WorldWideScience

Sample records for identifying distinct sets

  1. Salmonella Persistence in Tomatoes Requires a Distinct Set of Metabolic Functions Identified by Transposon Insertion Sequencing

    Science.gov (United States)

    Desai, Prerak; Porwollik, Steffen; Canals, Rocio; Perez, Daniel R.; Chu, Weiping; McClelland, Michael; Teplitski, Max

    2016-01-01

    ABSTRACT Human enteric pathogens, such as Salmonella spp. and verotoxigenic Escherichia coli, are increasingly recognized as causes of gastroenteritis outbreaks associated with the consumption of fruits and vegetables. Persistence in plants represents an important part of the life cycle of these pathogens. The identification of the full complement of Salmonella genes involved in the colonization of the model plant (tomato) was carried out using transposon insertion sequencing analysis. With this approach, 230,000 transposon insertions were screened in tomato pericarps to identify loci with reduction in fitness, followed by validation of the screen results using competition assays of the isogenic mutants against the wild type. A comparison with studies in animals revealed a distinct plant-associated set of genes, which only partially overlaps with the genes required to elicit disease in animals. De novo biosynthesis of amino acids was critical to persistence within tomatoes, while amino acid scavenging was prevalent in animal infections. Fitness reduction of the Salmonella amino acid synthesis mutants was generally more severe in the tomato rin mutant, which hyperaccumulates certain amino acids, suggesting that these nutrients remain unavailable to Salmonella spp. within plants. Salmonella lipopolysaccharide (LPS) was required for persistence in both animals and plants, exemplifying some shared pathogenesis-related mechanisms in animal and plant hosts. Similarly to phytopathogens, Salmonella spp. required biosynthesis of amino acids, LPS, and nucleotides to colonize tomatoes. Overall, however, it appears that while Salmonella shares some strategies with phytopathogens and taps into its animal virulence-related functions, colonization of tomatoes represents a distinct strategy, highlighting this pathogen's flexible metabolism. IMPORTANCE Outbreaks of gastroenteritis caused by human pathogens have been increasingly associated with foods of plant origin, with tomatoes

  2. An Objective Approach to Identify Spectral Distinctiveness for Hearing Impairment

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    Yeou-Jiunn Chen

    2013-01-01

    Full Text Available To facilitate the process of developing speech perception, speech-language pathologists have to teach a subject with hearing loss the differences between two syllables by manually enhancing acoustic cues of speech. However, this process is time consuming and difficult. Thus, this study proposes an objective approach to automatically identify the regions of spectral distinctiveness between two syllables, which is used for speech-perception training. To accurately represent the characteristics of speech, mel-frequency cepstrum coefficients are selected as analytical parameters. The mismatch between two syllables in time domain is handled by dynamic time warping. Further, a filter bank is adopted to estimate the components in different frequency bands, which are also represented as mel-frequency cepstrum coefficients. The spectral distinctiveness in different frequency bands is then easily estimated by using Euclidean metrics. Finally, a morphological gradient operator is applied to automatically identify the regions of spectral distinctiveness. To evaluate the proposed approach, the identified regions are manipulated and then the manipulated syllables are measured by a close-set based speech-perception test. The experimental results demonstrated that the identified regions of spectral distinctiveness are very useful in speech perception, which indeed can help speech-language pathologists in speech-perception training.

  3. Constructing Taxonomies to Identify Distinctive Forms of Primary Healthcare Organizations

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    Borgès Da Silva, Roxane; Pineault, Raynald; Hamel, Marjolaine; Levesque, Jean-Frédéric; Roberge, Danièle; Lamarche, Paul

    2013-01-01

    Background. Primary healthcare (PHC) renewal gives rise to important challenges for policy makers, managers, and researchers in most countries. Evaluating new emerging forms of organizations is therefore of prime importance in assessing the impact of these policies. This paper presents a set of methods related to the configurational approach and an organizational taxonomy derived from our analysis. Methods. In 2005, we carried out a study on PHC in two health and social services regions of Quebec that included urban, suburban, and rural areas. An organizational survey was conducted in 473 PHC practices. We used multidimensional nonparametric statistical methods, namely, multiple correspondence and principal component analyses, and an ascending hierarchical classification method to construct a taxonomy of organizations. Results. PHC organizations were classified into five distinct models: four professional and one community. Study findings indicate that the professional integrated coordination and the community model have great potential for organizational development since they are closest to the ideal type promoted by current reforms. Conclusion. Results showed that the configurational approach is useful to assess complex phenomena such as the organization of PHC. The analysis highlights the most promising organizational models. Our study enhances our understanding of organizational change in health services organizations. PMID:24959575

  4. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles

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    Farshad Farshidfar

    2017-03-01

    Full Text Available Cholangiocarcinoma (CCA is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance.

  5. Identifying Heterogeneities in Subsurface Environment using the Level Set Method

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    Lei, Hongzhuan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Lu, Zhiming [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Vesselinov, Velimir Valentinov [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-08-25

    These are slides from a presentation on identifying heterogeneities in subsurface environment using the level set method. The slides start with the motivation, then explain Level Set Method (LSM), the algorithms, some examples are given, and finally future work is explained.

  6. Your Divided Attention, Please! The Maintenance of Multiple Attentional Control Sets over Distinct Regions in Space

    Science.gov (United States)

    Adamo, Maha; Pun, Carson; Pratt, Jay; Ferber, Susanne

    2008-01-01

    When non-informative peripheral cues precede a target defined by a specific feature, cues that share the critical feature will capture attention while cues that do not will be effectively ignored. We tested whether different attentional control sets can be simultaneously maintained over distinct regions of space. Participants were instructed to…

  7. IMP-27, a Unique Metallo-β-Lactamase Identified in Geographically Distinct Isolates of Proteus mirabilis.

    Science.gov (United States)

    Dixon, Nyssa; Fowler, Randal C; Yoshizumi, A; Horiyama, Tsukasa; Ishii, Y; Harrison, Lucas; Geyer, Chelsie N; Moland, Ellen Smith; Thomson, Kenneth; Hanson, Nancy D

    2016-10-01

    A novel metallo-β-lactamase gene, blaIMP-27, was identified in unrelated Proteus mirabilis isolates from two geographically distinct locations in the United States. Both isolates harbor blaIMP-27 as part of the first gene cassette in a class 2 integron. Antimicrobial susceptibility testing indicated susceptibility to aztreonam, piperacillin-tazobactam, and ceftazidime but resistance to ertapenem. However, hydrolysis assays indicated that ceftazidime was a substrate for IMP-27. Copyright © 2016 Dixon et al.

  8. Identifying a set of influential spreaders in complex networks

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    Zhang, Jian-Xiong; Chen, Duan-Bing; Dong, Qiang; Zhao, Zhi-Dan

    2016-06-01

    Identifying a set of influential spreaders in complex networks plays a crucial role in effective information spreading. A simple strategy is to choose top-r ranked nodes as spreaders according to influence ranking method such as PageRank, ClusterRank and k-shell decomposition. Besides, some heuristic methods such as hill-climbing, SPIN, degree discount and independent set based are also proposed. However, these approaches suffer from a possibility that some spreaders are so close together that they overlap sphere of influence or time consuming. In this report, we present a simply yet effectively iterative method named VoteRank to identify a set of decentralized spreaders with the best spreading ability. In this approach, all nodes vote in a spreader in each turn, and the voting ability of neighbors of elected spreader will be decreased in subsequent turn. Experimental results on four real networks show that under Susceptible-Infected-Recovered (SIR) and Susceptible-Infected (SI) models, VoteRank outperforms the traditional benchmark methods on both spreading rate and final affected scale. What’s more, VoteRank has superior computational efficiency.

  9. CAsubtype: An R Package to Identify Gene Sets Predictive of Cancer Subtypes and Clinical Outcomes.

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    Kong, Hualei; Tong, Pan; Zhao, Xiaodong; Sun, Jielin; Li, Hua

    2018-03-01

    In the past decade, molecular classification of cancer has gained high popularity owing to its high predictive power on clinical outcomes as compared with traditional methods commonly used in clinical practice. In particular, using gene expression profiles, recent studies have successfully identified a number of gene sets for the delineation of cancer subtypes that are associated with distinct prognosis. However, identification of such gene sets remains a laborious task due to the lack of tools with flexibility, integration and ease of use. To reduce the burden, we have developed an R package, CAsubtype, to efficiently identify gene sets predictive of cancer subtypes and clinical outcomes. By integrating more than 13,000 annotated gene sets, CAsubtype provides a comprehensive repertoire of candidates for new cancer subtype identification. For easy data access, CAsubtype further includes the gene expression and clinical data of more than 2000 cancer patients from TCGA. CAsubtype first employs principal component analysis to identify gene sets (from user-provided or package-integrated ones) with robust principal components representing significantly large variation between cancer samples. Based on these principal components, CAsubtype visualizes the sample distribution in low-dimensional space for better understanding of the distinction between samples and classifies samples into subgroups with prevalent clustering algorithms. Finally, CAsubtype performs survival analysis to compare the clinical outcomes between the identified subgroups, assessing their clinical value as potentially novel cancer subtypes. In conclusion, CAsubtype is a flexible and well-integrated tool in the R environment to identify gene sets for cancer subtype identification and clinical outcome prediction. Its simple R commands and comprehensive data sets enable efficient examination of the clinical value of any given gene set, thus facilitating hypothesis generating and testing in biological and

  10. Reliability for systems of degrading components with distinct component shock sets

    International Nuclear Information System (INIS)

    Song, Sanling; Coit, David W.; Feng, Qianmei

    2014-01-01

    This paper studies reliability for multi-component systems subject to dependent competing risks of degradation wear and random shocks, with distinct shock sets. In practice, many systems are exposed to distinct and different types of shocks that can be categorized according to their sizes, function, affected components, etc. Previous research primarily focuses on simple systems with independent failure processes, systems with independent component time-to-failure, or components that share the same shock set or type of shocks. In our new model, we classify random shocks into different sets based on their sizes or function. Shocks with specific sizes or function can selectively affect one or more components in the system but not necessarily all components. Additionally the shocks from the different shock sets can arrive at different rates and have different relative magnitudes. Preventive maintenance (PM) optimization is conducted for the system with different component shock sets. Decision variables for two different maintenance scheduling problems, the PM replacement time interval, and the PM inspection time interval, are determined by minimizing a defined system cost rate. Sensitivity analysis is performed to provide insight into the behavior of the proposed maintenance policies. These models can be applied directly or customized for many complex systems that experience dependent competing failure processes with different component shock sets. A MEMS (Micro-electro mechanical systems) oscillator is a typical system subject to dependent and competing failure processes, and it is used as a numerical example to illustrate our new reliability and maintenance models

  11. Genetic approach identifies distinct asthma pathways in overweight vs normal weight children.

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    Butsch Kovacic, M; Martin, L J; Biagini Myers, J M; He, H; Lindsey, M; Mersha, T B; Khurana Hershey, G K

    2015-08-01

    The pathogenesis of asthma in the context of excess body weight may be distinct from asthma that develops in normal weight children. The study's objective was to explore the biology of asthma in the context of obesity and normal weight status using genetic methodologies. Associations between asthma and SNPs in 49 genes were assessed, as well as, interactions between SNPs and overweight status in child participants of the Greater Cincinnati Pediatric Clinic Repository. Asthma was significantly associated with weight (OR = 1.38; P = 0.037). The number of genes and the magnitude of their associations with asthma were notably greater when considering overweight children alone vs normal weight and overweight children together. When considering weight, distinct sets of asthma-associated genes were observed, many times with opposing effects. We demonstrated that the underlying heterogeneity of asthma is likely due in part to distinct pathogenetic pathways that depend on preceding/comorbid overweight and/or allergy. It is therefore important to consider both obesity and asthma when conducting studies of asthma. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Distinct Host Tropism Protein Signatures to Identify Possible Zoonotic Influenza A Viruses.

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    Eng, Christine L P; Tong, Joo Chuan; Tan, Tin Wee

    2016-01-01

    Zoonotic influenza A viruses constantly pose a health threat to humans as novel strains occasionally emerge from the avian population to cause human infections. Many past epidemic as well as pandemic strains have originated from avian species. While most viruses are restricted to their primary hosts, zoonotic strains can sometimes arise from mutations or reassortment, leading them to acquire the capability to escape host species barrier and successfully infect a new host. Phylogenetic analyses and genetic markers are useful in tracing the origins of zoonotic infections, but there are still no effective means to identify high risk strains prior to an outbreak. Here we show that distinct host tropism protein signatures can be used to identify possible zoonotic strains in avian species which have the potential to cause human infections. We have discovered that influenza A viruses can now be classified into avian, human, or zoonotic strains based on their host tropism protein signatures. Analysis of all influenza A viruses with complete proteome using the host tropism prediction system, based on machine learning classifications of avian and human viral proteins has uncovered distinct signatures of zoonotic strains as mosaics of avian and human viral proteins. This is in contrast with typical avian or human strains where they show mostly avian or human viral proteins in their signatures respectively. Moreover, we have found that zoonotic strains from the same influenza outbreaks carry similar host tropism protein signatures characteristic of a common ancestry. Our results demonstrate that the distinct host tropism protein signature in zoonotic strains may prove useful in influenza surveillance to rapidly identify potential high risk strains circulating in avian species, which may grant us the foresight in anticipating an impending influenza outbreak.

  13. MetaPhinder-Identifying Bacteriophage Sequences in Metagenomic Data Sets

    DEFF Research Database (Denmark)

    Jurtz, Vanessa Isabell; Villarroel, Julia; Lund, Ole

    2016-01-01

    genome structure of many bacteriophages. The method is demonstrated to outperform both BLAST methods based on single hits and methods based on k-mer comparisons. MetaPhinder is available as a web service at the Center for Genomic Epidemiology https://cge.cbs.dtu.dk/services/MetaPhinder/, while the source...... and understand them. Here we present MetaPhinder, a method to identify assembled genomic fragments (i.e. contigs) of phage origin in metage-nomic data sets. The method is based on a comparison to a database of whole genome bacteriophage sequences, integrating hits to multiple genomes to accomodate for the mosaic...... code can be downloaded from https://bitbucket.org/genomicepidemiology/metaphinder or https://github.com/vanessajurtz/MetaPhinder....

  14. Using instructional logs to identify quality in educational settings.

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    Rowan, Brian; Jacob, Robin; Correnti, Richard

    2009-01-01

    When attempting to identify educational settings that are most effective in improving student achievement, classroom process (that is, the way in which a teacher interacts with his or her students) is a key feature of interest. Unfortunately, high-quality assessment of the student-teacher interaction occurs all too infrequently, despite the critical role that understanding and measuring such processes can play in school improvement. This article discusses the strengths and weaknesses of two common approaches to studying these processes-direct classroom observation and annual surveys of teachers-and then describes the ways in which instructional logs can be used to overcome some of the limitations of these two approaches when gathering data on curriculum content and coverage. Classroom observations are expensive, require extensive training of raters to ensure consistency in the observations, and because of their expense generally cannot be conducted frequently enough to enable the researcher to generalize observational findings to the entire school year or illuminate the patterns of instructional change that occur across the school year. Annual surveys are less expensive but often suffer from self-report bias and the bias that occurs when teachers are asked to retrospectively report on their activities over the course of a single year. Instructional logs offer a valid, reliable, and relatively cost-effective alternative for collecting detailed information about classroom practice and can overcome some of the limitations of both observations and annual surveys.

  15. Multiple distinct subtypes of GABAergic neurons in mouse visual cortex identified by triple immunostaining

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    Yuri Gonchar

    2008-03-01

    Full Text Available The majority of cortical interneurons use GABA (gamma amino butyric acid as inhibitory neurotransmitter. GABAergic neurons are morphologically, connectionally, electrically and chemically heterogeneous. In rat cerebral cortex three distinct groups of GABAergic interneurons have been identifi ed by the expression of parvalbumin (PV, calretinin (CR and somatostatin (SOM. Recent studies in mouse cerebral cortex have revealed a different organization in which the CR and SOM populations are partially overlapping. Because CR and SOM neurons derive from different progenitors located in different embryonic structures, the coexpression of CR + SOM suggests that the chemical differentiation of interneurons is regulated postmitotically. Here, we have taken an important fi rst step towards understanding this process by triple immunostaining mouse visual cortex with a panel of antibodies, which has been used extensively for classifying developing interneurons. We have found at least 13 distinct groups of GABAergic neurons which include PV, CR, SOM, CCK (cholecystokinin, CR + SOM, CR + NPY (neuropeptide Y, CR + VIP (vasointestinal polypeptide, SOM + NPY, SOM + VIP, VIP + ChAT (choline acetyltransferase, CCK + NPY, CR + SOM + NPY and CR + SOM + VIP expressing cells. Triple immunostaining with PV, CR and SOM antibodies during postnatal development further showed that PV is never colocalized with CR and SOM. Importantly, expression of SOM and CR + SOM developed after the percentage of CR cells that do not express SOM has reached the mature level, suggesting that the chemical differentiation of SOM and CR + SOM neurons is a postnatal event, which may be controlled by transcriptional regulation.

  16. Transcriptome sequencing in pediatric acute lymphoblastic leukemia identifies fusion genes associated with distinct DNA methylation profiles

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    Yanara Marincevic-Zuniga

    2017-08-01

    Full Text Available Abstract Background Structural chromosomal rearrangements that lead to expressed fusion genes are a hallmark of acute lymphoblastic leukemia (ALL. In this study, we performed transcriptome sequencing of 134 primary ALL patient samples to comprehensively detect fusion transcripts. Methods We combined fusion gene detection with genome-wide DNA methylation analysis, gene expression profiling, and targeted sequencing to determine molecular signatures of emerging ALL subtypes. Results We identified 64 unique fusion events distributed among 80 individual patients, of which over 50% have not previously been reported in ALL. Although the majority of the fusion genes were found only in a single patient, we identified several recurrent fusion gene families defined by promiscuous fusion gene partners, such as ETV6, RUNX1, PAX5, and ZNF384, or recurrent fusion genes, such as DUX4-IGH. Our data show that patients harboring these fusion genes displayed characteristic genome-wide DNA methylation and gene expression signatures in addition to distinct patterns in single nucleotide variants and recurrent copy number alterations. Conclusion Our study delineates the fusion gene landscape in pediatric ALL, including both known and novel fusion genes, and highlights fusion gene families with shared molecular etiologies, which may provide additional information for prognosis and therapeutic options in the future.

  17. Comparative genomics identifies distinct lineages of S. Enteritidis from Queensland, Australia.

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    Graham, Rikki M A; Hiley, Lester; Rathnayake, Irani U; Jennison, Amy V

    2018-01-01

    Salmonella enterica is a major cause of gastroenteritis and foodborne illness in Australia where notification rates in the state of Queensland are the highest in the country. S. Enteritidis is among the five most common serotypes reported in Queensland and it is a priority for epidemiological surveillance due to concerns regarding its emergence in Australia. Using whole genome sequencing, we have analysed the genomic epidemiology of 217 S. Enteritidis isolates from Queensland, and observed that they fall into three distinct clades, which we have differentiated as Clades A, B and C. Phage types and MLST sequence types differed between the clades and comparative genomic analysis has shown that each has a unique profile of prophage and genomic islands. Several of the phage regions present in the S. Enteritidis reference strain P125109 were absent in Clades A and C, and these clades also had difference in the presence of pathogenicity islands, containing complete SPI-6 and SPI-19 regions, while P125109 does not. Antimicrobial resistance markers were found in 39 isolates, all but one of which belonged to Clade B. Phylogenetic analysis of the Queensland isolates in the context of 170 international strains showed that Queensland Clade B isolates group together with the previously identified global clade, while the other two clades are distinct and appear largely restricted to Australia. Locally sourced environmental isolates included in this analysis all belonged to Clades A and C, which is consistent with the theory that these clades are a source of locally acquired infection, while Clade B isolates are mostly travel related.

  18. A formal method for identifying distinct states of variability in time-varying sources: SGR A* as an example

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    Meyer, L.; Witzel, G.; Ghez, A. M. [Department of Physics and Astronomy, University of California, Los Angeles, CA 90095-1547 (United States); Longstaff, F. A. [UCLA Anderson School of Management, University of California, Los Angeles, CA 90095-1481 (United States)

    2014-08-10

    Continuously time variable sources are often characterized by their power spectral density and flux distribution. These quantities can undergo dramatic changes over time if the underlying physical processes change. However, some changes can be subtle and not distinguishable using standard statistical approaches. Here, we report a methodology that aims to identify distinct but similar states of time variability. We apply this method to the Galactic supermassive black hole, where 2.2 μm flux is observed from a source associated with Sgr A* and where two distinct states have recently been suggested. Our approach is taken from mathematical finance and works with conditional flux density distributions that depend on the previous flux value. The discrete, unobserved (hidden) state variable is modeled as a stochastic process and the transition probabilities are inferred from the flux density time series. Using the most comprehensive data set to date, in which all Keck and a majority of the publicly available Very Large Telescope data have been merged, we show that Sgr A* is sufficiently described by a single intrinsic state. However, the observed flux densities exhibit two states: noise dominated and source dominated. Our methodology reported here will prove extremely useful to assess the effects of the putative gas cloud G2 that is on its way toward the black hole and might create a new state of variability.

  19. Can the dissociative PTSD subtype be identified across two distinct trauma samples meeting caseness for PTSD?

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    Hansen, Maj; Műllerová, Jana; Elklit, Ask; Armour, Cherie

    2016-08-01

    For over a century, the occurrence of dissociative symptoms in connection to traumatic exposure has been acknowledged in the scientific literature. Recently, the importance of dissociation has also been recognized in the long-term traumatic response within the DSM-5 nomenclature. Several studies have confirmed the existence of the dissociative posttraumatic stress disorder (PTSD) subtype. However, there is a lack of studies investigating latent profiles of PTSD solely in victims with PTSD. This study investigates the possible presence of PTSD subtypes using latent class analysis (LCA) across two distinct trauma samples meeting caseness for DSM-5 PTSD based on self-reports (N = 787). Moreover, we assessed if a number of risk factors resulted in an increased probability of membership in a dissociative compared with a non-dissociative PTSD class. The results of LCA revealed a two-class solution with two highly symptomatic classes: a dissociative class and a non-dissociative class across both samples. Increased emotion-focused coping increased the probability of individuals being grouped into the dissociative class across both samples. Social support reduced the probability of individuals being grouped into the dissociative class but only in the victims of motor vehicle accidents (MVAs) suffering from whiplash. The results are discussed in light of their clinical implications and suggest that the dissociative subtype can be identified in victims of incest and victims of MVA suffering from whiplash meeting caseness for DSM-5 PTSD.

  20. Two distinct phenotypes of asthma in elite athletes identified by latent class analysis.

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    Couto, Mariana; Stang, Julie; Horta, Luís; Stensrud, Trine; Severo, Milton; Mowinckel, Petter; Silva, Diana; Delgado, Luís; Moreira, André; Carlsen, Kai-Håkon

    2015-01-01

    Clusters of asthma in athletes have been insufficiently studied. Therefore, the present study aimed to characterize asthma phenotypes in elite athletes using latent class analysis (LCA) and to evaluate its association with the type of sport practiced. In the present cross-sectional study, an analysis of athletes' records was carried out in databases of the Portuguese National Anti-Doping Committee and the Norwegian School of Sport Sciences. Athletes with asthma, diagnosed according to criteria given by the International Olympic Committee, were included for LCA. Sports practiced were categorized into water, winter and other sports. Of 324 files screened, 150 files belonged to asthmatic athletes (91 Portuguese; 59 Norwegian). LCA retrieved two clusters: "atopic asthma" defined by allergic sensitization, rhinitis and allergic co-morbidities and increased exhaled nitric oxide levels; and "sports asthma", defined by exercise-induced respiratory symptoms and airway hyperesponsiveness without allergic features. The risk of developing the phenotype "sports asthma" was significantly increased in athletes practicing water (OR = 2.87; 95% CI [1.82-4.51]) and winter (OR = 8.65; 95% CI [2.67-28.03]) sports, when compared with other athletes. Two asthma phenotypes were identified in elite athletes: "atopic asthma" and "sports asthma". The type of sport practiced was associated with different phenotypes: water and winter sport athletes had three- and ninefold increased risk of "sports asthma". Recognizing different phenotypes is clinically relevant as it would lead to distinct targeted treatments.

  1. Multiple gene analyses identify distinct “bois noir” phytoplasma genotypes in the Republic of Macedonia

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    Emilija KOSTADINOVSKA

    2015-01-01

    Full Text Available “Bois noir” (BN is a grapevine yellows disease, associated with phytoplasma strains related to ‘Candidatus Phytoplasma solani’, that causes severe losses to viticulture in the Euro-Mediterranean basin. Due to the complex ecological cycle of its etiological agent, BN epidemiology is only partially known, and no effective control strategies have been developed. Numerous studies have focused on molecular characterization of BN phytoplasma strains, to identify molecular markers useful to accurately describe their genetic diversity, geographic distribution and host range. In the present study, a multiple gene analysess were carried out on 16S rRNA, tuf, vmp1, and stamp genes to study the genetic variability among 18 BN phytoplasma strains detected in diverse regions of the Republic of Macedonia. Restriction fragment length polymorphism (RFLP assays showed the presence of one 16S rRNA (16SrXII-A, two tuf (tuf-type a, tuf-type b, five vmp1 (V2-TA, V3, V4, V14, V18, and three stamp (S1, S2, S3 gene patterns among the examined strains. Based on the collective RFLP patterns, seven genotypes (Mac1 to Mac7 were described as evidence for genetic heterogeneity, and highlighting their prevalence and distribution in the investigated regions. Phylogenetic analyses on vmp1 and stamp genes underlined the affiliation of Macedonian BN phytoplasma strains to clusters associated with distinct ecologies.

  2. Distinct forms of the β subunit of GTP-binding regulatory proteins identified by molecular cloning

    International Nuclear Information System (INIS)

    Fong, H.K.W.; Amatruda, T.T. III; Birren, B.W.; Simon, M.I.

    1987-01-01

    Two distinct β subunits of guanine nucleotide-binding regulatory proteins have been identified by cDNA cloning and are referred to as β 1 and β 1 subunits. The bovine transducin β subunit (β 1 ) has been cloned previously. The author now isolated and analyzed cDNA clones that encode the β 2 subunit from bovine adrenal, bovine brain, and a human myeloid leukemia cell line, HL-60. The 340-residue M/sub r/ 37,329 Β 2 protein is 90% identical with β 1 in predicted amino acid sequence, and it is also organized as a series of repetitive homologous segments. The major mRNA that encodes the bovine β 2 subunit is 1.7 kilobases in length. It is expressed at lower levels than β 1 subunit mRNA in all tissues examined. The β 1 and β 2 messages are expressed in cloned human cell lines. Hybridization of cDNA probes to bovine DNA showed that β 1 and β 2 are encoded by separate genes. The amino acid sequences for the bovine and human β 2 subunit are identical, as are the amino acid sequences for the bovine and human β 1 subunit. This evolutionary conservation suggests that the two β subunits have different roles in the signal transduction process

  3. Functionally distinct amygdala subregions identified using DTI and high-resolution fMRI

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    Balderston, Nicholas L.; Schultz, Douglas H.; Hopkins, Lauren

    2015-01-01

    Although the amygdala is often directly linked with fear and emotion, amygdala neurons are activated by a wide variety of emotional and non-emotional stimuli. Different subregions within the amygdala may be engaged preferentially by different aspects of emotional and non-emotional tasks. To test this hypothesis, we measured and compared the effects of novelty and fear on amygdala activity. We used high-resolution blood oxygenation level-dependent (BOLD) imaging and streamline tractography to subdivide the amygdala into three distinct functional subunits. We identified a laterobasal subregion connected with the visual cortex that responds generally to visual stimuli, a non-projecting region that responds to salient visual stimuli, and a centromedial subregion connected with the diencephalon that responds only when a visual stimulus predicts an aversive outcome. We provide anatomical and functional support for a model of amygdala function where information enters through the laterobasal subregion, is processed by intrinsic circuits in the interspersed tissue, and is then passed to the centromedial subregion, where activation leads to behavioral output. PMID:25969533

  4. Drought Tolerance in Pinus halepensis Seed Sources As Identified by Distinctive Physiological and Molecular Markers.

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    Taïbi, Khaled; Del Campo, Antonio D; Vilagrosa, Alberto; Bellés, José M; López-Gresa, María Pilar; Pla, Davinia; Calvete, Juan J; López-Nicolás, José M; Mulet, José M

    2017-01-01

    Drought is one of the main constraints determining forest species growth, survival and productivity, and therefore one of the main limitations for reforestation or afforestation. The aim of this study is to characterize the drought response at the physiological and molecular level of different Pinus halepensis (common name Aleppo pine) seed sources, previously characterized in field trials as drought-sensitive or drought-tolerant. This approach aims to identify different traits capable of predicting the ability of formerly uncharacterized seedlings to cope with drought stress. Gas-exchange, water potential, photosynthetic pigments, soluble sugars, free amino acids, glutathione and proteomic analyses were carried out on control and drought-stressed seedlings in greenhouse conditions. Gas-exchange determinations were also assessed in field-planted seedlings in order to validate the greenhouse experimental conditions. Drought-tolerant seed sources presented higher values of photosynthetic rates, water use efficiency, photosynthetic pigments and soluble carbohydrates concentrations. We observed the same pattern of variation of photosynthesis rate and maximal efficiency of PSII in field. Interestingly drought-tolerant seed sources exhibited increased levels of glutathione, methionine and cysteine. The proteomic profile of drought tolerant seedlings identified two heat shock proteins and an enzyme related to methionine biosynthesis that were not present in drought sensitive seedlings, pointing to the synthesis of sulfur amino acids as a limiting factor for drought tolerance in Pinus halepensis . Our results established physiological and molecular traits useful as distinctive markers to predict drought tolerance in Pinus halepensis provenances that could be reliably used in reforestation programs in drought prone areas.

  5. Drought Tolerance in Pinus halepensis Seed Sources As Identified by Distinctive Physiological and Molecular Markers

    Directory of Open Access Journals (Sweden)

    Khaled Taïbi

    2017-07-01

    Full Text Available Drought is one of the main constraints determining forest species growth, survival and productivity, and therefore one of the main limitations for reforestation or afforestation. The aim of this study is to characterize the drought response at the physiological and molecular level of different Pinus halepensis (common name Aleppo pine seed sources, previously characterized in field trials as drought-sensitive or drought-tolerant. This approach aims to identify different traits capable of predicting the ability of formerly uncharacterized seedlings to cope with drought stress. Gas-exchange, water potential, photosynthetic pigments, soluble sugars, free amino acids, glutathione and proteomic analyses were carried out on control and drought-stressed seedlings in greenhouse conditions. Gas-exchange determinations were also assessed in field-planted seedlings in order to validate the greenhouse experimental conditions. Drought-tolerant seed sources presented higher values of photosynthetic rates, water use efficiency, photosynthetic pigments and soluble carbohydrates concentrations. We observed the same pattern of variation of photosynthesis rate and maximal efficiency of PSII in field. Interestingly drought-tolerant seed sources exhibited increased levels of glutathione, methionine and cysteine. The proteomic profile of drought tolerant seedlings identified two heat shock proteins and an enzyme related to methionine biosynthesis that were not present in drought sensitive seedlings, pointing to the synthesis of sulfur amino acids as a limiting factor for drought tolerance in Pinus halepensis. Our results established physiological and molecular traits useful as distinctive markers to predict drought tolerance in Pinus halepensis provenances that could be reliably used in reforestation programs in drought prone areas.

  6. Identifying Learning Preferences in Vocational Education and Training Classroom Settings

    Science.gov (United States)

    Smith, Peter J.

    2006-01-01

    This research was designed to assess whether teachers and trainers of vocational learners noted and valued differences in individual learning preferences and, if so, how those differences were observed in natural classroom, workshop or other formal learning settings. Data were collected from six vocational education and training (VET) learning…

  7. Transcriptome signature identifies distinct cervical pathways induced in lipopolysaccharide-mediated preterm birth.

    Science.gov (United States)

    Willcockson, Alexandra R; Nandu, Tulip; Liu, Cheuk-Lun; Nallasamy, Shanmugasundaram; Kraus, W Lee; Mahendroo, Mala

    2018-03-01

    With half a million babies born preterm each year in the USA and about 15 million worldwide, preterm birth (PTB) remains a global health issue. Preterm birth is a primary cause of infant morbidity and mortality and can impact lives long past infancy. The fact that there are numerous, and many currently unidentified, etiologies of PTB has hindered development of tools for risk evaluation and preventative therapies. Infection is estimated to be involved in nearly 40% of PTBs of known etiology; therefore, understanding how infection-mediated inflammation alters the cervical milieu and leads to preterm tissue biomechanical changes are questions of interest. Using RNA-seq, we identified enrichment of components involved in inflammasome activation and unique proteases in the mouse cervix during lipopolysaccharide (LPS)-mediated PTB and not physiologically at term before labor. Despite transcriptional induction of inflammasome components, there was no evidence of functional activation based on assessment of mature IL1B and IL18 proteins. The increased transcription of proteases that target both elastic fibers and collagen and concentration of myeloid-derived cells capable of protease synthesis in the cervical stroma support the structural disruption of elastic fibers as a functional output of protease activity. The recent demonstration that elastic fibers contribute to the biomechanical function of the pregnant cervix suggests their protease-induced disruption in the infection model of LPS-mediated PTB and may contribute to premature loss of mechanical competency and preterm delivery. Collectively, the transcriptomics and ultrastructural data provide new insights into the distinct mechanisms of premature cervical remodeling in response to infection.

  8. Drosophila ovipositor extension in mating behavior and egg deposition involves distinct sets of brain interneurons.

    Directory of Open Access Journals (Sweden)

    Ken-ichi Kimura

    Full Text Available Oviposition is a female-specific behavior that directly affects fecundity, and therefore fitness. If a fertilized female encounters another male that she has evaluated to be of better quality than her previous mate, it would be beneficial for her to remate with this male rather than depositing her eggs. Females who decided not to remate exhibited rejection behavior toward a courting male and engaged in oviposition. Although recent studies of Drosophila melanogaster identified sensory neurons and putative second-order ascending interneurons that mediate uterine afferents affecting female reproductive behavior, little is known about the brain circuitry that selectively activates rejection versus oviposition behaviors. We identified the sexually dimorphic pC2l and female-specific pMN2 neurons, two distinct classes of doublesex (dsx-expressing neurons that can initiate ovipositor extension associated with rejection and oviposition behavior, respectively. pC2l interneurons, which induce ovipositor extrusion for rejection in females, have homologues that control courtship behavior in males. Activation of these two classes of neurons appears to be mutually exclusive and each governs hierarchical control of the motor program in the VNC either for rejection or oviposition, contributing centrally to the switching on or off of the alternative motor programs.

  9. High-throughput bacterial SNP typing identifies distinct clusters of Salmonella Typhi causing typhoid in Nepalese children

    LENUS (Irish Health Repository)

    Holt, Kathryn E

    2010-05-31

    Abstract Background Salmonella Typhi (S. Typhi) causes typhoid fever, which remains an important public health issue in many developing countries. Kathmandu, the capital of Nepal, is an area of high incidence and the pediatric population appears to be at high risk of exposure and infection. Methods We recently defined the population structure of S. Typhi, using new sequencing technologies to identify nearly 2,000 single nucleotide polymorphisms (SNPs) that can be used as unequivocal phylogenetic markers. Here we have used the GoldenGate (Illumina) platform to simultaneously type 1,500 of these SNPs in 62 S. Typhi isolates causing severe typhoid in children admitted to Patan Hospital in Kathmandu. Results Eight distinct S. Typhi haplotypes were identified during the 20-month study period, with 68% of isolates belonging to a subclone of the previously defined H58 S. Typhi. This subclone was closely associated with resistance to nalidixic acid, with all isolates from this group demonstrating a resistant phenotype and harbouring the same resistance-associated SNP in GyrA (Phe83). A secondary clone, comprising 19% of isolates, was observed only during the second half of the study. Conclusions Our data demonstrate the utility of SNP typing for monitoring bacterial populations over a defined period in a single endemic setting. We provide evidence for genotype introduction and define a nalidixic acid resistant subclone of S. Typhi, which appears to be the dominant cause of severe pediatric typhoid in Kathmandu during the study period.

  10. Spatial and Single-Cell Transcriptional Profiling Identifies Functionally Distinct Human Dermal Fibroblast Subpopulations.

    Science.gov (United States)

    Philippeos, Christina; Telerman, Stephanie B; Oulès, Bénédicte; Pisco, Angela O; Shaw, Tanya J; Elgueta, Raul; Lombardi, Giovanna; Driskell, Ryan R; Soldin, Mark; Lynch, Magnus D; Watt, Fiona M

    2018-04-01

    Previous studies have shown that mouse dermis is composed of functionally distinct fibroblast lineages. To explore the extent of fibroblast heterogeneity in human skin, we used a combination of comparative spatial transcriptional profiling of human and mouse dermis and single-cell transcriptional profiling of human dermal fibroblasts. We show that there are at least four distinct fibroblast populations in adult human skin, not all of which are spatially segregated. We define markers permitting their isolation and show that although marker expression is lost in culture, different fibroblast subpopulations retain distinct functionality in terms of Wnt signaling, responsiveness to IFN-γ, and ability to support human epidermal reconstitution when introduced into decellularized dermis. These findings suggest that ex vivo expansion or in vivo ablation of specific fibroblast subpopulations may have therapeutic applications in wound healing and diseases characterized by excessive fibrosis. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  11. What Makes Counsellors Working in Primary Care Distinct from Counsellors Working in Other Settings?

    Science.gov (United States)

    Hudson-Allez, Glyn

    2000-01-01

    Counseling in primary care can be considered a fast-evolving profession that is distinct from counseling in the private sector. Differences in counselor roles, specifically confidentiality ethics and working hours, are discussed. Referrals and attrition are also discussed. The distinctiveness of primary care counseling versus working in more…

  12. Distinct developmental defense activations in barley embryos identified by transcriptome profiling

    DEFF Research Database (Denmark)

    Nielsen, ME; Lok, F; Nielsen, Henrik Bjørn

    2006-01-01

    analyses of > 22,000 genes, which together with measurements of jasmonic acid and salicylic acid during embryo development provide new information on the initiation in the developing barley embryo of at least two distinct types of developmental defense activation (DDA). Early DDA is characterized by the up......-regulation of several PR genes is notable. Throughout barley embryo development, there are no indications of an increased biosynthesis of either jasmonic acid or salicylic acid. Collectively, the results help explain how the proposed DDA enables protection of the developing barley embryo and grain for purposes...

  13. Distinct types of primary cutaneous large B-cell lymphoma identified by gene expression profiling.

    Science.gov (United States)

    Hoefnagel, Juliette J; Dijkman, Remco; Basso, Katia; Jansen, Patty M; Hallermann, Christian; Willemze, Rein; Tensen, Cornelis P; Vermeer, Maarten H

    2005-05-01

    In the European Organization for Research and Treatment of Cancer (EORTC) classification 2 types of primary cutaneous large B-cell lymphoma (PCLBCL) are distinguished: primary cutaneous follicle center cell lymphomas (PCFCCL) and PCLBCL of the leg (PCLBCL-leg). Distinction between both groups is considered important because of differences in prognosis (5-year survival > 95% and 52%, respectively) and the first choice of treatment (radiotherapy or systemic chemotherapy, respectively), but is not generally accepted. To establish a molecular basis for this subdivision in the EORTC classification, we investigated the gene expression profiles of 21 PCLBCLs by oligonucleotide microarray analysis. Hierarchical clustering based on a B-cell signature (7450 genes) classified PCLBCL into 2 distinct subgroups consisting of, respectively, 8 PCFCCLs and 13 PCLBCLsleg. PCLBCLs-leg showed increased expression of genes associated with cell proliferation; the proto-oncogenes Pim-1, Pim-2, and c-Myc; and the transcription factors Mum1/IRF4 and Oct-2. In the group of PCFCCL high expression of SPINK2 was observed. Further analysis suggested that PCFCCLs and PCLBCLs-leg have expression profiles similar to that of germinal center B-cell-like and activated B-cell-like diffuse large B-cell lymphoma, respectively. The results of this study suggest that different pathogenetic mechanisms are involved in the development of PCFCCLs and PCLBCLs-leg and provide molecular support for the subdivision used in the EORTC classification.

  14. Identifying Two Groups of Entitled Individuals: Cluster Analysis Reveals Emotional Stability and Self-Esteem Distinction.

