatric group has been recognized. Children (<10 years old usually present a more aggressive disease than adolescents (≥10–18 years old. By analyzing the expression of thyroid-specific genes in 38 sporadic pediatric tumors, we show that the expression of NIS, PDS, and TSHR was lower in children than adolescents (P<0.05. A linear regression confirmed the association between NIS expression and age. Most significantly, NIS was expressed at similar levels in DTC from children and adults, whereas PDS and TSHR expression was even lower in DTC from children, compared to adolescents and adults. Our data suggest that biological behaviors of DTC in adolescents might differ from those in children and adults. Therefore, the premise that the expression of thyroid-specific genes is higher in tumors from pediatric patients than in adults is not entirely true and might be too oversimplified.

  17. Uncovering potential downstream targets of oncogenic GRPR overexpression in prostate carcinomas harboring ETS rearrangements.

    Science.gov (United States)

    Santos, Joana; Mesquita, Diana; Barros-Silva, João D; Jerónimo, Carmen; Henrique, Rui; Morais, António; Paulo, Paula; Teixeira, Manuel R

    2015-01-01

    Gastrin-releasing peptide receptor (GRPR) is known to be overexpressed in several human malignancies, including prostate cancer, and has been implicated in multiple important neoplastic signaling pathways. We recently have shown that GRPR is an ERG and ETV1 target gene in prostate cancer, using a genome-wide scale and exon-level expression microarray platform. Due to its cellular localization, the relevance of its function and the availability of blocking agents, GRPR seems to be a promising candidate as therapeutic target. Our present work shows that effective knockdown of GRPR in LNCaP and VCaP cells attenuates their malignant phenotype by decreasing proliferation, invasion and anchorage-independent growth, while increasing apoptosis. Using an antibody microarray we were able to validate known and identify new targets of GRPR pathway, namely AKT1, PKCε, TYK2 and MST1. Finally, we show that overexpression of these GRPR targets is restricted to prostate carcinomas harboring ERG and/or ETV1 rearrangements, establishing their potential as therapeutic targets for these particular molecular subsets of the disease. PMID:26097883

  18. TEMPO: an ESA-funded project for uncovering significant features of the South Atlantic Anomaly

    Science.gov (United States)

    Pavón-Carrasco, F. Javier; De Santis, Angelo

    2016-04-01

    In this work we provide the last results of the ESA (European Space Agency) funded project TEMPO ("Is The Earth's Magnetic field POtentially reversing? New insights from Swarm mission"). The mail goal of this project is to analyse the time and spatial evolution of one of the most important features of the present geomagnetic field, i.e. the South Atlantic Anomaly (SAA). The region covered by this anomaly is characterized by values of geomagnetic field intensity around 30% lower than expected for those latitudes and extends over a large area in the South Atlantic Ocean, South America, South Africa and the Eastern Pacific Ocean. This large depression of the geomagnetic field strength has its origin in a prominent patch of reversed polarity flux in the Earth's outer core. The study of the SAA is an important challenge nowadays not only for the geomagnetic and paleomagnetic community, but also for other areas focused on the Earth Observation due to the protective role of this potential field against the charged particles forming the solar wind. A further increase of the SAA surface extent could have dramatic consequences for human health and technologies because a larger number of solar charged particles could reach the Earth's surface.

  19. Uncovering the Footprints of Erosion by On-Farm Maize Cultivation in a Hilly Tropical Landscape

    Directory of Open Access Journals (Sweden)

    Ravi Sangakkara

    2013-09-01

    Full Text Available A hilly region in Sri Lanka was considered to be degraded by erosion driven by intensive tobacco production, but what are reliable indicators of erosion? In addition to determining soil chemical and physical traits, maize was cropped with Nitrogen, Phosphorus and Potassium (NPK, PK recommended mineral fertilization and without fertilizer (ZERO in two major seasons(October–January in 2007/2008 and 2008/2009—Seasons 1 and 2 respectively on 92 farms at inclinations ranging from 0% to 65%. In a subset of steep farms (n = 21 an A horizon of 6 cm rather than of 26 cm was strong proof of erosion above 30% inclination. Below the A level, the thickness of the horizon was unaffected by inclination. Soil organic matter contents (SOM were generally low, more so at higher inclinations, probably due to greater erosion than at lower inclination. Maize yields decreased gradually with increasing inclination; at ZERO, effects of climate and soil moisture on yield were easier determined and were probably due to long-term erosion. However, despite an initial set of 119 farms, an exact metric classification of erosion was impossible. NPK strongly boosted yield. This was a positive sign that the deficits in chemical soil fertility were overriding physical soil weaknesses. The study illustrated that chemical soil fertility in these soils is easily amenable to modifications by mineral and organic manures.

  20. Genome reorganization in F1 hybrids uncovers the role of retrotransposons in reproductive isolation.

    Science.gov (United States)

    Senerchia, Natacha; Felber, François; Parisod, Christian

    2015-04-01

    Interspecific hybridization leads to new interactions among divergent genomes, revealing the nature of genetic incompatibilities having accumulated during and after the origin of species. Conflicts associated with misregulation of transposable elements (TEs) in hybrids expectedly result in their activation and genome-wide changes that may be key to species boundaries. Repetitive genomes of wild wheats have diverged under differential dynamics of specific long terminal repeat retrotransposons (LTR-RTs), offering unparalleled opportunities to address the underpinnings of plant genome reorganization by selfish sequences. Using reciprocal F1 hybrids between three Aegilops species, restructuring and epigenetic repatterning was assessed at random and LTR-RT sequences with amplified fragment length polymorphism and sequence-specific amplified polymorphisms as well as their methylation-sensitive counterparts, respectively. Asymmetrical reorganization of LTR-RT families predicted to cause conflicting interactions matched differential survival of F1 hybrids. Consistent with the genome shock model, increasing divergence of merged LTR-RTs yielded higher levels of changes in corresponding genome fractions and lead to repeated reorganization of LTR-RT sequences in F1 hybrids. Such non-random reorganization of hybrid genomes is coherent with the necessary repression of incompatible TE loci in support of hybrid viability and indicates that TE-driven genomic conflicts may represent an overlooked factor supporting reproductive isolation. PMID:25716787

  1. Comparative Perspective of Human Behavior Patterns to Uncover Ownership Bias among Mobile Phone Users

    Directory of Open Access Journals (Sweden)

    Ayumi Arai

    2016-06-01

    Full Text Available With the rapid spread of mobile devices, call detail records (CDRs from mobile phones provide more opportunities to incorporate dynamic aspects of human mobility in addressing societal issues. However, it has been increasingly observed that CDR data are not always representative of the population under study because it only includes device users alone. To understand the discrepancy between the population captured by CDRs and the general population, we profile principal populations of CDRs by analyzing routines based on time spent at key locations and compare these data with those of the general population. We employ a topic model to estimate typical routines of mobile phone users using CDRs as topics. The routines are extracted from field survey data and compared between those of the general population and mobile phone users. We found that there are two main population groups of mobile phone users in Dhaka: males engaged in an income-generating activity at a specific location other than home and females performing household tasks and spending most of their time at home. We determine that CDRs tend to omit students, who form a significant component of the Dhaka population.

  2. Sri Lankan National Melioidosis Surveillance Program Uncovers a Nationwide Distribution of Invasive Melioidosis.

    Science.gov (United States)

    Corea, Enoka M; Merritt, Adam J; Ler, Yi-Horng; Thevanesam, Vasanthi; Inglis, Timothy J J

    2016-02-01

    The epidemiologic status of melioidosis in Sri Lanka was unclear from the few previous case reports. We established laboratory support for a case definition and started a nationwide case-finding study. Suspected Burkholderia pseudomallei isolates were collated, identified by polymerase chain reaction assay, referred for Matrix Assisted Laser Desorption Ionization-Time of Flight analysis and multilocus sequence typing (MLST), and named according to the international MLST database. Between 2006 and early 2014, there were 32 patients with culture-confirmed melioidosis with an increasing annual total and a falling fatality rate. Patients were predominantly from rural communities, diabetic, and male. The major clinical presentations were sepsis, pneumonia, soft tissue and joint infections, and other focal infection. Burkholderia pseudomallei isolates came from all parts of Sri Lanka except the Sabaragamuwa Province, the south central hill country, and parts of northern Sri Lanka. Bacterial isolates belonged to 18 multilocus sequence types, one of which (ST 1137) was associated with septicemia and a single-organ focus (Fisher's exact, P = 0.004). Melioidosis is an established endemic infection throughout Sri Lanka, and is caused by multiple genotypes of B. pseudomallei, which form a distinct geographic group based upon related sequence types (BURST) cluster at the junction of the southeast Asian and Australasian clades. PMID:26621560

  3. An adaptive composite quantile approach to dimension reduction

    OpenAIRE

    Kong, Efang; Xia, Yingcun

    2014-01-01

    Sufficient dimension reduction [J. Amer. Statist. Assoc. 86 (1991) 316–342] has long been a prominent issue in multivariate nonparametric regression analysis. To uncover the central dimension reduction space, we propose in this paper an adaptive composite quantile approach. Compared to existing methods, (1) it requires minimal assumptions and is capable of revealing all dimension reduction directions; (2) it is robust against outliers and (3) it is structure-adaptive, thus more efficient. Asy...

  4. Distilling a Visual Network of Retinitis Pigmentosa Gene-Protein Interactions to Uncover New Disease Candidates.

    Directory of Open Access Journals (Sweden)

    Daniel Boloc

    Full Text Available Retinitis pigmentosa (RP is a highly heterogeneous genetic visual disorder with more than 70 known causative genes, some of them shared with other non-syndromic retinal dystrophies (e.g. Leber congenital amaurosis, LCA. The identification of RP genes has increased steadily during the last decade, and the 30% of the cases that still remain unassigned will soon decrease after the advent of exome/genome sequencing. A considerable amount of genetic and functional data on single RD genes and mutations has been gathered, but a comprehensive view of the RP genes and their interacting partners is still very fragmentary. This is the main gap that needs to be filled in order to understand how mutations relate to progressive blinding disorders and devise effective therapies.We have built an RP-specific network (RPGeNet by merging data from different sources: high-throughput data from BioGRID and STRING databases, manually curated data for interactions retrieved from iHOP, as well as interactions filtered out by syntactical parsing from up-to-date abstracts and full-text papers related to the RP research field. The paths emerging when known RP genes were used as baits over the whole interactome have been analysed, and the minimal number of connections among the RP genes and their close neighbors were distilled in order to simplify the search space.In contrast to the analysis of single isolated genes, finding the networks linking disease genes renders powerful etiopathological insights. We here provide an interactive interface, RPGeNet, for the molecular biologist to explore the network centered on the non-syndromic and syndromic RP and LCA causative genes. By integrating tissue-specific expression levels and phenotypic data on top of that network, a more comprehensive biological view will highlight key molecular players of retinal degeneration and unveil new RP disease candidates.

  5. The thrill of the chase: uncovering illegal sport hunting in Brazil through YouTube™ posts

    Directory of Open Access Journals (Sweden)

    Hani R. El Bizri

    2015-09-01

    Full Text Available The impacts of unregulated sport hunting can severely affect populations of target game species. Because hunting in Brazil is limited by law, obtaining data on illegal sport hunting in this country is challenging. We used an unusual online resource, YouTube™, to detect the occurrence of sport hunting in Brazil, measure the impacts of the activity on the main Brazilian game species and biomes, evaluate the opinions of hunters and internet users on sport hunting, and discuss the need for policy interventions in wildlife conservation in this country. We found 383 videos related to Brazilian sport hunting on YouTube™, accounting for more than 15 million views. Most videos were produced in the Cerrado (Brazilian savannah and approximately 70% of them depicted events of pursuit and killing of wild animals, especially lowland pacas (Cuniculus paca and armadillos (Family Dasypodidae. Videos were posted primarily in July and December, coinciding with the two main Brazilian vacation periods. Furthermore, the shotguns identified on videos show that sport hunters expend large sums of money to undertake their hunts. These results indicate that Brazilian sport hunters are possibly wealthier urban residents who travel to rural areas to hunt, contrasting with previous hunting studies in the country. Most viewers declared themselves in favor of sport hunting in comments (n = 2893 and ratings (n = 36,570 of the videos. Discussions generated by comments suggest that Brazilian sport hunters employ several informal management strategies to maintain game species stocks for future hunting and intensely question the restrictions of Brazilian environmental policies. Our results demonstrate that solutions are needed for the regulation of sport hunting in Brazil. Government actions, whether to increase surveillance or legalize hunting programs, should take into account the opinions of sport hunters and their perceptions on hunting dynamics to support effective policy

  6. Uncovering sexual abuse: evaluation of the effectiveness of The Victims of Violence and Abuse Prevention Programme.

    Science.gov (United States)

    Donohoe, J

    2010-02-01

    Discusses factors inhibiting open talk around a client's history of abuse including gender, age and diagnosis. * Evaluates the helpfulness of a training course designed to reduce and overcome these factors. * Aim of the evaluation is to help replicate the training nationally, following the positive impact found. Abstract Despite the high prevalence of sexual abuse among users of mental health services, it appears that mental health professionals are frequently unaware of clients' abuse histories. In order to address this, a Mental Health Trusts Collaboration Project of nine trusts was formed, which piloted delivering the Department of Health's Victims of Violence & Abuse Prevention Programme one-day education and training course regarding enquiring about histories of sexual abuse to various mental health practitioners. This hoped to educate practitioners in factors associated with victims and offenders, improve confidence and competence in asking about client's history of abuse and to increase awareness of the importance of asking. The purpose of this paper is to describe the impact of this course on mental health professionals' practice and attitudes in one of these nine trusts. It was found that since the delivery of the course, 44% (n= x) of professionals had been asking about abuse in 75-100% of cases. Gender, age and diagnosis of both the service users and the practitioners were all identified as factors potentially affecting practitioners' willingness to ask about abuse. Most importantly, 93% (n= x) of participants were found to feel they have the skills and knowledge to enquire about abuse and respond to disclosure in the appropriate way and 77% (n= x) of participants felt that this training had changed their clinical practice. The aim of this evaluation is to prove the effectiveness of the Department of Health's education and training course, which will help towards replicating the project nationally. PMID:20100302

  7. Microbiological study of fresh herbs from retail premises uncovers an international outbreak of salmonellosis.

    Science.gov (United States)

    Elviss, N C; Little, C L; Hucklesby, L; Sagoo, S; Surman-Lee, S; de Pinna, E; Threlfall, E J