    Science.gov (United States)

    Crowe, Michael L; LoPilato, Alexander C; Campbell, W Keith; Miller, Joshua D

    2016-12-01

    The present study hypothesized that there exist two distinct groups of entitled individuals: grandiose-entitled, and vulnerable-entitled. Self-report scores of entitlement were collected for 916 individuals using an online platform. Model-based cluster analyses were conducted on the individuals with scores one standard deviation above mean (n = 159) using the five-factor model dimensions as clustering variables. The results support the existence of two groups of entitled individuals categorized as emotionally stable and emotionally vulnerable. The emotionally stable cluster reported emotional stability, high self-esteem, more positive affect, and antisocial behavior. The emotionally vulnerable cluster reported low self-esteem and high levels of neuroticism, disinhibition, conventionality, psychopathy, negative affect, childhood abuse, intrusive parenting, and attachment difficulties. Compared to the control group, both clusters reported being more antagonistic, extraverted, Machiavellian, and narcissistic. These results suggest important differences are missed when simply examining the linear relationships between entitlement and various aspects of its nomological network.

  15. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles

    DEFF Research Database (Denmark)

    Farshidfar, Farshad; Zheng, Siyuan; Gingras, Marie-Claude

    2017-01-01

    Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahep...

  16. Independent component analysis of high-resolution imaging data identifies distinct functional domains

    DEFF Research Database (Denmark)

    Reidl, Juergen; Starke, Jens; Omer, David

    2007-01-01

    be automatically detected. In the visual cortex orientation columns can be extracted. In all cases artifacts due to movement, heartbeat or respiration were separated from the functional signal by sICA and could be removed from the data set. sICA is therefore a powerful technique for data compression, unbiased...

  17. Distinct and conserved prominin-1/CD133-positive retinal cell populations identified across species.

    Directory of Open Access Journals (Sweden)

    József Jászai

    2011-03-01

    Full Text Available Besides being a marker of various somatic stem cells in mammals, prominin-1 (CD133 plays a role in maintaining the photoreceptor integrity since mutations in the PROM1 gene are linked with retinal degeneration. In spite of that, little information is available regarding its distribution in eyes of non-mammalian vertebrates endowed with high regenerative abilities. To address this subject, prominin-1 cognates were isolated from axolotl, zebrafish and chicken, and their retinal compartmentalization was investigated and compared to that of their mammalian orthologue. Interestingly, prominin-1 transcripts--except for the axolotl--were not strictly restricted to the outer nuclear layer (i.e., photoreceptor cells, but they also marked distinct subdivisions of the inner nuclear layer (INL. In zebrafish, where the prominin-1 gene is duplicated (i.e., prominin-1a and prominin-1b, a differential expression was noted for both paralogues within the INL being localized either to its vitreal or scleral subdivision, respectively. Interestingly, expression of prominin-1a within the former domain coincided with Pax-6-positive cells that are known to act as progenitors upon injury-induced retino-neurogenesis. A similar, but minute population of prominin-1-positive cells located at the vitreal side of the INL was also detected in developing and adult mice. In chicken, however, prominin-1-positive cells appeared to be aligned along the scleral side of the INL reminiscent of zebrafish prominin-1b. Taken together our data indicate that in addition to conserved expression of prominin-1 in photoreceptors, significant prominin-1-expressing non-photoreceptor retinal cell populations are present in the vertebrate eye that might represent potential sources of stem/progenitor cells for regenerative therapies.

  18. Drought Tolerance in Pinus halepensis Seed Sources As Identified by Distinctive Physiological and Molecular Markers

    OpenAIRE

    Taïbi, Khaled; Campo, Antonio D. del; Vilagrosa Carmona, Alberto; Bellés, José M.; López-Gresa, María Pilar; Pla, Davinia; Calvete, Juan J.; López-Nicolás, José M.; Mulet, José M.

    2017-01-01

    Drought is one of the main constraints determining forest species growth, survival and productivity, and therefore one of the main limitations for reforestation or afforestation. The aim of this study is to characterize the drought response at the physiological and molecular level of different Pinus halepensis (common name Aleppo pine) seed sources, previously characterized in field trials as drought-sensitive or drought-tolerant. This approach aims to identify different traits capable of pre...

  19. Comparative genomic analysis of Helicobacter pylori from Malaysia identifies three distinct lineages suggestive of differential evolution.

    Science.gov (United States)

    Kumar, Narender; Mariappan, Vanitha; Baddam, Ramani; Lankapalli, Aditya K; Shaik, Sabiha; Goh, Khean-Lee; Loke, Mun Fai; Perkins, Tim; Benghezal, Mohammed; Hasnain, Seyed E; Vadivelu, Jamuna; Marshall, Barry J; Ahmed, Niyaz

    2015-01-01

    The discordant prevalence of Helicobacter pylori and its related diseases, for a long time, fostered certain enigmatic situations observed in the countries of the southern world. Variation in H. pylori infection rates and disease outcomes among different populations in multi-ethnic Malaysia provides a unique opportunity to understand dynamics of host-pathogen interaction and genome evolution. In this study, we extensively analyzed and compared genomes of 27 Malaysian H. pylori isolates and identified three major phylogeographic lineages: hspEastAsia, hpEurope and hpSouthIndia. The analysis of the virulence genes within the core genome, however, revealed a comparable pathogenic potential of the strains. In addition, we identified four genes limited to strains of East-Asian lineage. Our analyses identified a few strain-specific genes encoding restriction modification systems and outlined 311 core genes possibly under differential evolutionary constraints, among the strains representing different ethnic groups. The cagA and vacA genes also showed variations in accordance with the host genetic background of the strains. Moreover, restriction modification genes were found to be significantly enriched in East-Asian strains. An understanding of these variations in the genome content would provide significant insights into various adaptive and host modulation strategies harnessed by H. pylori to effectively persist in a host-specific manner. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  20. Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features.

    Directory of Open Access Journals (Sweden)

    Marcel Kool

    Full Text Available BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children. Despite recent improvements in cure rates, prediction of disease outcome remains a major challenge and survivors suffer from serious therapy-related side-effects. Recent data showed that patients with WNT-activated tumors have a favorable prognosis, suggesting that these patients could be treated less intensively, thereby reducing the side-effects. This illustrates the potential benefits of a robust classification of medulloblastoma patients and a detailed knowledge of associated biological mechanisms. METHODS AND FINDINGS: To get a better insight into the molecular biology of medulloblastoma we established mRNA expression profiles of 62 medulloblastomas and analyzed 52 of them also by comparative genomic hybridization (CGH arrays. Five molecular subtypes were identified, characterized by WNT signaling (A; 9 cases, SHH signaling (B; 15 cases, expression of neuronal differentiation genes (C and D; 16 and 11 cases, respectively or photoreceptor genes (D and E; both 11 cases. Mutations in beta-catenin were identified in all 9 type A tumors, but not in any other tumor. PTCH1 mutations were exclusively identified in type B tumors. CGH analysis identified several fully or partly subtype-specific chromosomal aberrations. Monosomy of chromosome 6 occurred only in type A tumors, loss of 9q mostly occurred in type B tumors, whereas chromosome 17 aberrations, most common in medulloblastoma, were strongly associated with type C or D tumors. Loss of the inactivated X-chromosome was highly specific for female cases of type C, D and E tumors. Gene expression levels faithfully reflected the chromosomal copy number changes. Clinicopathological features significantly different between the 5 subtypes included metastatic disease and age at diagnosis and histology. Metastatic disease at diagnosis was significantly associated with subtypes C and D and most strongly with subtype E

  1. Cartography of Pathway Signal Perturbations Identifies Distinct Molecular Pathomechanisms in Malignant and Chronic Lung Diseases

    Science.gov (United States)

    Arakelyan, Arsen; Nersisyan, Lilit; Petrek, Martin; Löffler-Wirth, Henry; Binder, Hans

    2016-01-01

    Lung diseases are described by a wide variety of developmental mechanisms and clinical manifestations. Accurate classification and diagnosis of lung diseases are the bases for development of effective treatments. While extensive studies are conducted toward characterization of various lung diseases at molecular level, no systematic approach has been developed so far. Here we have applied a methodology for pathway-centered mining of high throughput gene expression data to describe a wide range of lung diseases in the light of shared and specific pathway activity profiles. We have applied an algorithm combining a Pathway Signal Flow (PSF) algorithm for estimation of pathway activity deregulation states in lung diseases and malignancies, and a Self Organizing Maps algorithm for classification and clustering of the pathway activity profiles. The analysis results allowed clearly distinguish between cancer and non-cancer lung diseases. Lung cancers were characterized by pathways implicated in cell proliferation, metabolism, while non-malignant lung diseases were characterized by deregulations in pathways involved in immune/inflammatory response and fibrotic tissue remodeling. In contrast to lung malignancies, chronic lung diseases had relatively heterogeneous pathway deregulation profiles. We identified three groups of interstitial lung diseases and showed that the development of characteristic pathological processes, such as fibrosis, can be initiated by deregulations in different signaling pathways. In conclusion, this paper describes the pathobiology of lung diseases from systems viewpoint using pathway centered high-dimensional data mining approach. Our results contribute largely to current understanding of pathological events in lung cancers and non-malignant lung diseases. Moreover, this paper provides new insight into molecular mechanisms of a number of interstitial lung diseases that have been studied to a lesser extent. PMID:27200087

  2. Chlamydia infection across host species boundaries promotes distinct sets of transcribed anti-apoptotic factors.

    Directory of Open Access Journals (Sweden)

    Joshua eMessinger

    2015-12-01

    Full Text Available Chlamydiae, obligate intracellular bacteria, cause significant human and veterinary associated diseases. Having emerged an estimated 700-million years ago, these bacteria have twice adapted to humans as a host species, causing sexually transmitted infection (C. trachomatis and respiratory associated disease (C. pneumoniae. The principle mechanism of host cell defense against these intracellular bacteria is the induction of cell death via apoptosis. However, in the arms race of co-evolution, Chlamydiae have developed mechanisms to promote cell viability and inhibit cell death. Herein we examine the impact of Chlamydiae infection across multiple host species on transcription of anti-apoptotic genes. We found mostly distinct patterns of gene expression (Mcl1 and cIAPs elicited by each pathogen-host pair indicating Chlamydiae infection across host species boundaries does not induce a universally shared host response. Understanding species specific host-pathogen interactions is paramount to deciphering how potential pathogens become emerging diseases.

  3. Mental Health Literacy in Emerging Adults in a University Setting: Distinctions between Symptom Awareness and Appraisal

    Science.gov (United States)

    Gagnon, Michelle M.; Gelinas, Bethany L.; Friesen, Lindsay N.

    2017-01-01

    Despite the high prevalence of mental health concerns in university populations, students are unlikely to seek formal help. The current study examined help-seeking behaviors among emerging adults in a university setting using a mental health literacy framework. Responses from 122 university undergraduates were examined. Students ranged in age from…

  4. On the Distinction Between the Motivating Operation and Setting Event Concepts.

    Science.gov (United States)

    Nosik, Melissa R; Carr, James E

    2015-10-01

    In recent decades, behavior analysts have generally used two different concepts to speak about motivational influences on operant contingencies: setting event and motivating operation. Although both concepts still appear in the contemporary behavior-analytic literature and were designed to address the same antecedent phenomena, the concepts are quite different. The purpose of the present article is to describe and distinguish the concepts and to illustrate their current usage.

  5. Identifying and applying psychological theory to setting and achieving rehabilitation goals.

    Science.gov (United States)

    Scobbie, Lesley; Wyke, Sally; Dixon, Diane

    2009-04-01

    Goal setting is considered to be a fundamental part of rehabilitation; however, theories of behaviour change relevant to goal-setting practice have not been comprehensively reviewed. (i) To identify and discuss specific theories of behaviour change relevant to goal-setting practice in the rehabilitation setting. (ii) To identify 'candidate' theories that that offer most potential to inform clinical practice. The rehabilitation and self-management literature was systematically searched to identify review papers or empirical studies that proposed a specific theory of behaviour change relevant to setting and/or achieving goals in a clinical context. Data from included papers were extracted under the headings of: key constructs, clinical application and empirical support. Twenty-four papers were included in the review which proposed a total of five theories: (i) social cognitive theory, (ii) goal setting theory, (iii) health action process approach, (iv) proactive coping theory, and (v) the self-regulatory model of illness behaviour. The first three of these theories demonstrated most potential to inform clinical practice, on the basis of their capacity to inform interventions that resulted in improved patient outcomes. Social cognitive theory, goal setting theory and the health action process approach are theories of behaviour change that can inform clinicians in the process of setting and achieving goals in the rehabilitation setting. Overlapping constructs within these theories have been identified, and can be applied in clinical practice through the development and evaluation of a goal-setting practice framework.

  6. Early and long-standing rheumatoid arthritis: distinct molecular signatures identified by gene-expression profiling in synovia

    Science.gov (United States)

    Lequerré, Thierry; Bansard, Carine; Vittecoq, Olivier; Derambure, Céline; Hiron, Martine; Daveau, Maryvonne; Tron, François; Ayral, Xavier; Biga, Norman; Auquit-Auckbur, Isabelle; Chiocchia, Gilles; Le Loët, Xavier; Salier, Jean-Philippe

    2009-01-01

    Introduction Rheumatoid arthritis (RA) is a heterogeneous disease and its underlying molecular mechanisms are still poorly understood. Because previous microarray studies have only focused on long-standing (LS) RA compared to osteoarthritis, we aimed to compare the molecular profiles of early and LS RA versus control synovia. Methods Synovial biopsies were obtained by arthroscopy from 15 patients (4 early untreated RA, 4 treated LS RA and 7 controls, who had traumatic or mechanical lesions). Extracted mRNAs were used for large-scale gene-expression profiling. The different gene-expression combinations identified by comparison of profiles of early, LS RA and healthy synovia were linked to the biological processes involved in each situation. Results Three combinations of 719, 116 and 52 transcripts discriminated, respectively, early from LS RA, and early or LS RA from healthy synovia. We identified several gene clusters and distinct molecular signatures specifically expressed during early or LS RA, thereby suggesting the involvement of different pathophysiological mechanisms during the course of RA. Conclusions Early and LS RA have distinct molecular signatures with different biological processes participating at different times during the course of the disease. These results suggest that better knowledge of the main biological processes involved at a given RA stage might help to choose the most appropriate treatment. PMID:19563633

  7. Comparative analysis of Edwardsiella isolates from fish in the eastern United States identifies two distinct genetic taxa amongst organisms phenotypically classified as E. tarda

    Science.gov (United States)

    Griffin, Matt J.; Quiniou, Sylvie M.; Cody, Theresa; Tabuchi, Maki; Ware, Cynthia; Cipriano, Rocco C.; Mauel, Michael J.; Soto, Esteban

    2013-01-01

    Edwardsiella tarda, a Gram-negative member of the family Enterobacteriaceae, has been implicated in significant losses in aquaculture facilities worldwide. Here, we assessed the intra-specific variability of E. tarda isolates from 4 different fish species in the eastern United States. Repetitive sequence mediated PCR (rep-PCR) using 4 different primer sets (ERIC I & II, ERIC II, BOX, and GTG5) and multi-locus sequence analysis of 16S SSU rDNA, groEl, gyrA, gyrB, pho, pgi, pgm, and rpoA gene fragments identified two distinct genotypes of E. tarda (DNA group I; DNA group II). Isolates that fell into DNA group II demonstrated more similarity to E. ictaluri than DNA group I, which contained the reference E. tarda strain (ATCC #15947). Conventional PCR analysis using published E. tarda-specific primer sets yielded variable results, with several primer sets producing no observable amplification of target DNA from some isolates. Fluorometric determination of G + C content demonstrated 56.4% G + C content for DNA group I, 60.2% for DNA group II, and 58.4% for E. ictaluri. Surprisingly, these isolates were indistinguishable using conventional biochemical techniques, with all isolates demonstrating phenotypic characteristics consistent with E. tarda. Analysis using two commercial test kits identified multiple phenotypes, although no single metabolic characteristic could reliably discriminate between genetic groups. Additionally, anti-microbial susceptibility and fatty acid profiles did not demonstrate remarkable differences between groups. The significant genetic variation (<90% similarity at gyrA, gyrB, pho, phi and pgm; <40% similarity by rep-PCR) between these groups suggests organisms from DNA group II may represent an unrecognized, genetically distinct taxa of Edwardsiella that is phenotypically indistinguishable from E. tarda.

  8. Full genome sequencing and genetic characterization of Eubenangee viruses identify Pata virus as a distinct species within the genus Orbivirus.

    Directory of Open Access Journals (Sweden)

    Manjunatha N Belaganahalli

    Full Text Available Eubenangee virus has previously been identified as the cause of Tammar sudden death syndrome (TSDS. Eubenangee virus (EUBV, Tilligery virus (TILV, Pata virus (PATAV and Ngoupe virus (NGOV are currently all classified within the Eubenangee virus species of the genus Orbivirus, family Reoviridae. Full genome sequencing confirmed that EUBV and TILV (both of which are from Australia show high levels of aa sequence identity (>92% in the conserved polymerase VP1(Pol, sub-core VP3(T2 and outer core VP7(T13 proteins, and are therefore appropriately classified within the same virus species. However, they show much lower amino acid (aa identity levels in their larger outer-capsid protein VP2 (<53%, consistent with membership of two different serotypes - EUBV-1 and EUBV-2 (respectively. In contrast PATAV showed significantly lower levels of aa sequence identity with either EUBV or TILV (with <71% in VP1(Pol and VP3(T2, and <57% aa identity in VP7(T13 consistent with membership of a distinct virus species. A proposal has therefore been sent to the Reoviridae Study Group of ICTV to recognise 'Pata virus' as a new Orbivirus species, with the PATAV isolate as serotype 1 (PATAV-1. Amongst the other orbiviruses, PATAV shows closest relationships to Epizootic Haemorrhagic Disease virus (EHDV, with 80.7%, 72.4% and 66.9% aa identity in VP3(T2, VP1(Pol, and VP7(T13 respectively. Although Ngoupe virus was not available for these studies, like PATAV it was isolated in Central Africa, and therefore seems likely to also belong to the new species, possibly as a distinct 'type'. The data presented will facilitate diagnostic assay design and the identification of additional isolates of these viruses.

  9. Machine Learning Methods Improve Prognostication, Identify Clinically Distinct Phenotypes, and Detect Heterogeneity in Response to Therapy in a Large Cohort of Heart Failure Patients.

    Science.gov (United States)

    Ahmad, Tariq; Lund, Lars H; Rao, Pooja; Ghosh, Rohit; Warier, Prashant; Vaccaro, Benjamin; Dahlström, Ulf; O'Connor, Christopher M; Felker, G Michael; Desai, Nihar R

    2018-04-12

    Whereas heart failure (HF) is a complex clinical syndrome, conventional approaches to its management have treated it as a singular disease, leading to inadequate patient care and inefficient clinical trials. We hypothesized that applying advanced analytics to a large cohort of HF patients would improve prognostication of outcomes, identify distinct patient phenotypes, and detect heterogeneity in treatment response. The Swedish Heart Failure Registry is a nationwide registry collecting detailed demographic, clinical, laboratory, and medication data and linked to databases with outcome information. We applied random forest modeling to identify predictors of 1-year survival. Cluster analysis was performed and validated using serial bootstrapping. Association between clusters and survival was assessed with Cox proportional hazards modeling and interaction testing was performed to assess for heterogeneity in response to HF pharmacotherapy across propensity-matched clusters. Our study included 44 886 HF patients enrolled in the Swedish Heart Failure Registry between 2000 and 2012. Random forest modeling demonstrated excellent calibration and discrimination for survival (C-statistic=0.83) whereas left ventricular ejection fraction did not (C-statistic=0.52): there were no meaningful differences per strata of left ventricular ejection fraction (1-year survival: 80%, 81%, 83%, and 84%). Cluster analysis using the 8 highest predictive variables identified 4 clinically relevant subgroups of HF with marked differences in 1-year survival. There were significant interactions between propensity-matched clusters (across age, sex, and left ventricular ejection fraction and the following medications: diuretics, angiotensin-converting enzyme inhibitors, β-blockers, and nitrates, P <0.001, all). Machine learning algorithms accurately predicted outcomes in a large data set of HF patients. Cluster analysis identified 4 distinct phenotypes that differed significantly in outcomes and in

  10. Integrative genome-wide expression profiling identifies three distinct molecular subgroups of renal cell carcinoma with different patient outcome

    Directory of Open Access Journals (Sweden)

    Beleut Manfred

    2012-07-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC is characterized by a number of diverse molecular aberrations that differ among individuals. Recent approaches to molecularly classify RCC were based on clinical, pathological as well as on single molecular parameters. As a consequence, gene expression patterns reflecting the sum of genetic aberrations in individual tumors may not have been recognized. In an attempt to uncover such molecular features in RCC, we used a novel, unbiased and integrative approach. Methods We integrated gene expression data from 97 primary RCC of different pathologic parameters, 15 RCC metastases as well as 34 cancer cell lines for two-way nonsupervised hierarchical clustering using gene groups suggested by the PANTHER Classification System. We depicted the genomic landscape of the resulted tumor groups by means of Single Nuclear Polymorphism (SNP technology. Finally, the achieved results were immunohistochemically analyzed using a tissue microarray (TMA composed of 254 RCC. Results We found robust, genome wide expression signatures, which split RCC into three distinct molecular subgroups. These groups remained stable even if randomly selected gene sets were clustered. Notably, the pattern obtained from RCC cell lines was clearly distinguishable from that of primary tumors. SNP array analysis demonstrated differing frequencies of chromosomal copy number alterations among RCC subgroups. TMA analysis with group-specific markers showed a prognostic significance of the different groups. Conclusion We propose the existence of characteristic and histologically independent genome-wide expression outputs in RCC with potential biological and clinical relevance.

  11. Identification of distinct SET/TAF-Ibeta domains required for core histone binding and quantitative characterisation of the interaction.

    Science.gov (United States)

    Karetsou, Zoe; Emmanouilidou, Anastasia; Sanidas, Ioannis; Liokatis, Stamatis; Nikolakaki, Eleni; Politou, Anastasia S; Papamarcaki, Thomais

    2009-04-09

    The assembly of nucleosomes to higher-order chromatin structures is finely tuned by the relative affinities of histones for chaperones and nucleosomal binding sites. The myeloid leukaemia protein SET/TAF-Ibeta belongs to the NAP1 family of histone chaperones and participates in several chromatin-based mechanisms, such as chromatin assembly, nucleosome reorganisation and transcriptional activation. To better understand the histone chaperone function of SET/TAF-Ibeta, we designed several SET/TAF-Ibeta truncations, examined their structural integrity by circular Dichroism and assessed qualitatively and quantitatively the histone binding properties of wild-type protein and mutant forms using GST-pull down experiments and fluorescence spectroscopy-based binding assays. Wild type SET/TAF-Ibeta binds to histones H2B and H3 with Kd values of 2.87 and 0.15 microM, respectively. The preferential binding of SET/TAF-Ibeta to histone H3 is mediated by its central region and the globular part of H3. On the contrary, the acidic C-terminal tail and the amino-terminal dimerisation domain of SET/TAF-Ibeta, as well as the H3 amino-terminal tail, are dispensable for this interaction. This type of analysis allowed us to assess the relative affinities of SET/TAF-Ibeta for different histones and identify the domains of the protein required for effective histone recognition. Our findings are consistent with recent structural studies of SET/TAF-Ibeta and can be valuable to understand the role of SET/TAF-Ibeta in chromatin function.

  12. Identification of distinct SET/TAF-Iβ domains required for core histone binding and quantitative characterisation of the interaction

    Science.gov (United States)

    Karetsou, Zoe; Emmanouilidou, Anastasia; Sanidas, Ioannis; Liokatis, Stamatis; Nikolakaki, Eleni; Politou, Anastasia S; Papamarcaki, Thomais

    2009-01-01

    Background The assembly of nucleosomes to higher-order chromatin structures is finely tuned by the relative affinities of histones for chaperones and nucleosomal binding sites. The myeloid leukaemia protein SET/TAF-Iβ belongs to the NAP1 family of histone chaperones and participates in several chromatin-based mechanisms, such as chromatin assembly, nucleosome reorganisation and transcriptional activation. To better understand the histone chaperone function of SET/TAF-Iβ, we designed several SET/TAF-Iβ truncations, examined their structural integrity by circular Dichroism and assessed qualitatively and quantitatively the histone binding properties of wild-type protein and mutant forms using GST-pull down experiments and fluorescence spectroscopy-based binding assays. Results Wild type SET/TAF-Iβ binds to histones H2B and H3 with Kd values of 2.87 and 0.15 μM, respectively. The preferential binding of SET/TAF-Iβ to histone H3 is mediated by its central region and the globular part of H3. On the contrary, the acidic C-terminal tail and the amino-terminal dimerisation domain of SET/TAF-Iβ, as well as the H3 amino-terminal tail, are dispensable for this interaction. Conclusion This type of analysis allowed us to assess the relative affinities of SET/TAF-Iβ for different histones and identify the domains of the protein required for effective histone recognition. Our findings are consistent with recent structural studies of SET/TAF-Iβ and can be valuable to understand the role of SET/TAF-Iβ in chromatin function. PMID:19358706

  13. Genome-Wide Temporal Expression Profiling in Caenorhabditis elegans Identifies a Core Gene Set Related to Long-Term Memory.

    Science.gov (United States)

    Freytag, Virginie; Probst, Sabine; Hadziselimovic, Nils; Boglari, Csaba; Hauser, Yannick; Peter, Fabian; Gabor Fenyves, Bank; Milnik, Annette; Demougin, Philippe; Vukojevic, Vanja; de Quervain, Dominique J-F; Papassotiropoulos, Andreas; Stetak, Attila

    2017-07-12

    The identification of genes related to encoding, storage, and retrieval of memories is a major interest in neuroscience. In the current study, we analyzed the temporal gene expression changes in a neuronal mRNA pool during an olfactory long-term associative memory (LTAM) in Caenorhabditis elegans hermaphrodites. Here, we identified a core set of 712 (538 upregulated and 174 downregulated) genes that follows three distinct temporal peaks demonstrating multiple gene regulation waves in LTAM. Compared with the previously published positive LTAM gene set (Lakhina et al., 2015), 50% of the identified upregulated genes here overlap with the previous dataset, possibly representing stimulus-independent memory-related genes. On the other hand, the remaining genes were not previously identified in positive associative memory and may specifically regulate aversive LTAM. Our results suggest a multistep gene activation process during the formation and retrieval of long-term memory and define general memory-implicated genes as well as conditioning-type-dependent gene sets. SIGNIFICANCE STATEMENT The identification of genes regulating different steps of memory is of major interest in neuroscience. Identification of common memory genes across different learning paradigms and the temporal activation of the genes are poorly studied. Here, we investigated the temporal aspects of Caenorhabditis elegans gene expression changes using aversive olfactory associative long-term memory (LTAM) and identified three major gene activation waves. Like in previous studies, aversive LTAM is also CREB dependent, and CREB activity is necessary immediately after training. Finally, we define a list of memory paradigm-independent core gene sets as well as conditioning-dependent genes. Copyright © 2017 the authors 0270-6474/17/376661-12$15.00/0.

  14. Distinct Bacterial Microbiomes Associate with the Deep-Sea Coral Eguchipsammia fistula from the Red Sea and from Aquaria Settings

    KAUST Repository

    Röthig, Till

    2017-08-10

    Microbial communities associated with deep-sea corals are beginning to be studied in earnest and the contribution of the microbiome to host organismal function remains to be investigated. In this regard, the ability of the microbiome to adjust to prevailing environmental conditions might provide clues to its functional importance. In this study, we characterized bacterial community composition associated with the deep-sea coral Eguchipsammia fistula under natural (in situ) and aquaria (ex situ) settings using 16S rRNA gene amplicon sequencing. We compared freshly collected Red Sea coral specimens with those reared for >1 year at conditions that partially differed from the natural environment, in particular regarding increased oxygen and food availability under ex situ conditions. We found substantial differences between the microbiomes associated with corals under both environmental settings. The core microbiome comprised only six bacterial taxa consistently present in all corals, whereas the majority of bacteria were exclusively associated either with freshly collected corals or corals under long-term reared aquaria settings. Putative functional profiling of microbial communities showed that corals in their natural habitat were enriched for processes indicative of a carbon- and nitrogen-limited environment, which might be reflective of differences in diet under in situ and ex situ conditions. The ability of E. fistula to harbor distinct microbiomes under different environmental settings might contribute to the flexibility and phenotypic plasticity of this cosmopolitan coral. Future efforts should further assess the role of these different bacteria in holobiont function, in particular since E. fistula is naturally present in markedly different environments.

  15. Distinct Bacterial Microbiomes Associate with the Deep-Sea Coral Eguchipsammia fistula from the Red Sea and from Aquaria Settings

    KAUST Repository

    Rö thig, Till; Roik, Anna Krystyna; Yum, Lauren; Voolstra, Christian R.

    2017-01-01

    Microbial communities associated with deep-sea corals are beginning to be studied in earnest and the contribution of the microbiome to host organismal function remains to be investigated. In this regard, the ability of the microbiome to adjust to prevailing environmental conditions might provide clues to its functional importance. In this study, we characterized bacterial community composition associated with the deep-sea coral Eguchipsammia fistula under natural (in situ) and aquaria (ex situ) settings using 16S rRNA gene amplicon sequencing. We compared freshly collected Red Sea coral specimens with those reared for >1 year at conditions that partially differed from the natural environment, in particular regarding increased oxygen and food availability under ex situ conditions. We found substantial differences between the microbiomes associated with corals under both environmental settings. The core microbiome comprised only six bacterial taxa consistently present in all corals, whereas the majority of bacteria were exclusively associated either with freshly collected corals or corals under long-term reared aquaria settings. Putative functional profiling of microbial communities showed that corals in their natural habitat were enriched for processes indicative of a carbon- and nitrogen-limited environment, which might be reflective of differences in diet under in situ and ex situ conditions. The ability of E. fistula to harbor distinct microbiomes under different environmental settings might contribute to the flexibility and phenotypic plasticity of this cosmopolitan coral. Future efforts should further assess the role of these different bacteria in holobiont function, in particular since E. fistula is naturally present in markedly different environments.

  16. Single-cell quantitative HER2 measurement identifies heterogeneity and distinct subgroups within traditionally defined HER2-positive patients.

    Science.gov (United States)

    Onsum, Matthew D; Geretti, Elena; Paragas, Violette; Kudla, Arthur J; Moulis, Sharon P; Luus, Lia; Wickham, Thomas J; McDonagh, Charlotte F; MacBeath, Gavin; Hendriks, Bart S

    2013-11-01

    Human epidermal growth factor receptor 2 (HER2) is an important biomarker for breast and gastric cancer prognosis and patient treatment decisions. HER2 positivity, as defined by IHC or fluorescent in situ hybridization testing, remains an imprecise predictor of patient response to HER2-targeted therapies. Challenges to correct HER2 assessment and patient stratification include intratumoral heterogeneity, lack of quantitative and/or objective assays, and differences between measuring HER2 amplification at the protein versus gene level. We developed a novel immunofluorescence method for quantitation of HER2 protein expression at the single-cell level on FFPE patient samples. Our assay uses automated image analysis to identify and classify tumor versus non-tumor cells, as well as quantitate the HER2 staining for each tumor cell. The HER2 staining level is converted to HER2 protein expression using a standard cell pellet array stained in parallel with the tissue sample. This approach allows assessment of HER2 expression and heterogeneity within a tissue section at the single-cell level. By using this assay, we identified distinct subgroups of HER2 heterogeneity within traditional definitions of HER2 positivity in both breast and gastric cancers. Quantitative assessment of intratumoral HER2 heterogeneity may offer an opportunity to improve the identification of patients likely to respond to HER2-targeted therapies. The broad applicability of the assay was demonstrated by measuring HER2 expression profiles on multiple tumor types, and on normal and diseased heart tissues. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  17. Subchronic and chronic PCP treatment produces temporally distinct deficits in attentional set shifting and prepulse inhibition in rats.

    Science.gov (United States)

    Egerton, Alice; Reid, Lee; McGregor, Sandie; Cochran, Susan M; Morris, Brian J; Pratt, Judith A

    2008-05-01

    We have previously demonstrated that subchronic (five daily administrations of 2.6 mg/kg PCP) and chronic intermittent administration of 2.6 mg/kg PCP to rats produces hypofrontality and other neurochemical changes akin to schizophrenia pathology (Cochran et al., Neuropsychopharmacology, 28:265-275, 2003). We sought to determine whether behavioral alterations related to discrete aspects of schizophrenia are also induced by these PCP treatment regimes. Following administration of vehicle or PCP according to the protocols described above, rats were assessed for attentional set shifting ability, prepulse inhibition (PPI), or social interaction and the locomotor response to a challenge dose of amphetamine. Ability to shift attentional set was impaired 72 h after the last PCP administration following the subchronic and chronic intermittent treatment regimes. PPI was disrupted after each acute administration of PCP in animals under the subchronic treatment regime. However, PPI deficits were not sustained 72 h after the last of five daily administrations. In subchronic and chronic PCP treated animals, no change was found in social interaction behavior, and there was little change in baseline or amphetamine-stimulated locomotor activity, employed as an indicator of dopaminergic hyperfunction. The temporally distinct behavioral effects of these PCP treatment regimes suggest that PPI deficits relate directly to acute NMDA receptor antagonism, whereas the more enduring set shifting deficits relate to the longer term consequences of NMDA receptor blockade. Therefore, these subchronic and chronic PCP treatment regimes produce hypofrontality (Cochran et al., Neuropsychopharmacology, 28:265-275, 2003) and associated prefrontal cortex-dependent deficits in behavioral flexibility which mirror core deficits in schizophrenia.

  18. Experimentally-derived fibroblast gene signatures identify molecular pathways associated with distinct subsets of systemic sclerosis patients in three independent cohorts.

    Directory of Open Access Journals (Sweden)

    Michael E Johnson

    Full Text Available Genome-wide expression profiling in systemic sclerosis (SSc has identified four 'intrinsic' subsets of disease (fibroproliferative, inflammatory, limited, and normal-like, each of which shows deregulation of distinct signaling pathways; however, the full set of pathways contributing to this differential gene expression has not been fully elucidated. Here we examine experimentally derived gene expression signatures in dermal fibroblasts for thirteen different signaling pathways implicated in SSc pathogenesis. These data show distinct and overlapping sets of genes induced by each pathway, allowing for a better understanding of the molecular relationship between profibrotic and immune signaling networks. Pathway-specific gene signatures were analyzed across a compendium of microarray datasets consisting of skin biopsies from three independent cohorts representing 80 SSc patients, 4 morphea, and 26 controls. IFNα signaling showed a strong association with early disease, while TGFβ signaling spanned the fibroproliferative and inflammatory subsets, was associated with worse MRSS, and was higher in lesional than non-lesional skin. The fibroproliferative subset was most strongly associated with PDGF signaling, while the inflammatory subset demonstrated strong activation of innate immune pathways including TLR signaling upstream of NF-κB. The limited and normal-like subsets did not show associations with fibrotic and inflammatory mediators such as TGFβ and TNFα. The normal-like subset showed high expression of genes associated with lipid signaling, which was absent in the inflammatory and limited subsets. Together, these data suggest a model by which IFNα is involved in early disease pathology, and disease severity is associated with active TGFβ signaling.

  19. SU-F-T-312: Identifying Distinct Radiation Therapy Plan Classes Through Multi-Dimensional Analysis of Plan Complexity Metrics

    Energy Technology Data Exchange (ETDEWEB)

    Desai, V; Labby, Z; Culberson, W [University of Wisc Madison, Madison, WI (United States)

    2016-06-15

    Purpose: To determine whether body site-specific treatment plans form unique “plan class” clusters in a multi-dimensional analysis of plan complexity metrics such that a single beam quality correction determined for a representative plan could be universally applied within the “plan class”, thereby increasing the dosimetric accuracy of a detector’s response within a subset of similarly modulated nonstandard deliveries. Methods: We collected 95 clinical volumetric modulated arc therapy (VMAT) plans from four body sites (brain, lung, prostate, and spine). The lung data was further subdivided into SBRT and non-SBRT data for a total of five plan classes. For each control point in each plan, a variety of aperture-based complexity metrics were calculated and stored as unique characteristics of each patient plan. A multiple comparison of means analysis was performed such that every plan class was compared to every other plan class for every complexity metric in order to determine which groups could be considered different from one another. Statistical significance was assessed after correcting for multiple hypothesis testing. Results: Six out of a possible 10 pairwise plan class comparisons were uniquely distinguished based on at least nine out of 14 of the proposed metrics (Brain/Lung, Brain/SBRT lung, Lung/Prostate, Lung/SBRT Lung, Lung/Spine, Prostate/SBRT Lung). Eight out of 14 of the complexity metrics could distinguish at least six out of the possible 10 pairwise plan class comparisons. Conclusion: Aperture-based complexity metrics could prove to be useful tools to quantitatively describe a distinct class of treatment plans. Certain plan-averaged complexity metrics could be considered unique characteristics of a particular plan. A new approach to generating plan-class specific reference (pcsr) fields could be established through a targeted preservation of select complexity metrics or a clustering algorithm that identifies plans exhibiting similar

  20. Resolving tumor heterogeneity: genes involved in chordoma cell development identified by low-template analysis of morphologically distinct cells.

    Directory of Open Access Journals (Sweden)

    Amin El-Heliebi

    Full Text Available The classical sacrococcygeal chordoma tumor presents with a typical morphology of lobulated myxoid tumor tissue with cords, strands and nests of tumor cells. The population of cells consists of small non-vacuolated cells, intermediate cells with a wide range of vacuolization and large heavily vacuolated (physaliferous cells. To date analysis was only performed on bulk tumor mass because of its rare incidence, lack of suited model systems and technical limitations thereby neglecting its heterogeneous composition. We intended to clarify whether the observed cell types are derived from genetically distinct clones or represent different phenotypes. Furthermore, we aimed at elucidating the differences between small non-vacuolated and large physaliferous cells on the genomic and transcriptomic level. Phenotype-specific analyses of small non-vacuolated and large physaliferous cells in two independent chordoma cell lines yielded four candidate genes involved in chordoma cell development. UCHL3, coding for an ubiquitin hydrolase, was found to be over-expressed in the large physaliferous cell phenotype of MUG-Chor1 (18.7-fold and U-CH1 (3.7-fold cells. The mannosyltransferase ALG11 (695-fold and the phosphatase subunit PPP2CB (18.6-fold were found to be up-regulated in large physaliferous MUG-Chor1 cells showing a similar trend in U-CH1 cells. TMEM144, an orphan 10-transmembrane family receptor, yielded contradictory data as cDNA microarray analysis showed up- but RT-qPCR data down-regulation in large physaliferous MUG-Chor1 cells. Isolation of few but morphologically identical cells allowed us to overcome the limitations of bulk analysis in chordoma research. We identified the different chordoma cell phenotypes to be part of a developmental process and discovered new genes linked to chordoma cell development representing potential targets for further research in chordoma tumor biology.

  1. Galanin-immunoreactivity identifies a distinct population of inhibitory interneurons in laminae I-III of the rat spinal cord

    Directory of Open Access Journals (Sweden)

    Watanabe Masahiko

    2011-05-01

    Full Text Available Abstract Background Inhibitory interneurons constitute 30-40% of neurons in laminae I-III and have an important anti-nociceptive role. However, because of the difficulty in classifying them we know little about their organisation. Previous studies have identified 3 non-overlapping groups of inhibitory interneuron, which contain neuropeptide Y (NPY, neuronal nitric oxide synthase (nNOS or parvalbumin, and have shown that these differ in postsynaptic targets. Some inhibitory interneurons contain galanin and the first aim of this study was to determine whether these form a different population from those containing NPY, nNOS or parvalbumin. We also estimated the proportion of neurons and GABAergic axons that contain galanin in laminae I-III. Results Galanin cells were concentrated in laminae I-IIo, with few in laminae IIi-III. Galanin showed minimal co-localisation with NPY, nNOS or parvalbumin in laminae I-II, but most galanin-containing cells in lamina III were nNOS-positive. Galanin cells constituted ~7%, 3% and 2% of all neurons in laminae I, II and III, and we estimate that this corresponds to 26%, 10% and 5% of the GABAergic neurons in these laminae. However, galanin was only found in ~6% of GABAergic boutons in laminae I-IIo, and ~1% of those in laminae IIi-III. Conclusions These results show that galanin, NPY, nNOS and parvalbumin can be used to define four distinct neurochemical populations of inhibitory interneurons. Together with results of a recent study, they suggest that the galanin and NPY populations account for around half of the inhibitory interneurons in lamina I and a quarter of those in lamina II.

  2. CD45RC isoform expression identifies functionally distinct T cell subsets differentially distributed between healthy individuals and AAV patients.

    Directory of Open Access Journals (Sweden)

    Laurence Ordonez

    Full Text Available In animal models of anti-neutrophil cytoplasmic antibody (ANCA-associated vasculitis (AAV, the proportion of CD45RC T cell subsets is important for disease susceptibility. Their human counterparts are, however, functionally ill defined. In this report, we studied their distribution in healthy controls (HC, AAV patients and in Systemic lupus erythematous (SLE patients as disease controls. We showed that CD45RC expression level on human CD4 and CD8 T cells identifies subsets that are highly variable among individuals. Interestingly, AAV patients exhibit an increased proportion of CD45RC(low CD4 T cells as compared to HC and SLE patients. This increase is stable over time and independent of AAV subtype, ANCA specificity, disease duration, or number of relapses. We also analyzed the cytokine profile of purified CD4 and CD8 CD45RC T cell subsets from HC, after stimulation with anti-CD3 and anti-CD28 mAbs. The CD45RC subsets exhibit different cytokine profiles. Type-1 cytokines (IL-2, IFN-gamma and TNF-alpha were produced by all CD45RC T cell subsets, while the production of IL-17, type-2 (IL-4, IL-5 and regulatory (IL-10 cytokines was restricted to the CD45RC(low subset. In conclusion, we have shown that CD45RC expression divides human T cells in functionally distinct subsets that are imbalanced in AAV. Since this imbalance is stable over time and independent of several disease parameters, we hypothesize that this is a pre-existing immune abnormality involved in the etiology of AAV.

  3. Identifying elementary iterated systems through algorithmic inference: The Cantor set example

    Energy Technology Data Exchange (ETDEWEB)

    Apolloni, Bruno [Dipartimento di Scienze dell' Informazione, Universita degli Studi di Milano, Via Comelico 39/41, 20135 Milan (Italy)]. E-mail: apolloni@dsi.unimi.it; Bassis, Simone [Dipartimento di Scienze dell' Informazione, Universita degli Studi di Milano, Via Comelico 39/41, 20135 Milan (Italy)]. E-mail: bassis@dsi.unimi.it

    2006-10-15

    We come back to the old problem of fractal identification within the new framework of algorithmic Inference. The key points are: (i) to identify sufficient statistics to be put in connection with the unknown values of the fractal parameters, and (ii) to manage the timing of the iterated process through spatial statistics. We fill these tasks successfully with the Cantor sets. We are able to compute confidence intervals for both the scaling parameter {theta} and the iteration number n at which we are observing a set. We both check numerically the coverage of these intervals and delineate a general strategy for affording more complex iterated systems.

  4. Identifying Knowledge Gaps in Clinicians Who Evaluate and Treat Vocal Performing Artists in College Health Settings.

    Science.gov (United States)

    McKinnon-Howe, Leah; Dowdall, Jayme

    2018-05-01

    The goal of this study was to identify knowledge gaps in clinicians who evaluate and treat performing artists for illnesses and injuries that affect vocal function in college health settings. This pilot study utilized a web-based cross-sectional survey design incorporating common clinical scenarios to test knowledge of evaluation and management strategies in the vocal performing artist. A web-based survey was administered to a purposive sample of 28 clinicians to identify the approach utilized to evaluate and treat vocal performing artists in college health settings, and factors that might affect knowledge gaps and influence referral patterns to voice specialists. Twenty-eight clinicians were surveyed, with 36% of respondents incorrectly identifying appropriate vocal hygiene measures, 56% of respondents failing to identify symptoms of vocal fold hemorrhage, 84% failing to identify other indications for referral to a voice specialist, 96% of respondents acknowledging unfamiliarity with the Voice Handicap Index and the Singers Voice Handicap Index, and 68% acknowledging unfamiliarity with the Reflux Symptom Index. The data elucidated specific knowledge gaps in college health providers who are responsible for evaluating and treating common illnesses that affect vocal function, and triaging and referring students experiencing symptoms of potential vocal emergencies. Future work is needed to improve the standard of care for this population. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  5. Integrating the nursing management minimum data set into the logical observation identifier names and codes system.

    Science.gov (United States)

    Subramanian, Amarnath; Westra, Bonnie; Matney, Susan; Wilson, Patricia S; Delaney, Connie W; Huff, Stan; Huff, Stanley M; Huber, Diane

    2008-11-06

    This poster describes the process used to integrate the Nursing Management Minimum Data Set (NMMDS), an instrument to measure the nursing context of care, into the Logical Observation Identifier Names and Codes (LOINC) system to facilitate contextualization of quality measures. Integration of the first three of 18 elements resulted in 48 new codes including five panels. The LOINC Clinical Committee has approved the presented mapping for their next release.

  6. Use of GIS to identify optimal settings for cancer prevention and control in African American communities

    Science.gov (United States)

    Alcaraz, Kassandra I.; Kreuter, Matthew W.; Bryan, Rebecca P.

    2009-01-01

    Objective Rarely have Geographic Information Systems (GIS) been used to inform community-based outreach and intervention planning. This study sought to identify community settings most likely to reach individuals from geographically localized areas. Method An observational study conducted in an urban city in Missouri during 2003–2007 placed computerized breast cancer education kiosks in seven types of community settings: beauty salons, churches, health fairs, neighborhood health centers, Laundromats, public libraries and social service agencies. We used GIS to measure distance between kiosk users’ (n=7,297) home ZIP codes and the location where they used the kiosk. Mean distances were compared across settings. Results Mean distance between individuals’ home ZIP codes and the location where they used the kiosk varied significantly (pLaundromats (2.3 miles) and public libraries (2.8 miles) and greatest among kiosk users at health fairs (7.6 miles). Conclusion Some community settings are more likely than others to reach highly localized populations. A better understanding of how and where to reach specific populations can complement the progress already being made in identifying populations at increased disease risk. PMID:19422844

  7. A scalable method for identifying frequent subtrees in sets of large phylogenetic trees.

    Science.gov (United States)

    Ramu, Avinash; Kahveci, Tamer; Burleigh, J Gordon

    2012-10-03

    We consider the problem of finding the maximum frequent agreement subtrees (MFASTs) in a collection of phylogenetic trees. Existing methods for this problem often do not scale beyond datasets with around 100 taxa. Our goal is to address this problem for datasets with over a thousand taxa and hundreds of trees. We develop a heuristic solution that aims to find MFASTs in sets of many, large phylogenetic trees. Our method works in multiple phases. In the first phase, it identifies small candidate subtrees from the set of input trees which serve as the seeds of larger subtrees. In the second phase, it combines these small seeds to build larger candidate MFASTs. In the final phase, it performs a post-processing step that ensures that we find a frequent agreement subtree that is not contained in a larger frequent agreement subtree. We demonstrate that this heuristic can easily handle data sets with 1000 taxa, greatly extending the estimation of MFASTs beyond current methods. Although this heuristic does not guarantee to find all MFASTs or the largest MFAST, it found the MFAST in all of our synthetic datasets where we could verify the correctness of the result. It also performed well on large empirical data sets. Its performance is robust to the number and size of the input trees. Overall, this method provides a simple and fast way to identify strongly supported subtrees within large phylogenetic hypotheses.

  8. A cross-study gene set enrichment analysis identifies critical pathways in endometriosis

    Directory of Open Access Journals (Sweden)

    Bai Chunyan

    2009-09-01

    Full Text Available Abstract Background Endometriosis is an enigmatic disease. Gene expression profiling of endometriosis has been used in several studies, but few studies went further to classify subtypes of endometriosis based on expression patterns and to identify possible pathways involved in endometriosis. Some of the observed pathways are more inconsistent between the studies, and these candidate pathways presumably only represent a fraction of the pathways involved in endometriosis. Methods We applied a standardised microarray preprocessing and gene set enrichment analysis to six independent studies, and demonstrated increased concordance between these gene datasets. Results We find 16 up-regulated and 19 down-regulated pathways common in ovarian endometriosis data sets, 22 up-regulated and one down-regulated pathway common in peritoneal endometriosis data sets. Among them, 12 up-regulated and 1 down-regulated were found consistent between ovarian and peritoneal endometriosis. The main canonical pathways identified are related to immunological and inflammatory disease. Early secretory phase has the most over-represented pathways in the three uterine cycle phases. There are no overlapping significant pathways between the dataset from human endometrial endothelial cells and the datasets from ovarian endometriosis which used whole tissues. Conclusion The study of complex diseases through pathway analysis is able to highlight genes weakly connected to the phenotype which may be difficult to detect by using classical univariate statistics. By standardised microarray preprocessing and GSEA, we have increased the concordance in identifying many biological mechanisms involved in endometriosis. The identified gene pathways will shed light on the understanding of endometriosis and promote the development of novel therapies.

  9. Identifying finite-time coherent sets from limited quantities of Lagrangian data

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Matthew O. [Program in Applied and Computational Mathematics, Princeton University, New Jersey 08544 (United States); Rypina, Irina I. [Department of Physical Oceanography, Woods Hole Oceanographic Institute, Massachusetts 02543 (United States); Rowley, Clarence W. [Department of Mechanical and Aerospace Engineering, Princeton University, New Jersey 08544 (United States)

    2015-08-15

    A data-driven procedure for identifying the dominant transport barriers in a time-varying flow from limited quantities of Lagrangian data is presented. Our approach partitions state space into coherent pairs, which are sets of initial conditions chosen to minimize the number of trajectories that “leak” from one set to the other under the influence of a stochastic flow field during a pre-specified interval in time. In practice, this partition is computed by solving an optimization problem to obtain a pair of functions whose signs determine set membership. From prior experience with synthetic, “data rich” test problems, and conceptually related methods based on approximations of the Perron-Frobenius operator, we observe that the functions of interest typically appear to be smooth. We exploit this property by using the basis sets associated with spectral or “mesh-free” methods, and as a result, our approach has the potential to more accurately approximate these functions given a fixed amount of data. In practice, this could enable better approximations of the coherent pairs in problems with relatively limited quantities of Lagrangian data, which is usually the case with experimental geophysical data. We apply this method to three examples of increasing complexity: The first is the double gyre, the second is the Bickley Jet, and the third is data from numerically simulated drifters in the Sulu Sea.

  10. Identifying finite-time coherent sets from limited quantities of Lagrangian data

    International Nuclear Information System (INIS)

    Williams, Matthew O.; Rypina, Irina I.; Rowley, Clarence W.

    2015-01-01

    A data-driven procedure for identifying the dominant transport barriers in a time-varying flow from limited quantities of Lagrangian data is presented. Our approach partitions state space into coherent pairs, which are sets of initial conditions chosen to minimize the number of trajectories that “leak” from one set to the other under the influence of a stochastic flow field during a pre-specified interval in time. In practice, this partition is computed by solving an optimization problem to obtain a pair of functions whose signs determine set membership. From prior experience with synthetic, “data rich” test problems, and conceptually related methods based on approximations of the Perron-Frobenius operator, we observe that the functions of interest typically appear to be smooth. We exploit this property by using the basis sets associated with spectral or “mesh-free” methods, and as a result, our approach has the potential to more accurately approximate these functions given a fixed amount of data. In practice, this could enable better approximations of the coherent pairs in problems with relatively limited quantities of Lagrangian data, which is usually the case with experimental geophysical data. We apply this method to three examples of increasing complexity: The first is the double gyre, the second is the Bickley Jet, and the third is data from numerically simulated drifters in the Sulu Sea

  11. Identifying finite-time coherent sets from limited quantities of Lagrangian data.

    Science.gov (United States)

    Williams, Matthew O; Rypina, Irina I; Rowley, Clarence W

    2015-08-01

    A data-driven procedure for identifying the dominant transport barriers in a time-varying flow from limited quantities of Lagrangian data is presented. Our approach partitions state space into coherent pairs, which are sets of initial conditions chosen to minimize the number of trajectories that "leak" from one set to the other under the influence of a stochastic flow field during a pre-specified interval in time. In practice, this partition is computed by solving an optimization problem to obtain a pair of functions whose signs determine set membership. From prior experience with synthetic, "data rich" test problems, and conceptually related methods based on approximations of the Perron-Frobenius operator, we observe that the functions of interest typically appear to be smooth. We exploit this property by using the basis sets associated with spectral or "mesh-free" methods, and as a result, our approach has the potential to more accurately approximate these functions given a fixed amount of data. In practice, this could enable better approximations of the coherent pairs in problems with relatively limited quantities of Lagrangian data, which is usually the case with experimental geophysical data. We apply this method to three examples of increasing complexity: The first is the double gyre, the second is the Bickley Jet, and the third is data from numerically simulated drifters in the Sulu Sea.

  12. kmer-SVM: a web server for identifying predictive regulatory sequence features in genomic data sets

    Science.gov (United States)

    Fletez-Brant, Christopher; Lee, Dongwon; McCallion, Andrew S.; Beer, Michael A.

    2013-01-01

    Massively parallel sequencing technologies have made the generation of genomic data sets a routine component of many biological investigations. For example, Chromatin immunoprecipitation followed by sequence assays detect genomic regions bound (directly or indirectly) by specific factors, and DNase-seq identifies regions of open chromatin. A major bottleneck in the interpretation of these data is the identification of the underlying DNA sequence code that defines, and ultimately facilitates prediction of, these transcription factor (TF) bound or open chromatin regions. We have recently developed a novel computational methodology, which uses a support vector machine (SVM) with kmer sequence features (kmer-SVM) to identify predictive combinations of short transcription factor-binding sites, which determine the tissue specificity of these genomic assays (Lee, Karchin and Beer, Discriminative prediction of mammalian enhancers from DNA sequence. Genome Res. 2011; 21:2167–80). This regulatory information can (i) give confidence in genomic experiments by recovering previously known binding sites, and (ii) reveal novel sequence features for subsequent experimental testing of cooperative mechanisms. Here, we describe the development and implementation of a web server to allow the broader research community to independently apply our kmer-SVM to analyze and interpret their genomic datasets. We analyze five recently published data sets and demonstrate how this tool identifies accessory factors and repressive sequence elements. kmer-SVM is available at http://kmersvm.beerlab.org. PMID:23771147

  13. Instruments to Identify Commercially Sexually Exploited Children: Feasibility of Use in an Emergency Department Setting.

    Science.gov (United States)

    Armstrong, Stephanie

    2017-12-01

    This review examines the screening instruments that are in existence today to identify commercially sexually exploited children. The instruments are compared and evaluated for their feasibility of use in an emergency department setting. Four electronic databases were searched to identify screening instruments that assessed solely for commercial sexual exploitation. Search terms included "commercially sexually exploited children," "CSEC," "domestic minor sex trafficking," "DMST," "juvenile sex trafficking," and "JST." Those terms were then searched in combination with each of the following: "tools," "instruments," "screening," "policies," "procedures," "data collection," "evidence," and "validity." Six screening instruments were found to meet the inclusion criteria. Variation among instruments included number of questions, ease of administration, information sources, scoring methods, and training information provided. Two instruments were determined to be highly feasible for use in the emergency department setting, those being the Asian Health Services and Banteay Srei's CSEC Screening Protocol and Greenbaum et al's CSEC/child sex trafficking 6-item screening tool. A current dearth of screening instruments was confirmed. It is recommended that additional screening instruments be created to include developmentally appropriate instruments for preadolescent children. Numerous positive features were identified within the instruments in this review and are suggested for use in future screening instruments, including succinctness, a simple format, easy administration, training materials, sample questions, multiple information sources, designation of questions requiring mandatory reporting, a straightforward scoring system, and an algorithm format.

  14. Exome sequencing identifies mutations in ABCD1 and DACH2 in two brothers with a distinct phenotype

    OpenAIRE

    Zhang, Yanliang; Liu, Yanhui; Li, Ya; Duan, Yong; Zhang, Keyun; Wang, Junwang; Dai, Yong

    2014-01-01

    Background We report on two brothers with a distinct syndromic phenotype and explore the potential pathogenic cause. Methods Cytogenetic tests and exome sequencing were performed on the two brothers and their parents. Variants detected by exome sequencing were validated by Sanger sequencing. Results The main phenotype of the two brothers included congenital language disorder, growth retardation, intellectual disability, difficulty in standing and walking, and urinary and fecal incontinence. T...

  15. Analysis of gene expression data from non-small cell lung carcinoma cell lines reveals distinct sub-classes from those identified at the phenotype level.

    Directory of Open Access Journals (Sweden)

    Andrew R Dalby

    Full Text Available Microarray data from cell lines of Non-Small Cell Lung Carcinoma (NSCLC can be used to look for differences in gene expression between the cell lines derived from different tumour samples, and to investigate if these differences can be used to cluster the cell lines into distinct groups. Dividing the cell lines into classes can help to improve diagnosis and the development of screens for new drug candidates. The micro-array data is first subjected to quality control analysis and then subsequently normalised using three alternate methods to reduce the chances of differences being artefacts resulting from the normalisation process. The final clustering into sub-classes was carried out in a conservative manner such that sub-classes were consistent across all three normalisation methods. If there is structure in the cell line population it was expected that this would agree with histological classifications, but this was not found to be the case. To check the biological consistency of the sub-classes the set of most strongly differentially expressed genes was be identified for each pair of clusters to check if the genes that most strongly define sub-classes have biological functions consistent with NSCLC.

  16. Pareto Optimization Identifies Diverse Set of Phosphorylation Signatures Predicting Response to Treatment with Dasatinib.

    Science.gov (United States)

    Klammer, Martin; Dybowski, J Nikolaj; Hoffmann, Daniel; Schaab, Christoph

    2015-01-01

    Multivariate biomarkers that can predict the effectiveness of targeted therapy in individual patients are highly desired. Previous biomarker discovery studies have largely focused on the identification of single biomarker signatures, aimed at maximizing prediction accuracy. Here, we present a different approach that identifies multiple biomarkers by simultaneously optimizing their predictive power, number of features, and proximity to the drug target in a protein-protein interaction network. To this end, we incorporated NSGA-II, a fast and elitist multi-objective optimization algorithm that is based on the principle of Pareto optimality, into the biomarker discovery workflow. The method was applied to quantitative phosphoproteome data of 19 non-small cell lung cancer (NSCLC) cell lines from a previous biomarker study. The algorithm successfully identified a total of 77 candidate biomarker signatures predicting response to treatment with dasatinib. Through filtering and similarity clustering, this set was trimmed to four final biomarker signatures, which then were validated on an independent set of breast cancer cell lines. All four candidates reached the same good prediction accuracy (83%) as the originally published biomarker. Although the newly discovered signatures were diverse in their composition and in their size, the central protein of the originally published signature - integrin β4 (ITGB4) - was also present in all four Pareto signatures, confirming its pivotal role in predicting dasatinib response in NSCLC cell lines. In summary, the method presented here allows for a robust and simultaneous identification of multiple multivariate biomarkers that are optimized for prediction performance, size, and relevance.

  17. Priority setting partnership to identify the top 10 research priorities for the management of Parkinson's disease.

    Science.gov (United States)

    Deane, Katherine H O; Flaherty, Helen; Daley, David J; Pascoe, Roland; Penhale, Bridget; Clarke, Carl E; Sackley, Catherine; Storey, Stacey

    2014-12-14

    This priority setting partnership was commissioned by Parkinson's UK to encourage people with direct and personal experience of the condition to work together to identify and prioritise the top 10 evidential uncertainties that impact on everyday clinical practice for the management of Parkinson's disease (PD). The UK. Anyone with experience of PD including: people with Parkinson's (PwP), carers, family and friends, healthcare and social care professionals. Non-clinical researchers and employees of pharmaceutical or medical devices companies were excluded. 1000 participants (60% PwP) provided ideas on research uncertainties, 475 (72% PwP) initially prioritised them and 27 (37% PwP) stakeholders agreed a final top 10. Using a modified nominal group technique, participants were surveyed to identify what issues for the management of PD needed research. Unique research questions unanswered by current evidence were identified and participants were asked to identify their top 10 research priorities from this list. The top 26 uncertainties were presented to a consensus meeting with key stakeholders to agree the top 10 research priorities. 1000 participants provided 4100 responses, which contained 94 unique unanswered research questions that were initially prioritised by 475 participants. A consensus meeting with 27 stakeholders agreed the top 10 research priorities. The overarching research aspiration was an effective cure for PD. The top 10 research priorities for PD management included the need to address motor symptoms (balance and falls, and fine motor control), non-motor symptoms (sleep and urinary dysfunction), mental health issues (stress and anxiety, dementia and mild cognitive impairments), side effects of medications (dyskinesia) and the need to develop interventions specific to the phenotypes of PD and better monitoring methods. These research priorities identify crucial gaps in the existing evidence to address everyday practicalities in the management of the

  18. Single-molecule spectroscopy of LHCSR1 protein dynamics identifies two distinct states responsible for multi-timescale photosynthetic photoprotection

    Science.gov (United States)

    Kondo, Toru; Pinnola, Alberta; Chen, Wei Jia; Dall'Osto, Luca; Bassi, Roberto; Schlau-Cohen, Gabriela S.

    2017-08-01

    In oxygenic photosynthesis, light harvesting is regulated to safely dissipate excess energy and prevent the formation of harmful photoproducts. Regulation is known to be necessary for fitness, but the molecular mechanisms are not understood. One challenge has been that ensemble experiments average over active and dissipative behaviours, preventing identification of distinct states. Here, we use single-molecule spectroscopy to uncover the photoprotective states and dynamics of the light-harvesting complex stress-related 1 (LHCSR1) protein, which is responsible for dissipation in green algae and moss. We discover the existence of two dissipative states. We find that one of these states is activated by pH and the other by carotenoid composition, and that distinct protein dynamics regulate these states. Together, these two states enable the organism to respond to two types of intermittency in solar intensity—step changes (clouds and shadows) and ramp changes (sunrise), respectively. Our findings reveal key control mechanisms underlying photoprotective dissipation, with implications for increasing biomass yields and developing robust solar energy devices.

  19. Different sets of ER-resident J-proteins regulate distinct polar nuclear-membrane fusion events in Arabidopsis thaliana.

    Science.gov (United States)

    Maruyama, Daisuke; Yamamoto, Masaya; Endo, Toshiya; Nishikawa, Shuh-ichi

    2014-11-01

    Angiosperm female gametophytes contain a central cell with two polar nuclei. In many species, including Arabidopsis thaliana, the polar nuclei fuse during female gametogenesis. We previously showed that BiP, an Hsp70 in the endoplasmic reticulum (ER), was essential for membrane fusion during female gametogenesis. Hsp70 function requires partner proteins for full activity. J-domain containing proteins (J-proteins) are the major Hsp70 functional partners. A. thaliana ER contains three soluble J-proteins, AtERdj3A, AtERdj3B, and AtP58(IPK). Here, we analyzed mutants of these proteins and determined that double-mutant ovules lacking AtP58(IPK) and AtERdj3A or AtERdj3B were defective in polar nuclear fusion. Electron microscopy analysis identified that polar nuclei were in close contact, but no membrane fusion occurred in mutant ovules lacking AtP58(IPK) and AtERdj3A. The polar nuclear outer membrane appeared to be connected via the ER remaining at the inner unfused membrane in mutant ovules lacking AtP58(IPK) and AtERdj3B. These results indicate that ER-resident J-proteins, AtP58(IPK)/AtERdj3A and AtP58(IPK)/AtERdj3B, function at distinct steps of polar nuclear-membrane fusion. Similar to the bip1 bip2 double mutant female gametophytes, the aterdj3a atp58(ipk) double mutant female gametophytes defective in fusion of the outer polar nuclear membrane displayed aberrant endosperm proliferation after fertilization with wild-type pollen. However, endosperm proliferated normally after fertilization of the aterdj3b atp58(ipk) double mutant female gametophytes defective in fusion of the inner membrane. Our results indicate that the polar nuclear fusion defect itself does not cause an endosperm proliferation defect. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  20. Meta-analysis of Drosophila circadian microarray studies identifies a novel set of rhythmically expressed genes.

    Directory of Open Access Journals (Sweden)

    Kevin P Keegan

    2007-11-01

    Full Text Available Five independent groups have reported microarray studies that identify dozens of rhythmically expressed genes in the fruit fly Drosophila melanogaster. Limited overlap among the lists of discovered genes makes it difficult to determine which, if any, exhibit truly rhythmic patterns of expression. We reanalyzed data from all five reports and found two sources for the observed discrepancies, the use of different expression pattern detection algorithms and underlying variation among the datasets. To improve upon the methods originally employed, we developed a new analysis that involves compilation of all existing data, application of identical transformation and standardization procedures followed by ANOVA-based statistical prescreening, and three separate classes of post hoc analysis: cross-correlation to various cycling waveforms, autocorrelation, and a previously described fast Fourier transform-based technique. Permutation-based statistical tests were used to derive significance measures for all post hoc tests. We find application of our method, most significantly the ANOVA prescreening procedure, significantly reduces the false discovery rate relative to that observed among the results of the original five reports while maintaining desirable statistical power. We identify a set of 81 cycling transcripts previously found in one or more of the original reports as well as a novel set of 133 transcripts not found in any of the original studies. We introduce a novel analysis method that compensates for variability observed among the original five Drosophila circadian array reports. Based on the statistical fidelity of our meta-analysis results, and the results of our initial validation experiments (quantitative RT-PCR, we predict many of our newly found genes to be bona fide cyclers, and suggest that they may lead to new insights into the pathways through which clock mechanisms regulate behavioral rhythms.

  1. Development of Multiplexed Marker Sets to Identify the Most Relevant Poplar Species for Breeding

    Directory of Open Access Journals (Sweden)

    Hilke Schroeder

    2017-12-01

    Full Text Available Within the genus Populus, about 30 species are classified into six sections, of which some are cross-compatible. Besides naturally occurring hybrids, huge breeding programs have led to a high number of artificially produced hybrids, for which the determination of genetically involved species by morphological characteristics is often difficult. This necessitates the use of molecular markers for the identification of both maternal as well as paternal species, and in the case of complex hybrids, the genealogy. For this reason, we developed new chloroplast and nuclear markers for the differentiation of up to 19 poplar species, with one to 32 individuals per species regularly used in breeding programs based on already known barcoding, other chloroplast regions, and nuclear genes of interest. We developed methods to identify species by either species-specific nucleotide variations or, when no initial information for the species was given, by using a set of markers either in a procedure of exclusion or in a multiplexed marker set. The developed markers can all be used with low-cost equipment, and some can additionally be applied using a genetic analyzer. We combined these markers in multiplexes for a very fast and easy-to-use application for the identification of poplar species and their hybrids.

  2. Exome sequencing identifies mutations in ABCD1 and DACH2 in two brothers with a distinct phenotype.

    Science.gov (United States)

    Zhang, Yanliang; Liu, Yanhui; Li, Ya; Duan, Yong; Zhang, Keyun; Wang, Junwang; Dai, Yong

    2014-09-19

    We report on two brothers with a distinct syndromic phenotype and explore the potential pathogenic cause. Cytogenetic tests and exome sequencing were performed on the two brothers and their parents. Variants detected by exome sequencing were validated by Sanger sequencing. The main phenotype of the two brothers included congenital language disorder, growth retardation, intellectual disability, difficulty in standing and walking, and urinary and fecal incontinence. To the best of our knowledge, no similar phenotype has been reported previously. No abnormalities were detected by G-banding chromosome analysis or array comparative genomic hybridization. However, exome sequencing revealed novel mutations in the ATP-binding cassette, sub-family D member 1 (ABCD1) and Dachshund homolog 2 (DACH2) genes in both brothers. The ABCD1 mutation was a missense mutation c.1126G > C in exon 3 leading to a p.E376Q substitution. The DACH2 mutation was also a missense mutation c.1069A > T in exon 6, leading to a p.S357C substitution. The mother was an asymptomatic heterozygous carrier. Plasma levels of very-long-chain fatty acids were increased in both brothers, suggesting a diagnosis of adrenoleukodystrophy (ALD); however, their phenotype was not compatible with any reported forms of ALD. DACH2 plays an important role in the regulation of brain and limb development, suggesting that this mutation may be involved in the phenotype of the two brothers. The distinct phenotype demonstrated by these two brothers might represent a new form of ALD or a new syndrome. The combination of mutations in ABCD1 and DACH2 provides a plausible mechanism for this phenotype.

  3. Local realism versus quantum theory: Violation of the generalized spin-s Bell inequalities for a set of three distinct axes

    International Nuclear Information System (INIS)

    Ardehali, M.

    1990-01-01

    Some simple inequalities which demonstrate the incompatibility of local realism with quantum theory are derived. They establish, for the first time, necessary conditions for violation of the generalized spin-s Bell inequalities for a set of three distinct noncoplanar axes. For s=1/2, however, these inequalities are equivalent to Wigner's results, thus giving necessary and sufficient conditions

  4. Identifying signs and symptoms of intimate partner violence in an oncology setting.

    Science.gov (United States)

    Mick, JoAnn

    2006-08-01

    Domestic violence (DV), or intimate partner violence (IPV), is a prevailing problem in public health. Often, healthcare providers may be the first people that victims of DV will approach to reveal their problem or seek assistance. IPV is a pattern of control using assault and intimidating behaviors that has devastating effects on individuals, their families, and communities. Oncology nurses need to become familiar with common indicators of DV so that signs and symptoms of abuse can be identified when assessing patients in an oncology setting. Standards of oncology nursing practice support that the psychosocial impact of cancer on patients and their families or significant others needs to be considered at all stages of diagnosis and treatment. The psychosocial impact of other personal situations or concerns, such as IPV, can add to the complexity of cancer management. Routine screening for signs and symptoms of psychosocial distress helps identify patients who require additional interventions. Oncology nursing practice is based on a holistic approach to patient care, which supports that identification of physical and psychosocial needs are equally important. Oncology nursing provides many unique opportunities to help patients cope with cancer. Routine nursing assessment for signs and symptoms of abuse will provide an opportunity to assist patients with cancer to manage not only the life-threatening aspects of their diagnosis but also the life-threatening aspects of IPV.

  5. Prediction potential of candidate biomarker sets identified and validated on gene expression data from multiple datasets

    Directory of Open Access Journals (Sweden)

    Karacali Bilge

    2007-10-01

    Full Text Available Abstract Background Independently derived expression profiles of the same biological condition often have few genes in common. In this study, we created populations of expression profiles from publicly available microarray datasets of cancer (breast, lymphoma and renal samples linked to clinical information with an iterative machine learning algorithm. ROC curves were used to assess the prediction error of each profile for classification. We compared the prediction error of profiles correlated with molecular phenotype against profiles correlated with relapse-free status. Prediction error of profiles identified with supervised univariate feature selection algorithms were compared to profiles selected randomly from a all genes on the microarray platform and b a list of known disease-related genes (a priori selection. We also determined the relevance of expression profiles on test arrays from independent datasets, measured on either the same or different microarray platforms. Results Highly discriminative expression profiles were produced on both simulated gene expression data and expression data from breast cancer and lymphoma datasets on the basis of ER and BCL-6 expression, respectively. Use of relapse-free status to identify profiles for prognosis prediction resulted in poorly discriminative decision rules. Supervised feature selection resulted in more accurate classifications than random or a priori selection, however, the difference in prediction error decreased as the number of features increased. These results held when decision rules were applied across-datasets to samples profiled on the same microarray platform. Conclusion Our results show that many gene sets predict molecular phenotypes accurately. Given this, expression profiles identified using different training datasets should be expected to show little agreement. In addition, we demonstrate the difficulty in predicting relapse directly from microarray data using supervised machine

  6. MM2-thalamic Creutzfeldt-Jakob disease: neuropathological, biochemical and transmission studies identify a distinctive prion strain.

    Science.gov (United States)

    Moda, Fabio; Suardi, Silvia; Di Fede, Giuseppe; Indaco, Antonio; Limido, Lucia; Vimercati, Chiara; Ruggerone, Margherita; Campagnani, Ilaria; Langeveld, Jan; Terruzzi, Alessandro; Brambilla, Antonio; Zerbi, Pietro; Fociani, Paolo; Bishop, Matthew T; Will, Robert G; Manson, Jean C; Giaccone, Giorgio; Tagliavini, Fabrizio

    2012-09-01

    In Creutzfeldt-Jakob disease (CJD), molecular typing based on the size of the protease resistant core of the disease-associated prion protein (PrP(Sc) ) and the M/V polymorphism at codon 129 of the PRNP gene correlates with the clinico-pathologic subtypes. Approximately 95% of the sporadic 129MM CJD patients are characterized by cerebral deposition of type 1 PrP(Sc) and correspond to the classic clinical CJD phenotype. The rare 129MM CJD patients with type 2 PrP(Sc) are further subdivided in a cortical and a thalamic form also indicated as sporadic fatal insomnia. We observed two young patients with MM2-thalamic CJD. Main neuropathological features were diffuse, synaptic PrP immunoreactivity in the cerebral cortex and severe neuronal loss and gliosis in the thalamus and olivary nucleus. Western blot analysis showed the presence of type 2A PrP(Sc) . Challenge of transgenic mice expressing 129MM human PrP showed that MM2-thalamic sporadic CJD (sCJD) was able to transmit the disease, at variance with MM2-cortical sCJD. The affected mice showed deposition of type 2A PrP(Sc) , a scenario that is unprecedented in this mouse line. These data indicate that MM2-thalamic sCJD is caused by a prion strain distinct from the other sCJD subtypes including the MM2-cortical form. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

  7. Signaling profiling at the single-cell level identifies a distinct signaling signature in murine hematopoietic stem cells.

    Science.gov (United States)

    Du, Juan; Wang, Jinyong; Kong, Guangyao; Jiang, Jing; Zhang, Jingfang; Liu, Yangang; Tong, Wei; Zhang, Jing

    2012-07-01

    Hematopoietic stem cell (HSC) function is tightly regulated by cytokine signaling. Although phospho-flow cytometry allows us to study signaling in defined populations of cells, there has been tremendous hurdle to carry out this study in rare HSCs due to unrecoverable critical HSC markers, low HSC number, and poor cell recovery rate. Here, we overcame these difficulties and developed a "HSC phospho-flow" method to analyze cytokine signaling in murine HSCs at the single-cell level and compare HSC signaling profile to that of multipotent progenitors (MPPs), a cell type immediately downstream of HSCs, and commonly used Lin(-) cKit(+) cells (LK cells, enriched for myeloid progenitors). We chose to study signaling evoked from three representative cytokines, stem cell factor (SCF) and thrombopoietin (TPO) that are essential for HSC function and granulocyte macrophage-colony-stimulating factor (GM-CSF) that is dispensable for HSCs. HSCs display a distinct TPO and GM-CSF signaling signature from MPPs and LK cells, which highly correlates with receptor surface expression. In contrast, although majority of LK cells express lower levels of cKit than HSCs and MPPs, SCF-evoked ERK1/2 activation in LK cells shows a significantly increased magnitude for a prolonged period. These results suggest that specific cellular context plays a more important role than receptor surface expression in SCF signaling. Our study of HSC signaling at the homeostasis stage paves the way to investigate signaling changes in HSCs under conditions of stress, aging, and hematopoietic diseases. Copyright © 2012 AlphaMed Press.

  8. Distinct anatomical correlates of discriminability and criterion setting in verbal recognition memory revealed by lesion-symptom mapping

    NARCIS (Netherlands)

    Biesbroek, J Matthijs; van Zandvoort, Martine J E; Kappelle, L Jaap; Schoo, Linda; Kuijf, Hugo J; Velthuis, Birgitta K; Biessels, Geert Jan; Postma, Albert

    2014-01-01

    Recognition memory, that is, the ability to judge whether an item has been previously encountered in a particular context, depends on two factors: discriminability and criterion setting. Discriminability draws on memory processes while criterion setting (i.e., the application of a threshold

  9. Distinct anatomical correlates of discriminability and criterion setting in verbal recognition memory revealed by lesion-symptom mapping

    NARCIS (Netherlands)

    Biesbroek, J. Matthijs; van Zandvoort, Martine J E; Kappelle, L. Jaap; Schoo, Linda; Kuijf, Hugo J.; Velthuis, BK; Biessels, Geert Jan; Postma, Albert

    2015-01-01

    Recognition memory, that is, the ability to judge whether an item has been previously encountered in a particular context, depends on two factors: discriminability and criterion setting. Discriminability draws on memory processes while criterion setting (i.e., the application of a threshold

  10. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits

    DEFF Research Database (Denmark)

    Speliotes, Elizabeth K; Yerges-Armstrong, Laura M; Wu, Jun

    2011-01-01

    steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (~26%-27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n¿=¿880 to 3,070). By carrying out a fixed-effects meta......-analysis of genome-wide association (GWA) results between CT hepatic steatosis and ~2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome......Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic...

  11. Distinct Molecular Signature of Murine Fetal Liver and Adult Hematopoietic Stem Cells Identify Novel Regulators of Hematopoietic Stem Cell Function.

    Science.gov (United States)

    Manesia, Javed K; Franch, Monica; Tabas-Madrid, Daniel; Nogales-Cadenas, Ruben; Vanwelden, Thomas; Van Den Bosch, Elisa; Xu, Zhuofei; Pascual-Montano, Alberto; Khurana, Satish; Verfaillie, Catherine M

    2017-04-15

    During ontogeny, fetal liver (FL) acts as a major site for hematopoietic stem cell (HSC) maturation and expansion, whereas HSCs in the adult bone marrow (ABM) are largely quiescent. HSCs in the FL possess faster repopulation capacity as compared with ABM HSCs. However, the molecular mechanism regulating the greater self-renewal potential of FL HSCs has not yet extensively been assessed. Recently, we published RNA sequencing-based gene expression analysis on FL HSCs from 14.5-day mouse embryo (E14.5) in comparison to the ABM HSCs. We reanalyzed these data to identify key transcriptional regulators that play important roles in the expansion of HSCs during development. The comparison of FL E14.5 with ABM HSCs identified more than 1,400 differentially expressed genes. More than 200 genes were shortlisted based on the gene ontology (GO) annotation term "transcription." By morpholino-based knockdown studies in zebrafish, we assessed the function of 18 of these regulators, previously not associated with HSC proliferation. Our studies identified a previously unknown role for tdg, uhrf1, uchl5, and ncoa1 in the emergence of definitive hematopoiesis in zebrafish. In conclusion, we demonstrate that identification of genes involved in transcriptional regulation differentially expressed between expanding FL HSCs and quiescent ABM HSCs, uncovers novel regulators of HSC function.

  12. Setting Priorities for Diabetic Retinopathy Clinical Research and Identifying Evidence Gaps.

    Science.gov (United States)

    Le, Jimmy T; Hutfless, Susan; Li, Tianjing; Bressler, Neil M; Heyward, James; Bittner, Ava K; Glassman, Adam; Dickersin, Kay

    2017-01-01

    Prioritizing comparative effectiveness research may contribute to obtaining answers that clinicians perceive they need and may minimize research that could be considered wasteful. Our objective was to identify evidence gaps and set priorities for new systematic reviews and randomized controlled trials for managing diabetic retinopathy (DR), including diabetic macular edema (DME). Cross-sectional study. Diabetic Retinopathy Clinical Research Network (DRCR.net) investigators. We provided recommendations from the American Academy of Ophthalmology's 2012 Preferred Practice Patterns for Diabetic Retinopathy as 91 answerable clinical research questions about intervention effectiveness to 410 DRCR.net investigators to rate each question's importance from 0 (not important) to 10 (very important) using a 2-round Delphi survey and to suggest additional questions. We considered questions as high priority if at least 75% of respondents to both rounds assigned an importance rating of 5 or more in round 2. We also extracted outcome measures relevant to DR and asked respondents to identify those that must be measured in all studies. We mapped Cochrane reviews published up to March 2016 to high-priority clinical research questions. Ranking of importance of each clinical question. Thirty-two individuals completed rounds 1 and 2 and suggested 15 questions. Among the final list of 106 clinical research questions, 22 questions met our definition of high priority: 9 of 22 concerned the effectiveness of anti-VEGF therapy, and 13 of 22 focused on how often patients should be followed up (re-examination) and treatment effectiveness in patients with specific characteristics (e.g., DME). Outcomes that 75% or more of respondents marked as "must be measured in all studies" included visual acuity and visual loss, death of participants, and intraocular pressure. Only 1 prioritized question was associated with conclusive evidence from a Cochrane systematic review. A limited response rate among

  13. Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer.