    2009-08-31

    This Local Authorities Co-ordinators of Regulatory Services/Health Protection Agency study was prompted by the increasing concern regarding the microbiological safety of ready-to-eat salad vegetable products, particularly fresh herbs. During May to October 2007, 3760 ready-to-eat fresh herbs, of different varieties, were sampled across the UK to assess their microbiological safety in relation to salmonella contamination and levels of Escherichia coli. Sixty (1.6%) herb samples were found to be of unsatisfactory quality according to Regulation (EC) No. 2073/2005 on the microbiological criteria of foodstuffs, i.e. contaminated with Salmonella spp. and/or containing E. coli at >10(3) cfu/g. When criteria in the PHLS Microbiological Guidelines for some ready-to-eat foods (2000) were used, 117 (3.9%) of herb samples were of unsatisfactory quality due to the presence of salmonella and/or E. coli at > or = 10(2) cfu/g. Eighteen (0.5%) samples of six different herb types were contaminated with Salmonella spp.: identified as serotypes Senftenberg (8), Agona (2), Anatum (1), Durban (1), Javiana (1), Mgulani (1), Montevideo (1), Unnamed (I 16:g, t: z42) (1), Virchow (1) and mixed Newport & Virchow (1). In each case the retailer and the UK Food Standards Agency were immediately informed and remedial action taken. Samples contaminated with S. Senftenberg were specifically associated with basil grown in Israel. Thirty-two human cases of S. Senftenberg infection were subsequently identified throughout England and Wales and a further 19 in Scotland, Denmark, The Netherlands and the USA. The strain of S. Senftenberg identified from the basil and that from cases had an indistinguishable molecular profile, suggesting a likely connection between consumption of basil and human infection. The presence of Salmonella spp. is unacceptable in ready-to-foods such as fresh herbs. This study highlights the necessity of applying good agricultural and hygiene practices pre-, during and post

  8. Atmospheric pollution history at Linfen (China) uncovered by magnetic and chemical parameters of sediments from a water reservoir

    International Nuclear Information System (INIS)

    We studied magnetic and chemical parameters of sediments from sediments of a water reservoir at Linfen (China) in order to quantitatively reconstruct the atmospheric pollution history in this region. The results show that the main magnetic phases are magnetite and maghemite originating from the surrounding catchment and from anthropogenic activities, and there is a significant positive relationship between magnetic concentration parameters and heavy metals concentrations, indicating that magnetic proxies can be used to monitor the anthropogenic pollution. In order to uncover the atmospheric pollution history, we combined the known events of environmental improvement with variations of magnetic susceptibility (χ) and heavy metals along the cores to obtain a detailed chronological framework. In addition, air comprehensive pollution index (ACPI) was reconstructed from regression equation among magnetic and chemical parameters as well as atmospheric monitoring data. Based on these results, the atmospheric pollution history was successfully reconstructed. - Highlights: • Magnetic proxies can be used to monitor the heavy mental pollution in sediments. • Accurate age model was obtained using known events of environmental improvement. • Regression equation was obtained among sediment records and monitoring data. • Atmospheric pollution history was quantitatively reconstructed. - Atmospheric pollution history was quantitatively reconstructed using magnetic and chemical records of reservoir sediments combined with atmospheric monitoring data

  9. Sustained adrenergic signaling leads to increased metastasis in ovarian cancer via increased PGE2 synthesis.

    Science.gov (United States)

    Nagaraja, A S; Dorniak, P L; Sadaoui, N C; Kang, Y; Lin, T; Armaiz-Pena, G; Wu, S Y; Rupaimoole, R; Allen, J K; Gharpure, K M; Pradeep, S; Zand, B; Previs, R A; Hansen, J M; Ivan, C; Rodriguez-Aguayo, C; Yang, P; Lopez-Berestein, G; Lutgendorf, S K; Cole, S W; Sood, A K

    2016-05-01

    Adrenergic stimulation adversely affects tumor growth and metastasis, but the underlying mechanisms are not well understood. Here, we uncovered a novel mechanism by which catecholamines induce inflammation by increasing prostaglandin E2 (PGE2) levels in ovarian cancer cells. Metabolic changes in tumors isolated from patients with depression and mice subjected to restraint stress showed elevated PGE2 levels. Increased metabolites, PTGS2 and PTGES protein levels were found in Skov3-ip1 and HeyA8 cells treated with norepinephrine (NE), and these changes were shown to be mediated by ADRB2 receptor signaling. Silencing PTGS2 resulted in significantly decreased migration and invasion in ovarian cancer cells in the presence of NE and decreased tumor burden and metastasis in restraint stress orthotopic models. In human ovarian cancer samples, concurrent increased ADRB2, PTGS2 and PTGES expression was associated with reduced overall and progression-free patient survival. In conclusion, increased adrenergic stimulation results in increased PGE2 synthesis via ADRB2-Nf-kB-PTGS2 axis, which drives tumor growth and metastasis. PMID:26257064

  10. Meta-analysis and other approaches for synthesizing structured and unstructured data in plant pathology.

    Science.gov (United States)

    Scherm, H; Thomas, C S; Garrett, K A; Olsen, J M

    2014-01-01

    The term data deluge is used widely to describe the rapidly accelerating growth of information in the technical literature, in scientific databases, and in informal sources such as the Internet and social media. The massive volume and increased complexity of information challenge traditional methods of data analysis but at the same time provide unprecedented opportunities to test hypotheses or uncover new relationships via mining of existing databases and literature. In this review, we discuss analytical approaches that are beginning to be applied to help synthesize the vast amount of information generated by the data deluge and thus accelerate the pace of discovery in plant pathology. We begin with a review of meta-analysis as an established approach for summarizing standardized (structured) data across the literature. We then turn to examples of synthesizing more complex, unstructured data sets through a range of data-mining approaches, including the incorporation of 'omics data in epidemiological analyses. We conclude with a discussion of methodologies for leveraging information contained in novel, open-source data sets through web crawling, text mining, and social media analytics, primarily in the context of digital disease surveillance. Rapidly evolving computational resources provide platforms for integrating large and complex data sets, motivating research that will draw on new types and scales of information to address big questions. PMID:25001455

  11. Sporty materials uncovered

    OpenAIRE

    Kevin Edwards

    2004-01-01

    Materials in Sports Equipment is a welcome addition to books on materials engineering, says Kevin Edwards. It fills a gap in coverage of the important sports market, where advances in materials can lead to improved performance.

  12. The discovery uncovered

    CERN Multimedia

    Antonella Del Rosso

    2016-01-01

    Almost exactly one hundred years after the publication of Einstein’s paper on General Relativity, the LIGO and Virgo collaborations have published a paper in which they show a gravitational signal emitted by the merger of two black holes. The signal has been observed with 5-sigma accuracy and is the first direct observation of gravitational waves.   On Thursday, 11 February, Barry Clark Barish, one of the fathers of the LIGO experiment, presented the latest results in a packed Auditorium. Ripples in space-time, the fabric of the Universe: this is how we can picture gravitational waves. In his visionary paper published in June 1916, Einstein predicted that masses deform space-time and, therefore, any change in their position causes a distortion that propagates at the speed of light, resulting in gravitational waves.   It wasn’t until 1975, almost 60 years later, that Russell Hulse and Joseph Taylor, who were awarded the Nobel Prize in 1993, inferred t...

  13. Uncovering Prepositional Senses

    DEFF Research Database (Denmark)

    Lassen, Tine

    set of rules. These rules were transformed into a dictionary of prepositional senses, where, given a preposition and a sense, ontological affinities are expressed as restrictions on the ontological types of the arguments. Thus, the essential results of this research is knowledge about the relations...

  14. Uncovering the unarchived web

    OpenAIRE

    Samar, Thaer; Huurdeman, H.C.; Ben-David, A.; Kamps, J.; Vries, de, H.J.C.

    2014-01-01

    Many national and international heritage institutes realize the importance of archiving the web for future culture heritage. Web archiving is currently performed either by harvesting a national domain, or by crawling a pre-defined list of websites selected by the archiving institution. In either method, crawling results in more information being harvested than just the websites intended for preservation; which could be used to reconstruct impressions of pages that existed on the live web of t...

  15. Uncovering the unarchived web

    NARCIS (Netherlands)

    Samar, T.; Huurdeman, H.C.; Ben-David, A.; Kamps, J.; Vries, A.P. de

    2014-01-01

    Many national and international heritage institutes realize the importance of archiving the web for future culture heritage. Web archiving is currently performed either by harvesting a national domain, or by crawling a pre-defined list of websites selected by the archiving institution. In either met

  16. Uncovering Plagiarism Networks

    OpenAIRE

    Freire, Manuel; Cebrian, Manuel; del Rosal, Emilio

    2007-01-01

    Plagiarism detection in educational programming assignments is still a problematic issue in terms of resource waste, ethical controversy, legal risks, and technical complexity. This paper presents AC, a modular plagiarism detection system. The design is portable across platforms and assignment formats and provides easy extraction into the internal assignment representation. Multiple similarity measures have been incorporated, both existing and newly-developed. Statistical analysis and several...

  17. Uncovering the Missing Routes

    DEFF Research Database (Denmark)

    Tsirogiannis, Constantinos; Tsirogiannis, Christos

    2016-01-01

    In the present work we model and analyse the global network of the illegal trade in antiquities. Our goal is to use this network to estimate for any given artefact the potential sequence of people in the network among whom this artefact was traded. For this reason, we have implemented and evaluated...... three different algorithms that estimate potential trade routes within the network. We also evaluate the performance of a popular method that estimates direct links in the network, links which may not have been documented in the police records....

  18. Deschooling Society, Uncovering Illich

    Science.gov (United States)

    Bauer, Norman J.

    1972-01-01

    Critical analysis of the work of Ivan D. Illich, crediting him with providing a significant contribution to current efforts by a number of thinkers to reenergize our cultural consciousness relative to the insidious effects which institutional dependency fosters. (Author/GB)

  19. Uncovering the Cornfield

    DEFF Research Database (Denmark)

    Carter, Dale

    2015-01-01

    Observers agree that a pivotal factor in the abandonment of the Beach Boys’ Smile album in 1967 was the hostility shown by group members to some of Brian Wilson co-writer Van Dyke Parks’s lyrics. The latter still tend, however, to be cited more than they are analyzed. This reading of the song...

  20. Sporty materials uncovered

    Directory of Open Access Journals (Sweden)

    Kevin Edwards

    2004-03-01

    Full Text Available Materials in Sports Equipment is a welcome addition to books on materials engineering, says Kevin Edwards. It fills a gap in coverage of the important sports market, where advances in materials can lead to improved performance.

  1. The defect level and ideal thermal conductivity of graphene uncovered by residual thermal reffusivity at the 0 K limit.

    Science.gov (United States)

    Xie, Yangsu; Xu, Zaoli; Xu, Shen; Cheng, Zhe; Hashemi, Nastaran; Deng, Cheng; Wang, Xinwei

    2015-06-14

    Due to its intriguing thermal and electrical properties, graphene has been widely studied for potential applications in sensor and energy devices. However, the reported value for its thermal conductivity spans from dozens to thousands of W m(-1) K(-1) due to different levels of alternations and defects in graphene samples. In this work, the thermal diffusivity of suspended four-layered graphene foam (GF) is characterized from room temperature (RT) down to 17 K. For the first time, we identify the defect level in graphene by evaluating the inverse of thermal diffusivity (termed "thermal reffusivity": Θ) at the 0 K limit. By using the Debye model of Θ = Θ0 + C× e(-θ/2T) and fitting the Θ-T curve to the point of T = 0 K, we identify the defect level (Θ0) and determine the Debye temperature of graphene. Θ0 is found to be 1878 s m(-2) for the studied GF and 43-112 s m(-2) for three highly crystalline graphite materials. This uncovers a 16-43-fold higher defect level in GF than that in pyrolytic graphite. In GF, the phonon mean free path solely induced by defects and boundary scattering is determined as 166 nm. The Debye temperature of graphene is determined to be 1813 K, which is very close to the average theoretical Debye temperature (1911 K) of the three acoustic phonon modes in graphene. By subtracting the defect effect, we report the ideal thermal diffusivity and conductivity (κideal) of graphene presented in the 3D foam structure in the range of 33-299 K. Detailed physics based on chemical composition and structure analysis are given to explain the κideal-T profile by comparing with those reported for suspended graphene. PMID:25981826

  2. A genome-wide immunodetection screen in S. cerevisiae uncovers novel genes involved in lysosomal vacuole function and morphology.

    Directory of Open Access Journals (Sweden)

    Florante Ricarte

    Full Text Available Vacuoles of yeast Saccharomyces cerevisiae are functionally analogous to mammalian lysosomes. Both are cellular organelles responsible for macromolecular degradation, ion/pH homeostasis, and stress survival. We hypothesized that undefined gene functions remain at post-endosomal stage of vacuolar events and performed a genome-wide screen directed at such functions at the late endosome and vacuole interface - ENV genes. The immunodetection screen was designed to identify mutants that internally accumulate precursor form of the vacuolar hydrolase carboxypeptidase Y (CPY. Here, we report the uncovering and initial characterizations of twelve ENV genes. The small size of the collection and the lack of genes previously identified with vacuolar events are suggestive of the intended exclusive functional interface of the screen. Most notably, the collection includes four novel genes ENV7, ENV9, ENV10, and ENV11, and three genes previously linked to mitochondrial processes - MAM3, PCP1, PPE1. In all env mutants, vesicular trafficking stages were undisturbed in live cells as assessed by invertase and active α-factor secretion, as well as by localization of the endocytic fluorescent marker FM4-64 to the vacuole. Several mutants exhibit defects in stress survival functions associated with vacuoles. Confocal fluorescence microscopy revealed the collection to be significantly enriched in vacuolar morphologies suggestive of fusion and fission defects. These include the unique phenotype of lumenal vesicles within vacuoles in the novel env9Δ mutant and severely fragmented vacuoles upon deletion of GET4, a gene recently implicated in tail anchored membrane protein insertion. Thus, our results establish new gene functions in vacuolar function and morphology, and suggest a link between vacuolar and mitochondrial events.

  3. Coalescent-Based Species Delimitation Approach Uncovers High Cryptic Diversity in the Cosmopolitan Lichen-Forming Fungal Genus Protoparmelia (Lecanorales, Ascomycota)

    OpenAIRE

    Singh, Garima; Grande, Francesco Dal; Pradeep K. Divakar; Otte, Jürgen; Leavitt, Steven D; Szczepanska, Katarzyna; Crespo, Ana; Rico, Víctor J.; Aptroot, André; Cáceres, Marcela Eugenia da Silva; Lumbsch, Helge Thorsten; Schmitt, Imke

    2015-01-01

    Species recognition in lichen-forming fungi has been a challenge because of unsettled species concepts, few taxonomically relevant traits, and limitations of traditionally used morphological and chemical characters for identifying closely related species. Here we analyze species diversity in the cosmopolitan genus Protoparmelia s.l. The ~25 described species in this group occur across diverse habitats from the boreal -arctic/alpine to the tropics, but their relationship to each other remains ...