    Science.gov (United States)

    Michaut, Magali; Chin, Suet-Feung; Majewski, Ian; Severson, Tesa M; Bismeijer, Tycho; de Koning, Leanne; Peeters, Justine K; Schouten, Philip C; Rueda, Oscar M; Bosma, Astrid J; Tarrant, Finbarr; Fan, Yue; He, Beilei; Xue, Zheng; Mittempergher, Lorenza; Kluin, Roelof J C; Heijmans, Jeroen; Snel, Mireille; Pereira, Bernard; Schlicker, Andreas; Provenzano, Elena; Ali, Hamid Raza; Gaber, Alexander; O'Hurley, Gillian; Lehn, Sophie; Muris, Jettie J F; Wesseling, Jelle; Kay, Elaine; Sammut, Stephen John; Bardwell, Helen A; Barbet, Aurélie S; Bard, Floriane; Lecerf, Caroline; O'Connor, Darran P; Vis, Daniël J; Benes, Cyril H; McDermott, Ultan; Garnett, Mathew J; Simon, Iris M; Jirström, Karin; Dubois, Thierry; Linn, Sabine C; Gallagher, William M; Wessels, Lodewyk F A; Caldas, Carlos; Bernards, Rene

    2016-01-05

    Invasive lobular carcinoma (ILC) is the second most frequently occurring histological breast cancer subtype after invasive ductal carcinoma (IDC), accounting for around 10% of all breast cancers. The molecular processes that drive the development of ILC are still largely unknown. We have performed a comprehensive genomic, transcriptomic and proteomic analysis of a large ILC patient cohort and present here an integrated molecular portrait of ILC. Mutations in CDH1 and in the PI3K pathway are the most frequent molecular alterations in ILC. We identified two main subtypes of ILCs: (i) an immune related subtype with mRNA up-regulation of PD-L1, PD-1 and CTLA-4 and greater sensitivity to DNA-damaging agents in representative cell line models; (ii) a hormone related subtype, associated with Epithelial to Mesenchymal Transition (EMT), and gain of chromosomes 1q and 8q and loss of chromosome 11q. Using the somatic mutation rate and eIF4B protein level, we identified three groups with different clinical outcomes, including a group with extremely good prognosis. We provide a comprehensive overview of the molecular alterations driving ILC and have explored links with therapy response. This molecular characterization may help to tailor treatment of ILC through the application of specific targeted, chemo- and/or immune-therapies.

  14. IS3 profiling identifies the enterohaemorrhagic Escherichia coli O-island 62 in a distinct enteroaggregative E. coli lineage

    Directory of Open Access Journals (Sweden)

    Okeke Iruka N

    2011-03-01

    Full Text Available Abstract Background Enteroaggregative Escherichia coli (EAEC are important diarrhoeal pathogens that are defined by a HEp-2 adherence assay performed in specialist laboratories. Multilocus sequence typing (MLST has revealed that aggregative adherence is convergent, providing an explanation for why not all EAEC hybridize with the plasmid-derived probe for this category, designated CVD432. Some EAEC lineages are globally disseminated or more closely associated with disease. Results To identify genetic loci conserved within significant EAEC lineages, but absent from non-EAEC, IS3-based PCR profiles were generated for 22 well-characterised EAEC strains. Six bands that were conserved among, or missing from, specific EAEC lineages were cloned and sequenced. One band corresponded to the aggR gene, a plasmid-encoded regulator that has been used as a diagnostic target but predominantly detects EAEC bearing the plasmid already marked by CVD432. The sequence from a second band was homologous to an open-reading frame within the cryptic enterohaemorrhagic E. coli (EHEC O157 genomic island, designated O-island 62. Screening of an additional 46 EAEC strains revealed that the EHEC O-island 62 was only present in those EAEC strains belonging to the ECOR phylogenetic group D, largely comprised of sequence type (ST complexes 31, 38 and 394. Conclusions The EAEC 042 gene orf1600, which lies within the EAEC equivalent of O-island 62 island, can be used as a marker for EAEC strains belonging to the ECOR phylogenetic group D. The discovery of EHEC O-island 62 in EAEC validates the genetic profiling approach for identifying conserved loci among phylogenetically related strains.

  15. Sets of RNA repeated tags and hybridization-sensitive fluorescent probes for distinct images of RNA in a living cell.

    Directory of Open Access Journals (Sweden)

    Takeshi Kubota

    Full Text Available BACKGROUND: Imaging the behavior of RNA in a living cell is a powerful means for understanding RNA functions and acquiring spatiotemporal information in a single cell. For more distinct RNA imaging in a living cell, a more effective chemical method to fluorescently label RNA is now required. In addition, development of the technology labeling with different colors for different RNA would make it easier to analyze plural RNA strands expressing in a cell. METHODOLOGY/PRINCIPAL FINDINGS: Tag technology for RNA imaging in a living cell has been developed based on the unique chemical functions of exciton-controlled hybridization-sensitive oligonucleotide (ECHO probes. Repetitions of selected 18-nucleotide RNA tags were incorporated into the mRNA 3'-UTR. Pairs with complementary ECHO probes exhibited hybridization-sensitive fluorescence emission for the mRNA expressed in a living cell. The mRNA in a nucleus was detected clearly as fluorescent puncta, and the images of the expression of two mRNAs were obtained independently and simultaneously with two orthogonal tag-probe pairs. CONCLUSIONS/SIGNIFICANCE: A compact and repeated label has been developed for RNA imaging in a living cell, based on the photochemistry of ECHO probes. The pairs of an 18-nt RNA tag and the complementary ECHO probes are highly thermostable, sequence-specifically emissive, and orthogonal to each other. The nucleotide length necessary for one tag sequence is much shorter compared with conventional tag technologies, resulting in easy preparation of the tag sequences with a larger number of repeats for more distinct RNA imaging.

  16. Promoter Hypermethylation Profiling Identifies Subtypes of Head and Neck Cancer with Distinct Viral, Environmental, Genetic and Survival Characteristics.

    Directory of Open Access Journals (Sweden)

    Javed Hussain Choudhury

    Full Text Available Epigenetic and genetic alteration plays a major role to the development of head and neck squamous cell carcinoma (HNSCC. Consumption of tobacco (smoking/chewing and human papilloma virus (HPV are also associated with an increase the risk of HNSCC. Promoter hypermethylation of the tumor suppression genes is related with transcriptional inactivation and loss of gene expression. We investigated epigenetic alteration (promoter methylation of tumor-related genes/loci in tumor tissues in the context of genetic alteration, viral infection, and tobacco exposure and survival status.The study included 116 tissue samples (71 tumor and 45 normal tissues from the Northeast Indian population. Methylation specific polymerase chain reaction (MSP was used to determine the methylation status of 10 tumor-related genes/loci (p16, DAPK, RASSF1, BRAC1, GSTP1, ECAD, MLH1, MINT1, MINT2 and MINT31. Polymorphisms of CYP1A1, GST (M1 & T1, XRCC1and XRCC2 genes were studied by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP and multiplex-PCR respectively.Unsupervised hierarchical clustering analysis based on methylation pattern had identified two tumor clusters, which significantly differ by CpG island methylator phenotype (CIMP, tobacco, GSTM1, CYP1A1, HPV and survival status. Analyzing methylation of genes/loci individually, we have found significant higher methylation of DAPK, RASSF1, p16 and MINT31 genes (P = 0.031, 0.013, 0.031 and 0.015 respectively in HPV (+ cases compared to HPV (-. Furthermore, a CIMP-high and Cluster-1 characteristic was also associated with poor survival.Promoter methylation profiles reflecting a correlation with tobacco, HPV, survival status and genetic alteration and may act as a marker to determine subtypes and patient outcome in HNSCC.

  17. Promoter Hypermethylation Profiling Identifies Subtypes of Head and Neck Cancer with Distinct Viral, Environmental, Genetic and Survival Characteristics

    Science.gov (United States)

    Choudhury, Javed Hussain; Ghosh, Sankar Kumar

    2015-01-01

    Background Epigenetic and genetic alteration plays a major role to the development of head and neck squamous cell carcinoma (HNSCC). Consumption of tobacco (smoking/chewing) and human papilloma virus (HPV) are also associated with an increase the risk of HNSCC. Promoter hypermethylation of the tumor suppression genes is related with transcriptional inactivation and loss of gene expression. We investigated epigenetic alteration (promoter methylation of tumor-related genes/loci) in tumor tissues in the context of genetic alteration, viral infection, and tobacco exposure and survival status. Methodology The study included 116 tissue samples (71 tumor and 45 normal tissues) from the Northeast Indian population. Methylation specific polymerase chain reaction (MSP) was used to determine the methylation status of 10 tumor-related genes/loci (p16, DAPK, RASSF1, BRAC1, GSTP1, ECAD, MLH1, MINT1, MINT2 and MINT31). Polymorphisms of CYP1A1, GST (M1 & T1), XRCC1and XRCC2 genes were studied by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and multiplex-PCR respectively. Principal Findings Unsupervised hierarchical clustering analysis based on methylation pattern had identified two tumor clusters, which significantly differ by CpG island methylator phenotype (CIMP), tobacco, GSTM1, CYP1A1, HPV and survival status. Analyzing methylation of genes/loci individually, we have found significant higher methylation of DAPK, RASSF1, p16 and MINT31genes (P = 0.031, 0.013, 0.031 and 0.015 respectively) in HPV (+) cases compared to HPV (-). Furthermore, a CIMP-high and Cluster-1 characteristic was also associated with poor survival. Conclusions Promoter methylation profiles reflecting a correlation with tobacco, HPV, survival status and genetic alteration and may act as a marker to determine subtypes and patient outcome in HNSCC. PMID:26098903

  18. Microarray analysis identifies a common set of cellular genes modulated by different HCV replicon clones

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    Gerosolimo Germano

    2008-06-01

    Full Text Available Abstract Background Hepatitis C virus (HCV RNA synthesis and protein expression affect cell homeostasis by modulation of gene expression. The impact of HCV replication on global cell transcription has not been fully evaluated. Thus, we analysed the expression profiles of different clones of human hepatoma-derived Huh-7 cells carrying a self-replicating HCV RNA which express all viral proteins (HCV replicon system. Results First, we compared the expression profile of HCV replicon clone 21-5 with both the Huh-7 parental cells and the 21-5 cured (21-5c cells. In these latter, the HCV RNA has been eliminated by IFN-α treatment. To confirm data, we also analyzed microarray results from both the 21-5 and two other HCV replicon clones, 22-6 and 21-7, compared to the Huh-7 cells. The study was carried out by using the Applied Biosystems (AB Human Genome Survey Microarray v1.0 which provides 31,700 probes that correspond to 27,868 human genes. Microarray analysis revealed a specific transcriptional program induced by HCV in replicon cells respect to both IFN-α-cured and Huh-7 cells. From the original datasets of differentially expressed genes, we selected by Venn diagrams a final list of 38 genes modulated by HCV in all clones. Most of the 38 genes have never been described before and showed high fold-change associated with significant p-value, strongly supporting data reliability. Classification of the 38 genes by Panther System identified functional categories that were significantly enriched in this gene set, such as histones and ribosomal proteins as well as extracellular matrix and intracellular protein traffic. The dataset also included new genes involved in lipid metabolism, extracellular matrix and cytoskeletal network, which may be critical for HCV replication and pathogenesis. Conclusion Our data provide a comprehensive analysis of alterations in gene expression induced by HCV replication and reveal modulation of new genes potentially useful

  19. Identifying genetic marker sets associated with phenotypes via an efficient adaptive score test

    KAUST Repository

    Cai, T.; Lin, X.; Carroll, R. J.

    2012-01-01

    the overall effect of a marker-set have been actively studied in recent years. For example, score tests derived under an Empirical Bayes (EB) framework (Liu and others, 2007. Semiparametric regression of multidimensional genetic pathway data: least

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

    Science.gov (United States)

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

    2012-03-01

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

  1. Drosophila Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution

    Science.gov (United States)

    Leung, Wilson; Shaffer, Christopher D.; Reed, Laura K.; Smith, Sheryl T.; Barshop, William; Dirkes, William; Dothager, Matthew; Lee, Paul; Wong, Jeannette; Xiong, David; Yuan, Han; Bedard, James E. J.; Machone, Joshua F.; Patterson, Seantay D.; Price, Amber L.; Turner, Bryce A.; Robic, Srebrenka; Luippold, Erin K.; McCartha, Shannon R.; Walji, Tezin A.; Walker, Chelsea A.; Saville, Kenneth; Abrams, Marita K.; Armstrong, Andrew R.; Armstrong, William; Bailey, Robert J.; Barberi, Chelsea R.; Beck, Lauren R.; Blaker, Amanda L.; Blunden, Christopher E.; Brand, Jordan P.; Brock, Ethan J.; Brooks, Dana W.; Brown, Marie; Butzler, Sarah C.; Clark, Eric M.; Clark, Nicole B.; Collins, Ashley A.; Cotteleer, Rebecca J.; Cullimore, Peterson R.; Dawson, Seth G.; Docking, Carter T.; Dorsett, Sasha L.; Dougherty, Grace A.; Downey, Kaitlyn A.; Drake, Andrew P.; Earl, Erica K.; Floyd, Trevor G.; Forsyth, Joshua D.; Foust, Jonathan D.; Franchi, Spencer L.; Geary, James F.; Hanson, Cynthia K.; Harding, Taylor S.; Harris, Cameron B.; Heckman, Jonathan M.; Holderness, Heather L.; Howey, Nicole A.; Jacobs, Dontae A.; Jewell, Elizabeth S.; Kaisler, Maria; Karaska, Elizabeth A.; Kehoe, James L.; Koaches, Hannah C.; Koehler, Jessica; Koenig, Dana; Kujawski, Alexander J.; Kus, Jordan E.; Lammers, Jennifer A.; Leads, Rachel R.; Leatherman, Emily C.; Lippert, Rachel N.; Messenger, Gregory S.; Morrow, Adam T.; Newcomb, Victoria; Plasman, Haley J.; Potocny, Stephanie J.; Powers, Michelle K.; Reem, Rachel M.; Rennhack, Jonathan P.; Reynolds, Katherine R.; Reynolds, Lyndsey A.; Rhee, Dong K.; Rivard, Allyson B.; Ronk, Adam J.; Rooney, Meghan B.; Rubin, Lainey S.; Salbert, Luke R.; Saluja, Rasleen K.; Schauder, Taylor; Schneiter, Allison R.; Schulz, Robert W.; Smith, Karl E.; Spencer, Sarah; Swanson, Bryant R.; Tache, Melissa A.; Tewilliager, Ashley A.; Tilot, Amanda K.; VanEck, Eve; Villerot, Matthew M.; Vylonis, Megan B.; Watson, David T.; Wurzler, Juliana A.; Wysocki, Lauren M.; Yalamanchili, Monica; Zaborowicz, Matthew A.; Emerson, Julia A.; Ortiz, Carlos; Deuschle, Frederic J.; DiLorenzo, Lauren A.; Goeller, Katie L.; Macchi, Christopher R.; Muller, Sarah E.; Pasierb, Brittany D.; Sable, Joseph E.; Tucci, Jessica M.; Tynon, Marykathryn; Dunbar, David A.; Beken, Levent H.; Conturso, Alaina C.; Danner, Benjamin L.; DeMichele, Gabriella A.; Gonzales, Justin A.; Hammond, Maureen S.; Kelley, Colleen V.; Kelly, Elisabeth A.; Kulich, Danielle; Mageeney, Catherine M.; McCabe, Nikie L.; Newman, Alyssa M.; Spaeder, Lindsay A.; Tumminello, Richard A.; Revie, Dennis; Benson, Jonathon M.; Cristostomo, Michael C.; DaSilva, Paolo A.; Harker, Katherine S.; Jarrell, Jenifer N.; Jimenez, Luis A.; Katz, Brandon M.; Kennedy, William R.; Kolibas, Kimberly S.; LeBlanc, Mark T.; Nguyen, Trung T.; Nicolas, Daniel S.; Patao, Melissa D.; Patao, Shane M.; Rupley, Bryan J.; Sessions, Bridget J.; Weaver, Jennifer A.; Goodman, Anya L.; Alvendia, Erica L.; Baldassari, Shana M.; Brown, Ashley S.; Chase, Ian O.; Chen, Maida; Chiang, Scott; Cromwell, Avery B.; Custer, Ashley F.; DiTommaso, Tia M.; El-Adaimi, Jad; Goscinski, Nora C.; Grove, Ryan A.; Gutierrez, Nestor; Harnoto, Raechel S.; Hedeen, Heather; Hong, Emily L.; Hopkins, Barbara L.; Huerta, Vilma F.; Khoshabian, Colin; LaForge, Kristin M.; Lee, Cassidy T.; Lewis, Benjamin M.; Lydon, Anniken M.; Maniaci, Brian J.; Mitchell, Ryan D.; Morlock, Elaine V.; Morris, William M.; Naik, Priyanka; Olson, Nicole C.; Osterloh, Jeannette M.; Perez, Marcos A.; Presley, Jonathan D.; Randazzo, Matt J.; Regan, Melanie K.; Rossi, Franca G.; Smith, Melanie A.; Soliterman, Eugenia A.; Sparks, Ciani J.; Tran, Danny L.; Wan, Tiffany; Welker, Anne A.; Wong, Jeremy N.; Sreenivasan, Aparna; Youngblom, Jim; Adams, Andrew; Alldredge, Justin; Bryant, Ashley; Carranza, David; Cifelli, Alyssa; Coulson, Kevin; Debow, Calise; Delacruz, Noelle; Emerson, Charlene; Farrar, Cassandra; Foret, Don; Garibay, Edgar; Gooch, John; Heslop, Michelle; Kaur, Sukhjit; Khan, Ambreen; Kim, Van; Lamb, Travis; Lindbeck, Peter; Lucas, Gabi; Macias, Elizabeth; Martiniuc, Daniela; Mayorga, Lissett; Medina, Joseph; Membreno, Nelson; Messiah, Shady; Neufeld, Lacey; Nguyen, San Francisco; Nichols, Zachary; Odisho, George; Peterson, Daymon; Rodela, Laura; Rodriguez, Priscilla; Rodriguez, Vanessa; Ruiz, Jorge; Sherrill, Will; Silva, Valeria; Sparks, Jeri; Statton, Geeta; Townsend, Ashley; Valdez, Isabel; Waters, Mary; Westphal, Kyle; Winkler, Stacey; Zumkehr, Joannee; DeJong, Randall J.; Hoogewerf, Arlene J.; Ackerman, Cheri M.; Armistead, Isaac O.; Baatenburg, Lara; Borr, Matthew J.; Brouwer, Lindsay K.; Burkhart, Brandon J.; Bushhouse, Kelsey T.; Cesko, Lejla; Choi, Tiffany Y. Y.; Cohen, Heather; Damsteegt, Amanda M.; Darusz, Jess M.; Dauphin, Cory M.; Davis, Yelena P.; Diekema, Emily J.; Drewry, Melissa; Eisen, Michelle E. M.; Faber, Hayley M.; Faber, Katherine J.; Feenstra, Elizabeth; Felzer-Kim, Isabella T.; Hammond, Brandy L.; Hendriksma, Jesse; Herrold, Milton R.; Hilbrands, Julia A.; Howell, Emily J.; Jelgerhuis, Sarah A.; Jelsema, Timothy R.; Johnson, Benjamin K.; Jones, Kelly K.; Kim, Anna; Kooienga, Ross D.; Menyes, Erika E.; Nollet, Eric A.; Plescher, Brittany E.; Rios, Lindsay; Rose, Jenny L.; Schepers, Allison J.; Scott, Geoff; Smith, Joshua R.; Sterling, Allison M.; Tenney, Jenna C.; Uitvlugt, Chris; VanDyken, Rachel E.; VanderVennen, Marielle; Vue, Samantha; Kokan, Nighat P.; Agbley, Kwabea; Boham, Sampson K.; Broomfield, Daniel; Chapman, Kayla; Dobbe, Ali; Dobbe, Ian; Harrington, William; Ibrahem, Marwan; Kennedy, Andre; Koplinsky, Chad A.; Kubricky, Cassandra; Ladzekpo, Danielle; Pattison, Claire; Ramirez, Roman E.; Wande, Lucia; Woehlke, Sarah; Wawersik, Matthew; Kiernan, Elizabeth; Thompson, Jeffrey S.; Banker, Roxanne; Bartling, Justina R.; Bhatiya, Chinmoy I.; Boudoures, Anna L.; Christiansen, Lena; Fosselman, Daniel S.; French, Kristin M.; Gill, Ishwar S.; Havill, Jessen T.; Johnson, Jaelyn L.; Keny, Lauren J.; Kerber, John M.; Klett, Bethany M.; Kufel, Christina N.; May, Francis J.; Mecoli, Jonathan P.; Merry, Callie R.; Meyer, Lauren R.; Miller, Emily G.; Mullen, Gregory J.; Palozola, Katherine C.; Pfeil, Jacob J.; Thomas, Jessica G.; Verbofsky, Evan M.; Spana, Eric P.; Agarwalla, Anant; Chapman, Julia; Chlebina, Ben; Chong, Insun; Falk, I.N.; Fitzgibbons, John D.; Friedman, Harrison; Ighile, Osagie; Kim, Andrew J.; Knouse, Kristin A.; Kung, Faith; Mammo, Danny; Ng, Chun Leung; Nikam, Vinayak S.; Norton, Diana; Pham, Philip; Polk, Jessica W.; Prasad, Shreya; Rankin, Helen; Ratliff, Camille D.; Scala, Victoria; Schwartz, Nicholas U.; Shuen, Jessica A.; Xu, Amy; Xu, Thomas Q.; Zhang, Yi; Rosenwald, Anne G.; Burg, Martin G.; Adams, Stephanie J.; Baker, Morgan; Botsford, Bobbi; Brinkley, Briana; Brown, Carter; Emiah, Shadie; Enoch, Erica; Gier, Chad; Greenwell, Alyson; Hoogenboom, Lindsay; Matthews, Jordan E.; McDonald, Mitchell; Mercer, Amanda; Monsma, Nicholaus; Ostby, Kristine; Ramic, Alen; Shallman, Devon; Simon, Matthew; Spencer, Eric; Tomkins, Trisha; Wendland, Pete; Wylie, Anna; Wolyniak, Michael J.; Robertson, Gregory M.; Smith, Samuel I.; DiAngelo, Justin R.; Sassu, Eric D.; Bhalla, Satish C.; Sharif, Karim A.; Choeying, Tenzin; Macias, Jason S.; Sanusi, Fareed; Torchon, Karvyn; Bednarski, April E.; Alvarez, Consuelo J.; Davis, Kristen C.; Dunham, Carrie A.; Grantham, Alaina J.; Hare, Amber N.; Schottler, Jennifer; Scott, Zackary W.; Kuleck, Gary A.; Yu, Nicole S.; Kaehler, Marian M.; Jipp, Jacob; Overvoorde, Paul J.; Shoop, Elizabeth; Cyrankowski, Olivia; Hoover, Betsy; Kusner, Matt; Lin, Devry; Martinov, Tijana; Misch, Jonathan; Salzman, Garrett; Schiedermayer, Holly; Snavely, Michael; Zarrasola, Stephanie; Parrish, Susan; Baker, Atlee; Beckett, Alissa; Belella, Carissa; Bryant, Julie; Conrad, Turner; Fearnow, Adam; Gomez, Carolina; Herbstsomer, Robert A.; Hirsch, Sarah; Johnson, Christen; Jones, Melissa; Kabaso, Rita; Lemmon, Eric; Vieira, Carolina Marques dos Santos; McFarland, Darryl; McLaughlin, Christopher; Morgan, Abbie; Musokotwane, Sepo; Neutzling, William; Nietmann, Jana; Paluskievicz, Christina; Penn, Jessica; Peoples, Emily; Pozmanter, Caitlin; Reed, Emily; Rigby, Nichole; Schmidt, Lasse; Shelton, Micah; Shuford, Rebecca; Tirasawasdichai, Tiara; Undem, Blair; Urick, Damian; Vondy, Kayla; Yarrington, Bryan; Eckdahl, Todd T.; Poet, Jeffrey L.; Allen, Alica B.; Anderson, John E.; Barnett, Jason M.; Baumgardner, Jordan S.; Brown, Adam D.; Carney, Jordan E.; Chavez, Ramiro A.; Christgen, Shelbi L.; Christie, Jordan S.; Clary, Andrea N.; Conn, Michel A.; Cooper, Kristen M.; Crowley, Matt J.; Crowley, Samuel T.; Doty, Jennifer S.; Dow, Brian A.; Edwards, Curtis R.; Elder, Darcie D.; Fanning, John P.; Janssen, Bridget M.; Lambright, Anthony K.; Lane, Curtiss E.; Limle, Austin B.; Mazur, Tammy; McCracken, Marly R.; McDonough, Alexa M.; Melton, Amy D.; Minnick, Phillip J.; Musick, Adam E.; Newhart, William H.; Noynaert, Joseph W.; Ogden, Bradley J.; Sandusky, Michael W.; Schmuecker, Samantha M.; Shipman, Anna L.; Smith, Anna L.; Thomsen, Kristen M.; Unzicker, Matthew R.; Vernon, William B.; Winn, Wesley W.; Woyski, Dustin S.; Zhu, Xiao; Du, Chunguang; Ament, Caitlin; Aso, Soham; Bisogno, Laura Simone; Caronna, Jason; Fefelova, Nadezhda; Lopez, Lenin; Malkowitz, Lorraine; Marra, Jonathan; Menillo, Daniella; Obiorah, Ifeanyi; Onsarigo, Eric Nyabeta; Primus, Shekerah; Soos, Mahdi; Tare, Archana; Zidan, Ameer; Jones, Christopher J.; Aronhalt, Todd; Bellush, James M.; Burke, Christa; DeFazio, Steve; Does, Benjamin R.; Johnson, Todd D.; Keysock, Nicholas; Knudsen, Nelson H.; Messler, James; Myirski, Kevin; Rekai, Jade Lea; Rempe, Ryan Michael; Salgado, Michael S.; Stagaard, Erica; Starcher, Justin R.; Waggoner, Andrew W.; Yemelyanova, Anastasia K.; Hark, Amy T.; Bertolet, Anne; Kuschner, Cyrus E.; Parry, Kesley; Quach, Michael; Shantzer, Lindsey; Shaw, Mary E.; Smith, Mary A.; Glenn, Omolara; Mason, Portia; Williams, Charlotte; Key, S. Catherine Silver; Henry, Tyneshia C. P.; Johnson, Ashlee G.; White, Jackie X.; Haberman, Adam; Asinof, Sam; Drumm, Kelly; Freeburg, Trip; Safa, Nadia; Schultz, Darrin; Shevin, Yakov; Svoronos, Petros; Vuong, Tam; Wellinghoff, Jules; Hoopes, Laura L. M.; Chau, Kim M.; Ward, Alyssa; Regisford, E. Gloria C.; Augustine, LaJerald; Davis-Reyes, Brionna; Echendu, Vivienne; Hales, Jasmine; Ibarra, Sharon; Johnson, Lauriaun; Ovu, Steven; Braverman, John M.; Bahr, Thomas J.; Caesar, Nicole M.; Campana, Christopher; Cassidy, Daniel W.; Cognetti, Peter A.; English, Johnathan D.; Fadus, Matthew C.; Fick, Cameron N.; Freda, Philip J.; Hennessy, Bryan M.; Hockenberger, Kelsey; Jones, Jennifer K.; King, Jessica E.; Knob, Christopher R.; Kraftmann, Karen J.; Li, Linghui; Lupey, Lena N.; Minniti, Carl J.; Minton, Thomas F.; Moran, Joseph V.; Mudumbi, Krishna; Nordman, Elizabeth C.; Puetz, William J.; Robinson, Lauren M.; Rose, Thomas J.; Sweeney, Edward P.; Timko, Ashley S.; Paetkau, Don W.; Eisler, Heather L.; Aldrup, Megan E.; Bodenberg, Jessica M.; Cole, Mara G.; Deranek, Kelly M.; DeShetler, Megan; Dowd, Rose M.; Eckardt, Alexandra K.; Ehret, Sharon C.; Fese, Jessica; Garrett, Amanda D.; Kammrath, Anna; Kappes, Michelle L.; Light, Morgan R.; Meier, Anne C.; O’Rouke, Allison; Perella, Mallory; Ramsey, Kimberley; Ramthun, Jennifer R.; Reilly, Mary T.; Robinett, Deirdre; Rossi, Nadine L.; Schueler, Mary Grace; Shoemaker, Emma; Starkey, Kristin M.; Vetor, Ashley; Vrable, Abby; Chandrasekaran, Vidya; Beck, Christopher; Hatfield, Kristen R.; Herrick, Douglas A.; Khoury, Christopher B.; Lea, Charlotte; Louie, Christopher A.; Lowell, Shannon M.; Reynolds, Thomas J.; Schibler, Jeanine; Scoma, Alexandra H.; Smith-Gee, Maxwell T.; Tuberty, Sarah; Smith, Christopher D.; Lopilato, Jane E.; Hauke, Jeanette; Roecklein-Canfield, Jennifer A.; Corrielus, Maureen; Gilman, Hannah; Intriago, Stephanie; Maffa, Amanda; Rauf, Sabya A.; Thistle, Katrina; Trieu, Melissa; Winters, Jenifer; Yang, Bib; Hauser, Charles R.; Abusheikh, Tariq; Ashrawi, Yara; Benitez, Pedro; Boudreaux, Lauren R.; Bourland, Megan; Chavez, Miranda; Cruz, Samantha; Elliott, GiNell; Farek, Jesse R.; Flohr, Sarah; Flores, Amanda H.; Friedrichs, Chelsey; Fusco, Zach; Goodwin, Zane; Helmreich, Eric; Kiley, John; Knepper, John Mark; Langner, Christine; Martinez, Megan; Mendoza, Carlos; Naik, Monal; Ochoa, Andrea; Ragland, Nicolas; Raimey, England; Rathore, Sunil; Reza, Evangelina; Sadovsky, Griffin; Seydoux, Marie-Isabelle B.; Smith, Jonathan E.; Unruh, Anna K.; Velasquez, Vicente; Wolski, Matthew W.; Gosser, Yuying; Govind, Shubha; Clarke-Medley, Nicole; Guadron, Leslie; Lau, Dawn; Lu, Alvin; Mazzeo, Cheryl; Meghdari, Mariam; Ng, Simon; Pamnani, Brad; Plante, Olivia; Shum, Yuki Kwan Wa; Song, Roy; Johnson, Diana E.; Abdelnabi, Mai; Archambault, Alexi; Chamma, Norma; Gaur, Shailly; Hammett, Deborah; Kandahari, Adrese; Khayrullina, Guzal; Kumar, Sonali; Lawrence, Samantha; Madden, Nigel; Mandelbaum, Max; Milnthorp, Heather; Mohini, Shiv; Patel, Roshni; Peacock, Sarah J.; Perling, Emily; Quintana, Amber; Rahimi, Michael; Ramirez, Kristen; Singhal, Rishi; Weeks, Corinne; Wong, Tiffany; Gillis, Aubree T.; Moore, Zachary D.; Savell, Christopher D.; Watson, Reece; Mel, Stephanie F.; Anilkumar, Arjun A.; Bilinski, Paul; Castillo, Rostislav; Closser, Michael; Cruz, Nathalia M.; Dai, Tiffany; Garbagnati, Giancarlo F.; Horton, Lanor S.; Kim, Dongyeon; Lau, Joyce H.; Liu, James Z.; Mach, Sandy D.; Phan, Thu A.; Ren, Yi; Stapleton, Kenneth E.; Strelitz, Jean M.; Sunjed, Ray; Stamm, Joyce; Anderson, Morgan C.; Bonifield, Bethany Grace; Coomes, Daniel; Dillman, Adam; Durchholz, Elaine J.; Fafara-Thompson, Antoinette E.; Gross, Meleah J.; Gygi, Amber M.; Jackson, Lesley E.; Johnson, Amy; Kocsisova, Zuzana; Manghelli, Joshua L.; McNeil, Kylie; Murillo, Michael; Naylor, Kierstin L.; Neely, Jessica; Ogawa, Emmy E.; Rich, Ashley; Rogers, Anna; Spencer, J. Devin; Stemler, Kristina M.; Throm, Allison A.; Van Camp, Matt; Weihbrecht, Katie; Wiles, T. Aaron; Williams, Mallory A.; Williams, Matthew; Zoll, Kyle; Bailey, Cheryl; Zhou, Leming; Balthaser, Darla M.; Bashiri, Azita; Bower, Mindy E.; Florian, Kayla A.; Ghavam, Nazanin; Greiner-Sosanko, Elizabeth S.; Karim, Helmet; Mullen, Victor W.; Pelchen, Carly E.; Yenerall, Paul M.; Zhang, Jiayu; Rubin, Michael R.; Arias-Mejias, Suzette M.; Bermudez-Capo, Armando G.; Bernal-Vega, Gabriela V.; Colon-Vazquez, Mariela; Flores-Vazquez, Arelys; Gines-Rosario, Mariela; Llavona-Cartagena, Ivan G.; Martinez-Rodriguez, Javier O.; Ortiz-Fuentes, Lionel; Perez-Colomba, Eliezer O.; Perez-Otero, Joseph; Rivera, Elisandra; Rodriguez-Giron, Luke J.; Santiago-Sanabria, Arnaldo J.; Senquiz-Gonzalez, Andrea M.; delValle, Frank R. 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    2015-01-01

    The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu. PMID:25740935

  2. Drosophila muller f elements maintain a distinct set of genomic properties over 40 million years of evolution.

    Science.gov (United States)

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Braverman, John M; Bahr, Thomas J; Caesar, Nicole M; Campana, Christopher; Cassidy, Daniel W; Cognetti, Peter A; English, Johnathan D; Fadus, Matthew C; Fick, Cameron N; Freda, Philip J; Hennessy, Bryan M; Hockenberger, Kelsey; Jones, Jennifer K; King, Jessica E; Knob, Christopher R; Kraftmann, Karen J; Li, Linghui; Lupey, Lena N; Minniti, Carl J; Minton, Thomas F; Moran, Joseph V; Mudumbi, Krishna; Nordman, Elizabeth C; Puetz, William J; Robinson, Lauren M; Rose, Thomas J; Sweeney, Edward P; Timko, Ashley S; Paetkau, Don W; Eisler, Heather L; Aldrup, Megan E; Bodenberg, Jessica M; Cole, Mara G; Deranek, Kelly M; DeShetler, Megan; Dowd, Rose M; Eckardt, Alexandra K; Ehret, Sharon C; Fese, Jessica; Garrett, Amanda D; Kammrath, Anna; Kappes, Michelle L; Light, Morgan R; Meier, Anne C; O'Rouke, Allison; Perella, Mallory; Ramsey, Kimberley; Ramthun, Jennifer R; Reilly, Mary T; Robinett, Deirdre; Rossi, Nadine L; Schueler, Mary Grace; Shoemaker, Emma; Starkey, Kristin M; Vetor, Ashley; Vrable, Abby; Chandrasekaran, Vidya; Beck, Christopher; Hatfield, Kristen R; Herrick, Douglas A; Khoury, Christopher B; Lea, Charlotte; Louie, Christopher A; Lowell, Shannon M; Reynolds, Thomas J; Schibler, Jeanine; Scoma, Alexandra H; Smith-Gee, Maxwell T; Tuberty, Sarah; Smith, Christopher D; Lopilato, Jane E; Hauke, Jeanette; Roecklein-Canfield, Jennifer A; Corrielus, Maureen; Gilman, Hannah; Intriago, Stephanie; Maffa, Amanda; Rauf, Sabya A; Thistle, Katrina; Trieu, Melissa; Winters, Jenifer; Yang, Bib; Hauser, Charles R; Abusheikh, Tariq; Ashrawi, Yara; Benitez, Pedro; Boudreaux, Lauren R; Bourland, Megan; Chavez, Miranda; Cruz, Samantha; Elliott, GiNell; Farek, Jesse R; Flohr, Sarah; Flores, Amanda H; Friedrichs, Chelsey; Fusco, Zach; Goodwin, Zane; Helmreich, Eric; Kiley, John; Knepper, John Mark; Langner, Christine; Martinez, Megan; Mendoza, Carlos; Naik, Monal; Ochoa, Andrea; Ragland, Nicolas; Raimey, England; Rathore, Sunil; Reza, Evangelina; Sadovsky, Griffin; Seydoux, Marie-Isabelle B; Smith, Jonathan E; Unruh, Anna K; Velasquez, Vicente; Wolski, Matthew W; Gosser, Yuying; Govind, Shubha; Clarke-Medley, Nicole; Guadron, Leslie; Lau, Dawn; Lu, Alvin; Mazzeo, Cheryl; Meghdari, Mariam; Ng, Simon; Pamnani, Brad; Plante, Olivia; Shum, Yuki Kwan Wa; Song, Roy; Johnson, Diana E; Abdelnabi, Mai; Archambault, Alexi; Chamma, Norma; Gaur, Shailly; Hammett, Deborah; Kandahari, Adrese; Khayrullina, Guzal; Kumar, Sonali; Lawrence, Samantha; Madden, Nigel; Mandelbaum, Max; Milnthorp, Heather; Mohini, Shiv; Patel, Roshni; Peacock, Sarah J; Perling, Emily; Quintana, Amber; Rahimi, Michael; Ramirez, Kristen; Singhal, Rishi; Weeks, Corinne; Wong, Tiffany; Gillis, Aubree T; Moore, Zachary D; Savell, Christopher D; Watson, Reece; Mel, Stephanie F; Anilkumar, Arjun A; Bilinski, Paul; Castillo, Rostislav; Closser, Michael; Cruz, Nathalia M; Dai, Tiffany; Garbagnati, Giancarlo F; Horton, Lanor S; Kim, Dongyeon; Lau, Joyce H; Liu, James Z; Mach, Sandy D; Phan, Thu A; Ren, Yi; Stapleton, Kenneth E; Strelitz, Jean M; Sunjed, Ray; Stamm, Joyce; Anderson, Morgan C; Bonifield, Bethany Grace; Coomes, Daniel; Dillman, Adam; Durchholz, Elaine J; Fafara-Thompson, Antoinette E; Gross, Meleah J; Gygi, Amber M; Jackson, Lesley E; Johnson, Amy; Kocsisova, Zuzana; Manghelli, Joshua L; McNeil, Kylie; Murillo, Michael; Naylor, Kierstin L; Neely, Jessica; Ogawa, Emmy E; Rich, Ashley; Rogers, Anna; Spencer, J Devin; Stemler, Kristina M; Throm, Allison A; Van Camp, Matt; Weihbrecht, Katie; Wiles, T Aaron; Williams, Mallory A; Williams, Matthew; Zoll, Kyle; Bailey, Cheryl; Zhou, Leming; Balthaser, Darla M; Bashiri, Azita; Bower, Mindy E; Florian, Kayla A; Ghavam, Nazanin; Greiner-Sosanko, Elizabeth S; Karim, Helmet; Mullen, Victor W; Pelchen, Carly E; Yenerall, Paul M; Zhang, Jiayu; Rubin, Michael R; Arias-Mejias, Suzette M; Bermudez-Capo, Armando G; Bernal-Vega, Gabriela V; Colon-Vazquez, Mariela; Flores-Vazquez, Arelys; Gines-Rosario, Mariela; Llavona-Cartagena, Ivan G; Martinez-Rodriguez, Javier O; Ortiz-Fuentes, Lionel; Perez-Colomba, Eliezer O; Perez-Otero, Joseph; Rivera, Elisandra; Rodriguez-Giron, Luke J; Santiago-Sanabria, Arnaldo J; Senquiz-Gonzalez, Andrea M; delValle, Frank R Soto; Vargas-Franco, Dorianmarie; Velázquez-Soto, Karla I; Zambrana-Burgos, Joan D; Martinez-Cruzado, Juan Carlos; Asencio-Zayas, Lillyann; Babilonia-Figueroa, Kevin; Beauchamp-Pérez, Francis D; Belén-Rodríguez, Juliana; Bracero-Quiñones, Luciann; Burgos-Bula, Andrea P; Collado-Méndez, Xavier A; Colón-Cruz, Luis R; Correa-Muller, Ana I; Crooke-Rosado, Jonathan L; Cruz-García, José M; Defendini-Ávila, Marianna; Delgado-Peraza, Francheska M; Feliciano-Cancela, Alex J; Gónzalez-Pérez, Valerie M; Guiblet, Wilfried; Heredia-Negrón, Aldo; Hernández-Muñiz, Jennifer; Irizarry-González, Lourdes N; Laboy-Corales, Ángel L; Llaurador-Caraballo, Gabriela A; Marín-Maldonado, Frances; Marrero-Llerena, Ulises; Martell-Martínez, Héctor A; Martínez-Traverso, Idaliz M; Medina-Ortega, Kiara N; Méndez-Castellanos, Sonya G; Menéndez-Serrano, Krizia C; Morales-Caraballo, Carol I; Ortiz-DeChoudens, Saryleine; Ortiz-Ortiz, Patricia; Pagán-Torres, Hendrick; Pérez-Afanador, Diana; Quintana-Torres, Enid M; Ramírez-Aponte, Edwin G; Riascos-Cuero, Carolina; Rivera-Llovet, Michelle S; Rivera-Pagán, Ingrid T; Rivera-Vicéns, Ramón E; Robles-Juarbe, Fabiola; Rodríguez-Bonilla, Lorraine; Rodríguez-Echevarría, Brian O; Rodríguez-García, Priscila M; Rodríguez-Laboy, Abneris E; Rodríguez-Santiago, Susana; Rojas-Vargas, Michael L; Rubio-Marrero, Eva N; Santiago-Colón, Albeliz; Santiago-Ortiz, Jorge L; Santos-Ramos, Carlos E; Serrano-González, Joseline; Tamayo-Figueroa, Alina M; Tascón-Peñaranda, Edna P; Torres-Castillo, José L; Valentín-Feliciano, Nelson A; Valentín-Feliciano, Yashira M; Vargas-Barreto, Nadyan M; Vélez-Vázquez, Miguel; Vilanova-Vélez, Luis R; Zambrana-Echevarría, Cristina; MacKinnon, Christy; Chung, Hui-Min; Kay, Chris; Pinto, Anthony; Kopp, Olga R; Burkhardt, Joshua; Harward, Chris; Allen, Robert; Bhat, Pavan; Chang, Jimmy Hsiang-Chun; Chen, York; Chesley, Christopher; Cohn, Dara; DuPuis, David; Fasano, Michael; Fazzio, Nicholas; Gavinski, Katherine; Gebreyesus, Heran; Giarla, Thomas; Gostelow, Marcus; Greenstein, Rachel; Gunasinghe, Hashini; Hanson, Casey; Hay, Amanda; He, Tao Jian; Homa, Katie; Howe, Ruth; Howenstein, Jeff; Huang, Henry; Khatri, Aaditya; Kim, Young Lu; Knowles, Olivia; Kong, Sarah; Krock, Rebecca; Kroll, Matt; Kuhn, Julia; Kwong, Matthew; Lee, Brandon; Lee, Ryan; Levine, Kevin; Li, Yedda; Liu, Bo; Liu, Lucy; Liu, Max; Lousararian, Adam; Ma, Jimmy; Mallya, Allyson; Manchee, Charlie; Marcus, Joseph; McDaniel, Stephen; Miller, Michelle L; Molleston, Jerome M; Diez, Cristina Montero; Ng, Patrick; Ngai, Natalie; Nguyen, Hien; Nylander, Andrew; Pollack, Jason; Rastogi, Suchita; Reddy, Himabindu; Regenold, Nathaniel; Sarezky, Jon; Schultz, Michael; Shim, Jien; Skorupa, Tara; Smith, Kenneth; Spencer, Sarah J; Srikanth, Priya; Stancu, Gabriel; Stein, Andrew P; Strother, Marshall; Sudmeier, Lisa; Sun, Mengyang; Sundaram, Varun; Tazudeen, Noor; Tseng, Alan; Tzeng, Albert; Venkat, Rohit; Venkataram, Sandeep; Waldman, Leah; Wang, Tracy; Yang, Hao; Yu, Jack Y; Zheng, Yin; Preuss, Mary L; Garcia, Angelica; Juergens, Matt; Morris, Robert W; Nagengast, Alexis A; Azarewicz, Julie; Carr, Thomas J; Chichearo, Nicole; Colgan, Mike; Donegan, Megan; Gardner, Bob; Kolba, Nik; Krumm, Janice L; Lytle, Stacey; MacMillian, Laurell; Miller, Mary; Montgomery, Andrew; Moretti, Alysha; Offenbacker, Brittney; Polen, Mike; Toth, John; Woytanowski, John; Kadlec, Lisa; Crawford, Justin; Spratt, Mary L; Adams, Ashley L; Barnard, Brianna K; Cheramie, Martin N; Eime, Anne M; Golden, Kathryn L; Hawkins, Allyson P; Hill, Jessica E; Kampmeier, Jessica A; Kern, Cody D; Magnuson, Emily E; Miller, Ashley R; Morrow, Cody M; Peairs, Julia C; Pickett, Gentry L; Popelka, Sarah A; Scott, Alexis J; Teepe, Emily J; TerMeer, Katie A; Watchinski, Carmen A; Watson, Lucas A; Weber, Rachel E; Woodard, Kate A; Barnard, Daron C; Appiah, Isaac; Giddens, Michelle M; McNeil, Gerard P; Adebayo, Adeola; Bagaeva, Kate; Chinwong, Justina; Dol, Chrystel; George, Eunice; Haltaufderhyde, Kirk; Haye, Joanna; Kaur, Manpreet; Semon, Max; Serjanov, Dmitri; Toorie, Anika; Wilson, Christopher; Riddle, Nicole C; Buhler, Jeremy; Mardis, Elaine R; Elgin, Sarah C R

    2015-03-04

    The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25-50%) than euchromatic reference regions (3-11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11-27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4-3.6 vs. 8.4-8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu. Copyright © 2015 Leung et al.