  4. Coalescent-based species delimitation approach uncovers high cryptic diversity in the cosmopolitan lichen-forming fungal genus Protoparmelia (Lecanorales, Ascomycota).

    Science.gov (United States)

    Singh, Garima; Dal Grande, Francesco; Divakar, Pradeep K; Otte, Jürgen; Leavitt, Steven D; Szczepanska, Katarzyna; Crespo, Ana; Rico, Víctor J; Aptroot, André; Cáceres, Marcela Eugenia da Silva; Lumbsch, H Thorsten; Schmitt, Imke

    2015-01-01

    Species recognition in lichen-forming fungi has been a challenge because of unsettled species concepts, few taxonomically relevant traits, and limitations of traditionally used morphological and chemical characters for identifying closely related species. Here we analyze species diversity in the cosmopolitan genus Protoparmelia s.l. The ~25 described species in this group occur across diverse habitats from the boreal-arctic/alpine to the tropics, but their relationship to each other remains unexplored. In this study, we inferred the phylogeny of 18 species currently assigned to this genus based on 160 specimens and six markers: mtSSU, nuLSU, ITS, RPB1, MCM7, and TSR1. We assessed the circumscription of species-level lineages in Protoparmelia s. str. using two coalescent-based species delimitation methods--BP&P and spedeSTEM. Our results suggest the presence of a tropical and an extra-tropical lineage, and eleven previously unrecognized distinct species-level lineages in Protoparmelia s. str. Several cryptic lineages were discovered as compared to phenotype-based species delimitation. Many of the putative species are supported by geographic evidence. PMID:25932996

  5. Coalescent-based species delimitation approach uncovers high cryptic diversity in the cosmopolitan lichen-forming fungal genus Protoparmelia (Lecanorales, Ascomycota.

    Directory of Open Access Journals (Sweden)

    Garima Singh

    Full Text Available Species recognition in lichen-forming fungi has been a challenge because of unsettled species concepts, few taxonomically relevant traits, and limitations of traditionally used morphological and chemical characters for identifying closely related species. Here we analyze species diversity in the cosmopolitan genus Protoparmelia s.l. The ~25 described species in this group occur across diverse habitats from the boreal-arctic/alpine to the tropics, but their relationship to each other remains unexplored. In this study, we inferred the phylogeny of 18 species currently assigned to this genus based on 160 specimens and six markers: mtSSU, nuLSU, ITS, RPB1, MCM7, and TSR1. We assessed the circumscription of species-level lineages in Protoparmelia s. str. using two coalescent-based species delimitation methods--BP&P and spedeSTEM. Our results suggest the presence of a tropical and an extra-tropical lineage, and eleven previously unrecognized distinct species-level lineages in Protoparmelia s. str. Several cryptic lineages were discovered as compared to phenotype-based species delimitation. Many of the putative species are supported by geographic evidence.

  6. Bacillus thuringiensis toxin resistance mechanisms among Lepidoptera: progress on genomic approaches to uncover causal mutations in the European corn borer, Ostrinia nubilalis.

    Science.gov (United States)

    Coates, Brad S

    2016-06-01

    Transgenic plants that express Bacillus thuringiensis (Bt) crystal (Cry) protein toxins (Bt crops) effectively control feeding by the European corn borer, Ostrinia nubilalis, although documented resistance evolution among a number of species in both the laboratory and field has heightened concerns about the durability of this technology. Research has provided major insights into the mutations that alter Bt toxin binding receptor structure and function within the midgut of Lepidoptera that directly impacts the efficacy of Bt toxins, and potentially leads to the evolution of resistance to Bt crops in the field. In this manuscript we provide an overview of available data on the identification of genes involved in high levels of resistance to Cry toxins, with emphasis on resistance described for O. nubilalis as the main target of Bt corn. PMID:27436734

  7. Risk of Post-ERCP Pancreatitis after placement of Covered versus Uncovered Self-Expandable Biliary Metal Stents: A Systematic Review and Meta-Analysis

    OpenAIRE

    Yaseen Alastal; Tariq Hammad; Muhammad Ali Khan; Khalil, Basmah W.; Sobia Khan; Mohammad Kashif Ismail; Ali Nawras; Aijaz Sofi

    2008-01-01

    Background Self-expandable metal stents are commonly used in the management of malignant biliary obstruction due to higher patency rates compared to plastic stents. Development of covered self-expandable metal stents has led to extended stent patency compared to uncovered self-expandable metal stents. However, there are concerns that deployment of covered self-expandable metal stents may be associated with higher risk of post-endoscopic retrograde cholangio-pancreatography pancreatitis, acute...

  8. Serial insertion of bilateral uncovered metal stents for malignant hilar obstruction using an 8 Fr biliary system: a case series of 17 consecutive patients

    OpenAIRE

    Hsieh, Jennifer; Thosani, Amar; Grunwald, Matthew; Nagula, Satish; Bucobo, Juan Carlos; Jonathan M Buscaglia

    2015-01-01

    Controversy exists over the need for unilateral versus bilateral stent placement in patients with malignant obstruction at the biliary hilum. Placement of bilateral uncovered self-expanding metal stent (UCSEMS) at this location is technically challenging, and generally associated with lower rates of procedural success. Serial insertion of side-by-side UCSEMS may be especially difficult when simultaneous deployment is not possible using larger stent delivery catheters. In this single-center, r...

  9. Increasing Emotional Intelligence through Training: Current Status and Future Directions

    Directory of Open Access Journals (Sweden)

    Nicola S. Schutte

    2013-04-01

    Full Text Available Emotional intelligence consists of adaptive emotional functioning involving inter-related competencies relating to perception, understanding, utilising and managing emotions in the self and others. Researchers in diverse fields have studied emotional intelligence and found the construct to be associated with a variety of intrapersonal and interpersonal factors such as mental health, relationship satisfaction, and work performance. This article reviews research investigating the impact of training in emotional-intelligence skills. The results indicate that it is possible to increase emotional intelligence and that such training has the potential to lead to other positive outcomes. The paper offers suggestions about how future research, from diverse disciplines,can uncover what types of training most effectively increase emotional intelligence and produce related beneficial outcomes.

  10. How to increase living donation.

    Science.gov (United States)

    Davis, Connie L

    2011-04-01

    Living donation is the key to increasing access to successful solid organ transplantation worldwide. However, the means to expanding the number of living donors on a global scale are not known. Although there have been many suggestions for the best approach, cultural issues may limit the effectiveness of some strategies. Only a few ideas have been studied, and one in particular- outright payment to donors - may raise ethical issues that are difficult to surmount and might negatively alter altruistic behavior. With respect to the present environment, this article will describe some of the approaches that are being discussed to increase the number of living donors, with a particular focus on kidney transplantation. PMID:21210867

  11. Impact of environmental inputs on reverse-engineering approach to network structures

    Directory of Open Access Journals (Sweden)

    Buchanan-Wollaston Vicky

    2009-12-01

    Full Text Available Abstract Background Uncovering complex network structures from a biological system is one of the main topic in system biology. The network structures can be inferred by the dynamical Bayesian network or Granger causality, but neither techniques have seriously taken into account the impact of environmental inputs. Results With considerations of natural rhythmic dynamics of biological data, we propose a system biology approach to reveal the impact of environmental inputs on network structures. We first represent the environmental inputs by a harmonic oscillator and combine them with Granger causality to identify environmental inputs and then uncover the causal network structures. We also generalize it to multiple harmonic oscillators to represent various exogenous influences. This system approach is extensively tested with toy models and successfully applied to a real biological network of microarray data of the flowering genes of the model plant Arabidopsis Thaliana. The aim is to identify those genes that are directly affected by the presence of the sunlight and uncover the interactive network structures associating with flowering metabolism. Conclusion We demonstrate that environmental inputs are crucial for correctly inferring network structures. Harmonic causal method is proved to be a powerful technique to detect environment inputs and uncover network structures, especially when the biological data exhibit periodic oscillations.

  12. Does nationalization increase stakeholder democracy?

    OpenAIRE

    Simeon Scott

    2010-01-01

    Purpose – The purpose of this paper is to investigate the theory and practice of stakeholder democracy. After examining the liberal notion of representative democracy, the paper seeks to identify the democratic deficit associated with the shareholder and stakeholder approaches to corporate governance. Investigating stakeholder democracy in nationalized industries in both market- and state-capitalist societies, the argument presented is that neither type of society has significantly increased ...

  13. How trade unions increase welfare

    OpenAIRE

    Donado, Alejandro; Klaus WALDE

    2010-01-01

    Historically, worker movements have played a crucial role in making workplaces safer. Firms traditionally oppose better health standards. According to our interpretation, workplace safety is costly for firms but increases the average health of workers and thereby the aggregate labour supply. A laissez-faire approach in which firms set safety standards is suboptimal as workers are not fully informed of health risks associated with jobs. Safety standards set by better-informed trade unions are ...

  14. Covered versus Uncovered Self-Expandable Metal Stents for Managing Malignant Distal Biliary Obstruction: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Jinjin Li

    Full Text Available To compare the efficacy of using covered self-expandable metal stents (CSEMSs and uncovered self-expandable metal stents (UCSEMSs to treat objective jaundice caused by an unresectable malignant tumor.We performed a comprehensive electronic search from 1980 to May 2015. All randomized controlled trials comparing the use of CSEMSs and UCSEMSs to treat malignant distal biliary obstruction were included.The analysis included 1417 patients enrolled in 14 trials. We did not detect significant differences between the UCSEMS group and the CSEMS group in terms of cumulative stent patency (hazard ratio (HR 0.93, 95% confidence interval (CI 0.19-4.53; p = 0.93, I2 = 0%, patient survival (HR 0.77, 95% CI 0.05-10.87; p = 0.85, I2 = 0%, overall stent dysfunction (relative ratio (RR 0.85, M-H, random, 95% CI 0.57-1.25; p = 0.83, I2 = 63%, the overall complication rate (RR 1.26, M-H, fixed, 95% CI 0.94-1.68; p = 0.12, I2 = 0% or the change in serum bilirubin (weighted mean difference (WMD -0.13, IV fixed, 95% CI 0.56-0.3; p = 0.55, I2 = 0%. However, we did detect a significant difference in the main causes of stent dysfunction between the two groups. In particular, the CSEMS group exhibited a lower rate of tumor ingrowth (RR 0.25, M-H, random, 95% CI 0.12-0.52; p = 0.002, I2 = 40% but a higher rate of tumor overgrowth (RR 1.76, M-H, fixed, 95% CI 1.03-3.02; p = 0.04, I2 = 0%. Patients with CSEMSs also exhibited a higher migration rate (RR 9.33, M-H, fixed, 95% CI 2.54-34.24; p = 0.008, I2 = 0% and a higher rate of sludge formation (RR 2.47, M-H, fixed, 95% CI 1.36-4.50; p = 0.003, I2 = 0%.Our meta-analysis indicates that there is no significant difference in primary stent patency and stent dysfunction between CSEMSs and UCSEMSs during the period from primary stent insertion to primary stent dysfunction or patient death. However, when taking further management for occluded stents into consideration, CSEMSs is a better choice for patients with malignant biliary

  15. Transcript profiles uncover temporal and stress-induced changes of metabolic pathways in germinating sugar beet seeds

    Directory of Open Access Journals (Sweden)

    Windhövel Andrea

    2008-12-01

    Full Text Available Abstract Background With a cultivation area of 1.75 Mio ha and sugar yield of 16.7 Mio tons in 2006, sugar beet is a crop of great economic importance in Europe. The productivity of sugar beet is determined significantly by seed vigour and field emergence potential; however, little is known about the molecular mechanisms underlying these traits. Both traits exhibit large variations within sugar beet germplasm that have been difficult to ascribe to either environmental or genetic causes. Among potential targets for trait improvement, an enhancement of stress tolerance is considered because of the high negative influence of environmental stresses on trait parameters. Extending our knowledge of genetic and molecular determinants of sugar beet germination, stress response and adaptation mechanisms would facilitate the detection of new targets for breeding crop with an enhanced field emergence potential. Results To gain insight into the sugar beet germination we initiated an analysis of gene expression in a well emerging sugar beet hybrid showing high germination potential under various environmental conditions. A total of 2,784 ESTs representing 2,251 'unigenes' was generated from dry mature and germinating seeds. Analysis of the temporal expression of these genes during germination under non-stress conditions uncovered drastic transcriptional changes accompanying a shift from quiescent to metabolically active stages of the plant life cycle. Assay of germination under stressful conditions revealed 157 genes showing significantly different expression patterns in response to stress. As deduced from transcriptome data, stress adaptation mechanisms included an alteration in reserve mobilization pathways, an accumulation of the osmoprotectant glycine betaine, late embryogenesis abundant proteins and detoxification enzymes. The observed transcriptional changes are supposed to be regulated by ABA-dependent signal transduction pathway. Conclusion This study

  16. Comparative analysis of the Photorhabdus luminescens and the Yersinia enterocolitica genomes: uncovering candidate genes involved in insect pathogenicity

    Directory of Open Access Journals (Sweden)

    Fuchs Thilo M

    2008-01-01

    Full Text Available Abstract Background Photorhabdus luminescens and Yersinia enterocolitica are both enteric bacteria which are associated with insects. P. luminescens lives in symbiosis with soil nematodes and is highly pathogenic towards insects but not to humans. In contrast, Y. enterocolitica is widely found in the environment and mainly known to cause gastroenteritis in men, but has only recently been shown to be also toxic for insects. It is expected that both pathogens share an overlap of genetic determinants that play a role within the insect host. Results A selective genome comparison was applied. Proteins belonging to the class of two-component regulatory systems, quorum sensing, universal stress proteins, and c-di-GMP signalling have been analysed. The interorganismic synopsis of selected regulatory systems uncovered common and distinct signalling mechanisms of both pathogens used for perception of signals within the insect host. Particularly, a new class of LuxR-like regulators was identified, which might be involved in detecting insect-specific molecules. In addition, the genetic overlap unravelled a two-component system that is unique for the genera Photorhabdus and Yersinia and is therefore suggested to play a major role in the pathogen-insect relationship. Our analysis also highlights factors of both pathogens that are expressed at low temperatures as encountered in insects in contrast to higher (body temperature, providing evidence that temperature is a yet under-investigated environmental signal for bacterial adaptation to various hosts. Common degradative metabolic pathways are described that might be used to explore nutrients within the insect gut or hemolymph, thus enabling the proliferation of P. luminescens and Y. enterocolitica in their invertebrate hosts. A strikingly higher number of genes encoding insecticidal toxins and other virulence factors in P. luminescens compared to Y. enterocolitica correlates with the higher virulence of P

  17. A study of multidimensional modeling approaches for data warehouse

    Science.gov (United States)

    Yusof, Sharmila Mat; Sidi, Fatimah; Ibrahim, Hamidah; Affendey, Lilly Suriani

    2016-08-01

    Data warehouse system is used to support the process of organizational decision making. Hence, the system must extract and integrate information from heterogeneous data sources in order to uncover relevant knowledge suitable for decision making process. However, the development of data warehouse is a difficult and complex process especially in its conceptual design (multidimensional modeling). Thus, there have been various approaches proposed to overcome the difficulty. This study surveys and compares the approaches of multidimensional modeling and highlights the issues, trend and solution proposed to date. The contribution is on the state of the art of the multidimensional modeling design.

  18. Increases in Problem Drinking

    Science.gov (United States)

    ... Increases in Problem Drinking Join the Fight Against Superbugs Featured Website: Genetic and Rare Diseases Information Center ... Increases in Problem Drinking Join the Fight Against Superbugs Featured Website: Genetic and Rare Diseases Information Center ...

  19. ATP increases within the lumen of the endoplasmic reticulum upon intracellular Ca2+ release

    OpenAIRE

    Vishnu, Neelanjan; Jadoon Khan, Muhammad; Karsten, Felix; Groschner, Lukas N.; Waldeck-Weiermair, Markus; Rost, Rene; Hallström, Seth; Imamura, Hiromi; Graier, Wolfgang F; Malli, Roland

    2014-01-01

    Multiple functions of the endoplasmic reticulum (ER) essentially depend on ATP within this organelle. However, little is known about ER ATP dynamics and the regulation of ER ATP import. Here we describe real-time recordings of ER ATP fluxes in single cells using an ER-targeted, genetically encoded ATP sensor. In vitro experiments prove that the ATP sensor is both Ca2+ and redox insensitive, which makes it possible to monitor Ca2+-coupled ER ATP dynamics specifically. The approach uncovers a c...

  20. INCREASING WATERFLOOD RESERVES IN THE WILMINGTON OIL FIELD THROUGH IMPROVED RESERVOIR CHARACTERIZATION AND RESERVOIR MANAGEMENT

    Energy Technology Data Exchange (ETDEWEB)

    Scott Walker; Chris Phillips; Roy Koerner; Don Clarke; Dan Moos; Kwasi Tagbor

    2002-02-28

    This project increased recoverable waterflood reserves in slope and basin reservoirs through improved reservoir characterization and reservoir management. The particular application of this project is in portions of Fault Blocks IV and V of the Wilmington Oil Field, in Long Beach, California, but the approach is widely applicable in slope and basin reservoirs. Transferring technology so that it can be applied in other sections of the Wilmington Field and by operators in other slope and basin reservoirs is a primary component of the project. This project used advanced reservoir characterization tools, including the pulsed acoustic cased-hole logging tool, geologic three-dimensional (3-D) modeling software, and commercially available reservoir management software to identify sands with remaining high oil saturation following waterflood. Production from the identified high oil saturated sands was stimulated by recompleting existing production and injection wells in these sands using conventional means as well as a short radius redrill candidate. Although these reservoirs have been waterflooded over 40 years, researchers have found areas of remaining oil saturation. Areas such as the top sand in the Upper Terminal Zone Fault Block V, the western fault slivers of Upper Terminal Zone Fault Block V, the bottom sands of the Tar Zone Fault Block V, and the eastern edge of Fault Block IV in both the Upper Terminal and Lower Terminal Zones all show significant remaining oil saturation. Each area of interest was uncovered emphasizing a different type of reservoir characterization technique or practice. This was not the original strategy but was necessitated by the different levels of progress in each of the project activities.

  1. Danube region strategy: Arguments for a territorial capital based multilevel approach

    Directory of Open Access Journals (Sweden)

    Giffinger Rudolf

    2010-01-01

    Full Text Available During the last months the discussion on a strategy for the Danube Region as a new approach for a European macro-region has been intensified, predominantly within the area of Central and South-Eastern Europe. Evidently the territory of the Danube Region is characterized by a divergent group of countries concerning the process of integration and the preconditions in geographic, economic, cultural and socio-demographic terms. Besides, the region’s spatial development shows divergent trends causing increasing regional disparities. Therefore, territorial cohesion - understood as intensified functional interrelations and strategic cooperation - is jeopardized in manifold ways. Hence, the main objective of this paper is to discuss the basic features of a strategy aiming at strengthening the polycentric development on different spatial levels. We start by assuming that the development of every city (as an element of the urban system depends on its territorial capital and relevant assets providing location based advantages regarding its competitiveness on different spatial levels. Therefore we uncover what we understand as assets driving urban development. In this context the meaning of polycentric development and the importance of polycentric structures as an asset of a city’s territorial capital is being revealed. Based on these conceptual considerations we examine some relevant features of the urban polycentric system in the Danube region and finally argue that a multilevel and evidence based approach should be evolved facing the differences in the preconditions and already existing assets of spatial development.

  2. CoCoRaHS (The Community Collaborative Rain, Hail and Snow Network): Analysis of Participant Survey Data to Uncover Learning through Participation

    Science.gov (United States)

    Holzer, M. A.; Zimmerman, T.; Doesken, N. J.; Reges, H. W.; Newman, N.; Turner, J.; Schwalbe, Z.

    2010-12-01

    CoCoRaHS (The Community Collaborative Rain, Hail and Snow network) is based out of Fort Collins Colorado and is an extremely successful citizen science project with over 15,000 volunteers collecting valuable precipitation data. Forecasters and scientists use data from this dense network to illuminate and illustrate the high small-scale variability of precipitation across the nation. This presentation will discuss the results of a survey of CoCoRaHS participants as related to 1) citizen scientists’ motivation and learning; 2) the challenges of identifying how people learn science in citizen science projects; and 3) a potential research-based framework for how people learn through engaging in the data collection within in a citizen science project. A comprehensive survey of 14,500 CoCoRaHS observers was recently conducted to uncover participant perceptions of numerous aspects of the CoCoRaHS program, including its goal of increasing climate literacy. The survey yielded a response rate of over 50%, and included measures of motivation, engagement and learning. In relationship to motivation and learning, the survey revealed that most (57.1%) observers would make precipitation observations regardless of being a CoCoRaHS volunteer, therefore their motivation is related to their inherent level of interest in weather. Others are motivated by their desire to learn more about weather and climate, they want to contribute to a scientific project, they think its fun, and/or it provides a sense of community. Because so many respondents already had knowledge and interest in weather and climate, identifying how and what people learn through participating was a challenge. However, the narrow project focus of collecting and reporting of local precipitation assisted in identifying aspects of learning. For instance, most (46.4%) observers said they increased their knowledge about the local variability in precipitation even though they had been collecting precipitation data for many

  3. A Social Marketing Approach To Increasing Breast Cancer Screening Rates.

    Science.gov (United States)

    Bryant, Carol A.; Forthofer, Melinda S.; McCormack Brown, Kelli; Alfonso, Moya Lynn; Quinn, Gwen

    2000-01-01

    Used social marketing to identify factors influencing women's breast cancer screening behaviors. Data from focus groups and interviews with diverse women highlighted women's attitudes, knowledge, and barriers regarding screening. Results were used to develop a comprehensive social marketing plan to motivate irregular users of breast cancer…

  4. Utilizing a Narrative Approach to Increasing Intimacy after Prostate Cancer

    Science.gov (United States)

    McCoy, Megan; Stinson, Morgan A.; Bermudez, J. Maria; Gladney, Leslie A.

    2013-01-01

    Attitudes about sexual intimacy are an important aspect of relationship satisfaction, especially for couples dealing with prostate cancer. Prostate cancer can have profound effects on men and their partners, and more research is needed to better understand potential sexual barriers for these couples. Five major themes identified in the literature…

  5. CIA increases cybersecurity Integrated approach to digital risks

    International Nuclear Information System (INIS)

    The article gives an overview of activities of the cybersecurity group, which was set up in order to go a step further. They have launched a project to manage cybersecurity. The underlying principle is a general pattern that determines policies and the responsibilities for risk management.

  6. Risk of Post-ERCP Pancreatitis after placement of Covered versus Uncovered Self-Expandable Biliary Metal Stents: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yaseen Alastal

    2008-09-01

    Full Text Available Background Self-expandable metal stents are commonly used in the management of malignant biliary obstruction due to higher patency rates compared to plastic stents. Development of covered self-expandable metal stents has led to extended stent patency compared to uncovered self-expandable metal stents. However, there are concerns that deployment of covered self-expandable metal stents may be associated with higher risk of post-endoscopic retrograde cholangio-pancreatography pancreatitis, acute cholecystitis and stent migration. Objective We performed this meta-analysis to assess the risk of post-endoscopic retrograde cholangio-pancreatography pancreatitis and other adverse events (acute cholecystitis and stent migration with biliary covered self-expandable metal stents compared to uncovered self-expandable metal stents. We also assessed the proportion of stent patency at 6 and 12 months between the two groups. Methods We searched MedLine, EMBASE, Cochrane database, ISI Web of Science and Scopus from January 1989 through June, 2014, to identify randomized controlled trials and observational studies that provided data on the risk of post-endoscopic retrograde cholangio-pancreatography pancreatitis and other adverse events following the placement of covered self-expandable metal stents versus uncovered self-expandable metal stents in patients with biliary obstruction. The Mantel–Haenszel method was used to pool data of post-endoscopic retrograde cholangio- pancreatography pancreatitis, acute cholecystitis, stent migration and proportion of stent patency over 6 and 12 months into fixed or random effect model of meta-analyses. Odds ratio was used to generate an overall effect estimate of the outcome. Results Eight studies (6 randomized controlled trials and 2 observational studies with a total of 1078 patients were included in the meta-analysis. The pooled odds ratio with 95% confidence intervals for risk of post-endoscopic retrograde cholangio

  7. 大型露天停车场雷电灾害分析与防护措施的研究%Lightning Hazard Analysis and Protective Measures of Large Uncovered Parking

    Institute of Scientific and Technical Information of China (English)

    赵涛; 李斐

    2014-01-01

    近年来,由于气候变化使强对流性天气不断增多,雷击事件频发。特别是空旷地区防雷设施不完善,防雷设施的缺乏,致使雷击造成人员伤亡和经济损失的事故时有发生。通过武汉经济技术开发区神龙汽车公司的露天停车场两次成品车遭受雷击事故的实地调查,就该村地理位置、气象资料、雷灾产生的原因进行了分析,提出了相应的雷电防护对策及建议。%In recent years, the climate change makes strong convective weather increasing and frequent lightning events. Especially in open areas, the lightning protection facilities in open areas are imperfect, even lack of lightning protection facilities, so the lightning casualties and economic losses occurred often. Through the fieldwork of the two lightning accident of finished car in uncovered parking of Shenlong Car company in Wuhan Economic and Technological Development Zone, the paper analyzes the location, meteorological data and the reasons of lightning disaster, and puts forward the corresponding countermeasures and suggestions for lightning protection.

  8. Global gene expression analysis using RNA-seq uncovered a new role for SR1/CAMTA3 transcription factor in salt stress.

    Science.gov (United States)

    Prasad, Kasavajhala V S K; Abdel-Hameed, Amira A E; Xing, Denghui; Reddy, Anireddy S N

    2016-01-01

    Abiotic and biotic stresses cause significant yield losses in all crops. Acquisition of stress tolerance in plants requires rapid reprogramming of gene expression. SR1/CAMTA3, a member of signal responsive transcription factors (TFs), functions both as a positive and a negative regulator of biotic stress responses and as a positive regulator of cold stress-induced gene expression. Using high throughput RNA-seq, we identified ~3000 SR1-regulated genes. Promoters of about 60% of the differentially expressed genes have a known DNA binding site for SR1, suggesting that they are likely direct targets. Gene ontology analysis of SR1-regulated genes confirmed previously known functions of SR1 and uncovered a potential role for this TF in salt stress. Our results showed that SR1 mutant is more tolerant to salt stress than the wild type and complemented line. Improved tolerance of sr1 seedlings to salt is accompanied with the induction of salt-responsive genes. Furthermore, ChIP-PCR results showed that SR1 binds to promoters of several salt-responsive genes. These results suggest that SR1 acts as a negative regulator of salt tolerance by directly repressing the expression of salt-responsive genes. Overall, this study identified SR1-regulated genes globally and uncovered a previously uncharacterized role for SR1 in salt stress response. PMID:27251464

  9. 人工环境下无覆盖土壤散湿量计算%Uncovered soil moisture gain calculation in artificial environment

    Institute of Scientific and Technical Information of China (English)

    胡晨炯; 邓辉炼

    2012-01-01

    Considering the situation of a ruins protection hall with a large floor proportion of uncovered soil in Guangzhou and borrowing some ideas from the calculation method and well-developed empirical formula of groundwater evaporation rate in hydro science, puts forward a method for calculating the uncovered soil moisture gain in artificial environment. In this method, outside evaporation capacity is characterized with the evaporation of exposed water surface and the water supply capacity of soil is characterized with groundwater evaporation coefficient. The design effect of the project indicates that the precision of the calculation method can meet the demand of engineering.%针对广州某遗址保护大厅内多为裸露土壤的情况,借鉴水利科学中潜水蒸发量的计算方法及成熟的相关经验公式,提出了人工环境下无覆盖土壤散湿量的计算方法.在该计算方法中,用暴露水面的蒸发量来表征外界蒸发能力,用潜水蒸发系数来表征土壤的输水能力.设计效果表明,该方法的计算精度能满足工程实际的需要.

  10. A genome-wide polyketide synthase deletion library uncovers novel genetic links to polyketides and meroterpenoids in Aspergillus nidulans

    DEFF Research Database (Denmark)

    Nielsen, Michael Lynge; Nielsen, Jakob Blæsbjerg; Rank, Christian; Klejnstrup, Marie Louise; Holm, Dorte Koefoed; Brogaard, Katrine Husted; Hansen, Bjarne Gram; Frisvad, Jens Christian; Larsen, Thomas Ostenfeld; Mortensen, Uffe Hasbro

    2011-01-01

    Fungi possess an advanced secondary metabolism that is regulated and coordinated in a complex manner depending on environmental challenges. To understand this complexity, a holistic approach is necessary. We initiated such an analysis in the important model fungus Aspergillus nidulans by...