  3. Identifying Symptoms of Depression and Anxiety in Students in the School Setting

    Science.gov (United States)

    Allison, Virginia L.; Nativio, Donna G.; Mitchell, Ann M.; Ren, Dianxu; Yuhasz, Janet

    2014-01-01

    Early detection of mental health problems in school-age children offers the opportunity for prompt referral to treatment which is critical to their success in school. School nurses are in a key position to screen for mental health issues in the school setting. This article discusses how school nurses began a new initiative to use two validated…

  4. 3D Printing in Instructional Settings: Identifying a Curricular Hierarchy of Activities

    Science.gov (United States)

    Brown, Abbie

    2015-01-01

    A report of a year-long study in which the author engaged in 3D printing activity in order to determine how to facilitate and support skill building, concept attainment, and increased confidence with its use among teachers. Use of 3D printing tools and their applications in instructional settings are discussed. A hierarchy of 3D printing…

  5. Identifying genetic marker sets associated with phenotypes via an efficient adaptive score test

    KAUST Repository

    Cai, T.

    2012-06-25

    In recent years, genome-wide association studies (GWAS) and gene-expression profiling have generated a large number of valuable datasets for assessing how genetic variations are related to disease outcomes. With such datasets, it is often of interest to assess the overall effect of a set of genetic markers, assembled based on biological knowledge. Genetic marker-set analyses have been advocated as more reliable and powerful approaches compared with the traditional marginal approaches (Curtis and others, 2005. Pathways to the analysis of microarray data. TRENDS in Biotechnology 23, 429-435; Efroni and others, 2007. Identification of key processes underlying cancer phenotypes using biologic pathway analysis. PLoS One 2, 425). Procedures for testing the overall effect of a marker-set have been actively studied in recent years. For example, score tests derived under an Empirical Bayes (EB) framework (Liu and others, 2007. Semiparametric regression of multidimensional genetic pathway data: least-squares kernel machines and linear mixed models. Biometrics 63, 1079-1088; Liu and others, 2008. Estimation and testing for the effect of a genetic pathway on a disease outcome using logistic kernel machine regression via logistic mixed models. BMC bioinformatics 9, 292-2; Wu and others, 2010. Powerful SNP-set analysis for case-control genome-wide association studies. American Journal of Human Genetics 86, 929) have been proposed as powerful alternatives to the standard Rao score test (Rao, 1948. Large sample tests of statistical hypotheses concerning several parameters with applications to problems of estimation. Mathematical Proceedings of the Cambridge Philosophical Society, 44, 50-57). The advantages of these EB-based tests are most apparent when the markers are correlated, due to the reduction in the degrees of freedom. In this paper, we propose an adaptive score test which up- or down-weights the contributions from each member of the marker-set based on the Z-scores of

  6. A new marker set that identifies fetal cells in maternal circulation with high specificity

    DEFF Research Database (Denmark)

    Hatt, Lotte; Brinch, Marie; Singh, Ripudaman

    2014-01-01

    were used for testing the marker-set CD105 and CD141 for fetal cell enrichment. Fetal cell candidates were subsequently stained by a cocktail of cytokeratin antibodies, and the gender of the fetal cells was explored by fluorescence in situ hybridization (FISH) of the X and Y chromosomes. RESULTS: Fetal...... cell candidates could be detected in 91% of the samples, and in 85% of the samples, it was possible to obtain X and Y chromosomal FISH results for gender determination. The concordance between gender determined by FISH on fetal cells in maternal blood and gender found at birth reached 100% if three...

  7. Identifying the barriers to conducting outcomes research in integrative health care clinic settings - a qualitative study

    Directory of Open Access Journals (Sweden)

    Findlay-Reece Barbara

    2010-01-01

    Full Text Available Abstract Background Integrative health care (IHC is an interdisciplinary blending of conventional medicine and complementary and alternative medicine (CAM with the purpose of enhancing patients' health. In 2006, we designed a study to assess outcomes that are relevant to people using such care. However, we faced major challenges in conducting this study and hypothesized that this might be due to the lack of a research climate in these clinics. To investigate these challenges, we initiated a further study in 2008, to explore the reasons why IHC clinics are not conducting outcomes research and to identify strategies for conducting successful in-house outcomes research programs. The results of the latter study are reported here. Methods A total of 25 qualitative interviews were conducted with key participants from 19 IHC clinics across Canada. Basic content analysis was used to identify key themes from the transcribed interviews. Results Barriers identified by participants fell into four categories: organizational culture, organizational resources, organizational environment and logistical challenges. Cultural challenges relate to the philosophy of IHC, organizational leadership and practitioner attitudes and beliefs. Participants also identified significant issues relating to their organization's lack of resources such as funding, compensation, infrastructure and partnerships/linkages. Environmental challenges such as the nature of a clinic's patient population and logistical issues such as the actual implementation of a research program and the applicability of research data also posed challenges to the conduct of research. Embedded research leadership, integration of personal and professional values about research, alignment of research activities and clinical workflow processes are some of the factors identified by participants that support IHC clinics' ability to conduct outcomes research. Conclusions Assessing and enhancing the broader

  8. Application of biclustering of gene expression data and gene set enrichment analysis methods to identify potentially disease causing nanomaterials

    Directory of Open Access Journals (Sweden)

    Andrew Williams

    2015-12-01

    Full Text Available Background: The presence of diverse types of nanomaterials (NMs in commerce is growing at an exponential pace. As a result, human exposure to these materials in the environment is inevitable, necessitating the need for rapid and reliable toxicity testing methods to accurately assess the potential hazards associated with NMs. In this study, we applied biclustering and gene set enrichment analysis methods to derive essential features of altered lung transcriptome following exposure to NMs that are associated with lung-specific diseases. Several datasets from public microarray repositories describing pulmonary diseases in mouse models following exposure to a variety of substances were examined and functionally related biclusters of genes showing similar expression profiles were identified. The identified biclusters were then used to conduct a gene set enrichment analysis on pulmonary gene expression profiles derived from mice exposed to nano-titanium dioxide (nano-TiO2, carbon black (CB or carbon nanotubes (CNTs to determine the disease significance of these data-driven gene sets.Results: Biclusters representing inflammation (chemokine activity, DNA binding, cell cycle, apoptosis, reactive oxygen species (ROS and fibrosis processes were identified. All of the NM studies were significant with respect to the bicluster related to chemokine activity (DAVID; FDR p-value = 0.032. The bicluster related to pulmonary fibrosis was enriched in studies where toxicity induced by CNT and CB studies was investigated, suggesting the potential for these materials to induce lung fibrosis. The pro-fibrogenic potential of CNTs is well established. Although CB has not been shown to induce fibrosis, it induces stronger inflammatory, oxidative stress and DNA damage responses than nano-TiO2 particles.Conclusion: The results of the analysis correctly identified all NMs to be inflammogenic and only CB and CNTs as potentially fibrogenic. In addition to identifying several

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

    Directory of Open Access Journals (Sweden)

    Robert Illingworth

    2008-01-01

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

  10. The structure and material composition of ossified aortic valves identified using a set of scientific methods

    Science.gov (United States)

    Zeman, Antonín; Šmíd, Michal; Havelcová, Martina; Coufalová, Lucie; Kučková, Štěpánka; Velčovská, Martina; Hynek, Radovan

    2013-11-01

    Degenerative aortic stenosis has become a common and dangerous disease in recent decades. This disease leads to the mineralization of aortic valves, their gradual thickening and loss of functionality. We studied the detailed assessment of the proportion and composition of inorganic and organic components in the ossified aortic valve, using a set of analytical methods applied in science: polarized light microscopy, scanning electron microscopy, X-ray fluorescence, X-ray diffraction, gas chromatography/mass spectrometry and liquid chromatography-tandem mass spectrometry. The sample valves showed the occurrence of phosphorus and calcium in the form of phosphate and calcium carbonate, hydroxyapatite, fluorapatite and hydroxy-fluorapatite, with varying content of inorganic components from 65 to 90 wt%, and with phased development of degenerative disability. The outer layers of the plaque contained an organic component with peptide bonds, fatty acids, proteins and cholesterol. The results show a correlation between the formation of fluorapatite in aortic valves and in other parts of the human bodies, associated with the formation of bones.

  11. Human body as a set of biometric features identified by means of optoelectronics

    Science.gov (United States)

    Podbielska, Halina; Bauer, Joanna

    2005-09-01

    Human body posses many unique, singular features that are impossible to copy or forge. Nowadays, to establish and to ensure the public security requires specially designed devices and systems. Biometrics is a field of science and technology, exploiting human body characteristics for people recognition. It identifies the most characteristic and unique ones in order to design and construct systems capable to recognize people. In this paper some overview is given, presenting the achievements in biometrics. The verification and identification process is explained, along with the way of evaluation of biometric recognition systems. The most frequently human biometrics used in practice are shortly presented, including fingerprints, facial imaging (including thermal characteristic), hand geometry and iris patterns.

  12. Suicide Risk Protocols: Addressing the Needs of High Risk Youths Identified through Suicide Prevention Efforts and in Clinical Settings

    Science.gov (United States)

    Heilbron, Nicole; Goldston, David; Walrath, Christine; Rodi, Michael; McKeon, Richard

    2013-01-01

    Several agencies have emphasized the importance of establishing clear protocols or procedures to address the needs of youths who are identified as suicidal through suicide prevention programs or in emergency department settings. What constitutes optimal guidelines for developing and implementing such protocols, however, is unclear. At the request…

  13. Effect of Modifying Intervention Set Size with Acquisition Rate Data among Students Identified with a Learning Disability

    Science.gov (United States)

    Haegele, Katherine; Burns, Matthew K.

    2015-01-01

    The amount of information that students can successfully learn and recall at least 1 day later is called an acquisition rate (AR) and is unique to the individual student. The current study extended previous drill rehearsal research with word recognition by (a) using students identified with a learning disability in reading, (b) assessing set sizes…

  14. Can children identify and achieve goals for intervention? A randomized trial comparing two goal-setting approaches.

    Science.gov (United States)

    Vroland-Nordstrand, Kristina; Eliasson, Ann-Christin; Jacobsson, Helén; Johansson, Ulla; Krumlinde-Sundholm, Lena

    2016-06-01

    The efficacy of two different goal-setting approaches (children's self-identified goals and goals identified by parents) were compared on a goal-directed, task-oriented intervention. In this assessor-blinded parallel randomized trial, 34 children with disabilities (13 males, 21 females; mean age 9y, SD 1y 4mo) were randomized using concealed allocation to one of two 8-week, goal-directed, task-oriented intervention groups with different goal-setting approaches: (1) children's self-identified goals (n=18) using the Perceived Efficacy and Goal-Setting System, or (2) goals identified by parents (n=16) using the Canadian Occupational Performance Measure (COPM). Participants were recruited through eight paediatric rehabilitation centres and randomized between October 2011 and May 2013. The primary outcome measure was the Goal Attainment Scaling and the secondary measure, the COPM performance scale (COPM-P). Data were collected pre- and post-intervention and at the 5-month follow-up. There was no evidence of a difference in mean characteristics at baseline between groups. There was evidence of an increase in mean goal attainment (mean T score) in both groups after intervention (child-goal group: estimated mean difference [EMD] 27.84, 95% CI 22.93-32.76; parent-goal group: EMD 21.42, 95% CI 16.16-26.67). There was no evidence of a difference in the mean T scores post-intervention between the two groups (EMD 6.42, 95% CI -0.80 to 13.65). These results were sustained at the 5-month follow-up. Children's self-identified goals are achievable to the same extent as parent-identified goals and remain stable over time. Thus children can be trusted to identify their own goals for intervention, thereby influencing their involvement in their intervention programmes. © 2015 Mac Keith Press.

  15. Targeting N-Glycan Cryptic Sugar Moieties for Broad-Spectrum Virus Neutralization: Progress in Identifying Conserved Molecular Targets in Viruses of Distinct Phylogenetic Origins

    Directory of Open Access Journals (Sweden)

    Denong Wang

    2015-03-01

    Full Text Available Identifying molecular targets for eliciting broadly virus-neutralizing antibodies is one of the key steps toward development of vaccines against emerging viral pathogens. Owing to genomic and somatic diversities among viral species, identifying protein targets for broad-spectrum virus neutralization is highly challenging even for the same virus, such as HIV-1. However, viruses rely on host glycosylation machineries to synthesize and express glycans and, thereby, may display common carbohydrate moieties. Thus, exploring glycan-binding profiles of broad-spectrum virus-neutralizing agents may provide key information to uncover the carbohydrate-based virus-neutralizing epitopes. In this study, we characterized two broadly HIV-neutralizing agents, human monoclonal antibody 2G12 and Galanthus nivalis lectin (GNA, for their viral targeting activities. Although these agents were known to be specific for oligomannosyl antigens, they differ strikingly in virus-binding activities. The former is HIV-1 specific; the latter is broadly reactive and is able to neutralize viruses of distinct phylogenetic origins, such as HIV-1, severe acute respiratory syndrome coronavirus (SARS-CoV, and human cytomegalovirus (HCMV. In carbohydrate microarray analyses, we explored the molecular basis underlying the striking differences in the spectrum of anti-virus activities of the two probes. Unlike 2G12, which is strictly specific for the high-density Man9GlcNAc2Asn (Man9-clusters, GNA recognizes a number of N-glycan cryptic sugar moieties. These include not only the known oligomannosyl antigens but also previously unrecognized tri-antennary or multi-valent GlcNAc-terminating N-glycan epitopes (Tri/m-Gn. These findings highlight the potential of N-glycan cryptic sugar moieties as conserved targets for broad-spectrum virus neutralization and suggest the GNA-model of glycan-binding warrants focused investigation.

  16. Gene-set analysis based on the pharmacological profiles of drugs to identify repurposing opportunities in schizophrenia.

    Science.gov (United States)

    de Jong, Simone; Vidler, Lewis R; Mokrab, Younes; Collier, David A; Breen, Gerome

    2016-08-01

    Genome-wide association studies (GWAS) have identified thousands of novel genetic associations for complex genetic disorders, leading to the identification of potential pharmacological targets for novel drug development. In schizophrenia, 108 conservatively defined loci that meet genome-wide significance have been identified and hundreds of additional sub-threshold associations harbour information on the genetic aetiology of the disorder. In the present study, we used gene-set analysis based on the known binding targets of chemical compounds to identify the 'drug pathways' most strongly associated with schizophrenia-associated genes, with the aim of identifying potential drug repositioning opportunities and clues for novel treatment paradigms, especially in multi-target drug development. We compiled 9389 gene sets (2496 with unique gene content) and interrogated gene-based p-values from the PGC2-SCZ analysis. Although no single drug exceeded experiment wide significance (corrected pneratinib. This is a proof of principle analysis showing the potential utility of GWAS data of schizophrenia for the direct identification of candidate drugs and molecules that show polypharmacy. © The Author(s) 2016.

  17. Using multiobjective tradeoff sets and Multivariate Regression Trees to identify critical and robust decisions for long term water utility planning

    Science.gov (United States)

    Smith, R.; Kasprzyk, J. R.; Balaji, R.

    2017-12-01

    In light of deeply uncertain factors like future climate change and population shifts, responsible resource management will require new types of information and strategies. For water utilities, this entails potential expansion and efficient management of water supply infrastructure systems for changes in overall supply; changes in frequency and severity of climate extremes such as droughts and floods; and variable demands, all while accounting for conflicting long and short term performance objectives. Multiobjective Evolutionary Algorithms (MOEAs) are emerging decision support tools that have been used by researchers and, more recently, water utilities to efficiently generate and evaluate thousands of planning portfolios. The tradeoffs between conflicting objectives are explored in an automated way to produce (often large) suites of portfolios that strike different balances of performance. Once generated, the sets of optimized portfolios are used to support relatively subjective assertions of priorities and human reasoning, leading to adoption of a plan. These large tradeoff sets contain information about complex relationships between decisions and between groups of decisions and performance that, until now, has not been quantitatively described. We present a novel use of Multivariate Regression Trees (MRTs) to analyze tradeoff sets to reveal these relationships and critical decisions. Additionally, when MRTs are applied to tradeoff sets developed for different realizations of an uncertain future, they can identify decisions that are robust across a wide range of conditions and produce fundamental insights about the system being optimized.

  18. Experience-based design for integrating the patient care experience into healthcare improvement: Identifying a set of reliable emotion words.

    Science.gov (United States)

    Russ, Lauren R; Phillips, Jennifer; Brzozowicz, Keely; Chafetz, Lynne A; Plsek, Paul E; Blackmore, C Craig; Kaplan, Gary S

    2013-12-01

    Experience-based design is an emerging method used to capture the emotional content of patient and family member healthcare experiences, and can serve as the foundation for patient-centered healthcare improvement. However, a core tool-the experience-based design questionnaire-requires words with consistent emotional meaning. Our objective was to identify and evaluate an emotion word set reliably categorized across the demographic spectrum as expressing positive, negative, or neutral emotions for experience-based design improvement work. We surveyed 407 patients, family members, and healthcare workers in 2011. Participants designated each of 67 potential emotion words as positive, neutral, or negative based on their emotional perception of the word. Overall agreement was assessed using the kappa statistic. Words were selected for retention in the final emotion word set based on 80% simple agreement on classification of meaning across subgroups. The participants were 47.9% (195/407) patients, 19.4% (33/407) family members and 32.7% (133/407) healthcare staff. Overall agreement adjusted for chance was moderate (k=0.55). However, agreement for positive (k=0.69) and negative emotions (k=0.68) was substantially higher, while agreement in the neutral category was low (k=0.11). There were 20 positive, 1 neutral, and 14 negative words retained for the final experience-based design emotion word set. We identified a reliable set of emotion words for experience questionnaires to serve as the foundation for patient-centered, experience-based redesign of healthcare. Incorporation of patient and family member perspectives in healthcare requires reliable tools to capture the emotional content of care touch points. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Proteome and metabolome profiling of cytokinin action in Arabidopsis identifying both distinct and similar responses to cytokinin down- and up-regulation.

    Science.gov (United States)

    Černý, Martin; Kuklová, Alena; Hoehenwarter, Wolfgang; Fragner, Lena; Novák, Ondrej; Rotková, Gabriela; Jedelsky, Petr L; Žáková, Katerina; Šmehilová, Mária; Strnad, Miroslav; Weckwerth, Wolfram; Brzobohaty, Bretislav

    2013-11-01

    In plants, numerous developmental processes are controlled by cytokinin (CK) levels and their ratios to levels of other hormones. While molecular mechanisms underlying the regulatory roles of CKs have been intensely researched, proteomic and metabolomic responses to CK deficiency are unknown. Transgenic Arabidopsis seedlings carrying inducible barley cytokinin oxidase/dehydrogenase (CaMV35S>GR>HvCKX2) and agrobacterial isopentenyl transferase (CaMV35S>GR>ipt) constructs were profiled to elucidate proteome- and metabolome-wide responses to down- and up-regulation of CK levels, respectively. Proteome profiling identified >1100 proteins, 155 of which responded to HvCKX2 and/or ipt activation, mostly involved in growth, development, and/or hormone and light signalling. The metabolome profiling covered 79 metabolites, 33 of which responded to HvCKX2 and/or ipt activation, mostly amino acids, carbohydrates, and organic acids. Comparison of the data sets obtained from activated CaMV35S>GR>HvCKX2 and CaMV35S>GR>ipt plants revealed unexpectedly extensive overlaps. Integration of the proteomic and metabolomic data sets revealed: (i) novel components of molecular circuits involved in CK action (e.g. ribosomal proteins); (ii) previously unrecognized links to redox regulation and stress hormone signalling networks; and (iii) CK content markers. The striking overlaps in profiles observed in CK-deficient and CK-overproducing seedlings might explain surprising previously reported similarities between plants with down- and up-regulated CK levels.

  20. HLA-DRB1 Analysis Identified a Genetically Unique Subset within Rheumatoid Arthritis and Distinct Genetic Background of Rheumatoid Factor Levels from Anticyclic Citrullinated Peptide Antibodies.

    Science.gov (United States)

    Hiwa, Ryosuke; Ikari, Katsunori; Ohmura, Koichiro; Nakabo, Shuichiro; Matsuo, Keitaro; Saji, Hiroh; Yurugi, Kimiko; Miura, Yasuo; Maekawa, Taira; Taniguchi, Atsuo; Yamanaka, Hisashi; Matsuda, Fumihiko; Mimori, Tsuneyo; Terao, Chikashi

    2018-04-01

    HLA-DRB1 is the most important locus associated with rheumatoid arthritis (RA) and anticitrullinated protein antibodies (ACPA). However, fluctuations of rheumatoid factor (RF) over the disease course have made it difficult to define fine subgroups according to consistent RF positivity for the analyses of genetic background and the levels of RF. A total of 2873 patients with RA and 2008 healthy controls were recruited. We genotyped HLA-DRB1 alleles for the participants and collected consecutive data of RF in the case subjects. In addition to RF+ and RF- subsets, we classified the RF+ subjects into group 1 (constant RF+) and group 2 (seroconversion). We compared HLA-DRB1 alleles between the RA subsets and controls and performed linear regression analysis to identify HLA-DRB1 alleles associated with maximal RF levels. Omnibus tests were conducted to assess important amino acid positions. RF positivity was 88%, and 1372 and 970 RF+ subjects were classified into groups 1 and 2, respectively. RF+ and RF- showed similar genetic associations to ACPA+ and ACPA- RA, respectively. We found that shared epitope (SE) was more enriched in group 2 than 1, p = 2.0 × 10 -5 , and that amino acid position 11 showed a significant association between 1 and 2, p = 2.7 × 10 -5 . These associations were independent of ACPA positivity. SE showed a tendency to be negatively correlated with RF titer (p = 0.012). HLA-DRB1*09:01, which reduces ACPA titer, was not associated with RF levels (p = 0.70). The seroconversion group was shown to have distinct genetic characteristics. The genetic architecture of RF levels is different from that of ACPA.

  1. Variation in tibial functionality and fracture susceptibility among healthy, young adults arises from the acquisition of biologically distinct sets of traits.

    Science.gov (United States)

    Jepsen, Karl J; Evans, Rachel; Negus, Charles H; Gagnier, Joel J; Centi, Amanda; Erlich, Tomer; Hadid, Amir; Yanovich, Ran; Moran, Daniel S

    2013-06-01

    Physiological systems like bone respond to many genetic and environmental factors by adjusting traits in a highly coordinated, compensatory manner to establish organ-level function. To be mechanically functional, a bone should be sufficiently stiff and strong to support physiological loads. Factors impairing this process are expected to compromise strength and increase fracture risk. We tested the hypotheses that individuals with reduced stiffness relative to body size will show an increased risk of fracturing and that reduced strength arises from the acquisition of biologically distinct sets of traits (ie, different combinations of morphological and tissue-level mechanical properties). We assessed tibial functionality retrospectively for 336 young adult women and men engaged in military training, and calculated robustness (total area/bone length), cortical area (Ct.Ar), and tissue-mineral density (TMD). These three traits explained 69% to 72% of the variation in tibial stiffness (p stress fracture based on radiography and scintigraphy. K-means cluster analysis was used to segregate men and women into subgroups based on robustness, Ct.Ar, and TMD adjusted for body size. Stiffness varied 37% to 42% among the clusters (p stress fracture cases segregated to three clusters (p fracture risk. Our results have important implications for developing personalized preventative diagnostics and treatments. Copyright © 2013 American Society for Bone and Mineral Research.

  2. Post-Colonization Interval Estimates Using Multi-Species Calliphoridae Larval Masses and Spatially Distinct Temperature Data Sets: A Case Study

    Science.gov (United States)

    Weatherbee, Courtney R.; Pechal, Jennifer L.; Stamper, Trevor; Benbow, M. Eric

    2017-01-01

    Common forensic entomology practice has been to collect the largest Diptera larvae from a scene and use published developmental data, with temperature data from the nearest weather station, to estimate larval development time and post-colonization intervals (PCIs). To evaluate the accuracy of PCI estimates among Calliphoridae species and spatially distinct temperature sources, larval communities and ambient air temperature were collected at replicate swine carcasses (N = 6) throughout decomposition. Expected accumulated degree hours (ADH) associated with Cochliomyia macellaria and Phormia regina third instars (presence and length) were calculated using published developmental data sets. Actual ADH ranges were calculated using temperatures recorded from multiple sources at varying distances (0.90 m–7.61 km) from the study carcasses: individual temperature loggers at each carcass, a local weather station, and a regional weather station. Third instars greatly varied in length and abundance. The expected ADH range for each species successfully encompassed the average actual ADH for each temperature source, but overall under-represented the range. For both calliphorid species, weather station data were associated with more accurate PCI estimates than temperature loggers associated with each carcass. These results provide an important step towards improving entomological evidence collection and analysis techniques, and developing forensic error rates. PMID:28375172

  3. Post-Colonization Interval Estimates Using Multi-Species Calliphoridae Larval Masses and Spatially Distinct Temperature Data Sets: A Case Study

    Directory of Open Access Journals (Sweden)

    Courtney R. Weatherbee

    2017-04-01

    Full Text Available Common forensic entomology practice has been to collect the largest Diptera larvae from a scene and use published developmental data, with temperature data from the nearest weather station, to estimate larval development time and post-colonization intervals (PCIs. To evaluate the accuracy of PCI estimates among Calliphoridae species and spatially distinct temperature sources, larval communities and ambient air temperature were collected at replicate swine carcasses (N = 6 throughout decomposition. Expected accumulated degree hours (ADH associated with Cochliomyia macellaria and Phormia regina third instars (presence and length were calculated using published developmental data sets. Actual ADH ranges were calculated using temperatures recorded from multiple sources at varying distances (0.90 m–7.61 km from the study carcasses: individual temperature loggers at each carcass, a local weather station, and a regional weather station. Third instars greatly varied in length and abundance. The expected ADH range for each species successfully encompassed the average actual ADH for each temperature source, but overall under-represented the range. For both calliphorid species, weather station data were associated with more accurate PCI estimates than temperature loggers associated with each carcass. These results provide an important step towards improving entomological evidence collection and analysis techniques, and developing forensic error rates.

  4. Transcriptional differences between normal and glioma-derived glial progenitor cells identify a core set of dysregulated genes.

    Science.gov (United States)

    Auvergne, Romane M; Sim, Fraser J; Wang, Su; Chandler-Militello, Devin; Burch, Jaclyn; Al Fanek, Yazan; Davis, Danielle; Benraiss, Abdellatif; Walter, Kevin; Achanta, Pragathi; Johnson, Mahlon; Quinones-Hinojosa, Alfredo; Natesan, Sridaran; Ford, Heide L; Goldman, Steven A

    2013-06-27

    Glial progenitor cells (GPCs) are a potential source of malignant gliomas. We used A2B5-based sorting to extract tumorigenic GPCs from human gliomas spanning World Health Organization grades II-IV. Messenger RNA profiling identified a cohort of genes that distinguished A2B5+ glioma tumor progenitor cells (TPCs) from A2B5+ GPCs isolated from normal white matter. A core set of genes and pathways was substantially dysregulated in A2B5+ TPCs, which included the transcription factor SIX1 and its principal cofactors, EYA1 and DACH2. Small hairpin RNAi silencing of SIX1 inhibited the expansion of glioma TPCs in vitro and in vivo, suggesting a critical and unrecognized role of the SIX1-EYA1-DACH2 system in glioma genesis or progression. By comparing the expression patterns of glioma TPCs with those of normal GPCs, we have identified a discrete set of pathways by which glial tumorigenesis may be better understood and more specifically targeted. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Mining environmental high-throughput sequence data sets to identify divergent amplicon clusters for phylogenetic reconstruction and morphotype visualization.

    Science.gov (United States)

    Gimmler, Anna; Stoeck, Thorsten

    2015-08-01

    Environmental high-throughput sequencing (envHTS) is a very powerful tool, which in protistan ecology is predominantly used for the exploration of diversity and its geographic and local patterns. We here used a pyrosequenced V4-SSU rDNA data set from a solar saltern pond as test case to exploit such massive protistan amplicon data sets beyond this descriptive purpose. Therefore, we combined a Swarm-based blastn network including 11 579 ciliate V4 amplicons to identify divergent amplicon clusters with targeted polymerase chain reaction (PCR) primer design for full-length small subunit of the ribosomal DNA retrieval and probe design for fluorescence in situ hybridization (FISH). This powerful strategy allows to benefit from envHTS data sets to (i) reveal the phylogenetic position of the taxon behind divergent amplicons; (ii) improve phylogenetic resolution and evolutionary history of specific taxon groups; (iii) solidly assess an amplicons (species') degree of similarity to its closest described relative; (iv) visualize the morphotype behind a divergent amplicons cluster; (v) rapidly FISH screen many environmental samples for geographic/habitat distribution and abundances of the respective organism and (vi) to monitor the success of enrichment strategies in live samples for cultivation and isolation of the respective organisms. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

  6. Two Sets of Piwi Proteins Are Involved in Distinct sRNA Pathways Leading to Elimination of Germline-Specific DNA

    Directory of Open Access Journals (Sweden)

    Dominique I. Furrer

    2017-07-01

    Full Text Available Piwi proteins and piRNAs protect eukaryotic germlines against the spread of transposons. During development in the ciliate Paramecium, two Piwi-dependent sRNA classes are involved in the elimination of transposons and transposon-derived DNA: scan RNAs (scnRNAs, associated with Ptiwi01 and Ptiwi09, and iesRNAs, whose binding partners we now identify as Ptiwi10 and Ptiwi11. scnRNAs derive from the maternal genome and initiate DNA elimination during development, whereas iesRNAs continue DNA targeting until the removal process is complete. Here, we show that scnRNAs and iesRNAs are processed by distinct Dicer-like proteins and bind Piwi proteins in a mutually exclusive manner, suggesting separate biogenesis pathways. We also demonstrate that the PTIWI10 gene is transcribed from the developing nucleus and that its transcription depends on prior DNA excision, suggesting a mechanism of gene expression control triggered by the removal of short DNA segments interrupting the gene.

  7. New strategy to identify radicals in a time evolving EPR data set by multivariate curve resolution-alternating least squares

    Energy Technology Data Exchange (ETDEWEB)

    Fadel, Maya Abou [LASIR CNRS UMR 8516, Université Lille 1, Sciences et Technologies, 59655 Villeneuve d' Ascq Cedex (France); Juan, Anna de [Chemometrics Group, Section of Analytical Chemistry, Universitat de Barcelona, Diagonal 645, 08028 Barcelona (Spain); Vezin, Hervé [LASIR CNRS UMR 8516, Université Lille 1, Sciences et Technologies, 59655 Villeneuve d' Ascq Cedex (France); Duponchel, Ludovic, E-mail: ludovic.duponchel@univ-lille1.fr [LASIR CNRS UMR 8516, Université Lille 1, Sciences et Technologies, 59655 Villeneuve d' Ascq Cedex (France)

    2016-12-01

    Electron paramagnetic resonance (EPR) spectroscopy is a powerful technique that is able to characterize radicals formed in kinetic reactions. However, spectral characterization of individual chemical species is often limited or even unmanageable due to the severe kinetic and spectral overlap among species in kinetic processes. Therefore, we applied, for the first time, multivariate curve resolution-alternating least squares (MCR-ALS) method to EPR time evolving data sets to model and characterize the different constituents in a kinetic reaction. Here we demonstrate the advantage of multivariate analysis in the investigation of radicals formed along the kinetic process of hydroxycoumarin in alkaline medium. Multiset analysis of several EPR-monitored kinetic experiments performed in different conditions revealed the individual paramagnetic centres as well as their kinetic profiles. The results obtained by MCR-ALS method demonstrate its prominent potential in analysis of EPR time evolved spectra. - Highlights: • A new strategy to identify radicals in a time evolving EPR data set. • Extraction of pure EPR spectral signatures and corresponding kinetic profiles. • The proposed method does not require any prior knowledge of the chemical system. • A multiset analysis in order to decrease rotational ambiguity.

  8. Resident and Facility Factors Associated With the Incidence of Urinary Tract Infections Identified in the Nursing Home Minimum Data Set.

    Science.gov (United States)

    Castle, Nicholas; Engberg, John B; Wagner, Laura M; Handler, Steven

    2017-02-01

    This research examined resident and facility-specific factors associated with a diagnosis of a urinary tract infection (UTI) in the nursing home setting. Minimum Data Set and Online Survey, Certification and Reporting system data were used to identify all nursing home residents in the United States on April 1, 2006, who did not have a UTI ( n = 1,138,418). Residents were followed until they contracted a UTI (9.5%), died (8.3%), left the nursing home (33.2%), or the year ended (49.0%). A Cox proportional hazards model was estimated, controlling for resident and facility characteristics and for the state of residence. The presence of an indwelling catheter was the primary predictor of whether a resident contracted a UTI (adjusted incidence ratio = 3.35, p factors such as percentage of Medicaid residents, for-profit, and chain status was less significant. Estimates regarding staffing levels indicate that increased contact hours with more highly educated nursing staff are associated with less catheter use. Several facility-specific risk factors are of significance. Of significance, UTIs may be reduced by modifying factors such as staffing levels.

  9. Sustainability in Health care by Allocating Resources Effectively (SHARE) 2: identifying opportunities for disinvestment in a local healthcare setting.

    Science.gov (United States)

    Harris, Claire; Allen, Kelly; King, Richard; Ramsey, Wayne; Kelly, Cate; Thiagarajan, Malar

    2017-05-05

    This is the second in a series of papers reporting a program of Sustainability in Health care by Allocating Resources Effectively (SHARE) in a local healthcare setting. Rising healthcare costs, continuing advances in health technologies and recognition of ineffective practices and systematic waste are driving disinvestment of health technologies and clinical practices that offer little or no benefit in order to maximise outcomes from existing resources. However there is little information to guide regional health services or individual facilities in how they might approach disinvestment locally. This paper outlines the investigation of potential settings and methods for decision-making about disinvestment in the context of an Australian health service. Methods include a literature review on the concepts and terminology relating to disinvestment, a survey of national and international researchers, and interviews and workshops with local informants. A conceptual framework was drafted and refined with stakeholder feedback. There is a lack of common terminology regarding definitions and concepts related to disinvestment and no guidance for an organisation-wide systematic approach to disinvestment in a local healthcare service. A summary of issues from the literature and respondents highlight the lack of theoretical knowledge and practical experience and provide a guide to the information required to develop future models or methods for disinvestment in the local context. A conceptual framework was developed. Three mechanisms that provide opportunities to introduce disinvestment decisions into health service systems and processes were identified. Presented in order of complexity, time to achieve outcomes and resources required they include 1) Explicit consideration of potential disinvestment in routine decision-making, 2) Proactive decision-making about disinvestment driven by available evidence from published research and local data, and 3) Specific exercises in

  10. A Prospective Cohort Study of Absconsion Incidents in Forensic Psychiatric Settings: Can We Identify Those at High-Risk?

    Directory of Open Access Journals (Sweden)

    Alexis E Cullen

    Full Text Available Incidents of absconsion in forensic psychiatric units can have potentially serious consequences, yet surprisingly little is known about the characteristics of patients who abscond from these settings. The few previous studies conducted to date have employed retrospective designs, and no attempt has been made to develop an empirically-derived risk assessment scale. In this prospective study, we aimed to identify predictors of absconsion over a two-year period and investigate the feasibility of developing a brief risk assessment scale.The study examined a representative sample of 135 patients treated in forensic medium- and low-secure wards. At baseline, demographic, clinical, treatment-related, and offending/behavioural factors were ascertained from electronic medical records and the treating teams. Incidents of absconsion (i.e., failure to return from leave, incidents of escape, and absconding whilst on escorted leave were assessed at a two-year follow-up. Logistic regression analyses were used to determine the strongest predictors of absconsion which were then weighted according to their ability to discriminate absconders and non-absconders. The predictive utility of a brief risk assessment scale based on these weighted items was evaluated using receiver operator characteristics (ROC.During the two-year follow-up period, 27 patients (20% absconded, accounting for 56 separate incidents. In multivariate analyses, four factors relating to offending and behaviour emerged as the strongest predictors of absconsion: history of sexual offending, previous absconsion, recent inpatient verbal aggression, and recent inpatient substance use. The weighted risk scale derived from these factors had moderate-to-good predictive accuracy (ROC area under the curve: 0.80; sensitivity: 067; specificity: 0.71, a high negative predictive value (0.91, but a low positive predictive value (0.34.Potentially-targetable recent behaviours, such as inpatient verbal aggression

  11. How do you assign persistent identifiers to extracts from large, complex, dynamic data sets that underpin scholarly publications?

    Science.gov (United States)

    Wyborn, Lesley; Car, Nicholas; Evans, Benjamin; Klump, Jens

    2016-04-01

    Persistent identifiers in the form of a Digital Object Identifier (DOI) are becoming more mainstream, assigned at both the collection and dataset level. For static datasets, this is a relatively straight-forward matter. However, many new data collections are dynamic, with new data being appended, models and derivative products being revised with new data, or the data itself revised as processing methods are improved. Further, because data collections are becoming accessible as services, researchers can log in and dynamically create user-defined subsets for specific research projects: they also can easily mix and match data from multiple collections, each of which can have a complex history. Inevitably extracts from such dynamic data sets underpin scholarly publications, and this presents new challenges. The National Computational Infrastructure (NCI) has been experiencing and making progress towards addressing these issues. The NCI is large node of the Research Data Services initiative (RDS) of the Australian Government's research infrastructure, which currently makes available over 10 PBytes of priority research collections, ranging from geosciences, geophysics, environment, and climate, through to astronomy, bioinformatics, and social sciences. Data are replicated to, or are produced at, NCI and then processed there to higher-level data products or directly analysed. Individual datasets range from multi-petabyte computational models and large volume raster arrays, down to gigabyte size, ultra-high resolution datasets. To facilitate access, maximise reuse and enable integration across the disciplines, datasets have been organized on a platform called the National Environmental Research Data Interoperability Platform (NERDIP). Combined, the NERDIP data collections form a rich and diverse asset for researchers: their co-location and standardization optimises the value of existing data, and forms a new resource to underpin data-intensive Science. New publication

  12. Pharmaceutical care issues identified by pharmacists in patients with diabetes, hypertension or hyperlipidaemia in primary care settings.

    Science.gov (United States)

    Chua, Siew Siang; Kok, Li Ching; Yusof, Faridah Aryani Md; Tang, Guang Hui; Lee, Shaun Wen Huey; Efendie, Benny; Paraidathathu, Thomas

    2012-11-12

    The roles of pharmacists have evolved from product oriented, dispensing of medications to more patient-focused services such as the provision of pharmaceutical care. Such pharmacy service is also becoming more widely practised in Malaysia but is not well documented. Therefore, this study is warranted to fill this information gap by identifying the types of pharmaceutical care issues (PCIs) encountered by primary care patients with diabetes mellitus, hypertension or hyperlipidaemia in Malaysia. This study was part of a large controlled trial that evaluated the outcomes of multiprofessional collaboration which involved medical general practitioners, pharmacists, dietitians and nurses in managing diabetes mellitus, hypertension and hyperlipidaemia in primary care settings. A total of 477 patients were recruited by 44 general practitioners in the Klang Valley. These patients were counselled by the various healthcare professionals and followed-up for 6 months. Of the 477 participants, 53.7% had at least one PCI, with a total of 706 PCIs. These included drug-use problems (33.3%), insufficient awareness and knowledge about disease condition and medication (20.4%), adverse drug reactions (15.6%), therapeutic failure (13.9%), drug-choice problems (9.5%) and dosing problems (3.4%). Non-adherence to medications topped the list of drug-use problems, followed by incorrect administration of medications. More than half of the PCIs (52%) were classified as probably clinically insignificant, 38.9% with minimal clinical significance, 8.9% as definitely clinically significant and could cause patient harm while one issue (0.2%) was classified as life threatening. The main causes of PCIs were deterioration of disease state which led to failure of therapy, and also presentation of new symptoms or indications. Of the 338 PCIs where changes were recommended by the pharmacist, 87.3% were carried out as recommended. This study demonstrates the importance of pharmacists working in

  13. Pharmaceutical care issues identified by pharmacists in patients with diabetes, hypertension or hyperlipidaemia in primary care settings

    Directory of Open Access Journals (Sweden)

    Chua Siew

    2012-11-01

    Full Text Available Abstract Background The roles of pharmacists have evolved from product oriented, dispensing of medications to more patient-focused services such as the provision of pharmaceutical care. Such pharmacy service is also becoming more widely practised in Malaysia but is not well documented. Therefore, this study is warranted to fill this information gap by identifying the types of pharmaceutical care issues (PCIs encountered by primary care patients with diabetes mellitus, hypertension or hyperlipidaemia in Malaysia. Methods This study was part of a large controlled trial that evaluated the outcomes of multiprofessional collaboration which involved medical general practitioners, pharmacists, dietitians and nurses in managing diabetes mellitus, hypertension and hyperlipidaemia in primary care settings. A total of 477 patients were recruited by 44 general practitioners in the Klang Valley. These patients were counselled by the various healthcare professionals and followed-up for 6 months. Results Of the 477 participants, 53.7% had at least one PCI, with a total of 706 PCIs. These included drug-use problems (33.3%, insufficient awareness and knowledge about disease condition and medication (20.4%, adverse drug reactions (15.6%, therapeutic failure (13.9%, drug-choice problems (9.5% and dosing problems (3.4%. Non-adherence to medications topped the list of drug-use problems, followed by incorrect administration of medications. More than half of the PCIs (52% were classified as probably clinically insignificant, 38.9% with minimal clinical significance, 8.9% as definitely clinically significant and could cause patient harm while one issue (0.2% was classified as life threatening. The main causes of PCIs were deterioration of disease state which led to failure of therapy, and also presentation of new symptoms or indications. Of the 338 PCIs where changes were recommended by the pharmacist, 87.3% were carried out as recommended. Conclusions This study

  14. Phylogenetic analysis and protein structure modelling identifies distinct Ca(2+)/Cation antiporters and conservation of gene family structure within Arabidopsis and rice species.

    Science.gov (United States)

    Pittman, Jon K; Hirschi, Kendal D

    2016-12-01

    The Ca(2+)/Cation Antiporter (CaCA) superfamily is an ancient and widespread family of ion-coupled cation transporters found in nearly all kingdoms of life. In animals, K(+)-dependent and K(+)-indendent Na(+)/Ca(2+) exchangers (NCKX and NCX) are important CaCA members. Recently it was proposed that all rice and Arabidopsis CaCA proteins should be classified as NCX proteins. Here we performed phylogenetic analysis of CaCA genes and protein structure homology modelling to further characterise members of this transporter superfamily. Phylogenetic analysis of rice and Arabidopsis CaCAs in comparison with selected CaCA members from non-plant species demonstrated that these genes form clearly distinct families, with the H(+)/Cation exchanger (CAX) and cation/Ca(2+) exchanger (CCX) families dominant in higher plants but the NCKX and NCX families absent. NCX-related Mg(2+)/H(+) exchanger (MHX) and CAX-related Na(+)/Ca(2+) exchanger-like (NCL) proteins are instead present. Analysis of genomes of ten closely-related rice species and four Arabidopsis-related species found that CaCA gene family structures are highly conserved within related plants, apart from minor variation. Protein structures were modelled for OsCAX1a and OsMHX1. Despite exhibiting broad structural conservation, there are clear structural differences observed between the different CaCA types. Members of the CaCA superfamily form clearly distinct families with different phylogenetic, structural and functional characteristics, and therefore should not be simply classified as NCX proteins, which should remain as a separate gene family.

  15. Scientific Issues Relevant to Setting Regulatory Criteria to Identify Endocrine-Disrupting Substances in the European Union.

    Science.gov (United States)

    Slama, Rémy; Bourguignon, Jean-Pierre; Demeneix, Barbara; Ivell, Richard; Panzica, Giancarlo; Kortenkamp, Andreas; Zoeller, R Thomas

    2016-10-01

    to setting regulatory criteria to identify endocrine disrupting substances in the European Union. Environ Health Perspect 124:1497-1503; http://dx.doi.org/10.1289/EHP217.

  16. Molecular dynamics simulations of site point mutations in the TPR domain of cyclophilin 40 identify conformational states with distinct dynamic and enzymatic properties

    Science.gov (United States)

    Gur, Mert; Blackburn, Elizabeth A.; Ning, Jia; Narayan, Vikram; Ball, Kathryn L.; Walkinshaw, Malcolm D.; Erman, Burak

    2018-04-01

    Cyclophilin 40 (Cyp40) is a member of the immunophilin family that acts as a peptidyl-prolyl-isomerase enzyme and binds to the heat shock protein 90 (Hsp90). Its structure comprises an N-terminal cyclophilin domain and a C-terminal tetratricopeptide (TPR) domain. Cyp40 is overexpressed in prostate cancer and certain T-cell lymphomas. The groove for Hsp90 binding on the TPR domain includes residues Lys227 and Lys308, referred to as the carboxylate clamp, and is essential for Cyp40-Hsp90 binding. In this study, the effect of two mutations, K227A and K308A, and their combinative mutant was investigated by performing a total of 5.76 μs of all-atom molecular dynamics (MD) simulations in explicit solvent. All simulations, except the K308A mutant, were found to adopt two distinct (extended or compact) conformers defined by different cyclophilin-TPR interdomain distances. The K308A mutant was only observed in the extended form which is observed in the Cyp40 X-ray structure. The wild-type, K227A, and combined mutant also showed bimodal distributions. The experimental melting temperature, Tm, values of the mutants correlate with the degree of compactness with the K308A extended mutant having a marginally lower melting temperature. Another novel measure of compactness determined from the MD data, the "coordination shell volume," also shows a direct correlation with Tm. In addition, the MD simulations show an allosteric effect with the mutations in the remote TPR domain having a pronounced effect on the molecular motions of the enzymatic cyclophilin domain which helps rationalise the experimentally observed increase in enzyme activity measured for all three mutations.

  17. Identifying Early Childhood Personality Dimensions Using the California Child Q-Set and Prospective Associations With Behavioral and Psychosocial Development

    OpenAIRE

    Wilson, Sylia; Schalet, Benjamin D.; Hicks, Brian M.; Zucker, Robert A.

    2013-01-01

    The present study used an empirical, “bottom-up” approach to delineate the structure of the California Child Q-Set (CCQ), a comprehensive set of personality descriptors, in a sample of 373 preschool-aged children. This approach yielded two broad trait dimensions, Adaptive Socialization (emotional stability, compliance, intelligence) and Anxious Inhibition (emotional/behavioral introversion). Results demonstrate the value of using empirical derivation to investigate the structure of personalit...

  18. Novel Method To Identify Source-Associated Phylogenetic Clustering Shows that Listeria monocytogenes Includes Niche-Adapted Clonal Groups with Distinct Ecological Preferences

    DEFF Research Database (Denmark)

    Nightingale, K. K.; Lyles, K.; Ayodele, M.

    2006-01-01

    population are identified (TreeStats test). Analysis of sequence data for 120 L. monocytogenes isolates revealed evidence of clustering between isolates from the same source, based on the phylogenies inferred from actA and inlA (P = 0.02 and P = 0.07, respectively; SourceCluster test). Overall, the Tree...... are biologically valid. Overall, our data show that (i) the SourceCluster and TreeStats tests can identify biologically meaningful source-associated phylogenetic clusters and (ii) L. monocytogenes includes clonal groups that have adapted to infect specific host species or colonize nonhost environments......., including humans, animals, and food. If the null hypothesis that the genetic distances for isolates within and between source populations are identical can be rejected (SourceCluster test), then particular clades in the phylogenetic tree with significant overrepresentation of sequences from a given source...

  19. Distinct high resolution genome profiles of early onset and late onset colorectal cancer integrated with gene expression data identify candidate susceptibility loci

    Directory of Open Access Journals (Sweden)

    Merok Marianne A

    2010-05-01

    Full Text Available Abstract Background Estimates suggest that up to 30% of colorectal cancers (CRC may develop due to an increased genetic risk. The mean age at diagnosis for CRC is about 70 years. Time of disease onset 20 years younger than the mean age is assumed to be indicative of genetic susceptibility. We have compared high resolution tumor genome copy number variation (CNV (Roche NimbleGen, 385 000 oligo CGH array in microsatellite stable (MSS tumors from two age groups, including 23 young at onset patients without known hereditary syndromes and with a median age of 44 years (range: 28-53 and 17 elderly patients with median age 79 years (range: 69-87. Our aim was to identify differences in the tumor genomes between these groups and pinpoint potential susceptibility loci. Integration analysis of CNV and genome wide mRNA expression data, available for the same tumors, was performed to identify a restricted candidate gene list. Results The total fraction of the genome with aberrant copy number, the overall genomic profile and the TP53 mutation spectrum were similar between the two age groups. However, both the number of chromosomal aberrations and the number of breakpoints differed significantly between the groups. Gains of 2q35, 10q21.3-22.1, 10q22.3 and 19q13.2-13.31 and losses from 1p31.3, 1q21.1, 2q21.2, 4p16.1-q28.3, 10p11.1 and 19p12, positions that in total contain more than 500 genes, were found significantly more often in the early onset group as compared to the late onset group. Integration analysis revealed a covariation of DNA copy number at these sites and mRNA expression for 107 of the genes. Seven of these genes, CLC, EIF4E, LTBP4, PLA2G12A, PPAT, RG9MTD2, and ZNF574, had significantly different mRNA expression comparing median expression levels across the transcriptome between the two groups. Conclusions Ten genomic loci, containing more than 500 protein coding genes, are identified as more often altered in tumors from early onset versus late

  20. Use of the International Classification of Functioning, Disability and Health to identify preliminary comprehensive and brief core sets for Guillain Barre syndrome.

    Science.gov (United States)

    Khan, Fary; Pallant, Julie F

    2011-01-01

    To identify the preliminary comprehensive and brief core sets for Guillain Barre syndrome (GBS), in a Delphi process using the International Classification of Functioning, Disability and Health (ICF). Focus groups and a consensus process were used to identify ICF core sets for GBS. This included: preliminary ICF studies; empirical patient data collection for 77 GBS participants; review of the evidence base and treatment in GBS literature followed by a Delphi exercise with 23 physicians and allied health professionals in Melbourne, Australia. The expert consensus selected 99 second level ICF categories (in three rounds) which identify health domains relevant to GBS for multidisciplinary assessment. These domains were consistent with current practice and existing GBS literature. The comprehensive core set includes: 27 (23%) categories from the component 'body function', 7 (12%) categories from 'body structures', 43 (36%) from 'activities and participation' and 22 (29%) from the component 'environmental' factors. The brief set comprised 20 categories, 20% of categories in the comprehensive core set. The core set categories for GBS-related health need to be addressed in multidisciplinary care programs. Future clinical 'rating' of this set may facilitate scale development using the ICF in GBS. Further research is needed to confirm the generalisability of this set in clinical settings.

  1. Transcriptomic analysis identifies gene networks regulated by estrogen receptor α (ERα) and ERβ that control distinct effects of different botanical estrogens

    Science.gov (United States)

    Gong, Ping; Madak-Erdogan, Zeynep; Li, Jilong; Cheng, Jianlin; Greenlief, C. Michael; Helferich, William G.; Katzenellenbogen, John A.

    2014-01-01

    gene regulations than E2. The distinctive patterns of gene regulation by the individual BEs and E2 may underlie differences in the activities of these soy and licorice-derived BEs in estrogen target cells containing different levels of the two ERs. PMID:25363786

  2. A systems biology approach identifies a R2R3 MYB gene subfamily with distinct and overlapping functions in regulation of aliphatic glucosinolates.

    Directory of Open Access Journals (Sweden)

    Ida Elken Sønderby

    Full Text Available BACKGROUND: Glucosinolates are natural metabolites in the order Brassicales that defend plants against both herbivores and pathogens and can attract specialized insects. Knowledge about the genes controlling glucosinolate regulation is limited. Here, we identify three R2R3 MYB transcription factors regulating aliphatic glucosinolate biosynthesis in Arabidopsis by combining several systems biology tools. METHODOLOGY/PRINCIPAL FINDINGS: MYB28 was identified as a candidate regulator of aliphatic glucosinolates based on its co-localization within a genomic region controlling variation both in aliphatic glucosinolate content (metabolite QTL and in transcript level for genes involved in the biosynthesis of aliphatic glucosinolates (expression QTL, as well as its co-expression with genes in aliphatic glucosinolate biosynthesis. A phylogenetic analysis with the R2R3 motif of MYB28 showed that it and two homologues, MYB29 and MYB76, were members of an Arabidopsis-specific clade that included three characterized regulators of indole glucosinolates. Over-expression of the individual MYB genes showed that they all had the capacity to increase the production of aliphatic glucosinolates in leaves and seeds and induce gene expression of aliphatic biosynthetic genes within leaves. Analysis of leaves and seeds of single knockout mutants showed that mutants of MYB29 and MYB76 have reductions in only short-chained aliphatic glucosinolates whereas a mutant in MYB28 has reductions in both short- and long-chained aliphatic glucosinolates. Furthermore, analysis of a double knockout in MYB28 and MYB29 identified an emergent property of the system since the absence of aliphatic glucosinolates in these plants could not be predicted by the chemotype of the single knockouts. CONCLUSIONS/SIGNIFICANCE: It seems that these cruciferous-specific MYB regulatory genes have evolved both overlapping and specific regulatory capacities. This provides a unique system within which to

  3. Identifying drug-induced repolarization abnormalities from distinct ECG patterns in congenital long QT syndrome: a study of sotalol effects on T-wave morphology

    DEFF Research Database (Denmark)

    Graff, Claus; Andersen, Mads P; Xue, Joel Q

    2009-01-01

    BACKGROUND: The electrocardiographic QT interval is used to identify drugs with potential harmful effects on cardiac repolarization in drug trials, but the variability of the measurement can mask drug-induced ECG changes. The use of complementary electrocardiographic indices of abnormal repolariz......BACKGROUND: The electrocardiographic QT interval is used to identify drugs with potential harmful effects on cardiac repolarization in drug trials, but the variability of the measurement can mask drug-induced ECG changes. The use of complementary electrocardiographic indices of abnormal...... are typical ECG patterns in LQT2. Blinded to labels, the new morphology measures were tested in a third group of 39 healthy subjects receiving sotalol. Over 3 days the sotalol group received 0, 160 and 320 mg doses, respectively, and a 12-lead Holter ECG was recorded for 22.5 hours each day. Drug...... with QTcF, p ECG patterns in LQT2 carriers effectively quantified repolarization changes induced by sotalol. Further studies are needed to validate whether this measure has...

  4. Distinctive Citizenship

    DEFF Research Database (Denmark)

    Kaur, Ravinder

    2009-01-01

    The refugee, in India's Partition history, appears as an enigmatic construct - part pitiful, part heroic, though mostly shorn of agency - representing the surface of the human tragedy of Partition. Yet this archetype masks the undercurrent of social distinctions that produced hierarchies of post...

  5. MicroRNA transfection and AGO-bound CLIP-seq data sets reveal distinct determinants of miRNA action

    DEFF Research Database (Denmark)

    Wen, Jiayu; Parker, Brian J; Jacobsen, Anders

    2011-01-01

    the predictive effect of target flanking features. We observe distinct target determinants between expression-based and CLIP-based data. Target flanking features such as flanking region conservation are an important AGO-binding determinant-we hypothesize that CLIP experiments have a preference for strongly bound......Microarray expression analyses following miRNA transfection/inhibition and, more recently, Argonaute cross-linked immunoprecipitation (CLIP)-seq assays have been used to detect miRNA target sites. CLIP and expression approaches measure differing stages of miRNA functioning-initial binding of the mi...... miRNP-target interactions involving adjacent RNA-binding proteins that increase the strength of cross-linking. In contrast, seed-related features are major determinants in expression-based studies, but less so for CLIP-seq studies, and increased miRNA concentrations typical of transfection studies...

  6. The goya mouse mutant reveals distinct newly identified roles for MAP3K1 in the development and survival of cochlear sensory hair cells

    Directory of Open Access Journals (Sweden)

    Andrew Parker

    2015-12-01

    Full Text Available Mitogen-activated protein kinase, MAP3K1, plays an important role in a number of cellular processes, including epithelial migration during eye organogenesis. In addition, studies in keratinocytes indicate that MAP3K1 signalling through JNK is important for actin stress fibre formation and cell migration. However, MAP3K1 can also act independently of JNK in the regulation of cell proliferation and apoptosis. We have identified a mouse mutant, goya, which exhibits the eyes-open-at-birth and microphthalmia phenotypes. In addition, these mice also have hearing loss. The goya mice carry a splice site mutation in the Map3k1 gene. We show that goya and kinase-deficient Map3k1 homozygotes initially develop supernumerary cochlear outer hair cells (OHCs that subsequently degenerate, and a progressive profound hearing loss is observed by 9 weeks of age. Heterozygote mice also develop supernumerary OHCs, but no cellular degeneration or hearing loss is observed. MAP3K1 is expressed in a number of inner-ear cell types, including outer and inner hair cells, stria vascularis and spiral ganglion. Investigation of targets downstream of MAP3K1 identified an increase in p38 phosphorylation (Thr180/Tyr182 in multiple cochlear tissues. We also show that the extra OHCs do not arise from aberrant control of proliferation via p27KIP1. The identification of the goya mutant reveals a signalling molecule involved with hair-cell development and survival. Mammalian hair cells do not have the ability to regenerate after damage, which can lead to irreversible sensorineural hearing loss. Given the observed goya phenotype, and the many diverse cellular processes that MAP3K1 is known to act upon, further investigation of this model might help to elaborate upon the mechanisms underlying sensory hair cell specification, and pathways important for their survival. In addition, MAP3K1 is revealed as a new candidate gene for human sensorineural hearing loss.

  7. The goya mouse mutant reveals distinct newly identified roles for MAP3K1 in the development and survival of cochlear sensory hair cells.

    Science.gov (United States)

    Parker, Andrew; Cross, Sally H; Jackson, Ian J; Hardisty-Hughes, Rachel; Morse, Susan; Nicholson, George; Coghill, Emma; Bowl, Michael R; Brown, Steve D M

    2015-12-01

    Mitogen-activated protein kinase, MAP3K1, plays an important role in a number of cellular processes, including epithelial migration during eye organogenesis. In addition, studies in keratinocytes indicate that MAP3K1 signalling through JNK is important for actin stress fibre formation and cell migration. However, MAP3K1 can also act independently of JNK in the regulation of cell proliferation and apoptosis. We have identified a mouse mutant, goya, which exhibits the eyes-open-at-birth and microphthalmia phenotypes. In addition, these mice also have hearing loss. The goya mice carry a splice site mutation in the Map3k1 gene. We show that goya and kinase-deficient Map3k1 homozygotes initially develop supernumerary cochlear outer hair cells (OHCs) that subsequently degenerate, and a progressive profound hearing loss is observed by 9 weeks of age. Heterozygote mice also develop supernumerary OHCs, but no cellular degeneration or hearing loss is observed. MAP3K1 is expressed in a number of inner-ear cell types, including outer and inner hair cells, stria vascularis and spiral ganglion. Investigation of targets downstream of MAP3K1 identified an increase in p38 phosphorylation (Thr180/Tyr182) in multiple cochlear tissues. We also show that the extra OHCs do not arise from aberrant control of proliferation via p27KIP1. The identification of the goya mutant reveals a signalling molecule involved with hair-cell development and survival. Mammalian hair cells do not have the ability to regenerate after damage, which can lead to irreversible sensorineural hearing loss. Given the observed goya phenotype, and the many diverse cellular processes that MAP3K1 is known to act upon, further investigation of this model might help to elaborate upon the mechanisms underlying sensory hair cell specification, and pathways important for their survival. In addition, MAP3K1 is revealed as a new candidate gene for human sensorineural hearing loss. © 2015. Published by The Company of

  8. Influence of the Training Set Value on the Quality of the Neural Network to Identify Selected Moulding Sand Properties

    Directory of Open Access Journals (Sweden)

    Jakubski J.

    2013-06-01

    Full Text Available Artificial neural networks are one of the modern methods of the production optimisation. An attempt to apply neural networks for controlling the quality of bentonite moulding sands is presented in this paper. This is the assessment method of sands suitability by means of detecting correlations between their individual parameters. This paper presents the next part of the study on usefulness of artificial neural networks to support rebonding of green moulding sand, using chosen properties of moulding sands, which can be determined fast. The effect of changes in the training set quantity on the quality of the network is presented in this article. It has been shown that a small change in the data set would change the quality of the network, and may also make it necessary to change the type of network in order to obtain good results.

  9. Identifying Early Childhood Personality Dimensions Using the California Child Q-Set and Prospective Associations With Behavioral and Psychosocial Development.

    Science.gov (United States)

    Wilson, Sylia; Schalet, Benjamin D; Hicks, Brian M; Zucker, Robert A

    2013-08-01

    The present study used an empirical, "bottom-up" approach to delineate the structure of the California Child Q-Set (CCQ), a comprehensive set of personality descriptors, in a sample of 373 preschool-aged children. This approach yielded two broad trait dimensions, Adaptive Socialization (emotional stability, compliance, intelligence) and Anxious Inhibition (emotional/behavioral introversion). Results demonstrate the value of using empirical derivation to investigate the structure of personality in young children, speak to the importance of early-evident personality traits for adaptive development, and are consistent with a growing body of evidence indicating that personality structure in young children is similar, but not identical to, that in adults, suggesting a model of broad personality dimensions in childhood that evolve into narrower traits in adulthood.

  10. Temporal relationship between cancer and myositis identifies two distinctive subgroups of cancers: impact on cancer risk and survival in patients with myositis.

    Science.gov (United States)

    Kang, Eun Ha; Lee, Sang Jin; Ascherman, Dana P; Lee, Yun Jong; Lee, Eun Young; Lee, Eun Bong; Song, Yeong Wook

    2016-09-01

    The aim was to compare standardized incidence ratios (SIRs) of cancers temporally related and unrelated to active myositis in patients with myositis. Fifty-two cancer cases were identified in 281 myositis patients. SIRs of cancers having temporal overlap with the active phase of myositis [cancers concurrent with active myositis (CAM), n = 30] and cancers not having such temporal overlap [cancers non-concurrent with active myositis (CNM), n = 22] were compared in 281 patients. Patients with CAM were older at diagnosis of myositis, had a greater tendency to be male, more frequent dysphagia and less frequent interstitial lung disease than patients with CNM. CAM SIR (95% CI) was 1.78 (1.19, 2.56) and CNM SIR 1.23 (0.75, 1.90). The peak SIR was observed in the seventh decade of life for CAM and in the third decade for CNM. When stratified by myositis-cancer intervals, CAM SIR was 9.94 (6.43, 14.67) within 1 year of myositis diagnosis, whereas no temporal relationship was found for CNM. Elevated SIRs were observed for oesophageal cancer [57.77 (11.91, 168.82)], non-Hodgkin's lymphoma [41.43 (13.45, 96.69)], adenocarcinoma of unknown primary origin [67.6 (18.42, 173.07]), lung cancer [7.27 (1.98, 18.61)] and ovarian cancer [19.15 (2.32, 69.17)] within 3 years of CAM diagnosis. The cancer stage at the time of diagnosis was more advanced in CAM than CNM (P < 0.001), with a correspondingly increased hazard ratio of mortality [4.3 (1.5, 12.7)] in patients with CAM vs CNM. A significantly elevated SIR was found for CAM, whereas there was a comparable SIR for CNM relative to the general population. Multiple types of cancers showed elevated SIRs among CAM, but none among CNM. Given that cancer stages in CAM were far advanced at diagnosis, mortality risk was greater in patients with CAM. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Identifying primary care patient safety research priorities in the UK: a James Lind Alliance Priority Setting Partnership.

    Science.gov (United States)

    Morris, Rebecca Lauren; Stocks, Susan Jill; Alam, Rahul; Taylor, Sian; Rolfe, Carly; Glover, Steven William; Whitcombe, Joanne; Campbell, Stephen M

    2018-02-28

    To identify the top 10 unanswered research questions for primary care patient safety research. A modified nominal group technique. UK. Anyone with experience of primary care including: patients, carers and healthcare professionals. 341 patients and 86 healthcare professionals submitted questions. A top 10, and top 30, future research questions for primary care patient safety. 443 research questions were submitted by 341 patients and 86 healthcare professionals, through a national survey. After checking for relevance and rephrasing, a total of 173 questions were collated into themes. The themes were largely focused on communication, team and system working, interfaces across primary and secondary care, medication, self-management support and technology. The questions were then prioritised through a national survey, the top 30 questions were taken forward to the final prioritisation workshop. The top 10 research questions focused on the most vulnerable in society, holistic whole-person care, safer communication and coordination between care providers, work intensity, continuity of care, suicide risk, complex care at home and confidentiality. This study was the first national prioritisation exercise to identify patient and healthcare professional priorities for primary care patient safety research. The research priorities identified a range of important gaps in the existing evidence to inform everyday practice to address primary care patient safety. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. Convergence of Multiple MAP3Ks on MKK3 Identifies a Set of Novel Stress MAPK Modules

    KAUST Repository

    Colcombet, Jean

    2016-12-22

    Since its first description in 1995 and functional characterization 12 years later, plant MKK3-type MAP2Ks have emerged as important integrators in plant signaling. Although they have received less attention than the canonical stress-activated mitogen-activated protein kinases (MAPKs), several recent publications shed light on their important roles in plant adaptation to environmental conditions. Nevertheless, the MKK3-related literature is complicated. This review summarizes the current knowledge and discrepancies on MKK3 MAPK modules in plants and highlights the singular role of MKK3 in green plants. In the light of the latest data, we hypothesize a general model that all clade-III MAP3Ks converge on MKK3 and C-group MAPKs, thereby defining a set of novel MAPK modules which are activated by stresses and internal signals through the transcriptional regulation of MAP3K genes.

  13. Integrating genome-wide association study and expression quantitative trait loci data identifies multiple genes and gene set associated with neuroticism.

    Science.gov (United States)

    Fan, Qianrui; Wang, Wenyu; Hao, Jingcan; He, Awen; Wen, Yan; Guo, Xiong; Wu, Cuiyan; Ning, Yujie; Wang, Xi; Wang, Sen; Zhang, Feng

    2017-08-01

    Neuroticism is a fundamental personality trait with significant genetic determinant. To identify novel susceptibility genes for neuroticism, we conducted an integrative analysis of genomic and transcriptomic data of genome wide association study (GWAS) and expression quantitative trait locus (eQTL) study. GWAS summary data was driven from published studies of neuroticism, totally involving 170,906 subjects. eQTL dataset containing 927,753 eQTLs were obtained from an eQTL meta-analysis of 5311 samples. Integrative analysis of GWAS and eQTL data was conducted by summary data-based Mendelian randomization (SMR) analysis software. To identify neuroticism associated gene sets, the SMR analysis results were further subjected to gene set enrichment analysis (GSEA). The gene set annotation dataset (containing 13,311 annotated gene sets) of GSEA Molecular Signatures Database was used. SMR single gene analysis identified 6 significant genes for neuroticism, including MSRA (p value=2.27×10 -10 ), MGC57346 (p value=6.92×10 -7 ), BLK (p value=1.01×10 -6 ), XKR6 (p value=1.11×10 -6 ), C17ORF69 (p value=1.12×10 -6 ) and KIAA1267 (p value=4.00×10 -6 ). Gene set enrichment analysis observed significant association for Chr8p23 gene set (false discovery rate=0.033). Our results provide novel clues for the genetic mechanism studies of neuroticism. Copyright © 2017. Published by Elsevier Inc.

  14. Superfund TIO videos. Set A. Identifying PRPS. Removal process: Removal site evaluation. Part 2. Audio-Visual

    International Nuclear Information System (INIS)

    1990-01-01

    The videotape is divided into three sections. Section 1 details the liability of Potentially Responsible Parties (PRPs) and describes the four classes of PRPs: current owners and operators, former owners and operators, generators, and transporters (if they selected the site). Section 2 lists the goals of the Potentially Responsible Party (PRP) search and explains how to identify key players during the PRP search. How to plan and conduct the PRP search is also outlined. Section 3 outlines the steps involved in conducting a removal site evaluation. A discussion of when to conduct a removal preliminary assessment, a removal site inspection, and an Engineering Evaluation/Cost Analysis (EE/AC) also is covered

  15. Screening for type 2 diabetes in a multiethnic setting using known risk factors to identify those at high risk

    DEFF Research Database (Denmark)

    Gray, Laura J.; Tringham, Jennifer R.; Davies, Melanie J.

    2010-01-01

    population to identify those with abnormal glucose tolerance. ethods: A sample of individuals aged 25-75 years (40-75 white European) with at least one risk factor for T2DM were invited for screening from 17 Leicestershire (UK) general practices or through a health awareness campaign. All participants...... received a 75 g oral glucose tolerance test, cardiovascular risk assessment, detailed medical and family histories and anthropometric measurements. Results: In the 3,225 participants who were screened. 640 (20%) were found to have some form of abnormal glucose tolerance of whom 4% had T2DM, 3% impaired...

  16. Genome-wide methylation analysis identifies a core set of hypermethylated genes in CIMP-H colorectal cancer.

    Science.gov (United States)

    McInnes, Tyler; Zou, Donghui; Rao, Dasari S; Munro, Francesca M; Phillips, Vicky L; McCall, John L; Black, Michael A; Reeve, Anthony E; Guilford, Parry J

    2017-03-28

    Aberrant DNA methylation profiles are a characteristic of all known cancer types, epitomized by the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC). Hypermethylation has been observed at CpG islands throughout the genome, but it is unclear which factors determine whether an individual island becomes methylated in cancer. DNA methylation in CRC was analysed using the Illumina HumanMethylation450K array. Differentially methylated loci were identified using Significance Analysis of Microarrays (SAM) and the Wilcoxon Signed Rank (WSR) test. Unsupervised hierarchical clustering was used to identify methylation subtypes in CRC. In this study we characterized the DNA methylation profiles of 94 CRC tissues and their matched normal counterparts. Consistent with previous studies, unsupervized hierarchical clustering of genome-wide methylation data identified three subtypes within the tumour samples, designated CIMP-H, CIMP-L and CIMP-N, that showed high, low and very low methylation levels, respectively. Differential methylation between normal and tumour samples was analysed at the individual CpG level, and at the gene level. The distribution of hypermethylation in CIMP-N tumours showed high inter-tumour variability and appeared to be highly stochastic in nature, whereas CIMP-H tumours exhibited consistent hypermethylation at a subset of genes, in addition to a highly variable background of hypermethylated genes. EYA4, TFPI2 and TLX1 were hypermethylated in more than 90% of all tumours examined. One-hundred thirty-two genes were hypermethylated in 100% of CIMP-H tumours studied and these were highly enriched for functions relating to skeletal system development (Bonferroni adjusted p value =2.88E-15), segment specification (adjusted p value =9.62E-11), embryonic development (adjusted p value =1.52E-04), mesoderm development (adjusted p value =1.14E-20), and ectoderm development (adjusted p value =7.94E-16). Our genome-wide characterization of DNA

  17. Sheeppox virus SPPV14 encodes a Bcl-2-like cell death inhibitor that counters a distinct set of mammalian proapoptotic proteins.

    Science.gov (United States)

    Okamoto, Toru; Campbell, Stephanie; Mehta, Ninad; Thibault, John; Colman, Peter M; Barry, Michele; Huang, David C S; Kvansakul, Marc

    2012-11-01

    Many viruses express inhibitors of programmed cell death (apoptosis), thereby countering host defenses that would otherwise rapidly clear infected cells. To counter this, viruses such as adenoviruses and herpesviruses express recognizable homologs of the mammalian prosurvival protein Bcl-2. In contrast, the majority of poxviruses lack viral Bcl-2 (vBcl-2) homologs that are readily identified by sequence similarities. One such virus, myxoma virus, which is the causative agent of myxomatosis, expresses a virulence factor that is a potent inhibitor of apoptosis. In spite of the scant sequence similarity to Bcl-2, myxoma virus M11L adopts an almost identical 3-dimensional fold. We used M11L as bait in a sequence similarity search for other Bcl-2-like proteins and identified six putative vBcl-2 proteins from poxviruses. Some are potent inhibitors of apoptosis, in particular sheeppox virus SPPV14, which inhibited cell death induced by multiple agents. Importantly, SPPV14 compensated for the loss of antiapoptotic F1L in vaccinia virus and acts to directly counter the cell death mediators Bax and Bak. SPPV14 also engages a unique subset of the death-promoting BH3-only ligands, including Bim, Puma, Bmf, and Hrk. This suggests that SPPV14 may have been selected for specific biological roles as a virulence factor for sheeppox virus.

  18. MGMT methylation analysis of glioblastoma on the Infinium methylation BeadChip identifies two distinct CpG regions associated with gene silencing and outcome, yielding a prediction model for comparisons across datasets, tumor grades, and CIMP-status.

    Science.gov (United States)

    Bady, Pierre; Sciuscio, Davide; Diserens, Annie-Claire; Bloch, Jocelyne; van den Bent, Martin J; Marosi, Christine; Dietrich, Pierre-Yves; Weller, Michael; Mariani, Luigi; Heppner, Frank L; Mcdonald, David R; Lacombe, Denis; Stupp, Roger; Delorenzi, Mauro; Hegi, Monika E

    2012-10-01

    The methylation status of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene is an important predictive biomarker for benefit from alkylating agent therapy in glioblastoma. Recent studies in anaplastic glioma suggest a prognostic value for MGMT methylation. Investigation of pathogenetic and epigenetic features of this intriguingly distinct behavior requires accurate MGMT classification to assess high throughput molecular databases. Promoter methylation-mediated gene silencing is strongly dependent on the location of the methylated CpGs, complicating classification. Using the HumanMethylation450 (HM-450K) BeadChip interrogating 176 CpGs annotated for the MGMT gene, with 14 located in the promoter, two distinct regions in the CpG island of the promoter were identified with high importance for gene silencing and outcome prediction. A logistic regression model (MGMT-STP27) comprising probes cg12434587 [corrected] and cg12981137 provided good classification properties and prognostic value (kappa = 0.85; log-rank p CIMP) positive tumors was found in glioblastomas from The Cancer Genome Atlas than in low grade and anaplastic glioma cohorts, while in CIMP-negative gliomas MGMT was classified as methylated in approximately 50 % regardless of tumor grade. The proposed MGMT-STP27 prediction model allows mining of datasets derived on the HM-450K or HM-27K BeadChip to explore effects of distinct epigenetic context of MGMT methylation suspected to modulate treatment resistance in different tumor types.

  19. Can traditional birth attendants be trained to accurately identify septic infants, initiate antibiotics, and refer in a rural African setting?

    Science.gov (United States)

    Gill, Christopher John; MacLeod, William B; Phiri-Mazala, Grace; Guerina, Nicholas G; Mirochnick, Mark; Knapp, Anna B; Hamer, Davidson H

    2014-08-01

    Neonatal sepsis is a major cause of neonatal mortality. In populations with limited access to health care, early identification of bacterial infections and initiation of antibiotics by community health workers (CHWs) could be lifesaving. It is unknown whether this strategy would be feasible using traditional birth attendants (TBAs), a cadre of CHWs who typically have limited training and educational backgrounds. We analyzed data from the intervention arm of a cluster-randomized trial involving TBAs in Lufwanyama District, Zambia, from June 2006 to November 2008. TBAs followed neonates for signs of potential infection through 28 days of life. If any of 16 criteria were met, TBAs administered oral amoxicillin and facilitated referral to a rural health center. Our analysis included 1,889 neonates with final vital status by day 28. TBAs conducted a median of 2 (interquartile range 2-6) home visits (51.4% in week 1 and 48.2% in weeks 2-4) and referred 208 neonates (11%) for suspected sepsis. Of referred neonates, 176/208 (84.6%) completed their referral. Among neonates given amoxicillin, 171/183 (93.4%) were referred; among referred neonates, 171/208 (82.2%) received amoxicillin. Referral and/or initiation of antibiotics were strongly associated with neonatal death (for referral, relative risk [RR] = 7.93, 95% confidence interval [CI] = 4.4-14.3; for amoxicillin administration, RR = 4.7, 95% CI = 2.4-8.7). Neonates clinically judged to be "extremely sick" by the referring TBA were at greatest risk of death (RR = 8.61, 95% CI = 4.0-18.5). The strategy of administering a first dose of antibiotics and referring based solely on the clinical evaluation of a TBA is feasible and could be effective in reducing neonatal mortality in remote rural settings.

  20. Novel archaeal tetraether lipids with a cyclohexyl ring identified in Fayetteville Green Lake, NY, and other sulfidic lacustrine settings.