  11. Meeting increased demand.

    Science.gov (United States)

    Blair, Andrew

    2004-07-01

    New Zealand is a little country with a little economy but with a population that's rapidly aging. New Zealand's population is only 4.3 million people. It's GDP is only $US58.6 billion (2002). New Zealand's expenditure on health as a percentage of GDP is not out of line with that of other countries. As a nation we have been increasing expenditure on health over recent years. In 1990 we spent 7% of GDP on health. In 1995 that increased to 7.65% and is now 8.3%. However, in per capita terms our expenditure on health does not compare so well with like countries. The size of New Zealand's economy is restricting what our country spends on health. Health is already the second highest demand on the New Zealand tax dollar. The tolerance of New Zealanders would be challenged if a Government attempted to increase taxes further to meet the growing demands for expenditure on health, but at the same time the population's expectations are increasing. This is the challenging situation we face today. What lies ahead? Like all industrialized countries New Zealand is facing an aging population. The population below age 40 is decreasing, but it is increasing significantly over that age. 16% of the population is currently aged over 60. By 2051 this proportion will almost double to just over 31%. Coupled with the aging population is increased awareness and expectations, as access to options for treatment and technology becomes readily accessible to the population through such media as the internet. The extent of the impact of the aging population can be clearly represented by focusing on one specialty such as orthopaedics. The New Zealand Orthopaecic Association undertook a study in July 2003 which concluded (among other things) that as a result of the projected aging of the population, over the next 50 years: Musculo-skeletal operations will increase by over 30%. The number of hip replacements will nearly double. The incidence of osteoporosis will increase by a massive 201%. The number

  12. Exergames: Increasing Physical Activity through Effective Instruction

    Science.gov (United States)

    Rudella, Jennifer L.; Butz, Jennifer V.

    2015-01-01

    Due to the growing obesity epidemic in the United States, educators must consider new ways to increase physical activity in an effort to address obesity. There are a variety of ways educators can increase physical activity in the classroom, and exergames--video games that require physical movement in order to play--are a modern-day approach to…

  13. Impact of environmental inputs on reverse-engineering approach to network structures

    OpenAIRE

    Buchanan-Wollaston Vicky; Sinfield James L; Wu Jianhua; Feng Jianfeng

    2009-01-01

    Abstract Background Uncovering complex network structures from a biological system is one of the main topic in system biology. The network structures can be inferred by the dynamical Bayesian network or Granger causality, but neither techniques have seriously taken into account the impact of environmental inputs. Results With considerations of natural rhythmic dynamics of biological data, we propose a system biology approach to reveal the impact of environmental inputs on network structures. ...

  14. Seismic waves increase permeability.

    Science.gov (United States)

    Elkhoury, Jean E; Brodsky, Emily E; Agnew, Duncan C

    2006-06-29

    Earthquakes have been observed to affect hydrological systems in a variety of ways--water well levels can change dramatically, streams can become fuller and spring discharges can increase at the time of earthquakes. Distant earthquakes may even increase the permeability in faults. Most of these hydrological observations can be explained by some form of permeability increase. Here we use the response of water well levels to solid Earth tides to measure permeability over a 20-year period. At the time of each of seven earthquakes in Southern California, we observe transient changes of up to 24 degrees in the phase of the water level response to the dilatational volumetric strain of the semidiurnal tidal components of wells at the Piñon Flat Observatory in Southern California. After the earthquakes, the phase gradually returns to the background value at a rate of less than 0.1 degrees per day. We use a model of axisymmetric flow driven by an imposed head oscillation through a single, laterally extensive, confined, homogeneous and isotropic aquifer to relate the phase response to aquifer properties. We interpret the changes in phase response as due to changes in permeability. At the time of the earthquakes, the permeability at the site increases by a factor as high as three. The permeability increase depends roughly linearly on the amplitude of seismic-wave peak ground velocity in the range of 0.21-2.1 cm s(-1). Such permeability increases are of interest to hydrologists and oil reservoir engineers as they affect fluid flow and might determine long-term evolution of hydrological and oil-bearing systems. They may also be interesting to seismologists, as the resulting pore pressure changes can affect earthquakes by changing normal stresses on faults. PMID:16810253

  15. Increasing mobile radiography productivity.

    Science.gov (United States)

    Wong, Edward; Lung, Ngan Tsz; Ng, Kris; Jeor, Patrick

    2013-01-01

    Mobile radiography using computed radiography (CR) cassettes is a common equipment combination with a workflow bottleneck limited by location of CR readers. Advent of direct digital radiography (DDR) mobile x-ray machines removes this limitation by immediate image review and quality control. Through the use of key performance indicators (KPIs), the increase in efficiency can be quantified. PMID:23986937

  16. Increased urinary orosomucoid excretion

    DEFF Research Database (Denmark)

    Christiansen, M S; Iversen, K; Larsen, C T;

    2009-01-01

    OBJECTIVE: In a previous study, urinary orosomucoid excretion rate (UOER) independently predicted cardiovascular mortality in patients with type 2 diabetes. The aim of the present study was to determine whether increased UOER is associated with cardiovascular risk factors such as inflammation, im...

  17. Does salt increase thirst?

    Science.gov (United States)

    Leshem, Micah

    2015-02-01

    Our diet is believed to be overly rich in sodium, and it is commonly believed that sodium intake increases drinking. Hence the concern of a possible contribution of dietary sodium to beverage intake which in turn may contribute to obesity and ill health. Here we examine whether voluntary, acute intake of a sodium load, as occurs in routine eating and snacking, increases thirst and drinking. We find that after ingesting 3.5 or 4.4 g NaCl (men) and 1.9 or 3.7 g (women) on nuts during 15 minutes, there is no increase in thirst or drinking of freely available water in the following 2 h compared with eating similar amounts of sugared or unflavored nuts. This suggests that routine ingestion of boluses of salt (~30-40% of daily intake for men, ~ 20-40% for women) does not increase drinking. Methodological concerns such as about nuts as vehicle for sodium suggest further research to establish the generalizability of this unexpected result. PMID:25447020

  18. Uncovering the links between brand choice and personal values among young consumers in Spain and the UK

    OpenAIRE

    Dibley, Anne

    2004-01-01

    This PhD thesis presents an exploratory study examining how successfully the meansend chain model can be applied to 11-12 year old British and Spanish girls, and whether a clear association exists between their personal values and the snacks and clothing brands they choose. This study draws on the subjective-interpretive epistemology, and takes a qualitative, depth interview approach. The author uses the laddering technique to build a mental map ofbenefits offered by differe...

  19. Uncovering the molecular machinery of the human spindle--an integration of wet and dry systems biology.

    Science.gov (United States)

    Rojas, Ana M; Santamaria, Anna; Malik, Rainer; Jensen, Thomas Skøt; Körner, Roman; Morilla, Ian; de Juan, David; Krallinger, Martin; Hansen, Daniel Aaen; Hoffmann, Robert; Lees, Jonathan; Reid, Adam; Yeats, Corin; Wehner, Anja; Elowe, Sabine; Clegg, Andrew B; Brunak, Søren; Nigg, Erich A; Orengo, Christine; Valencia, Alfonso; Ranea, Juan A G

    2012-01-01

    The mitotic spindle is an essential molecular machine involved in cell division, whose composition has been studied extensively by detailed cellular biology, high-throughput proteomics, and RNA interference experiments. However, because of its dynamic organization and complex regulation it is difficult to obtain a complete description of its molecular composition. We have implemented an integrated computational approach to characterize novel human spindle components and have analysed in detail the individual candidates predicted to be spindle proteins, as well as the network of predicted relations connecting known and putative spindle proteins. The subsequent experimental validation of a number of predicted novel proteins confirmed not only their association with the spindle apparatus but also their role in mitosis. We found that 75% of our tested proteins are localizing to the spindle apparatus compared to a success rate of 35% when expert knowledge alone was used. We compare our results to the previously published MitoCheck study and see that our approach does validate some findings by this consortium. Further, we predict so-called "hidden spindle hub", proteins whose network of interactions is still poorly characterised by experimental means and which are thought to influence the functionality of the mitotic spindle on a large scale. Our analyses suggest that we are still far from knowing the complete repertoire of functionally important components of the human spindle network. Combining integrated bio-computational approaches and single gene experimental follow-ups could be key to exploring the still hidden regions of the human spindle system. PMID:22427808

  20. Evaluating six soft approaches

    DEFF Research Database (Denmark)

    Sørensen, Lene Tolstrup; Vidal, Rene Victor Valqui

    2008-01-01

    The paper introduces and evaluates six soft approaches used in strategy development and planning. We take a planner's perspective on discussing the concepts of strategy development and planning. This means that we see strategy development and planning as learning processes based on Ackoff......, Strategic Option Development and Analysis, Strategic Choice Approach and Soft Systems Methodology. Evaluations of each methodology are carried out using a conceptual framework in which the organisation, the result, the process and the technology of the specific approach are taken into consideration. Using...... such a conceptual framework for evaluations of soft approaches increases the understanding of them, their transparency, and their usability in practice....

  1. Sources of increased danger

    International Nuclear Information System (INIS)

    The present and future facts of absolute liability under specific laws will have to be supplemented by the legislator, and the claims for damages will have to be limited to physical and material damage. The formulation should be about as follows: 'If a person is killed by a source of increased danger or damage done to his/her body or health or material damage done, the owner of that source will be liable for payment of damages'. A standard of this kind has good chances of being realized and applied in German or even European technical and social developments of the future. The general clause of absolute reliability for sources of increased danger depends on the judge's decision and models so far, also of other countries, give no cause to doubt this. (orig./HP)

  2. Increasing income inequality

    DEFF Research Database (Denmark)

    Frederiksen, Anders; Poulsen, Odile

    In recent decades most developed countries have experienced an increase in income inequality. In this paper, we use an equilibrium search framework to shed additional light on what is causing an income distribution to change. The major benefit of the model is that it can accommodate shocks to the...... shocks to the employees' relative productivity, i.e., skill-biased technological change, are unlikely to have caused the increase in income inequality....... skill composition in the market, employee bargaining power and productivity. Further, when our model is subjected to skill-upgrading and changes in employee bargaining power, it is capable of predicting the recent changes observed in the Danish income distribution. In addition, the model emphasizes that...

  3. Condom use increasing.

    Science.gov (United States)

    Finger, W R

    1998-01-01

    Condom use is central to the prevention of AIDS among people at risk for contracting HIV. As such, condom use is increasing dramatically even though many men say that they do not like using them. Condom sales through social marketing campaigns have increased dramatically in some countries, where tens of millions of condoms are sold annually. For example, during the period 1991-96, annual social marketing sales increased about five-fold in Ethiopia to 21 million, and nine-fold in Brazil to 27 million. These sales reflect the success of condom social marketing campaigns in making condoms accessible and largely affordable. There is also a greater general awareness of AIDS than there used to be, and communication campaigns have shown that condoms are an effective solution. More condoms still need to be used in the ongoing struggle against HIV/AIDS. The author discusses the factors which affect the limited acceptance of condoms, condom use outside of marriage, social marketing, and family planning programs. PMID:12293530

  4. Multidimensional Poverty Indices and First Order Dominance Techniques: An Empirical Comparison of Different Approaches

    DEFF Research Database (Denmark)

    Hussain, M. Azhar; Permanyer, Iñaki

    2016-01-01

    In this paper we contrast different perspectives to the measurement of multidimensional poverty. Using data from 38 Demographic and Health Surveys around the developing world, we have compared the performance of two broad approaches: multidimensional poverty indices and first order dominance...... techniques (FOD). Our empirical findings suggest that the FOD approach might be a reasonable cost-effective alternative to the United Nations Development Program (UNDP)’s flagship poverty indicator: the Multidimensional Poverty Index (MPI). To the extent that the FOD approach is able to uncover the socio...

  5. High Heels Increase Women's Attractiveness.

    Science.gov (United States)

    Guéguen, Nicolas

    2015-11-01

    Research has found that the appearance of women's apparel helps increase their attractiveness as rated by men and that men care more about physical features in potential opposite-sex mates. However, the effect of sartorial appearance has received little interest from scientists. In a series of studies, the length of women's shoe heels was examined. A woman confederate wearing black shoes with 0, 5, or 9 cm heels asked men for help in various circumstances. In Study 1, she asked men to respond to a short survey on gender equality. In Study 2, the confederate asked men and women to participate in a survey on local food habit consumption. In Study 3, men and women in the street were observed while walking in back of the female confederate who dropped a glove apparently unaware of her loss. It was found that men's helping behavior increased as soon as heel length increased. However, heel length had no effect on women's helping behavior. It was also found that men spontaneously approached women more quickly when they wore high-heeled shoes (Study 4). Change in gait, foot-size judgment, and misattribution of sexiness and sexual intent were used as possible explanations. PMID:25408499

  6. Evaluating a physician leadership development program - a mixed methods approach.

    Science.gov (United States)

    Throgmorton, Cheryl; Mitchell, Trey; Morley, Tom; Snyder, Marijo

    2016-05-16

    Purpose - With the extent of change in healthcare today, organizations need strong physician leaders. To compensate for the lack of physician leadership education, many organizations are sending physicians to external leadership programs or developing in-house leadership programs targeted specifically to physicians. The purpose of this paper is to outline the evaluation strategy and outcomes of the inaugural year of a Physician Leadership Academy (PLA) developed and implemented at a Michigan-based regional healthcare system. Design/methodology/approach - The authors applied the theoretical framework of Kirkpatrick's four levels of evaluation and used surveys, observations, activity tracking, and interviews to evaluate the program outcomes. The authors applied grounded theory techniques to the interview data. Findings - The program met targeted outcomes across all four levels of evaluation. Interview themes focused on the significance of increasing self-awareness, building relationships, applying new skills, and building confidence. Research limitations/implications - While only one example, this study illustrates the importance of developing the evaluation strategy as part of the program design. Qualitative research methods, often lacking from learning evaluation design, uncover rich themes of impact. The study supports how a PLA program can enhance physician learning, engagement, and relationship building throughout and after the program. Physician leaders' partnership with organization development and learning professionals yield results with impact to individuals, groups, and the organization. Originality/value - Few studies provide an in-depth review of evaluation methods and outcomes of physician leadership development programs. Healthcare organizations seeking to develop similar in-house programs may benefit applying the evaluation strategy outlined in this study. PMID:27119393

  7. Uncovering the Molecular Machinery of the Human Spindle—An Integration of Wet and Dry Systems Biology

    Science.gov (United States)

    Körner, Roman; Morilla, Ian; de Juan, David; Krallinger, Martin; Hansen, Daniel Aaen; Hoffmann, Robert; Lees, Jonathan; Reid, Adam; Yeats, Corin; Wehner, Anja; Elowe, Sabine; Clegg, Andrew B.; Brunak, Søren; Nigg, Erich A.; Orengo, Christine; Valencia, Alfonso; Ranea, Juan A. G.

    2012-01-01

    The mitotic spindle is an essential molecular machine involved in cell division, whose composition has been studied extensively by detailed cellular biology, high-throughput proteomics, and RNA interference experiments. However, because of its dynamic organization and complex regulation it is difficult to obtain a complete description of its molecular composition. We have implemented an integrated computational approach to characterize novel human spindle components and have analysed in detail the individual candidates predicted to be spindle proteins, as well as the network of predicted relations connecting known and putative spindle proteins. The subsequent experimental validation of a number of predicted novel proteins confirmed not only their association with the spindle apparatus but also their role in mitosis. We found that 75% of our tested proteins are localizing to the spindle apparatus compared to a success rate of 35% when expert knowledge alone was used. We compare our results to the previously published MitoCheck study and see that our approach does validate some findings by this consortium. Further, we predict so-called “hidden spindle hub”, proteins whose network of interactions is still poorly characterised by experimental means and which are thought to influence the functionality of the mitotic spindle on a large scale. Our analyses suggest that we are still far from knowing the complete repertoire of functionally important components of the human spindle network. Combining integrated bio-computational approaches and single gene experimental follow-ups could be key to exploring the still hidden regions of the human spindle system. PMID:22427808

  8. Evaluating six soft approaches

    Directory of Open Access Journals (Sweden)

    Lene Sørensen

    2008-09-01

    Full Text Available The paper introduces and evaluates six soft approaches used in strategy development and planning. We take a planner’s perspective on discussing the concepts of strategy development and planning. This means that we see strategy development and planning as learning processes based on Ackoff’s interactive planning principles to be supported by soft approaches in carrying out the principles in action. These six soft approaches are suitable for supporting various steps of the strategy development and planning process. These are the SWOT analysis, the Future Workshop, the Scenario methodology, Strategic Option Development and Analysis, Strategic Choice Approach and Soft Systems Methodology. Evaluations of each methodology are carried out using a conceptual framework in which the organisation, the result, the process and the technology of the specific approach are taken into consideration. Using such a conceptual framework for evaluations of soft approaches increases the understanding of them, their transparency, and their usability in practice.

  9. Unified theory in the worldline approach

    Directory of Open Access Journals (Sweden)

    James P. Edwards

    2015-11-01

    Full Text Available We explore unified field theories based on the gauge groups SU(5 and SO(10 using the worldline approach for chiral fermions with a Wilson loop coupling to a background gauge field. Representing path ordering and chiral projection operators with functional integrals has previously reproduced the sum over the chiralities and representations of standard model particles in a compact way. This paper shows that for SU(5 the 5¯ and 10 representations – into which the Georgi–Glashow model places the left-handed fermionic content of the standard model – appear naturally and with the familiar chirality. We carry out the same analysis for flipped SU(5 and uncover a link to SO(10 unified theory. We pursue this by exploring the SO(10 theory in the same framework, the less established unified theory based on SU(6 and briefly consider the Pati–Salam model using SU(4×SU(2×SU(2.

  10. Unified theory in the worldline approach

    Science.gov (United States)

    Edwards, James P.

    2015-11-01

    We explore unified field theories based on the gauge groups SU (5) and SO (10) using the worldline approach for chiral fermions with a Wilson loop coupling to a background gauge field. Representing path ordering and chiral projection operators with functional integrals has previously reproduced the sum over the chiralities and representations of standard model particles in a compact way. This paper shows that for SU (5) the 5 bar and 10 representations - into which the Georgi-Glashow model places the left-handed fermionic content of the standard model - appear naturally and with the familiar chirality. We carry out the same analysis for flipped SU (5) and uncover a link to SO (10) unified theory. We pursue this by exploring the SO (10) theory in the same framework, the less established unified theory based on SU (6) and briefly consider the Pati-Salam model using SU (4) × SU (2) × SU (2).

  11. CHINA INCREASED PETROLEUM TAX

    Institute of Scientific and Technical Information of China (English)

    Mu Xueping

    2005-01-01

    @@ After half a year's gestation and adjustment, the State Administration of Taxation finally set new tax rate of petroleum resources. Notification issued by the Ministry of Finance and the State Administration of Taxation said the petroleum resources tax standard would be lifted nationwide, after the tax rate adjustment, tax on crude oil would be increased to RMB 14-30 yuan per ton and that on natural gas to RMB 7-15 yuan per thousand cubic meters. The new tax rate has been effective nationwide since July 1.

  12. Uncovering the secret lives of sewer rats (Rattus norvegicus): Movements, distribution and population dynamics revealed by a capture-mark-recapture study

    DEFF Research Database (Denmark)

    Heiberg, Ann-Charlotte; Sluydts, Vincent; Leirs, Herwig E.l.

    2012-01-01

    behaviour of these populations. Aims.: The study aimed to uncover the population dynamics, movements and distribution of rats in populations living in sewers. Methods.: We studied rats in a capture–mark–recapture study in two adjacent but separate sewer systems in suburban Copenhagen, Denmark, covering a...... surface area of 30 Ha. Multiple-capture live traps were placed in manholes in public sewers; animals were marked individually and data were collected every fourth week for a period of almost 3 years. Key results.: In total, 332 individual rats were trapped. Approximately one-third were only caught once...... dimensions. Juvenile rats were captured more in the smaller and drier sewer sections. Activity areas of rats of both sexes overlapped partially, and observations of bite wounds were rare, suggesting a high degree of tolerance. The average maximal distance covered by rats was ~200 m for both sexes. Day...

  13. Palliation of Pyloric Stenosis Caused by Gastric Cancer Using an Endoscopically Placed Covered Ultraflex Stent: Covered Stent Inside an Occluded Uncovered Stent

    International Nuclear Information System (INIS)

    A 71-year-old man developed pyloric stenosis caused by gastric cancer. Vomiting and nausea resolved after the insertion of an uncovered Ultraflex stent (length 10 cm, inner diameter 18u23 mm) through a 7-cm-long stenosis, and the patient was able to eat a soft diet. After 6 weeks, stent occlusion occurred due to tumor ingrowth and accumulation of food residue. Endoscopic observation showed a very narrow residual lumen. A covered Ultraflex stent (length 10 cm, inner diameter 18u23 mm) was inserted through the first stent and expanded to its maximum diameter over the next 2 days. The patient's vomiting and nausea improved rapidly. He died 6 months after the second stenting procedure, from metastatic tumor spread, having remained free of nausea and vomiting. In this case, a covered metallic stent prevented tumor ingrowth and maintained gastrointestinal patency

  14. Serial insertion of bilateral uncovered metal stents for malignant hilar obstruction using an 8 Fr biliary system: a case series of 17 consecutive patients.

    Science.gov (United States)

    Hsieh, Jennifer; Thosani, Amar; Grunwald, Matthew; Nagula, Satish; Bucobo, Juan Carlos; Buscaglia, Jonathan M

    2015-10-01

    Controversy exists over the need for unilateral versus bilateral stent placement in patients with malignant obstruction at the biliary hilum. Placement of bilateral uncovered self-expanding metal stent (UCSEMS) at this location is technically challenging, and generally associated with lower rates of procedural success. Serial insertion of side-by-side UCSEMS may be especially difficult when simultaneous deployment is not possible using larger stent delivery catheters. In this single-center, retrospective case series of all patients who underwent bilateral placement of uncovered Wallflex(TM) biliary stents between July 2008 and July 2014, we evaluate the feasibility, technical success, and safety of patients undergoing serial insertion of bilateral UCSEMS using the 8 Fr Wallflex(TM) biliary system for malignant hilar obstruction. A total of 17 patients were included. Primary cholangiocarcinoma, Bismuth IV, was the most common diagnosis. Mean procedure time was 54.4 minutes. Overall procedural technical success was achieved in 17/17 patients. Stricture dilation was necessary prior to Wallflex(TM) insertion in 8/17 patients (47.1%). Transpapillary extension of two stents was performed in all patients. There were no cases of stent deployment malfunction, or inability to insert or deploy the 2(nd) stent. Nine of 17 patients (52.9%) required inpatient hospitalization following ERCP; the most common indications were abdominal pain and need for IV antibiotics. There was one case of ERCP-related cholangitis otherwise; there were no other major complications. Bilateral, serial insertion of UCSEMS using the 8 Fr Wallflex(TM) biliary system in malignant hilar obstruction is feasible with an excellent technical success profile. Using this device for side-by-side deployment of UCSEMS appears to be safe in the majority of patients. PMID:26605283

  15. Integration of small RNAs, degradome and transcriptome sequencing in hyperaccumulator Sedum alfredii uncovers a complex regulatory network and provides insights into cadmium phytoremediation.

    Science.gov (United States)

    Han, Xiaojiao; Yin, Hengfu; Song, Xixi; Zhang, Yunxing; Liu, Mingying; Sang, Jiang; Jiang, Jing; Li, Jihong; Zhuo, Renying

    2016-06-01

    The hyperaccumulating ecotype of Sedum alfredii Hance is a cadmium (Cd)/zinc/lead co-hyperaccumulating species of Crassulaceae. It is a promising phytoremediation candidate accumulating substantial heavy metal ions without obvious signs of poisoning. However, few studies have focused on the regulatory roles of miRNAs and their targets in the hyperaccumulating ecotype of S. alfredii. Here, we combined analyses of the transcriptomics, sRNAs and the degradome to generate a comprehensive resource focused on identifying key regulatory miRNA-target circuits under Cd stress. A total of 87 721 unigenes and 356 miRNAs were identified by deep sequencing, and 79 miRNAs were differentially expressed under Cd stress. Furthermore, 754 target genes of 194 miRNAs were validated by degradome sequencing. A gene ontology (GO) enrichment analysis of differential miRNA targets revealed that auxin, redox-related secondary metabolism and metal transport pathways responded to Cd stress. An integrated analysis uncovered 39 pairs of miRNA targets that displayed negatively correlated expression profiles. Ten miRNA-target pairs also exhibited negative correlations according to a real-time quantitative PCR analysis. Moreover, a coexpression regulatory network was constructed based on profiles of differentially expressed genes. Two hub genes, ARF4 (auxin response factor 4) and AAP3 (amino acid permease 3), which might play central roles in the regulation of Cd-responsive genes, were uncovered. These results suggest that comprehensive analyses of the transcriptomics, sRNAs and the degradome provided a useful platform for investigating Cd hyperaccumulation in S. alfredii, and may provide new insights into the genetic engineering of phytoremediation. PMID:26801211

  16. DIANA-mirExTra v2.0: Uncovering microRNAs and transcription factors with crucial roles in NGS expression data.

    Science.gov (United States)

    Vlachos, Ioannis S; Vergoulis, Thanasis; Paraskevopoulou, Maria D; Lykokanellos, Filopoimin; Georgakilas, Georgios; Georgiou, Penny; Chatzopoulos, Serafeim; Karagkouni, Dimitra; Christodoulou, Foteini; Dalamagas, Theodore; Hatzigeorgiou, Artemis G

    2016-07-01

    Differential expression analysis (DEA) is one of the main instruments utilized for revealing molecular mechanisms in pathological and physiological conditions. DIANA-mirExTra v2.0 (http://www.microrna.gr/mirextrav2) performs a combined DEA of mRNAs and microRNAs (miRNAs) to uncover miRNAs and transcription factors (TFs) playing important regulatory roles between two investigated states. The web server uses as input miRNA/RNA-Seq read count data sets that can be uploaded for analysis. Users can combine their data with 350 small-RNA-Seq and 65 RNA-Seq in-house analyzed libraries which are provided by DIANA-mirExTra v2.0.The web server utilizes miRNA:mRNA, TF:mRNA and TF:miRNA interactions derived from extensive experimental data sets. More than 450 000 miRNA interactions and 2 000 000 TF binding sites from specific or high-throughput techniques have been incorporated, while accurate miRNA TSS annotation is obtained from microTSS experimental/in silico framework. These comprehensive data sets enable users to perform analyses based solely on experimentally supported information and to uncover central regulators within sequencing data: miRNAs controlling mRNAs and TFs regulating mRNA or miRNA expression. The server also supports predicted miRNA:gene interactions from DIANA-microT-CDS for 4 species (human, mouse, nematode and fruit fly). DIANA-mirExTra v2.0 has an intuitive user interface and is freely available to all users without any login requirement. PMID:27207881

  17. Uncovering and responding to needs for sexual and reproductive health care among poor urban female adolescents in Nicaragua.

    NARCIS (Netherlands)

    Meuwissen, L.E.; Gorter, A.C.; Segura, Z.; Kester, A.D.M.; Knottnerus, J.A.