    Science.gov (United States)

    Liu, Xiao-Lei; De Santiago Torio, Ana; Bosak, Tanja; Summons, Roger Everett

    2016-05-30

    The meromictic Fayetteville Green Lake (FGL) is of significant geobiological interest because of microbial cycling of sulfur within and below the permanent chemocline and in the euxinic deep waters. Studies of glycerol dibiphytanyl glycerol tetraethers (GDGTs) may help shed light on understanding the activity of archaeal communities in these habitats. Normal-phase and reversed-phase liquid chromatography/mass spectrometry (LC/MS) analysis on total lipid extracts of environmental samples revealed series of GDGTs with different biphytane structures. Comparison of the mass spectrum of biphytane obtained from separated novel GDGTs with that of a synthetic C 40 biphytane confirms our structural assignments. A unique cyclohexyl ring configured in the middle of a C 40 biphytane chain was identified in these novel GDGTs. We suggest the trivial name S-GDGTs for these compounds, where 'S' stands for 'sulfidic' and 'six-membered ring'. S-GDGT derivatives composed of biphytanes modified with double bonds and cyclopentane rings were also detected in the samples we analyzed. Intact polar lipid precursors of S-GDGT include compounds with mono- and diglycosyl head groups. The carbon isotopic composition of S-GDGTs and their occurrence in FGL, Messel Shale as well as Salt Pond and salt marshes on Cape Cod suggest that S-GDGTs may be produced by chemoautotrophic archaea that prefer sulfidic conditions. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  1. High-throughput drug screen identifies chelerythrine as a selective inducer of death in a TSC2-null setting.

    Science.gov (United States)

    Medvetz, Doug; Sun, Yang; Li, Chenggang; Khabibullin, Damir; Balan, Murugabaskar; Parkhitko, Andrey; Priolo, Carmen; Asara, John M; Pal, Soumitro; Yu, Jane; Henske, Elizabeth P

    2015-01-01

    Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome associated with tumors of the brain, heart, kidney, and lung. The TSC protein complex inhibits the mammalian or mechanistic target of rapamycin complex 1 (mTORC1). Inhibitors of mTORC1, including rapamycin, induce a cytostatic response in TSC tumors, resulting in temporary disease stabilization and prompt regrowth when treatment is stopped. The lack of TSC-specific cytotoxic therapies represents an important unmet clinical need. Using a high-throughput chemical screen in TSC2-deficient, patient-derived cells, we identified a series of molecules antagonized by rapamycin and therefore selective for cells with mTORC1 hyperactivity. In particular, the cell-permeable alkaloid chelerythrine induced reactive oxygen species (ROS) and depleted glutathione (GSH) selectively in TSC2-null cells based on metabolic profiling. N-acetylcysteine or GSH cotreatment protected TSC2-null cells from chelerythrine's effects, indicating that chelerythrine-induced cell death is ROS dependent. Induction of heme-oxygenase-1 (HMOX1/HO-1) with hemin also blocked chelerythrine-induced cell death. In vivo, chelerythrine inhibited the growth of TSC2-null xenograft tumors with no evidence of systemic toxicity with daily treatment over an extended period of time. This study reports the results of a bioactive compound screen and the identification of a potential lead candidate that acts via a novel oxidative stress-dependent mechanism to selectively induce necroptosis in TSC2-deficient tumors. This study demonstrates that TSC2-deficient tumor cells are hypersensitive to oxidative stress-dependent cell death, and provide critical proof of concept that TSC2-deficient cells can be therapeutically targeted without the use of a rapalog to induce a cell death response. ©2014 American Association for Cancer Research.

  2. Development of the policy indicator checklist: a tool to identify and measure policies for calorie-dense foods and sugar-sweetened beverages across multiple settings.

    Science.gov (United States)

    Lee, Rebecca E; Hallett, Allen M; Parker, Nathan; Kudia, Ousswa; Kao, Dennis; Modelska, Maria; Rifai, Hanadi; O'Connor, Daniel P

    2015-05-01

    We developed the policy indicator checklist (PIC) to identify and measure policies for calorie-dense foods and sugar-sweetened beverages to determine how policies are clustered across multiple settings. In 2012 and 2013 we used existing literature, policy documents, government recommendations, and instruments to identify key policies. We then developed the PIC to examine the policy environments across 3 settings (communities, schools, and early care and education centers) in 8 communities participating in the Childhood Obesity Research Demonstration Project. Principal components analysis revealed 5 components related to calorie-dense food policies and 4 components related to sugar-sweetened beverage policies. Communities with higher youth and racial/ethnic minority populations tended to have fewer and weaker policy environments concerning calorie-dense foods and healthy foods and beverages. The PIC was a helpful tool to identify policies that promote healthy food environments across multiple settings and to measure and compare the overall policy environments across communities. There is need for improved coordination across settings, particularly in areas with greater concentration of youths and racial/ethnic minority populations. Policies to support healthy eating are not equally distributed across communities, and disparities continue to exist in nutrition policies.

  3. Validating the Copenhagen Psychosocial Questionnaire (COPSOQ-II) Using Set-ESEM: Identifying Psychosocial Risk Factors in a Sample of School Principals.

    Science.gov (United States)

    Dicke, Theresa; Marsh, Herbert W; Riley, Philip; Parker, Philip D; Guo, Jiesi; Horwood, Marcus

    2018-01-01

    School principals world-wide report high levels of strain and attrition resulting in a shortage of qualified principals. It is thus crucial to identify psychosocial risk factors that reflect principals' occupational wellbeing. For this purpose, we used the Copenhagen Psychosocial Questionnaire (COPSOQ-II), a widely used self-report measure covering multiple psychosocial factors identified by leading occupational stress theories. We evaluated the COPSOQ-II regarding factor structure and longitudinal, discriminant, and convergent validity using latent structural equation modeling in a large sample of Australian school principals ( N = 2,049). Results reveal that confirmatory factor analysis produced marginally acceptable model fit. A novel approach we call set exploratory structural equation modeling (set-ESEM), where cross-loadings were only allowed within a priori defined sets of factors, fit well, and was more parsimonious than a full ESEM. Further multitrait-multimethod models based on the set-ESEM confirm the importance of a principal's psychosocial risk factors; Stressors and depression were related to demands and ill-being, while confidence and autonomy were related to wellbeing. We also show that working in the private sector was beneficial for showing a low psychosocial risk, while other demographics have little effects. Finally, we identify five latent risk profiles (high risk to no risk) of school principals based on all psychosocial factors. Overall the research presented here closes the theory application gap of a strong multi-dimensional measure of psychosocial risk-factors.

  4. A Model to Identify the Most Effective Business Rule in Information Systems using Rough Set Theory: Study on Loan Business Process

    Directory of Open Access Journals (Sweden)

    Mohammad Aghdasi

    2011-09-01

    In this paper, a practical model is used to identify the most effective rules in information systems. In this model, first, critical business attributes which fit to strategic expectations are taken into account. These are the attributes which their changes are more important than others in achieving the strategic expectations. To identify these attributes we utilize rough set theory. Those business rules which use critical information attribute in their structures are identified as the most effective business rules. The Proposed model helps information system developers to identify scope of effective business rules. It causes a decrease in time and cost of information system maintenance. Also it helps business analyst to focus on managing critical business attributes in order to achieve a specific goal.

  5. Identifying research priorities in anaesthesia and perioperative care: final report of the joint National Institute of Academic Anaesthesia/James Lind Alliance Research Priority Setting Partnership

    OpenAIRE

    Boney, O.; Bell, M.; Bell, N.; Conquest, A.; Cumbers, M.; Drake, S.; Galsworthy, M.; Gath, J.; Grocott, M. P.; Harris, E.; Howell, S.; Ingold, A.; Nathanson, M. H.; Pinkney, T.; Metcalf, L.

    2015-01-01

    Objective To identify research priorities for Anaesthesia and Perioperative Medicine. Design Prospective surveys and consensus meetings guided by an independent adviser. Setting UK. Participants 45 stakeholder organisations (25 professional, 20 patient/carer) affiliated as James Lind Alliance partners. Outcomes First ?ideas-gathering? survey: Free text research ideas and suggestions. Second ?prioritisation? survey: Shortlist of ?summary? research questions (derived from the first survey) rank...

  6. Application of Digital Object Identifiers to data sets at the NASA Goddard Earth Sciences Data and Information Services Center (GES DISC)

    Science.gov (United States)

    Vollmer, B.; Ostrenga, D.; Johnson, J. E.; Savtchenko, A. K.; Shen, S.; Teng, W. L.; Wei, J. C.

    2013-12-01

    Digital Object Identifiers (DOIs) are applied to selected data sets at the NASA Goddard Earth Sciences Data and Information Services Center (GES DISC). The DOI system provides an Internet resolution service for unique and persistent identifiers of digital objects. Products assigned DOIs include data from the NASA MEaSUREs Program, the Earth Observing System (EOS) Aqua Atmospheric Infrared Sounder (AIRS) and EOS Aura High Resolution Dynamics Limb Sounder (HIRDLS). DOIs are acquired and registered through EZID, California Digital Library and DataCite. GES DISC hosts a data set landing page associated with each DOI containing information on and access to the data including a recommended data citation when using the product in research or applications. This work includes participation with the earth science community (e.g., Earth Science Information Partners (ESIP) Federation) and the NASA Earth Science Data and Information System (ESDIS) Project to identify, establish and implement best practices for assigning DOIs and managing supporting information, including metadata, for earth science data sets. Future work includes (1) coordination with NASA mission Science Teams and other data providers on the assignment of DOIs for other GES DISC data holdings, particularly for future missions such as Orbiting Carbon Observatory -2 and -3 (OCO-2, OCO-3) and projects (MEaSUREs 2012), (2) construction of landing pages that are both human and machine readable, and (3) pursuing the linking of data and publications with tools such as the Thomson Reuters Data Citation Index.

  7. Using the International Classification of Functioning, Disability, and Health to identify outcome domains for a core outcome set for aphasia: a comparison of stakeholder perspectives.

    Science.gov (United States)

    Wallace, Sarah J; Worrall, Linda; Rose, Tanya; Le Dorze, Guylaine

    2017-11-12

    This study synthesised the findings of three separate consensus processes exploring the perspectives of key stakeholder groups about important aphasia treatment outcomes. This process was conducted to generate recommendations for outcome domains to be included in a core outcome set for aphasia treatment trials. International Classification of Functioning, Disability, and Health codes were examined to identify where the groups of: (1) people with aphasia, (2) family members, (3) aphasia researchers, and (4) aphasia clinicians/managers, demonstrated congruence in their perspectives regarding important treatment outcomes. Codes were contextualized using qualitative data. Congruence across three or more stakeholder groups was evident for ICF chapters: Mental functions; Communication; and Services, systems, and policies. Quality of life was explicitly identified by clinicians/managers and researchers, while people with aphasia and their families identified outcomes known to be determinants of quality of life. Core aphasia outcomes include: language, emotional wellbeing, communication, patient-reported satisfaction with treatment and impact of treatment, and quality of life. International Classification of Functioning, Disability, and Health coding can be used to compare stakeholder perspectives and identify domains for core outcome sets. Pairing coding with qualitative data may ensure important nuances of meaning are retained. Implications for rehabilitation The outcomes measured in treatment research should be relevant to stakeholders and support health care decision making. Core outcome sets (agreed, minimum set of outcomes, and outcome measures) are increasingly being used to ensure the relevancy and consistency of the outcomes measured in treatment studies. Important aphasia treatment outcomes span all components of the International Classification of Functioning, Disability, and Health. Stakeholders demonstrated congruence in the identification of important

  8. The ICF Core Sets for hearing loss--researcher perspective. Part I: Systematic review of outcome measures identified in audiological research.

    Science.gov (United States)

    Granberg, Sarah; Dahlström, Jennie; Möller, Claes; Kähäri, Kim; Danermark, Berth

    2014-02-01

    To review the literature in order to identify outcome measures used in research on adults with hearing loss (HL) as part of the ICF Core Sets development project, and to describe study and population characteristics of the reviewed studies. A systematic review methodology was applied using multiple databases. A comprehensive search was conducted and two search pools were created, pool I and pool II. The study population included adults (≥ 18 years of age) with HL and oral language as the primary mode of communication. 122 studies were included. Outcome measures were distinguished by 'instrument type', and 10 types were identified. In total, 246 (pool I) and 122 (pool II) different measures were identified, and only approximately 20% were extracted twice or more. Most measures were related to speech recognition. Fifty-one different questionnaires were identified. Many studies used small sample sizes, and the sex of participants was not revealed in several studies. The low prevalence of identified measures reflects a lack of consensus regarding the optimal outcome measures to use in audiology. Reflections and discussions are made in relation to small sample sizes and the lack of sex differentiation/descriptions within the included articles.

  9. A proteomics method using immunoaffinity fluorogenic derivatization-liquid chromatography/tandem mass spectrometry (FD-LC-MS/MS) to identify a set of interacting proteins.

    Science.gov (United States)

    Nakata, Katsunori; Saitoh, Ryoichi; Ishigai, Masaki; Imai, Kazuhiro

    2018-02-01

    Biological functions in organisms are usually controlled by a set of interacting proteins, and identifying the proteins that interact is useful for understanding the mechanism of the functions. Immunoprecipitation is a method that utilizes the affinity of an antibody to isolate and identify the proteins that have interacted in a biological sample. In this study, the FD-LC-MS/MS method, which involves fluorogenic derivatization followed by separation and quantification by HPLC and finally identification of proteins by HPLC-tandem mass spectrometry, was used to identify proteins in immunoprecipitated samples, using heat shock protein 90 (HSP90) as a model of an interacting protein in HepaRG cells. As a result, HSC70 protein, which was known to form a complex with HSP90, was isolated, together with three different types of HSP90-beta. The results demonstrated that the proposed immunoaffinity-FD-LC-MS/MS method could be useful for simultaneously detecting and identifying the proteins that interact with a certain protein. Copyright © 2017 John Wiley & Sons, Ltd.

  10. Identifying common impairments in frail and dependent older people: validation of the COPE assessment for non-specialised health workers in low resource primary health care settings.

    Science.gov (United States)

    A T, Jotheeswaran; Dias, Amit; Philp, Ian; Beard, John; Patel, Vikram; Prince, Martin

    2015-10-14

    Frail and dependent older people in resource-poor settings are poorly served by health systems that lack outreach capacity. The COPE (Caring for Older PEople) multidimensional assessment tool is designed to help community health workers (CHWs) identify clinically significant impairments and deliver evidence-based interventions Older people (n = 150) identified by CHWs as frail or dependent, were assessed at home by the CHW using the structured COPE assessment tool, generating information on impairments in nutrition, mobility, vision, hearing, continence, cognition, mood and behaviour. The older people were reassessed by local physicians who reached a clinical judgment regarding the presence or absence of the same impairments based upon clinical examination guided by the EASY-Care assessment tool. The COPE tool was considered easy to administer, and gave CHWs a sense of empowerment to understand and act upon the needs of older people. Agreement between COPE assessment by CHW and clinician assessors was modest (ranged from 45.8 to 91.3 %) for most impairments. However, the prevalence of impairments was generally higher according to clinicians, particularly for visual impairment (98.7 vs 45.8 %), cognitive impairment (78.4 vs. 38.2 %) and depression (82.0 vs. 59.9 %). Most cases identified by WHO-COPE were clinician confirmed (positive predictive values - 72.2 to 98.5 %), and levels of disability and needs for care among those identified by COPE were higher than those additionally identified by the clinician alone. The COPE is a feasible tool for the identification of specific impairments in frail dependent older people in the community. Those identified are likely to be confirmed as having clinically relevant problems by clinicians working in the same service, and the COPE may be particularly effective at targeting attention upon those with the most substantial unmet needs.

  11. Bi-directional gene set enrichment and canonical correlation analysis identify key diet-sensitive pathways and biomarkers of metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Gaora Peadar Ó

    2010-10-01

    Full Text Available Abstract Background Currently, a number of bioinformatics methods are available to generate appropriate lists of genes from a microarray experiment. While these lists represent an accurate primary analysis of the data, fewer options exist to contextualise those lists. The development and validation of such methods is crucial to the wider application of microarray technology in the clinical setting. Two key challenges in clinical bioinformatics involve appropriate statistical modelling of dynamic transcriptomic changes, and extraction of clinically relevant meaning from very large datasets. Results Here, we apply an approach to gene set enrichment analysis that allows for detection of bi-directional enrichment within a gene set. Furthermore, we apply canonical correlation analysis and Fisher's exact test, using plasma marker data with known clinical relevance to aid identification of the most important gene and pathway changes in our transcriptomic dataset. After a 28-day dietary intervention with high-CLA beef, a range of plasma markers indicated a marked improvement in the metabolic health of genetically obese mice. Tissue transcriptomic profiles indicated that the effects were most dramatic in liver (1270 genes significantly changed; p Conclusion Bi-directional gene set enrichment analysis more accurately reflects dynamic regulatory behaviour in biochemical pathways, and as such highlighted biologically relevant changes that were not detected using a traditional approach. In such cases where transcriptomic response to treatment is exceptionally large, canonical correlation analysis in conjunction with Fisher's exact test highlights the subset of pathways showing strongest correlation with the clinical markers of interest. In this case, we have identified selenoamino acid metabolism and steroid biosynthesis as key pathways mediating the observed relationship between metabolic health and high-CLA beef. These results indicate that this type of

  12. Evaluation of the feasibility and performance of early warning scores to identify patients at risk of adverse outcomes in a low-middle income country setting

    Science.gov (United States)

    Beane, Abi; De Silva, Ambepitiyawaduge Pubudu; De Silva, Nirodha; Sujeewa, Jayasingha A; Rathnayake, R M Dhanapala; Sigera, P Chathurani; Athapattu, Priyantha Lakmini; Mahipala, Palitha G; Rashan, Aasiyah; Munasinghe, Sithum Bandara; Jayasinghe, Kosala Saroj Amarasiri; Dondorp, Arjen M; Haniffa, Rashan

    2018-01-01

    Objective This study describes the availability of core parameters for Early Warning Scores (EWS), evaluates the ability of selected EWS to identify patients at risk of death or other adverse outcome and describes the burden of triggering that front-line staff would experience if implemented. Design Longitudinal observational cohort study. Setting District General Hospital Monaragala. Participants All adult (age >17 years) admitted patients. Main outcome measures Existing physiological parameters, adverse outcomes and survival status at hospital discharge were extracted daily from existing paper records for all patients over an 8-month period. Statistical analysis Discrimination for selected aggregate weighted track and trigger systems (AWTTS) was assessed by the area under the receiver operating characteristic (AUROC) curve. Performance of EWS are further evaluated at time points during admission and across diagnostic groups. The burden of trigger to correctly identify patients who died was evaluated using positive predictive value (PPV). Results Of the 16 386 patients included, 502 (3.06%) had one or more adverse outcomes (cardiac arrests, unplanned intensive care unit admissions and transfers). Availability of physiological parameters on admission ranged from 90.97% (95% CI 90.52% to 91.40%) for heart rate to 23.94% (95% CI 23.29% to 24.60%) for oxygen saturation. Ability to discriminate death on admission was less than 0.81 (AUROC) for all selected EWS. Performance of the best performing of the EWS varied depending on admission diagnosis, and was diminished at 24 hours prior to event. PPV was low (10.44%). Conclusion There is limited observation reporting in this setting. Indiscriminate application of EWS to all patients admitted to wards in this setting may result in an unnecessary burden of monitoring and may detract from clinician care of sicker patients. Physiological parameters in combination with diagnosis may have a place when applied on admission to

  13. Predicting and analyzing DNA-binding domains using a systematic approach to identifying a set of informative physicochemical and biochemical properties

    Science.gov (United States)

    2011-01-01

    Background Existing methods of predicting DNA-binding proteins used valuable features of physicochemical properties to design support vector machine (SVM) based classifiers. Generally, selection of physicochemical properties and determination of their corresponding feature vectors rely mainly on known properties of binding mechanism and experience of designers. However, there exists a troublesome problem for designers that some different physicochemical properties have similar vectors of representing 20 amino acids and some closely related physicochemical properties have dissimilar vectors. Results This study proposes a systematic approach (named Auto-IDPCPs) to automatically identify a set of physicochemical and biochemical properties in the AAindex database to design SVM-based classifiers for predicting and analyzing DNA-binding domains/proteins. Auto-IDPCPs consists of 1) clustering 531 amino acid indices in AAindex into 20 clusters using a fuzzy c-means algorithm, 2) utilizing an efficient genetic algorithm based optimization method IBCGA to select an informative feature set of size m to represent sequences, and 3) analyzing the selected features to identify related physicochemical properties which may affect the binding mechanism of DNA-binding domains/proteins. The proposed Auto-IDPCPs identified m=22 features of properties belonging to five clusters for predicting DNA-binding domains with a five-fold cross-validation accuracy of 87.12%, which is promising compared with the accuracy of 86.62% of the existing method PSSM-400. For predicting DNA-binding sequences, the accuracy of 75.50% was obtained using m=28 features, where PSSM-400 has an accuracy of 74.22%. Auto-IDPCPs and PSSM-400 have accuracies of 80.73% and 82.81%, respectively, applied to an independent test data set of DNA-binding domains. Some typical physicochemical properties discovered are hydrophobicity, secondary structure, charge, solvent accessibility, polarity, flexibility, normalized Van Der

  14. Sustainability in Health care by Allocating Resources Effectively (SHARE) 6: investigating methods to identify, prioritise, implement and evaluate disinvestment projects in a local healthcare setting.

    Science.gov (United States)

    Harris, Claire; Allen, Kelly; Brooke, Vanessa; Dyer, Tim; Waller, Cara; King, Richard; Ramsey, Wayne; Mortimer, Duncan

    2017-05-25

    This is the sixth in a series of papers reporting Sustainability in Health care by Allocating Resources Effectively (SHARE) in a local healthcare setting. The SHARE program was established to investigate a systematic, integrated, evidence-based approach to disinvestment within a large Australian health service. This paper describes the methods employed in undertaking pilot disinvestment projects. It draws a number of lessons regarding the strengths and weaknesses of these methods; particularly regarding the crucial first step of identifying targets for disinvestment. Literature reviews, survey, interviews, consultation and workshops were used to capture and process the relevant information. A theoretical framework was adapted for evaluation and explication of disinvestment projects, including a taxonomy for the determinants of effectiveness, process of change and outcome measures. Implementation, evaluation and costing plans were developed. Four literature reviews were completed, surveys were received from 15 external experts, 65 interviews were conducted, 18 senior decision-makers attended a data gathering workshop, 22 experts and local informants were consulted, and four decision-making workshops were undertaken. Mechanisms to identify disinvestment targets and criteria for prioritisation and decision-making were investigated. A catalogue containing 184 evidence-based opportunities for disinvestment and an algorithm to identify disinvestment projects were developed. An Expression of Interest process identified two potential disinvestment projects. Seventeen additional projects were proposed through a non-systematic nomination process. Four of the 19 proposals were selected as pilot projects but only one reached the implementation stage. Factors with potential influence on the outcomes of disinvestment projects are discussed and barriers and enablers in the pilot projects are summarised. This study provides an in-depth insight into the experience of disinvestment

  15. Identifying and intervening with substance-using women exposed to intimate partner violence: phenomenology, comorbidities, and integrated approaches within primary care and other agency settings.

    Science.gov (United States)

    Weaver, Terri L; Gilbert, Louisa; El-Bassel, Nabila; Resnick, Heidi S; Noursi, Samia

    2015-01-01

    Substance use and/or disorders (SUDs) have been identified as a significant correlate of intimate partner violence (IPV) exposure and present complex issues that intersect with the topography of IPV, attendant mental health, and physical co-morbidities and may pose barriers to primary care- and other agency-based screening and intervention efforts. Despite substantial research indicating significantly higher rates of all types and severity of IPV victimization among women with SUDs and bidirectional associations between partner or self-use of drugs or alcohol and IPV victimization, effective screening, brief interventions, coordinated systems of care, and treatment approaches to address these co-occurring problems remain very limited. We integrated select research examining the intersection of IPV victimization and SUDs and several comorbidities that have significant public health impact and provided recommendations for scaling up targeted interventions to redress these co-occurring problems among women in primary, emergency, and other care settings.

  16. The kidney cancer research priority-setting partnership: Identifying the top 10 research priorities as defined by patients, caregivers, and expert clinicians.

    Science.gov (United States)

    Jones, Jennifer; Bhatt, Jaimin; Avery, Jonathan; Laupacis, Andreas; Cowan, Katherine; Basappa, Naveen; Basiuk, Joan; Canil, Christina; Al-Asaaed, Sohaib; Heng, Daniel; Wood, Lori; Stacey, Dawn; Kollmannsberger, Christian; Jewett, Michael A S

    2017-12-01

    It is critically important to define disease-specific research priorities to better allocate limited resources. There is growing recognition of the value of involving patients and caregivers, as well as expert clinicians in this process. To our knowledge, this has not been done this way for kidney cancer. Using the transparent and inclusive process established by the James Lind Alliance, the Kidney Cancer Research Network of Canada (KCRNC) sponsored a collaborative consensus-based priority-setting partnership (PSP) to identify research priorities in the management of kidney cancer. The final result was identification of 10 research priorities for kidney cancer, which are discussed in the context of current initiatives and gaps in knowledge. This process provided a systematic and effective way to collaboratively establish research priorities with patients, caregivers, and clinicians, and provides a valuable resource for researchers and funding agencies.

  17. The use of camera traps to identify the set of scavengers preying on the carcass of a golden snub-nosed monkey (Rhinopithecus roxellana).

    Science.gov (United States)

    Huang, Zhi-Pang; Qi, Xiao-Guang; Garber, Paul A; Jin, Tong; Guo, Song-Tao; Li, Sheng; Li, Bao-Guo

    2014-01-01

    There exists very limited information on the set of scavengers that feed on the carcasses of wild primates. Here, we describe, based on information collected using a remote camera trap, carnivores consuming/scavenging the carcass of a wild golden snub-nosed monkey (Rhinopithecus roxellana) in the Laohegou Nature Reserve, Sichuan, China. During a 3 month behavioral and ecology study of a band of golden snub-nosed monkeys (March through May 2013), we encountered the carcass of an adult male (male golden snub-nosed monkeys weigh approximately 12-16 kg). After examining the dead monkey, we returned it to the death site and set out a camera trap to record the behavior and identity of scavengers. Over the course of 25 days, we collected 4145 photographs taken by the camera trap. Scavengers identified from these photographs include a masked civet (Paguma larvata), Asiatic black bear (Ursus thibetanus), large-billed crow (Corvus macrorhynchos) and the chestnut rat (Rattus fulvescens). No member of the golden snub-nosed monkey's social group, which was composed of approximately 120 individuals, was found to return to the general area of the death site. The masked civet fed principally on the face and intestines of the corpse at night, while the black bear consumed most of the body of the dead monkey during both the daytime and nighttime. These two taxa consumed virtually the entire carcass in one week. We suggest that the use of camera traps offers a powerful research tool to identify the scavenger community of a given ecosystem.

  18. Identifying trial recruitment uncertainties using a James Lind Alliance Priority Setting Partnership - the PRioRiTy (Prioritising Recruitment in Randomised Trials) study.

    Science.gov (United States)

    Healy, Patricia; Galvin, Sandra; Williamson, Paula R; Treweek, Shaun; Whiting, Caroline; Maeso, Beccy; Bray, Christopher; Brocklehurst, Peter; Moloney, Mary Clarke; Douiri, Abdel; Gamble, Carrol; Gardner, Heidi R; Mitchell, Derick; Stewart, Derek; Jordan, Joan; O'Donnell, Martin; Clarke, Mike; Pavitt, Sue H; Guegan, Eleanor Woodford; Blatch-Jones, Amanda; Smith, Valerie; Reay, Hannah; Devane, Declan

    2018-03-01

    Despite the problem of inadequate recruitment to randomised trials, there is little evidence to guide researchers on decisions about how people are effectively recruited to take part in trials. The PRioRiTy study aimed to identify and prioritise important unanswered trial recruitment questions for research. The PRioRiTy study - Priority Setting Partnership (PSP) included members of the public approached to take part in a randomised trial or who have represented participants on randomised trial steering committees, health professionals and research staff with experience of recruiting to randomised trials, people who have designed, conducted, analysed or reported on randomised trials and people with experience of randomised trials methodology. This partnership was aided by the James Lind Alliance and involved eight stages: (i) identifying a unique, relevant prioritisation area within trial methodology; (ii) establishing a steering group (iii) identifying and engaging with partners and stakeholders; (iv) formulating an initial list of uncertainties; (v) collating the uncertainties into research questions; (vi) confirming that the questions for research are a current recruitment challenge; (vii) shortlisting questions and (viii) final prioritisation through a face-to-face workshop. A total of 790 survey respondents yielded 1693 open-text answers to 6 questions, from which 1880 potential questions for research were identified. After merging duplicates, the number of questions was reduced to 496. Questions were combined further, and those that were submitted by fewer than 15 people and/or fewer than 6 of the 7 stakeholder groups were excluded from the next round of prioritisation resulting in 31 unique questions for research. All 31 questions were confirmed as being unanswered after checking relevant, up-to-date research evidence. The 10 highest priority questions were ranked at a face-to-face workshop. The number 1 ranked question was "How can randomised trials become

  19. Predictive validity of a service-setting-based measure to identify infancy mental health problems: a population-based cohort study.

    Science.gov (United States)

    Ammitzbøll, Janni; Thygesen, Lau Caspar; Holstein, Bjørn E; Andersen, Anette; Skovgaard, Anne Mette

    2018-06-01

    Measures to identify infancy mental health problems are essential to guide interventions and reduce the risk of developmental psychopathology in early years. We investigated a new service-setting-based measure the Copenhagen Infant Mental Health Screening (CIMHS) within the general child health surveillance by community health nurses (CHN). The study population of 2973 infants was assessed by CIMHS at age 9-10 months. A subsample of 416 children was examined at age 1½ years, using parent interviews including the Child Behavior Checklist (CBCL 1½-5), Check List of Autism and Toddlers (CHAT), Infant-Toddler Symptom Checklist (ITSCL), and the Bayley Scales of Infant and Toddler Development (BSID) and observations of behavior, communication, and interaction. Child mental disorders were diagnosed according to ICD-10 and parent-child relationship disorders according to DC:0-3R. Statistical analyses included logistic regression analyses adjusted and weighted to adjust for sampling and bias. CIMHS problems of sleep, feeding and eating, emotions, attention, communication, and language were associated with an up to fivefold increased risk of child mental disorders across the diagnostic spectrum of ICD-10 diagnoses. Homo-type continuity was seen in problems of sleep and feeding and eating being associated with a threefold increased risk of disorders within the same area, OR 3.0 (95% CI 1.6-5.4) and OR 2.7 (95% CI 1.7-4.2), respectively. The sensitivity at high CIMHS problem scores was 32% and specificity 86%. In summary, CIMHS identify a broad range of infants' mental health problems that are amenable to guide intervention within the general child health surveillance.

  20. Touch communicates distinct emotions.

    Science.gov (United States)

    Hertenstein, Matthew J; Keltner, Dacher; App, Betsy; Bulleit, Brittany A; Jaskolka, Ariane R

    2006-08-01

    The study of emotional signaling has focused almost exclusively on the face and voice. In 2 studies, the authors investigated whether people can identify emotions from the experience of being touched by a stranger on the arm (without seeing the touch). In the 3rd study, they investigated whether observers can identify emotions from watching someone being touched on the arm. Two kinds of evidence suggest that humans can communicate numerous emotions with touch. First, participants in the United States (Study 1) and Spain (Study 2) could decode anger, fear, disgust, love, gratitude, and sympathy via touch at much-better-than-chance levels. Second, fine-grained coding documented specific touch behaviors associated with different emotions. In Study 3, the authors provide evidence that participants can accurately decode distinct emotions by merely watching others communicate via touch. The findings are discussed in terms of their contributions to affective science and the evolution of altruism and cooperation. (c) 2006 APA, all rights reserved

  1. Cancer Screening Among Patients Who Self-Identify as Muslim: Combining Self-Reported Data with Medical Records in a Family Practice Setting.

    Science.gov (United States)

    Lofters, A K; Slater, M; Vahabi, M

    2018-02-01

    Cancer screening is a core component of family medicine but screening inequalities are well documented in Canada for foreign-born persons. Although people of Muslim faith and culture are the fastest growing immigrant population in Canada, there is little information in the literature about their cancer screening practices. Determining screening gaps could inform practice-based quality improvement initiatives. We conducted a retrospective chart review combining patient-level medical record data with self-reported religious affiliation to examine the relationship between religion and cancer screening in a large multi-site urban family practice. Religious affiliation was classified as Muslim, other affiliation, or atheist/no religious affiliation. 5311 patients were included in the study sample. Muslim patients were significantly less likely to prefer English for spoken communication than the other two groups, less likely to be Canadian-born, more likely to have a female family physician, and were over-represented in the lowest income quintile. Muslim women were most likely to be up-to-date on breast cancer screening (85.2 vs. 77.5 % for those with other religions vs. 69.5 % for those with no religious affiliation). There were no significant differences in cancer screening by physician sex. In this pilot study conducted within a primary care practice, we used self-reported data on religious affiliation to examine possible inequities in cancer screening and observed intriguing variations in screening by self-identified religious affiliation. Future efforts to collect and use similar patient-level data should incorporate non-official languages and intensively outreach to patients with less health system contact. Regardless, the family medicine context may be the ideal setting to collect and act on patient-level sociodemographic data such as religious affiliation.

  2. Diagnostic stability of autism spectrum disorder in toddlers prospectively identified in a community-based setting: Behavioural characteristics and predictors of change over time.

    Science.gov (United States)

    Barbaro, Josephine; Dissanayake, Cheryl

    2017-10-01

    Autism spectrum disorder diagnoses in toddlers have been established as accurate and stable across time in high-risk siblings and clinic-referred samples. Few studies have investigated diagnostic stability in children prospective identified in community-based settings. Furthermore, there is a dearth of evidence on the individual behaviours that predict diagnostic change over time. The stability and change of autism spectrum disorder diagnoses were investigated from 24 to 48 months in 77 children drawn from the Social Attention and Communication Study. Diagnostic stability was high, with 88.3% overall stability and 85.5% autism spectrum disorder stability. The behavioural markers at 24 months that contributed to diagnostic shift off the autism spectrum by 48 months included better eye contact, more directed vocalisations, the integration of gaze and directed vocalisations/gestures and higher non-verbal developmental quotient. These four variables correctly predicted 88.7% of children into the autism spectrum disorder-stable and autism spectrum disorder-crossover groups overall, with excellent prediction for the stable group (96.2%) and modest prediction for the crossover group (44.4%). Furthermore, non-verbal developmental quotient at 24 months accounted for the significant improvement across time in 'Social Affect' scores on the Autism Diagnostic Observation Schedule for both groups and was the only unique predictor of diagnostic crossover. These findings contribute to the body of evidence on the feasibility of diagnoses at earlier ages to facilitate children's access to interventions to promote positive developmental outcomes.

  3. Normative data set identifying properties of the macula across age groups: integration of visual function and retinal structure with microperimetry and spectral-domain optical coherence tomography.

    Science.gov (United States)

    Sabates, Felix N; Vincent, Ryan D; Koulen, Peter; Sabates, Nelson R; Gallimore, Gary

    2011-01-01

    A normative database of functional and structural parameters of the macula from normal subjects was established to identify reference points for the diagnosis of patients with macular disease using microperimetry and scanning laser ophthalmoscope/spectral-domain optical coherence tomography (SD-OCT). This was a community-based, prospective, cross-sectional study of 169 eyes from subjects aged 21 years to 85 years with best-corrected visual acuity of 20/25 or better and without any ocular disease. Full-threshold macular microperimetry combined with the acquisition of structural parameters of the macula with scanning laser ophthalmoscope/SD-OCT was recorded (SD-OCT/scanning laser ophthalmoscope with add-on Microperimetry module; OPKO). Fixation, central, subfield, and mean retinal thickness were acquired together with macular sensitivity function. Thickness and sensitivity as primary outcome measures were mapped and superimposed correlating topographically differentiated macular thickness with sensitivity. Statistical evaluation was performed with age, gender, and ethnicity as covariates. Subfield and mean retinal thickness and sensitivity were measured with macular microperimetry combined with SD-OCT and differentiated by macular topography and subjects' age, gender, and ethnicity. Mean retinal sensitivity and thickness were calculated for 169 healthy eyes (mean age, 48 ± 17 years). A statistically significant decrease in sensitivity was found only in the age group of participants ≥ 70 years and in peripheral portions of the macula in individuals aged ≥60 years and was more pronounced in the area surrounding the fovea than in the center of the macula, while retinal thickness did not change with age. No statistically significant differences in the primary outcome measures or their correlations were found when using gender or ethnicity as a covariate. A database for normal macular thickness and sensitivity was generated with a combined microperimetry SD

  4. Quantum Distinction: Quantum Distinctiones!

    OpenAIRE

    Zeps, Dainis

    2009-01-01

    10 pages; How many distinctions, in Latin, quantum distinctiones. We suggest approach of anthropic principle based on anthropic reference system which should be applied equally both in theoretical physics and in mathematics. We come to principle that within reference system of life subject of mathematics (that of thinking) should be equated with subject of physics (that of nature). For this reason we enter notions of series of distinctions, quantum distinction, and argue that quantum distinct...

  5. Distinct charge orders in the planes and chains of ortho-III-ordered YBa2Cu3O(6+δ) superconductors identified by resonant elastic x-ray scattering.

    Science.gov (United States)

    Achkar, A J; Sutarto, R; Mao, X; He, F; Frano, A; Blanco-Canosa, S; Le Tacon, M; Ghiringhelli, G; Braicovich, L; Minola, M; Sala, M Moretti; Mazzoli, C; Liang, Ruixing; Bonn, D A; Hardy, W N; Keimer, B; Sawatzky, G A; Hawthorn, D G

    2012-10-19

    Recently, charge density wave (CDW) order in the CuO(2) planes of underdoped YBa(2)Cu(3)O(6+δ) was detected using resonant soft x-ray scattering. An important question remains: is the chain layer responsible for this charge ordering? Here, we explore the energy and polarization dependence of the resonant scattering intensity in a detwinned sample of YBa(2)Cu(3)O(6.75) with ortho-III oxygen ordering in the chain layer. We show that the ortho-III CDW order in the chains is distinct from the CDW order in the planes. The ortho-III structure gives rise to a commensurate superlattice reflection at Q=[0.33 0 L] whose energy and polarization dependence agrees with expectations for oxygen ordering and a spatial modulation of the Cu valence in the chains. Incommensurate peaks at [0.30 0 L] and [0 0.30 L] from the CDW order in the planes are shown to be distinct in Q as well as their temperature, energy, and polarization dependence, and are thus unrelated to the structure of the chain layer. Moreover, the energy dependence of the CDW order in the planes is shown to result from a spatial modulation of energies of the Cu 2p to 3d(x(2)-y(2)) transition, similar to stripe-ordered 214 cuprates.

  6. Defining poverty as distinctively human

    Directory of Open Access Journals (Sweden)

    H.P.P. Lötter

    2007-05-01

    Full Text Available While it is relatively easy for most people to identify human beings suffering from poverty, it is rather more difficult to come to a proper understanding of poverty. In this article the author wants to deepen our understanding of poverty by interpreting the conventional definitions of poverty in a new light. The article starts with a defence of a claim that poverty is a concept uniquely applicable to humans. It then present a critical discussion of the distinction between absolute and relative poverty and it is then argued that a revision of this distinction can provide general standards applicable to humans everywhere.

  7. The Development of a Novel qPCR Assay-Set for Identifying Fecal Contamination Originating from Domestic Fowls and Waterfowl in Israel

    Directory of Open Access Journals (Sweden)

    Shoshanit eOhad

    2016-02-01

    Full Text Available The emerging Microbial Source Tracking (MST methodologies aim to identify fecal contamination originating from domestic and wild animals, and from humans. Avian MST is especially challenging, primarily because the Aves class includes both domesticated and wild species with highly diverse habitats and dietary characteristics. The quest for specific fecal bacterial MST markers can be difficult with respect to attaining sufficient assay sensitivity and specificity. The present study utilizes High Throughput Sequencing (HTS to screen bacterial 16S rRNA genes from fecal samples collected from both domestic and wild avian species. Operational taxonomic unit (OTU analysis was then performed, from which sequences were retained for downstream qPCR marker development. Identification of unique avian host DNA sequences, absent in non-avian hosts, was then carried out using a dedicated database of bacterial 16S rRNA gene taken from the Ribosomal Database Project. Six qPCR assays were developed targeting the 16S rRNA gene of Lactobacillus, Gallibacterium, Firmicutes, Fusobacteriaceae and other bacteria. Two assays (Av4143 and Av163 identified most of the avian fecal samples and demonstrated sensitivity values of 91% and 70%, respectively. The Av43 assay only identified droppings from battery hens and poultry, whereas each of the other three assays (Av24, Av13, and Av216 identified waterfowl species with lower sensitivities values. The development of an MST assay-panel, which includes both domestic and wild avian species, expands the currently known MST analysis capabilities for decoding fecal contamination.