    2006-01-01

    BACKGROUND: To meet the needs of female adolescents from low-income urban areas for sexual and reproductive health (SRH) care, vouchers providing free-of-charge access to SRH care at 19 primary care clinics were distributed in Managua, Nicaragua. These vouchers substantially increased the use of ser

  18. Gas revenue increasingly significant

    International Nuclear Information System (INIS)

    This paper briefly describes the wellhead prices of natural gas compared to crude oil over the past 70 years. Although natural gas prices have never reached price parity with crude oil, the relative value of a gas BTU has been increasing. It is one of the reasons that the total amount of money coming from natural gas wells is becoming more significant. From 1920 to 1955 the revenue at the wellhead for natural gas was only about 10% of the money received by producers. Most of the money needed for exploration, development, and production came from crude oil. At present, however, over 40% of the money from the upstream portion of the petroleum industry is from natural gas. As a result, in a few short years natural gas may become 50% of the money revenues generated from wellhead production facilities

  19. Metabolomic profiling of a modified alcohol liquid diet model for liver injury in the mouse uncovers new markers of disease

    International Nuclear Information System (INIS)

    Metabolomic evaluation of urine and liver was conducted to assess the biochemical changes that occur as a result of alcohol-induced liver injury. Male C57BL/6J mice were fed an isocaloric control- or alcohol-containing liquid diet with 35% of calories from corn oil, 18% protein and 47% carbohydrate/alcohol for up to 36 days ad libitum. Alcohol treatment was initiated at 7 g/kg/day and gradually reached a final dose of 21 g/kg/day. Urine samples were collected at 22, 30 and 36 days and, in additional treatment groups, liver and serum samples were harvested at 28 days. Steatohepatitis was induced in the alcohol-fed group since a 5-fold increase in serum alanine aminotransferase activity, a 6-fold increase in liver injury score (necrosis, inflammation and steatosis) and an increase in lipid peroxidation in liver were observed. Liver and urine samples were analyzed by nuclear magnetic resonance spectroscopy and electrospray infusion/Fourier transform ion cyclotron resonance-mass spectrometry. In livers of alcohol-treated mice the following changes were noted. Hypoxia and glycolysis were activated as evidenced by elevated levels of alanine and lactate. Tyrosine, which is required for L-DOPA and dopamine as well as thyroid hormones, was elevated possibly reflecting alterations of basal metabolism by alcohol. A 4-fold increase in the prostacyclin inhibitor 7,10,13,16-docosatetraenoic acid, a molecule important for regulation of platelet formation and blood clotting, may explain why chronic drinking causes serious bleeding problems. Metabolomic analysis of the urine revealed that alcohol treatment leads to decreased excretion of taurine, a metabolite of glutathione, and an increase in lactate, n-acetylglutamine and n-acetylglycine. Changes in the latter two metabolites suggest an inhibition of the kidney enzyme aminoacylase I and may be useful as markers for alcohol consumption

  20. Uncovering the hidden signature of a magmatic recharge at Piton de la Fournaise volcano using small earthquakes

    Science.gov (United States)

    Lengliné, O.; Duputel, Z.; Ferrazzini, V.

    2016-05-01

    We apply a template matching method to detect and locate preeruptive earthquakes at Piton de la Fournaise volcano in 2014 and 2015. This approach enabled the detection of many events and unveiled persistent seismicity features through multiple eruptions. Shallow earthquakes define a ring-shaped structure beneath the main crater. The repetitive occurrence of events along this structure suggests that it corresponds to a preexisting zone of weakness within the edifice. We also show evidence of deep magma transfer in 2015. More than 5000 deep earthquakes define an upward migration immediately followed by the occurrence of shallow events leading to an eruption 20 days later. This suggests the creation of a hydraulic connection between the lower part of the volcanic system and a magma reservoir located near sea level. We can envisage than such replenishments of the shallow reservoir occurred in the past but were undetected because of limited deep earthquake detections.

  1. Uncovering Underlying Assumptions Regarding Education and Technology in Educational Reform Efforts A conversation with Dr. Larry Johnson

    Directory of Open Access Journals (Sweden)

    Gabriela Melano

    2000-11-01

    Full Text Available Educational systems around the world, and specifically in the United States, have long been awaiting for genuine reform efforts. Technology is often perceived as a panacea, if not as a crucial instrument in any educational reform effort. In a conversation with one of his students, Doctor Johnson discusses how the underlying assumptions embedded in our current schooling practices need to be seriously reviewed before any technology strategy is considered. New understandings, as opposed to mere information, is what schools need to reach in order to transform themselves. Finally, Dr. Johnson provides two brief examples, one in the United States and another in México, were hermeneutical approaches have been used for educational reform endeavors.

  2. Mitochondrial biogenesis: pharmacological approaches.

    Science.gov (United States)

    Valero, Teresa

    2014-01-01

    Organelle biogenesis is concomitant to organelle inheritance during cell division. It is necessary that organelles double their size and divide to give rise to two identical daughter cells. Mitochondrial biogenesis occurs by growth and division of pre-existing organelles and is temporally coordinated with cell cycle events [1]. However, mitochondrial biogenesis is not only produced in association with cell division. It can be produced in response to an oxidative stimulus, to an increase in the energy requirements of the cells, to exercise training, to electrical stimulation, to hormones, during development, in certain mitochondrial diseases, etc. [2]. Mitochondrial biogenesis is therefore defined as the process via which cells increase their individual mitochondrial mass [3]. Recent discoveries have raised attention to mitochondrial biogenesis as a potential target to treat diseases which up to date do not have an efficient cure. Mitochondria, as the major ROS producer and the major antioxidant producer exert a crucial role within the cell mediating processes such as apoptosis, detoxification, Ca2+ buffering, etc. This pivotal role makes mitochondria a potential target to treat a great variety of diseases. Mitochondrial biogenesis can be pharmacologically manipulated. This issue tries to cover a number of approaches to treat several diseases through triggering mitochondrial biogenesis. It contains recent discoveries in this novel field, focusing on advanced mitochondrial therapies to chronic and degenerative diseases, mitochondrial diseases, lifespan extension, mitohormesis, intracellular signaling, new pharmacological targets and natural therapies. It contributes to the field by covering and gathering the scarcely reported pharmacological approaches in the novel and promising field of mitochondrial biogenesis. There are several diseases that have a mitochondrial origin such as chronic progressive external ophthalmoplegia (CPEO) and the Kearns- Sayre syndrome (KSS

  3. Increasing immunization coverage.

    Science.gov (United States)

    Hammer, Lawrence D; Curry, Edward S; Harlor, Allen D; Laughlin, James J; Leeds, Andrea J; Lessin, Herschel R; Rodgers, Chadwick T; Granado-Villar, Deise C; Brown, Jeffrey M; Cotton, William H; Gaines, Beverly Marie Madry; Gambon, Thresia B; Gitterman, Benjamin A; Gorski, Peter A; Kraft, Colleen A; Marino, Ronald Vincent; Paz-Soldan, Gonzalo J; Zind, Barbara

    2010-06-01

    In 1977, the American Academy of Pediatrics issued a statement calling for universal immunization of all children for whom vaccines are not contraindicated. In 1995, the policy statement "Implementation of the Immunization Policy" was published by the American Academy of Pediatrics, followed in 2003 with publication of the first version of this statement, "Increasing Immunization Coverage." Since 2003, there have continued to be improvements in immunization coverage, with progress toward meeting the goals set forth in Healthy People 2010. Data from the 2007 National Immunization Survey showed that 90% of children 19 to 35 months of age have received recommended doses of each of the following vaccines: inactivated poliovirus (IPV), measles-mumps-rubella (MMR), varicella-zoster virus (VZB), hepatitis B virus (HBV), and Haemophilus influenzae type b (Hib). For diphtheria and tetanus and acellular pertussis (DTaP) vaccine, 84.5% have received the recommended 4 doses by 35 months of age. Nevertheless, the Healthy People 2010 goal of at least 80% coverage for the full series (at least 4 doses of DTaP, 3 doses of IPV, 1 dose of MMR, 3 doses of Hib, 3 doses of HBV, and 1 dose of varicella-zoster virus vaccine) has not yet been met, and immunization coverage of adolescents continues to lag behind the goals set forth in Healthy People 2010. Despite these encouraging data, a vast number of new challenges that threaten continued success toward the goal of universal immunization coverage have emerged. These challenges include an increase in new vaccines and new vaccine combinations as well as a significant number of vaccines currently under development; a dramatic increase in the acquisition cost of vaccines, coupled with a lack of adequate payment to practitioners to buy and administer vaccines; unanticipated manufacturing and delivery problems that have caused significant shortages of various vaccine products; and the rise of a public antivaccination movement that uses the

  4. Single nucleotide resolution RNA-seq uncovers new regulatory mechanisms in the opportunistic pathogen [i]Streptococcus agalactiae[/i

    OpenAIRE

    Sauvage, Elisabeth; Sismeiro, Odile; Villain, Adrien; Da Cunha, Violette; Caliot, Marie-Elise; Dillies, Marie-Agnès; Trieu-Cuot, Patrick; Bouloc, Philippe; Lartigue, Marie-Frédérique; Glaser, Philippe

    2015-01-01

    Background Streptococcus agalactiae, or Group B Streptococcus, is a leading cause of neonatal infections and an increasing cause of infections in adults with underlying diseases. In an effort to reconstruct the transcriptional networks involved in S. agalactiae physiology and pathogenesis, we performed an extensive and robust characterization of its transcriptome through a combination of differential RNA-sequencing in eight different growth conditions or genetic backgrounds and strand-specifi...

  5. How can animal studies help to uncover the roles of genes implicated in human speech and language disorders?

    OpenAIRE

    Fisher, S

    2006-01-01

    The mysterious human propensity for acquiring speech and language has fascinated scientists for decades. A substantial body of evidence suggests that this capacity is rooted in aspects of neurodevelopment that are specified at the genomic level. Researchers have begun to identify genetic factors that increase susceptibility to developmental disorders of speech and language, thereby offering the first molecular entry points into neuronal mechanisms underlying human vocal communication. The ide...

  6. Upregulation of Glycans Containing 3’ Fucose in a Subset of Pancreatic Cancers Uncovered Using Fusion-Tagged Lectins

    OpenAIRE

    Singh, Sudhir; Pal, Kuntal; Yadav, Jessica; Tang, Huiyuan; Partyka, Katie; Kletter, Doron; Hsueh, Peter; Ensink, Elliot; Birendra, KC; Hostetter, Galen; Xu, H. Eric; Bern, Marshall; Smith, David F.; Mehta, Anand S.; Brand, Randall

    2015-01-01

    The fucose post-translational modification is frequently increased in pancreatic cancer, thus forming the basis for promising biomarkers, but a subset of pancreatic cancer patients does not elevate the known fucose-containing biomarkers. We hypothesized that such patients elevate glycan motifs with fucose in linkages and contexts different from the known fucose-containing biomarkers. We used a database of glycan array data to identify the lectins CCL2 to detect glycan motifs with fucose in a ...

  7. Uncovering Black/African American and Latina/o students' motivation to learn science: Affordances to science identity development

    Science.gov (United States)

    Mahfood, Denise Marcia

    The following dissertation reports on a qualitative exploration that serves two main goals: (1) to qualitatively define and highlight science motivation development of Black/African American and Latina/o students as they learn science in middle school, high school, and in college and (2) to reveal through personal narratives how successful entry and persistence in science by this particular group is linked to the development of their science identities. The targeted population for this study is undergraduate students of color in science fields at a college or university. The theoretical frameworks for this study are constructivist theory, motivation theory, critical theory, and identity theories. The methodological approach is narrative which includes students' science learning experiences throughout the course of their academic lives. I use The Science Motivation Questionnaire II to obtain baseline data to quantitatively assess for motivation to learn science. Data from semi-structured interviews from selected participants were collected, coded, and configured into a story, and emergent themes reveal the important role of science learning in both informal and formal settings, but especially in informal settings that contribute to better understandings of science and the development of science identities for these undergraduate students of color. The findings have implications for science teaching in schools and teacher professional development in science learning.

  8. In site bioimaging of hydrogen sulfide uncovers its pivotal role in regulating nitric oxide-induced lateral root formation.

    Directory of Open Access Journals (Sweden)

    Yan-Jun Li

    Full Text Available Hydrogen sulfide (H2S is an important gasotransmitter in mammals. Despite physiological changes induced by exogenous H2S donor NaHS to plants, whether and how H2S works as a true cellular signal in plants need to be examined. A self-developed specific fluorescent probe (WSP-1 was applied to track endogenous H2S in tomato (Solanum lycopersicum roots in site. Bioimaging combined with pharmacological and biochemical approaches were used to investigate the cross-talk among H2S, nitric oxide (NO, and Ca(2+ in regulating lateral root formation. Endogenous H2S accumulation was clearly associated with primordium initiation and lateral root emergence. NO donor SNP stimulated the generation of endogenous H2S and the expression of the gene coding for the enzyme responsible for endogenous H2S synthesis. Scavenging H2S or inhibiting H2S synthesis partially blocked SNP-induced lateral root formation and the expression of lateral root-related genes. The stimulatory effect of SNP on Ca(2+ accumulation and CaM1 (calmodulin 1 expression could be abolished by inhibiting H2S synthesis. Ca(2+ chelator or Ca(2+ channel blocker attenuated NaHS-induced lateral root formation. Our study confirmed the role of H2S as a cellular signal in plants being a mediator between NO and Ca(2+ in regulating lateral root formation.

  9. Genetic cell targeting uncovers specific neuronal types and distinct subregions in the bed nucleus of the stria terminalis.

    Science.gov (United States)

    Nguyen, Amanda Q; Dela Cruz, Julie A D; Sun, Yanjun; Holmes, Todd C; Xu, Xiangmin

    2016-08-15

    The bed nucleus of the stria terminalis (BNST) plays an important role in fear, stress, and anxiety. It contains a collection of subnuclei delineated by gross cytoarchitecture features; however, there has yet to be a systematic examination of specific BNST neuronal types and their associated neurochemical makeup. The present study focuses on improved characterization of the anterior BNST based on differing molecular and chemical expression aided by mouse genetics. Specific Cre driver lines crossed with a fluorescent reporter line were used for genetic cell targeting and immunochemical staining. Using this new approach, we were able to robustly identify specific excitatory and inhibitory cell types in the BNST. The presence and distribution of excitatory neurons were firmly established; glutamatergic neurons in the anterior BNST accounted for about 14% and 31% of dorsal and ventral BNST cells, respectively. GABAergic neurons expressing different isoforms of glutamic acid decarboxylase were found to have differential subregional distributions. Almost no parvalbumin-expressing cells were found in the BNST, while somatostatin-expressing cells and calretinin-expressing cells account for modest proportions of BNST cells. In addition, vasoactive intestinal peptide-expressing axonal plexuses were prominent in the oval and juxtacapsular subregions. In addition, we discovered that corticotropin-releasing hormone-expressing cells contain GABAergic and glutamatergic subpopulations. Together, this study reveals new information on excitatory and inhibitory neurons in the BNST, which will facilitate genetic dissection and functional studies of BNST subregions. J. Comp. Neurol. 524:2379-2399, 2016. © 2016 Wiley Periodicals, Inc. PMID:26718312

  10. Cyclist–motorist crash patterns in Denmark: A latent class clustering approach

    DEFF Research Database (Denmark)

    Kaplan, Sigal; Prato, Carlo Giacomo

    2013-01-01

    Objective: The current study aimed at uncovering patterns of cyclist–motorist crashes in Denmark and investigating their prevalence and severity. The importance of implementing clustering techniques for providing a holistic overview of vulnerable road users’ crash patterns derives from the need to...... prioritize safety issues and to devise efficient preventive measures. Method: The current study focused on cyclist–motorist crashes that occurred in Denmark during the period between 2007 and 2011. To uncover crash patterns, the current analysis applied latent class clustering, an unsupervised probabilistic...... clustering approach that relies on the statistical concept of likelihood and allows partial overlap across clusters. Results: The analysis yielded 13 distinguishable cyclist–motorist latent classes. Specific crash patterns for urban and rural areas were revealed. Prevalent features that allowed...

  11. Transcriptional profiling of C. elegans DAF-19 uncovers a ciliary base-associated protein and a CDK/CCRK/LF2p-related kinase required for intraflagellar transport.

    Science.gov (United States)

    Phirke, Prasad; Efimenko, Evgeni; Mohan, Swetha; Burghoorn, Jan; Crona, Filip; Bakhoum, Mathieu W; Trieb, Maria; Schuske, Kim; Jorgensen, Erik M; Piasecki, Brian P; Leroux, Michel R; Swoboda, Peter

    2011-09-01

    Cilia are ubiquitous cell surface projections that mediate various sensory- and motility-based processes and are implicated in a growing number of multi-organ genetic disorders termed ciliopathies. To identify new components required for cilium biogenesis and function, we sought to further define and validate the transcriptional targets of DAF-19, the ciliogenic C. elegans RFX transcription factor. Transcriptional profiling of daf-19 mutants (which do not form cilia) and wild-type animals was performed using embryos staged to when the cell types developing cilia in the worm, the ciliated sensory neurons (CSNs), still differentiate. Comparisons between the two populations revealed 881 differentially regulated genes with greater than a 1.5-fold increase or decrease in expression. A subset of these was confirmed by quantitative RT-PCR. Transgenic worms expressing transcriptional GFP fusions revealed CSN-specific expression patterns for 11 of 14 candidate genes. We show that two uncharacterized candidate genes, termed dyf-17 and dyf-18 because their corresponding mutants display dye-filling (Dyf) defects, are important for ciliogenesis. DYF-17 localizes at the base of cilia and is specifically required for building the distal segment of sensory cilia. DYF-18 is an evolutionarily conserved CDK7/CCRK/LF2p-related serine/threonine kinase that is necessary for the proper function of intraflagellar transport, a process critical for cilium biogenesis. Together, our microarray study identifies targets of the evolutionarily conserved RFX transcription factor, DAF-19, providing a rich dataset from which to uncover-in addition to DYF-17 and DYF-18-cellular components important for cilium formation and function. PMID:21740898

  12. Direct Estimate of the Spontaneous Mutation Rate Uncovers the Effects of Drift and Recombination in the Chlamydomonas reinhardtii Plastid Genome.

    Science.gov (United States)

    Ness, Rob W; Kraemer, Susanne A; Colegrave, Nick; Keightley, Peter D

    2016-03-01

    Plastids perform crucial cellular functions, including photosynthesis, across a wide variety of eukaryotes. Since endosymbiosis, plastids have maintained independent genomes that now display a wide diversity of gene content, genome structure, gene regulation mechanisms, and transmission modes. The evolution of plastid genomes depends on an input of de novo mutation, but our knowledge of mutation in the plastid is limited to indirect inference from patterns of DNA divergence between species. Here, we use a mutation accumulation experiment, where selection acting on mutations is rendered ineffective, combined with whole-plastid genome sequencing to directly characterize de novo mutation in Chlamydomonas reinhardtii. We show that the mutation rates of the plastid and nuclear genomes are similar, but that the base spectra of mutations differ significantly. We integrate our measure of the mutation rate with a population genomic data set of 20 individuals, and show that the plastid genome is subject to substantially stronger genetic drift than the nuclear genome. We also show that high levels of linkage disequilibrium in the plastid genome are not due to restricted recombination, but are instead a consequence of increased genetic drift. One likely explanation for increased drift in the plastid genome is that there are stronger effects of genetic hitchhiking. The presence of recombination in the plastid is consistent with laboratory studies in C. reinhardtii and demonstrates that although the plastid genome is thought to be uniparentally inherited, it recombines in nature at a rate similar to the nuclear genome. PMID:26615203

  13. A realistic bi-hemispheric model of the cerebellum uncovers the purpose of the abundant granule cells during motor control.

    Science.gov (United States)

    Pinzon-Morales, Ruben-Dario; Hirata, Yutaka

    2015-01-01

    The cerebellar granule cells (GCs) have been proposed to perform lossless, adaptive spatio-temporal coding of incoming sensory/motor information required by downstream cerebellar circuits to support motor learning, motor coordination, and cognition. Here we use a physio-anatomically inspired bi-hemispheric cerebellar neuronal network (biCNN) to selectively enable/disable the output of GCs and evaluate the behavioral and neural consequences during three different control scenarios. The control scenarios are a simple direct current motor (1 degree of freedom: DOF), an unstable two-wheel balancing robot (2 DOFs), and a simulation model of a quadcopter (6 DOFs). Results showed that adequate control was maintained with a relatively small number of GCs (< 200) in all the control scenarios. However, the minimum number of GCs required to successfully govern each control plant increased with their complexity (i.e., DOFs). It was also shown that increasing the number of GCs resulted in higher robustness against changes in the initialization parameters of the biCNN model (i.e., synaptic connections and synaptic weights). Therefore, we suggest that the abundant GCs in the cerebellar cortex provide the computational power during the large repertoire of motor activities and motor plants the cerebellum is involved with, and bring robustness against changes in the cerebellar microcircuit (e.g., neuronal connections). PMID:25983678

  14. A realistic bi-hemispheric model of the cerebellum uncovers the purpose of the abundant granule cells during motor control

    Directory of Open Access Journals (Sweden)

    Ruben Dario Pinzon Morales

    2015-05-01

    Full Text Available The cerebellar granule cells (GCs have been proposed to perform lossless, adaptive spatio-temporal coding of incoming sensory/motor information required by downstream cerebellar circuits to \\textcolor{red}{support} motor learning, motor coordination, and cognition. Here we use a physio-anatomically inspired bi-hemispheric cerebellar neuronal network (biCNN to selectively enable/disable the output of GCs and evaluate the behavioral and neural consequences during three different control scenarios. The control scenarios are a simple direct current motor (1 degree of freedom: DOF, an unstable two-wheel balancing robot (2 DOFs, and a simulation model of a quadcopter (6 DOFs. Results showed that adequate control was maintained with a relatively small number of GCs ($<$ 200 in all the control scenarios. However, the minimum number of GCs required to successfully govern each control plant increased with their complexity (i.e., DOFs. It was also shown that increasing the number of GCs resulted in higher robustness against changes in the initialization parameters of the biCNN model (i.e., synaptic connections and synaptic weights. Therefore, we suggest that the abundant GCs in the cerebellar cortex provide the computational power during the large repertoire of motor activities and motor plants the cerebellum is involved with, and bring robustness against changes in the cerebellar microcircuit (e.g., neuronal connections.

  15. Uncovering Arabidopsis membrane protein interactome enriched in transporters using mating-based split ubiquitin assays and classification models

    Directory of Open Access Journals (Sweden)

    Jin eChen

    2012-06-01

    Full Text Available High-throughput data are a double-edged sword; for the benefit of large amount of data, there is an associated cost of noise. To increase reliability and scalability of high-throughput protein interaction data generation, we tested the efficacy of classification to enrich potential protein-protein interactions (pPPIs. We applied this method to identify interactions among Arabidopsis membrane proteins enriched in transporters. We validated our method with multiple retests. Classification improved the quality of the ensuing interaction network and was effective in reducing the search space and increasing true positive rate. The final network of 541 interactions among 239 proteins (of which 179 are transporters is the first protein interaction network enriched in membrane transporters reported for any organism. This network has similar topological attributes to other published protein interaction networks. It also extends and fills gaps in currently available biological networks in plants and allows building a number of hypotheses about processes and mechanisms involving signal-transduction and transport systems.

  16. Combining comparative proteomics and molecular genetics uncovers regulators of synaptic and axonal stability and degeneration in vivo.

    Directory of Open Access Journals (Sweden)

    Thomas M Wishart

    Full Text Available Degeneration of synaptic and axonal compartments of neurons is an early event contributing to the pathogenesis of many neurodegenerative diseases, but the underlying molecular mechanisms remain unclear. Here, we demonstrate the effectiveness of a novel "top-down" approach for identifying proteins and functional pathways regulating neurodegeneration in distal compartments of neurons. A series of comparative quantitative proteomic screens on synapse-enriched fractions isolated from the mouse brain following injury identified dynamic perturbations occurring within the proteome during both initiation and onset phases of degeneration. In silico analyses highlighted significant clustering of proteins contributing to functional pathways regulating synaptic transmission and neurite development. Molecular markers of degeneration were conserved in injury and disease, with comparable responses observed in synapse-enriched fractions isolated from mouse models of Huntington's disease (HD and spinocerebellar ataxia type 5. An initial screen targeting thirteen degeneration-associated proteins using mutant Drosophila lines revealed six potential regulators of synaptic and axonal degeneration in vivo. Mutations in CALB2, ROCK2, DNAJC5/CSP, and HIBCH partially delayed injury-induced neurodegeneration. Conversely, mutations in DNAJC6 and ALDHA1 led to spontaneous degeneration of distal axons and synapses. A more detailed genetic analysis of DNAJC5/CSP mutants confirmed that loss of DNAJC5/CSP was neuroprotective, robustly delaying degeneration in axonal and synaptic compartments. Our study has identified conserved molecular responses occurring within synapse-enriched fractions of the mouse brain during the early stages of neurodegeneration, focused on functional networks modulating synaptic transmission and incorporating molecular chaperones, cytoskeletal modifiers, and calcium-binding proteins. We propose that the proteins and functional pathways identified in

  17. Target-Driven Positive Selection at Hot Spots of Scorpion Toxins Uncovers Their Potential in Design of Insecticides.

    Science.gov (United States)

    Zhu, Limei; Peigneur, Steve; Gao, Bin; Zhang, Shangfei; Tytgat, Jan; Zhu, Shunyi

    2016-08-01

    Positive selection sites (PSSs), a class of amino acid sites with an excess of nonsynonymous to synonymous substitutions, are indicators of adaptive molecular evolution and have been detected in many protein families involved in a diversity of biological processes by statistical approaches. However, few studies are conducted to evaluate their functional significance and the driving force behind the evolution (i.e., agent of selection). Scorpion α-toxins are a class of multigene family of peptide neurotoxins affecting voltage-gated Na(+ )(Nav) channels, whose members exhibit differential potency and preference for insect and mammalian Nav channels. In this study, we undertook a systematical molecular dissection of nearly all the PSSs newly characterized in the Mesobuthus α-toxin family and a two-residue insertion ((19)AlaPhe(20)) located within a positively selected loop via mutational analysis of α-like MeuNaTxα-5, one member affecting both insect and mammalian Nav channels. This allows to identify hot-spot residues on its functional face involved in interaction with the receptor site of Nav channels, which comprises two PSSs (Ile(40) and Leu(41)) and the small insertion, both located on two spatially separated functional loops. Mutations at these hot-spots resulted in a remarkably decreased anti-mammalian activity in MeuNaTxα-5 with partially impaired or enhanced insecticide activity, suggesting the potential of PSSs in designing promising candidate insecticides from scorpion α-like toxins. Based on an experiment-guided toxin-channel complex model and high evolutionary variability in the receptor site of predators and prey of scorpions, we provide new evidence for target-driven adaptive evolution of scorpion toxins to deal with their targets' diversity. PMID:27189560

  18. Uncovering SUMOylation Dynamics during Cell-Cycle Progression Reveals FoxM1 as a Key Mitotic SUMO Target Protein

    DEFF Research Database (Denmark)

    Schimmel, Joost; Eifler, Karolin; Sigurdsson, Jón Otti; Cuijpers, Sabine A G; Hendriks, Ivo A; Verlaan-de Vries, Matty; Kelstrup, Christian D; Francavilla, Chiara; Medema, René H; Olsen, Jesper Velgaard; Vertegaal, Alfred C O

    2014-01-01

    Loss of small ubiquitin-like modification (SUMOylation) in mice causes genomic instability due to the missegregation of chromosomes. Currently, little is known about the identity of relevant SUMO target proteins that are involved in this process and about global SUMOylation dynamics during cell-cycle...... progression. We performed a large-scale quantitative proteomics screen to address this and identified 593 proteins to be SUMO-2 modified, including the Forkhead box transcription factor M1 (FoxM1), a key regulator of cell-cycle progression and chromosome segregation. SUMOylation of FoxM1 peaks during G2 and M...... relieving FoxM1 autorepression. Cells deficient for FoxM1 SUMOylation showed increased levels of polyploidy. Our findings contribute to understanding the role of SUMOylation during cell-cycle progression....

  19. A joint analysis of transcriptomic and metabolomic data uncovers enhanced enzyme-metabolite coupling in breast cancer

    Science.gov (United States)

    Auslander, Noam; Yizhak, Keren; Weinstock, Adam; Budhu, Anuradha; Tang, Wei; Wang, Xin Wei; Ambs, Stefan; Ruppin, Eytan

    2016-07-01

    Disrupted regulation of cellular processes is considered one of the hallmarks of cancer. We analyze metabolomic and transcriptomic profiles jointly collected from breast cancer and hepatocellular carcinoma patients to explore the associations between the expression of metabolic enzymes and the levels of the metabolites participating in the reactions they catalyze. Surprisingly, both breast cancer and hepatocellular tumors exhibit an increase in their gene-metabolites associations compared to noncancerous adjacent tissues. Following, we build predictors of metabolite levels from the expression of the enzyme genes catalyzing them. Applying these predictors to a large cohort of breast cancer samples we find that depleted levels of key cancer-related metabolites including glucose, glycine, serine and acetate are significantly associated with improved patient survival. Thus, we show that the levels of a wide range of metabolites in breast cancer can be successfully predicted from the transcriptome, going beyond the limited set of those measured.

  20. Abnormal fault-recovery characteristics of the fault-tolerant multiprocessor uncovered using a new fault-injection methodology

    Science.gov (United States)

    Padilla, Peter A.

    1991-03-01

    An investigation was made in AIRLAB of the fault handling performance of the Fault Tolerant MultiProcessor (FTMP). Fault handling errors detected during fault injection experiments were characterized. In these fault injection experiments, the FTMP disabled a working unit instead of the faulted unit once in every 500 faults, on the average. System design weaknesses allow active faults to exercise a part of the fault management software that handles Byzantine or lying faults. Byzantine faults behave such that the faulted unit points to a working unit as the source of errors. The design's problems involve: (1) the design and interface between the simplex error detection hardware and the error processing software, (2) the functional capabilities of the FTMP system bus, and (3) the communication requirements of a multiprocessor architecture. These weak areas in the FTMP's design increase the probability that, for any hardware fault, a good line replacement unit (LRU) is mistakenly disabled by the fault management software.