  8. Identifying and Intervening with Substance-Using Women Exposed to Intimate Partner Violence: Phenomenology, Comorbidities, and Integrated Approaches Within Primary Care and Other Agency Settings

    OpenAIRE

    Weaver, Terri L.; Gilbert, Louisa; El-Bassel, Nabila; Resnick, Heidi S.; Noursi, Samia

    2015-01-01

    Substance use and/or disorders (SUDs) have been identified as a significant correlate of intimate partner violence (IPV) exposure and present complex issues that intersect with the topography of IPV, attendant mental health, and physical co-morbidities and may pose barriers to primary care- and other agency-based screening and intervention efforts. Despite substantial research indicating significantly higher rates of all types and severity of IPV victimization among women with SUDs and bidire...

  9. Anticancer properties of distinct antimalarial drug classes.

    Directory of Open Access Journals (Sweden)

    Rob Hooft van Huijsduijnen

    Full Text Available We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor, emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC50s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings.

  10. Anticancer Properties of Distinct Antimalarial Drug Classes

    Science.gov (United States)

    Hooft van Huijsduijnen, Rob; Guy, R. Kiplin; Chibale, Kelly; Haynes, Richard K.; Peitz, Ingmar; Kelter, Gerhard; Phillips, Margaret A.; Vennerstrom, Jonathan L.; Yuthavong, Yongyuth; Wells, Timothy N. C.

    2013-01-01

    We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase) inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase) and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor), emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC50s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings. PMID:24391728

  11. An alcohol-focused intervention versus a healthy living intervention for problem drinkers identified in a general hospital setting (ADAPTA): study protocol for a randomized, controlled pilot trial.

    Science.gov (United States)

    Watson, Judith; Tober, Gillian; Raistrick, Duncan; Mdege, Noreen; Dale, Veronica; Crosby, Helen; Godfrey, Christine; Lloyd, Charlie; Toner, Paul; Parrott, Steve

    2013-04-30

    Alcohol misuse is a major cause of premature mortality and ill health. Although there is a high prevalence of alcohol problems among patients presenting to general hospital, many of these people are not help seekers and do not engage in specialist treatment. Hospital admission is an opportunity to steer people towards specialist treatment, which can reduce health-care utilization and costs to the public sector and produce substantial individual health and social benefits. Alcohol misuse is associated with other lifestyle problems, which are amenable to intervention. It has been suggested that the development of a healthy or balanced lifestyle is potentially beneficial for reducing or abstaining from alcohol use, and relapse prevention. The aim of the study is to test whether or not the offer of a choice of health-related lifestyle interventions is more acceptable, and therefore able to engage more problem drinkers in treatment, than an alcohol-focused intervention. This is a pragmatic, randomized, controlled, open pilot study in a UK general hospital setting with concurrent economic evaluation and a qualitative component. Potential participants are those admitted to hospital with a diagnosis likely to be responsive to addiction interventions who score equal to or more than 16 on the Alcohol Use Disorders Identification Test (AUDIT). The main purpose of this pilot study is to evaluate the acceptability of two sorts of interventions (healthy living related versus alcohol focused) to the participants and to assess the components and processes of the design. Qualitative research will be undertaken to explore acceptability and the impact of the approach, assessment, recruitment and intervention on trial participants and non-participants. The effectiveness of the two treatments will be compared at 6 months using AUDIT scores as the primary outcome measure. There will be additional economic, qualitative and secondary outcome measurements. Development of the study was a

  12. Psychometric properties and reliability of the Assessment Screen to Identify Survivors Toolkit for Gender Based Violence (ASIST-GBV): results from humanitarian settings in Ethiopia and Colombia.

    Science.gov (United States)

    Vu, Alexander; Wirtz, Andrea; Pham, Kiemanh; Singh, Sonal; Rubenstein, Leonard; Glass, Nancy; Perrin, Nancy

    2016-01-01

    Refugees and internally displaced persons who are affected by armed-conflict are at increased vulnerability to some forms of sexual violence or other types of gender-based violence. A validated, brief and easy-to-administer screening tool will help service providers identify GBV survivors and refer them to appropriate GBV services. To date, no such GBV screening tool exists. We developed the 7-item ASIST-GBV screening tool from qualitative research that included individual interviews and focus groups with GBV refugee and IDP survivors. This study presents the psychometric properties of the ASIST-GBV with female refugees living in Ethiopia and IDPs in Colombia. Several strategies were used to validate ASIST-GBV, including a 3 month implementation to validate the brief screening tool with women/girls seeking health services, aged ≥15 years in Ethiopia (N = 487) and female IDPs aged ≥ 18 years in Colombia (N = 511). High proportions of women screened positive for past-year GBV according to the ASIST-GBV: 50.6 % in Ethiopia and 63.4 % in Colombia. The factor analysis identified a single dimension, meaning that all items loaded on the single factor. Cronbach's α = 0.77. A 2-parameter logistic IRT model was used for estimating the precision and discriminating power of each item. Item difficulty varied across the continuum of GBV experiences in the following order (lowest to highest): threats of violence (0.690), physical violence (1.28), forced sex (2.49), coercive sex for survival (2.25), forced marriage (3.51), and forced pregnancy (6.33). Discrimination results showed that forced pregnancy was the item with the strongest ability to discriminate between different levels of GBV. Physical violence and forced sex also have higher levels of discrimination with threats of violence discriminating among women at the low end of the GBV continuum and coercive sex for survival among women at the mid-range of the continuum. The findings demonstrate that

  13. Inside the "Black Box" of River Restoration: Using Catchment History to Identify Disturbance and Response Mechanisms to Set Targets for Process-Based Restoration

    Directory of Open Access Journals (Sweden)

    Sarah Mika

    2010-12-01

    Full Text Available Many river restoration projects fail. Inadequate project planning underpins many of the reasons given for failure (such as setting overly ambitious goals; selecting inappropriate sites and techniques; losing stakeholder motivation; and neglecting to monitor, assess, and document projects. Another major problem is the lack of an agreed guiding image to direct the activities aimed at restoring the necessary biophysical and ecological processes within the logistic constraints of on-ground works. Despite a rich literature defining the components of restoration project planning, restoration ecology currently lacks an explicit and logical means of moving from the initial project vision through to on-ground strategies. Yet this process is fundamental because it directly links the ecological goals of the project to the on-ground strategies used to achieve them. We present a planning process that explicitly uses an interdisciplinary mechanistic model of disturbance drivers and system responses to build from the initial project vision to the implementation of on-ground works. A worked example on the Upper Hunter River in southeastern Australia shows how understanding catchment history can reveal disturbance and response mechanisms, thus facilitating process-based restoration.

  14. Carbon and hydrogen isotopic composition of methane and C2+ alkanes in electrical spark discharge: implications for identifying sources of hydrocarbons in terrestrial and extraterrestrial settings.

    Science.gov (United States)

    Telling, Jon; Lacrampe-Couloume, Georges; Sherwood Lollar, Barbara

    2013-05-01

    The low-molecular-weight alkanes--methane, ethane, propane, and butane--are found in a wide range of terrestrial and extraterrestrial settings. The development of robust criteria for distinguishing abiogenic from biogenic alkanes is essential for current investigations of Mars' atmosphere and for future exobiology missions to other planets and moons. Here, we show that alkanes synthesized during gas-phase radical recombination reactions in electrical discharge experiments have values of δ(2)H(methane)>δ(2)H(ethane)>δ(2)H(propane), similar to those of the carbon isotopes. The distribution of hydrogen isotopes in gas-phase radical reactions is likely due to kinetic fractionations either (i) from the preferential incorporation of (1)H into longer-chain alkanes due to the more rapid rate of collisions of the smaller (1)H-containing molecules or (ii) by secondary ion effects. Similar δ(13)C(C1-C2+) and δ(2)H(C1-C2+) patterns may be expected in a range of extraterrestrial environments where gas-phase radical reactions dominate, including interstellar space, the atmosphere and liquid hydrocarbon lakes of Saturn's moon Titan, and the outer atmospheres of Jupiter, Saturn, Neptune, and Uranus. Radical recombination reactions at high temperatures and pressures may provide an explanation for the combined reversed δ(13)C(C1-C2+) and δ(2)H(C1-C2+) patterns of terrestrial alkanes documented at a number of high-temperature/pressure crustal sites.

  15. Identifying opportunities to increase HIV testing among mexican migrants: a call to step up efforts in health care and detention settings.

    Directory of Open Access Journals (Sweden)

    Ana P Martínez-Donate

    Full Text Available HIV testing and counseling is a critical component of HIV prevention efforts and core element of current "treatment as prevention" strategies. Mobility, low education and income, and limited access to health care put Latino migrants at higher risk for HIV and represent barriers for adequate levels of HIV testing in this population. We examined correlates of, and missed opportunities to increase, HIV testing for circular Mexican migrants in the U.S. We used data from a probability-based survey of returning Mexican migrants (N=1161 conducted in the border city of Tijuana, Mexico. We estimated last 12-months rates of HIV testing and the percentage of migrants who received other health care services or were detained in an immigration center, jail, or prison for 30 or more days in the U.S., but were not tested for HIV. Twenty-two percent of migrants received HIV testing in the last 12 months. In general, utilization of other health care services or detention for 30 or more days in the U.S. was a significant predictor of last 12-months HIV testing. Despite this association, we found evidence of missed opportunities to promote testing in healthcare and/or correctional or immigration detention centers. About 27.6% of migrants received other health care and/or were detained at least 30 days but not tested for HIV. Health care systems, jails and detention centers play an important role in increasing access to HIV testing among circular migrants, but there is room for improvement. Policies to offer opt-out, confidential HIV testing and counseling to Mexican migrants in these settings on a routine and ethical manner need to be designed and pilot tested. These policies could increase knowledge of HIV status, facilitate engagement in HIV treatment among a highly mobile population, and contribute to decrease incidence of HIV in the host and receiving communities.

  16. Identifying the distinct features of geometric structures for hole trapping to generate radicals on rutile TiO₂(110) in photooxidation using density functional theory calculations with hybrid functional.

    Science.gov (United States)

    Wang, Dong; Wang, Haifeng; Hu, P

    2015-01-21

    Using density functional theory calculations with HSE 06 functional, we obtained the structures of spin-polarized radicals on rutile TiO2(110), which is crucial to understand the photooxidation at the atomic level, and further calculate the thermodynamic stabilities of these radicals. By analyzing the results, we identify the structural features for hole trapping in the system, and reveal the mutual effects among the geometric structures, the energy levels of trapped hole states and their hole trapping capacities. Furthermore, the results from HSE 06 functional are compared to those from DFT + U and the stability trend of radicals against the number of slabs is tested. The effect of trapped holes on two important steps of the oxygen evolution reaction, i.e. water dissociation and the oxygen removal, is investigated and discussed.

  17. Under the radar: a cross-sectional study of the challenge of identifying at-risk alcohol consumption in the general practice setting.

    Science.gov (United States)

    Paul, Christine; Yoong, Sze Lin; Sanson-Fisher, Rob; Carey, Mariko; Russell, Grant; Makeham, Meredith

    2014-04-28

    Primary care providers are an important source of information regarding appropriate alcohol consumption. As early presentation to a provider for alcohol-related concerns is unlikely, it is important that providers are able to identify at-risk patients in order to provide appropriate advice. This study aimed to report the sensitivity, specificity, positive predictive value and negative predictive value of General Practitioner (GP) assessment of alcohol consumption compared to patient self-report, and explore characteristics associated with GP non-detection of at-risk status. GP practices were selected from metropolitan and regional locations in Australia. Eligible patients were adults presenting for general practice care who were able to understand English and provide informed consent. Patients completed a modified AUDIT-C by touchscreen computer as part of an omnibus health survey while waiting for their appointment. GPs completed a checklist for each patient, including whether the patient met current Australian guidelines for at-risk alcohol consumption. Patient self-report and GP assessments were compared for each patient. GPs completed the checklist for 1720 patients, yielding 1565 comparisons regarding alcohol consumption. The sensitivity of GPs' detection of at-risk alcohol consumption was 26.5%, with specificity of 96.1%. Higher patient education was associated with GP non-detection of at-risk status. GP awareness of which patients might benefit from advice regarding at-risk alcohol consumption appears low. Given the complexities associated with establishing whether alcohol consumption is 'at-risk', computer-based approaches to routine screening of patients are worthy of exploration as a method for prompting the provision of advice in primary care.

  18. Identifying research priorities in anaesthesia and perioperative care: final report of the joint National Institute of Academic Anaesthesia/James Lind Alliance Research Priority Setting Partnership.

    Science.gov (United States)

    Boney, Oliver; Bell, Madeline; Bell, Natalie; Conquest, Ann; Cumbers, Marion; Drake, Sharon; Galsworthy, Mike; Gath, Jacqui; Grocott, Michael P W; Harris, Emma; Howell, Simon; Ingold, Anthony; Nathanson, Michael H; Pinkney, Thomas; Metcalf, Leanne

    2015-12-16

    To identify research priorities for Anaesthesia and Perioperative Medicine. Prospective surveys and consensus meetings guided by an independent adviser. UK. 45 stakeholder organisations (25 professional, 20 patient/carer) affiliated as James Lind Alliance partners. First 'ideas-gathering' survey: Free text research ideas and suggestions. Second 'prioritisation' survey: Shortlist of 'summary' research questions (derived from the first survey) ranked by respondents in order of priority. Final 'top ten': Agreed by consensus at a final prioritisation workshop. First survey: 1420 suggestions received from 623 respondents (49% patients/public) were refined into a shortlist of 92 'summary' questions. Second survey: 1718 respondents each nominated up to 10 questions as research priorities. Top ten: The 25 highest-ranked questions advanced to the final workshop, where 23 stakeholders (13 professional, 10 patient/carer) agreed the 10 most important questions: ▸ What can we do to stop patients developing chronic pain after surgery? ▸ How can patient care around the time of emergency surgery be improved? ▸ What long-term harm may result from anaesthesia, particularly following repeated anaesthetics?▸ What outcomes should we use to measure the 'success' of anaesthesia and perioperative care? ▸ How can we improve recovery from surgery for elderly patients? ▸ For which patients does regional anaesthesia give better outcomes than general anaesthesia? ▸ What are the effects of anaesthesia on the developing brain? ▸ Do enhanced recovery programmes improve short and long-term outcomes? ▸ How can preoperative exercise or fitness training, including physiotherapy, improve outcomes after surgery? ▸ How can we improve communication between the teams looking after patients throughout their surgical journey? Almost 2000 stakeholders contributed their views regarding anaesthetic and perioperative research priorities. This is the largest example of patient and public

  19. Screening for type 2 diabetes in a multiethnic setting using known risk factors to identify those at high risk: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Laura J Gray

    2010-09-01

    Full Text Available Laura J Gray1, Jennifer R Tringham2, Melanie J Davies3, David R Webb3, Janet Jarvis4, Timothy C Skinner5, Azhar M Farooqi1, Kamlesh Khunti11Department of Health Sciences, University of Leicester, Leicester, UK; 2Department of Diabetes, Frimley Park Hospital, Surrey, UK; 3Department of Cardiovascular Sciences, University Hospitals of Leicester, Leicester, UK; 4University Hospitals Leicester, Leicester, UK; 5Flinders University Rural Clinical School, Flinders University, Renmark, AustraliaIntroduction: Screening enables the identification of type 2 diabetes mellitus (T2DM during its asymptomatic stage and therefore allows early intervention which may lead to fewer complications and improve outcomes. A targeted screening program was carried out in a United Kingdom (UK multiethnic population to identify those with abnormal glucose tolerance.Methods: A sample of individuals aged 25–75 years (40–75 white European with at least one risk factor for T2DM were invited for screening from 17 Leicestershire (UK general practices or through a health awareness campaign. All participants received a 75 g oral glucose tolerance test, cardiovascular risk assessment, detailed medical and family histories and anthropometric measurements.Results: In the 3,225 participants who were screened. 640 (20% were found to have some form of abnormal glucose tolerance of whom 4% had T2DM, 3% impaired fasting glucose (IFG, 10% impaired glucose tolerance (IGT and 3% both IFG and IGT. The odds of detecting IGT was approximately 60% greater (confounder-adjusted odds ratios [OR] 1.67 [1.22–2.29] in the South Asian population.Conclusions: Around one in five people who had targeted screening have IGT, IFG or T2DM, with a higher prevalence in those of South Asian origin. The prevalence of undetected T2DM is lower in South Asians compared to previously published studies and maybe due to increased awareness of this group being at high risk.Keywords: type 2 diabetes, screening

  20. Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting.

    Science.gov (United States)

    Natarajan, Pradeep; Young, Robin; Stitziel, Nathan O; Padmanabhan, Sandosh; Baber, Usman; Mehran, Roxana; Sartori, Samantha; Fuster, Valentin; Reilly, Dermot F; Butterworth, Adam; Rader, Daniel J; Ford, Ian; Sattar, Naveed; Kathiresan, Sekar

    2017-05-30

    burden of subclinical atherosclerosis and derive greater relative and absolute benefit from statin therapy to prevent a first coronary heart disease event. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00738725 (BioImage) and NCT00005130 (CARDIA). WOSCOPS was carried out and completed before the requirement for clinical trial registration. © 2017 American Heart Association, Inc.

  1. Epstein-Barr virus latent gene sequences as geographical markers of viral origin: unique EBNA3 gene signatures identify Japanese viruses as distinct members of the Asian virus family.

    Science.gov (United States)

    Sawada, Akihisa; Croom-Carter, Deborah; Kondo, Osamu; Yasui, Masahiro; Koyama-Sato, Maho; Inoue, Masami; Kawa, Keisei; Rickinson, Alan B; Tierney, Rosemary J

    2011-05-01

    Polymorphisms in Epstein-Barr virus (EBV) latent genes can identify virus strains from different human populations and individual strains within a population. An Asian EBV signature has been defined almost exclusively from Chinese viruses, with little information from other Asian countries. Here we sequenced polymorphic regions of the EBNA1, 2, 3A, 3B, 3C and LMP1 genes of 31 Japanese strains from control donors and EBV-associated T/NK-cell lymphoproliferative disease (T/NK-LPD) patients. Though identical to Chinese strains in their dominant EBNA1 and LMP1 alleles, Japanese viruses were subtly different at other loci. Thus, while Chinese viruses mainly fall into two families with strongly linked 'Wu' or 'Li' alleles at EBNA2 and EBNA3A/B/C, Japanese viruses all have the consensus Wu EBNA2 allele but fall into two families at EBNA3A/B/C. One family has variant Li-like sequences at EBNA3A and 3B and the consensus Li sequence at EBNA3C; the other family has variant Wu-like sequences at EBNA3A, variants of a low frequency Chinese allele 'Sp' at EBNA3B and a consensus Sp sequence at EBNA3C. Thus, EBNA3A/B/C allelotypes clearly distinguish Japanese from Chinese strains. Interestingly, most Japanese viruses also lack those immune-escape mutations in the HLA-A11 epitope-encoding region of EBNA3B that are so characteristic of viruses from the highly A11-positive Chinese population. Control donor-derived and T/NK-LPD-derived strains were similarly distributed across allelotypes and, by using allelic polymorphisms to track virus strains in patients pre- and post-haematopoietic stem-cell transplant, we show that a single strain can induce both T/NK-LPD and B-cell-lymphoproliferative disease in the same patient.

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

    Science.gov (United States)

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

    2016-01-01

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

  3. The methyltransferase NSD3 has chromatin-binding motifs, PHD5-C5HCH, that are distinct from other NSD (nuclear receptor SET domain) family members in their histone H3 recognition.

    Science.gov (United States)

    He, Chao; Li, Fudong; Zhang, Jiahai; Wu, Jihui; Shi, Yunyu

    2013-02-15

    The NSD (nuclear receptor SET domain-containing) family members, consisting of NSD1, NSD2 (MMSET/WHSC1), and NSD3 (WHSC1L1), are SET domain-containing methyltransferases and aberrant expression of each member has been implicated in multiple diseases. They have specific mono- and dimethylase activities for H3K36, whereas play nonredundant roles during development. Aside from the well characterized catalytic SET domain, NSD proteins have multiple potential chromatin-binding motifs that are clinically relevant, including the fifth plant homeodomain (PHD5) and the adjacent Cys-His-rich domain (C5HCH) located at the C terminus. Herein, we report the crystal structures of the PHD5-C5HCH module of NSD3, in the free state and in complex with H3(1-7) (H3 residues 1-7), H3(1-15) (H3 residues 1-15), and H3(1-15)K9me3 (H3 residues 1-15 with trimethylation on K9) peptides. These structures reveal that the PHD5 and C5HCH domains fold into a novel integrated PHD-PHD-like structural module with H3 peptide bound only on the surface of PHD5 and provide the molecular basis for the recognition of unmodified H3K4 and trimethylated H3K9 by NSD3 PHD5. Structural studies and binding assays show that differences exist in histone binding specificity of the PHD5 domain between three members of the NSD family. For NSD2, the PHD5-C5HCH:H3 N terminus interaction is largely conserved, although with a stronger preference for unmethylated H3K9 (H3K9me0) than trimethylated H3K9 (H3K9me3), and NSD1 PHD5-C5HCH does not bind to H3 peptides. Our results shed light on how NSD proteins that mediate H3K36 methylation are localized to specific genomic sites and provide implications for the mechanism of functional diversity of NSD proteins.

  4. Distinct HbA1c trajectories in a type 2 diabetes cohort

    NARCIS (Netherlands)

    Walraven, I.; Mast, M.R.; Hoekstra, T.; Jansen, A.P.D.; van der Heijden, A.A.W.A.; Rauh, S.P.; Rutters, F.; van 't Riet, E.; Elders, P.J.M.; Moll, A.C.; Polak, B.C.P.; Dekker, J.M.; Nijpels, G.

    2015-01-01

    Aims: The aim of this study was to identify subgroups of type 2 diabetes mellitus patients with distinct hemoglobin A1c (HbA1c) trajectories. Subgroup characteristics were determined and the prevalence of microvascular complications over time was investigated. Study design and setting: Data from a

  5. Neural correlates of the food/non-food visual distinction.

    Science.gov (United States)

    Tsourides, Kleovoulos; Shariat, Shahriar; Nejati, Hossein; Gandhi, Tapan K; Cardinaux, Annie; Simons, Christopher T; Cheung, Ngai-Man; Pavlovic, Vladimir; Sinha, Pawan

    2016-03-01

    An evolutionarily ancient skill we possess is the ability to distinguish between food and non-food. Our goal here is to identify the neural correlates of visually driven 'edible-inedible' perceptual distinction. We also investigate correlates of the finer-grained likability assessment. Our stimuli depicted food or non-food items with sub-classes of appealing or unappealing exemplars. Using data-classification techniques drawn from machine-learning, as well as evoked-response analyses, we sought to determine whether these four classes of stimuli could be distinguished based on the patterns of brain activity they elicited. Subjects viewed 200 images while in a MEG scanner. Our analyses yielded two successes and a surprising failure. The food/non-food distinction had a robust neural counterpart and emerged as early as 85 ms post-stimulus onset. The likable/non-likable distinction too was evident in the neural signals when food and non-food stimuli were grouped together, or when only the non-food stimuli were included in the analyses. However, we were unable to identify any neural correlates of this distinction when limiting the analyses only to food stimuli. Taken together, these positive and negative results further our understanding of the substrates of a set of ecologically important judgments and have clinical implications for conditions like eating-disorders and anhedonia. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Identifying Special Operations as a Distinct Foreign Policy Instrument

    DEFF Research Database (Denmark)

    Johnsen, Anton Asklund

    2017-01-01

    to clarify and explain what special operations strategic qualities exactly are. The author then elaborates on specific elements of special operations with a point of departure in the “cognitive maps of SOF” as formulated in the research question. The author recommends that in order to influence policy...... on special operations, it is essential to have insight into the instrument’s capabilities and limitations, as this provides the prerequisites for sound contextual strategic analysis....

  7. Distinctive Dynamic Capabilities for New Business Creation

    DEFF Research Database (Denmark)

    Rosenø, Axel; Enkel, Ellen; Mezger, Florian

    2013-01-01

    This study examines the distinctive dynamic capabilities for new business creation in established companies. We argue that these are very different from those for managing incremental innovation within a company's core business. We also propose that such capabilities are needed in both slow...... and fast-paced industries, and that similarities exist across industries. Hence, the study contributes to dynamic capabilities literature by: 1) identifying the distinctive dynamic capabilities for new business creation; 2) shifting focus away from dynamic capabilities in environments characterised by high...... clock-speed and uncertainty towards considering dynamic capabilities for the purpose of developing new businesses, which also implies a high degree of uncertainty. Based on interviews with 33 companies, we identify distinctive dynamic capabilities for new business creation, find that dynamic...

  8. Low sensitivity of qSOFA, SIRS criteria and sepsis definition to identify infected patients at risk of complication in the prehospital setting and at the emergency department triage.

    Science.gov (United States)

    Tusgul, Selin; Carron, Pierre-Nicolas; Yersin, Bertrand; Calandra, Thierry; Dami, Fabrice

    2017-11-03

    Sepsis is defined as life-threatening organ dysfunction caused by a host response to infection. The quick SOFA (qSOFA) score has been recently proposed as a new bedside clinical score to identify patients with suspected infection at risk of complication (intensive care unit (ICU) admission, in-hospital mortality). The aim of this study was to measure the sensitivity of the qSOFA score, SIRS criteria and sepsis definitions to identify the most serious sepsis cases in the prehospital setting and at the emergency department (ED) triage. We performed a retrospective study of all patients transported by emergency medical services (EMS) to the Lausanne University Hospital (CHUV) over twelve months. All patients with a suspected or proven infection after the ED workup were included. We retrospectively analysed the sensitivity of the qSOFA score (≥2 criteria), SIRS criteria (≥2 clinical criteria) and sepsis definition (SIRS criteria + one sign of organ dysfunction or hypoperfusion) in the pre-hospital setting and at the ED triage as predictors of ICU admission, ICU stay of ≥3 days and early (i.e. 48 h) mortality. No direct comparison between the three tools was attempted. Among 11,411 patients transported to the University hospital, 886 (7.8%) were included. In the pre-hospital setting, the sensitivity of qSOFA reached 36.3% for ICU admission, 17.4% for ICU stay of three days or more and 68.0% for 48 h mortality. The sensitivity of SIRS criteria reached 68.8% for ICU admission, 74.6% for ICU stay of three days or more and 64.0% for 48 h mortality. The sensitivity of sepsis definition did not reach 60% for any outcome. At ED triage, the sensitivity of qSOFA reached 31.2% for ICU admission, 30.5% for ICU stay of ≥3 days and 60.0% for mortality at 48 h. The sensitivity of SIRS criteria reached 58.8% for ICU admission, 57.6% for ICU stay of ≥3 days 80.0% for mortality at 48 h. The sensitivity of sepsis definition reached 60.0% for 48 h mortality. Incidence

  9. What makes health promotion research distinct?

    Science.gov (United States)

    Woodall, James; Warwick-Booth, Louise; South, Jane; Cross, Ruth

    2018-02-01

    There have been concerns about the decline of health promotion as a practice and discipline and, alongside this, calls for a clearer articulation of health promotion research and what, if anything, makes it distinct. This discussion paper, based on a review of the literature, the authors' own experiences in the field, and a workshop delivered by two of the authors at the 8th Nordic Health Promotion Conference, seeks to state the reasons why health promotion research is distinctive. While by no means exhaustive, the paper suggests four distinctive features. The paper hopes to be a catalyst to enable health promotion researchers to be explicit in their practice and to begin the process of developing an agreed set of research principles.

  10. Identifying and Prioritizing Gaps in Neuroendocrine Tumor Research: A Modified Delphi Process With Patients and Health Care Providers to Set the Research Action Plan for the Newly Formed Commonwealth Neuroendocrine Tumor Collaboration.

    Science.gov (United States)

    Segelov, Eva; Chan, David; Lawrence, Ben; Pavlakis, Nick; Kennecke, Hagen F; Jackson, Christopher; Law, Calvin; Singh, Simron

    2017-08-01

    Neuroendocrine tumors (NETs) are a diverse group of malignancies that pose challenges common to all rare tumors. The Commonwealth Neuroendocrine Tumor Collaboration (CommNETS) was established in 2015 to enhance outcomes for patients with NETs in Canada, Australia, and New Zealand. A modified Delphi process was undertaken involving patients, clinicians, and researchers to identify gaps in NETs research to produce a comprehensive and defensible research action plan. A three-round modified Delphi process was undertaken with larger representation than usual for medical consensus processes. Patient/advocate and health care provider/researcher expert panels undertook Round 1, which canvassed 17 research priorities and 42 potential topics; in Round 2, these priorities were ranked. Round 3 comprised a face-to-face meeting to generate final consensus rankings and formulate the research action plan. The Delphi groups consisted of 203 participants in Round 1 (64% health care providers/researchers, 36% patient/advocates; 52% Canadian, 32% Australian, and 17% New Zealander), of whom 132 participated in Round 2. The top eight priorities were biomarker development; peptide receptor radionuclide therapy optimization; trials of new agents in advanced NETs; functional imaging; sequencing therapies for metastatic NETs, including development of validated surrogate end points for studies; pathologic classification; early diagnosis; interventional therapeutics; and curative surgery. Two major areas were ranked significantly higher by patients/advocates: early diagnosis and curative surgery. Six CommNETS working parties were established. This modified Delphi process resulted in a well-founded set of research priorities for the newly formed CommNETS collaboration by involving a large, diverse group of stakeholders. This approach to setting a research agenda for a new collaborative group should be adopted to ensure that research plans reflect unmet needs and priorities in the field.

  11. Identifying and Prioritizing Gaps in Neuroendocrine Tumor Research: A Modified Delphi Process With Patients and Health Care Providers to Set the Research Action Plan for the Newly Formed Commonwealth Neuroendocrine Tumor Collaboration

    Directory of Open Access Journals (Sweden)

    Eva Segelov

    2017-08-01

    Full Text Available Purpose: Neuroendocrine tumors (NETs are a diverse group of malignancies that pose challenges common to all rare tumors. The Commonwealth Neuroendocrine Tumor Collaboration (CommNETS was established in 2015 to enhance outcomes for patients with NETs in Canada, Australia, and New Zealand. A modified Delphi process was undertaken involving patients, clinicians, and researchers to identify gaps in NETs research to produce a comprehensive and defensible research action plan. Methods: A three-round modified Delphi process was undertaken with larger representation than usual for medical consensus processes. Patient/advocate and health care provider/researcher expert panels undertook Round 1, which canvassed 17 research priorities and 42 potential topics; in Round 2, these priorities were ranked. Round 3 comprised a face-to-face meeting to generate final consensus rankings and formulate the research action plan. Results: The Delphi groups consisted of 203 participants in Round 1 (64% health care providers/researchers, 36% patient/advocates; 52% Canadian, 32% Australian, and 17% New Zealander, of whom 132 participated in Round 2. The top eight priorities were biomarker development; peptide receptor radionuclide therapy optimization; trials of new agents in advanced NETs; functional imaging; sequencing therapies for metastatic NETs, including development of validated surrogate end points for studies; pathologic classification; early diagnosis; interventional therapeutics; and curative surgery. Two major areas were ranked significantly higher by patients/advocates: early diagnosis and curative surgery. Six CommNETS working parties were established. Conclusion: This modified Delphi process resulted in a well-founded set of research priorities for the newly formed CommNETS collaboration by involving a large, diverse group of stakeholders. This approach to setting a research agenda for a new collaborative group should be adopted to ensure that research plans

  12. Settings for Suicide Prevention

    Science.gov (United States)

    ... Suicide Populations Racial/Ethnic Groups Older Adults Adolescents LGBT Military/Veterans Men Effective Prevention Comprehensive Approach Identify ... Based Prevention Settings American Indian/Alaska Native Settings Schools Colleges and Universities Primary Care Emergency Departments Behavioral ...

  13. Using the Consolidated Framework for Implementation Research to Identify Barriers and Facilitators for the Implementation of an Internet-Based Patient-Provider Communication Service in Five Settings: A Qualitative Study.

    Science.gov (United States)

    Varsi, Cecilie; Ekstedt, Mirjam; Gammon, Deede; Ruland, Cornelia M

    2015-11-18

    Although there is growing evidence of the positive effects of Internet-based patient-provider communication (IPPC) services for both patients and health care providers, their implementation into clinical practice continues to be a challenge. The 3 aims of this study were to (1) identify and compare barriers and facilitators influencing the implementation of an IPPC service in 5 hospital units using the Consolidated Framework for Implementation Research (CFIR), (2) assess the ability of the different constructs of CFIR to distinguish between high and low implementation success, and (3) compare our findings with those from other studies that used the CFIR to discriminate between high and low implementation success. This study was based on individual interviews with 10 nurses, 6 physicians, and 1 nutritionist who had used the IPPC to answer messages from patients. Of the 36 CFIR constructs, 28 were addressed in the interviews, of which 12 distinguished between high and low implementation units. Most of the distinguishing constructs were related to the inner setting domain of CFIR, indicating that institutional factors were particularly important for successful implementation. Health care providers' beliefs in the intervention as useful for themselves and their patients as well as the implementation process itself were also important. A comparison of constructs across ours and 2 other studies that also used the CFIR to discriminate between high and low implementation success showed that 24 CFIR constructs distinguished between high and low implementation units in at least 1 study; 11 constructs distinguished in 2 studies. However, only 2 constructs (patient need and resources and available resources) distinguished consistently between high and low implementation units in all 3 studies. The CFIR is a helpful framework for illuminating barriers and facilitators influencing IPPC implementation. However, CFIR's strength of being broad and comprehensive also limits its

  14. Practice Alignment and intent as distinctions for understanding cross-boundary knowledge creation practices in knowledge ecosystems

    DEFF Research Database (Denmark)

    Aaen, Mathias

    This paper explores how practice alignment and intent across organizational boundaries may serve as an explanation for collaborative knowledge creation in a knowledge ecosystem. The paper is based on a longitudinal case study of a large multinational knowledge ecosystem consisting of many...... communities of practices and organisations. By applying a practice theory approach to five data sets collected over a five-year period, the study investigates how two distinctions may serve as a potential gateway into understanding knowledge creation across boundaries. The two distinctions – practice...... are identified and discussed. Potential implications for organisational and knowledge ecosystem conceptions are identified and discussed for further research....

  15. Counselor Identity: Conformity or Distinction?

    Science.gov (United States)

    McLaughlin, Jerry E.; Boettcher, Kathryn

    2009-01-01

    The authors explore 3 debates in other disciplines similar to counseling's identity debate in order to learn about common themes and outcomes. Conformity, distinction, and cohesion emerged as common themes. They conclude that counselors should retain their distinctive, humanistic approach rather than conforming to the dominant, medical approach.

  16. California's "Bridge to Reform": identifying challenges and defining strategies for providers and policymakers implementing the Affordable Care Act in low-income HIV/AIDS care and treatment settings.

    Directory of Open Access Journals (Sweden)

    Patrick T Hazelton

    Full Text Available In preparation for full Affordable Care Act implementation, California has instituted two healthcare initiatives that provide comprehensive coverage for previously uninsured or underinsured individuals. For many people living with HIV, this has required transition either from the HIV-specific coverage of the Ryan White program to the more comprehensive coverage provided by the county-run Low-Income Health Programs or from Medicaid fee-for-service to Medicaid managed care. Patient advocates have expressed concern that these transitions may present implementation challenges that will need to be addressed if ambitious HIV prevention and treatment goals are to be achieved.30 semi-structured, in-depth interviews were conducted between October, 2012, and February, 2013, with policymakers and providers in 10 urban, suburban, and rural California counties. Interview topics included: continuity of patient care, capacity to handle payer source transitions, and preparations for healthcare reform implementation. Study team members reviewed interview transcripts to produce emergent themes, develop a codebook, build inter-rater reliability, and conduct analyses.Respondents supported the goals of the ACA, but reported clinic and policy-level challenges to maintaining patient continuity of care during the payer source transitions. They also identified strategies for addressing these challenges. Areas of focus included: gaps in communication to reach patients and develop partnerships between providers and policymakers, perceived inadequacy in new provider networks for delivering quality HIV care, the potential for clinics to become financially insolvent due to lower reimbursement rates, and increased administrative burdens for clinic staff and patients.California's new healthcare initiatives represent ambitious attempts to expand and improve health coverage for low-income individuals. The state's challenges in maintaining quality care and treatment for people

  17. California's “Bridge to Reform”: Identifying Challenges and Defining Strategies for Providers and Policymakers Implementing the Affordable Care Act in Low-Income HIV/AIDS Care and Treatment Settings

    Science.gov (United States)

    Hazelton, Patrick T.; Steward, Wayne T.; Collins, Shane P.; Gaffney, Stuart; Morin, Stephen F.; Arnold, Emily A.

    2014-01-01

    Background In preparation for full Affordable Care Act implementation, California has instituted two healthcare initiatives that provide comprehensive coverage for previously uninsured or underinsured individuals. For many people living with HIV, this has required transition either from the HIV-specific coverage of the Ryan White program to the more comprehensive coverage provided by the county-run Low-Income Health Programs or from Medicaid fee-for-service to Medicaid managed care. Patient advocates have expressed concern that these transitions may present implementation challenges that will need to be addressed if ambitious HIV prevention and treatment goals are to be achieved. Methods 30 semi-structured, in-depth interviews were conducted between October, 2012, and February, 2013, with policymakers and providers in 10 urban, suburban, and rural California counties. Interview topics included: continuity of patient care, capacity to handle payer source transitions, and preparations for healthcare reform implementation. Study team members reviewed interview transcripts to produce emergent themes, develop a codebook, build inter-rater reliability, and conduct analyses. Results Respondents supported the goals of the ACA, but reported clinic and policy-level challenges to maintaining patient continuity of care during the payer source transitions. They also identified strategies for addressing these challenges. Areas of focus included: gaps in communication to reach patients and develop partnerships between providers and policymakers, perceived inadequacy in new provider networks for delivering quality HIV care, the potential for clinics to become financially insolvent due to lower reimbursement rates, and increased administrative burdens for clinic staff and patients. Conclusions California's new healthcare initiatives represent ambitious attempts to expand and improve health coverage for low-income individuals. The state's challenges in maintaining quality care and

  18. Counting SET-free sets

    OpenAIRE

    Harman, Nate

    2016-01-01

    We consider the following counting problem related to the card game SET: How many $k$-element SET-free sets are there in an $n$-dimensional SET deck? Through a series of algebraic reformulations and reinterpretations, we show the answer to this question satisfies two polynomiality conditions.

  19. Distinction

    OpenAIRE

    2010-01-01

    Pr Serge Haroche La Médaille d’or 2009 du CNRS est décernée au Pr Serge Haroche, titulaire de la chaire de Physique quantique depuis 2001. Serge Haroche est spécialiste de physique atomique et d’optique quantique. Il est l’un des fondateurs de l’électrodynamique quantique en cavité, domaine qui permet, par des expériences conceptuellement simples, d’éclairer les fondements de la théorie quantique et de réaliser des prototypes de systèmes de traitement quantique de l’information. Serge Haroche...

  20. Identification of distinct phenotypes of locally advanced pancreatic adenocarcinoma.

    LENUS (Irish Health Repository)

    Teo, Minyuen

    2013-03-01

    A significant number of pancreatic ductal adenocarcinoma present as locally advanced disease. Optimal treatment remains controversial. We sought to analyze the clinical course of locally advanced pancreatic adenocarcinoma (LAPC) in order to identify potential distinct clinical phenotypes.

  1. Automatic sets and Delone sets

    International Nuclear Information System (INIS)

    Barbe, A; Haeseler, F von

    2004-01-01

    Automatic sets D part of Z m are characterized by having a finite number of decimations. They are equivalently generated by fixed points of certain substitution systems, or by certain finite automata. As examples, two-dimensional versions of the Thue-Morse, Baum-Sweet, Rudin-Shapiro and paperfolding sequences are presented. We give a necessary and sufficient condition for an automatic set D part of Z m to be a Delone set in R m . The result is then extended to automatic sets that are defined as fixed points of certain substitutions. The morphology of automatic sets is discussed by means of examples

  2. A Retrospective Study of the Incidence of Missed Opportunities in Identifying, Managing and Referring At-Risk of Overweight and Overweight Children and Adolescents in an Outpatient Primary Care Setting

    National Research Council Canada - National Science Library

    Quirke, Amy

    2004-01-01

    A descriptive study of the incidence of missed opportunities in identifying, managing and referring children and adolescents at-risk of overweight and overweight were conducted using a retrospective...

  3. A Novel Algorithm for the Generation of Distinct Kinematic Chain

    Science.gov (United States)

    Medapati, Sreenivasa Reddy; Kuchibhotla, Mallikarjuna Rao; Annambhotla, Balaji Srinivasa Rao

    2016-07-01

    Generation of distinct kinematic chains is an important topic in the design of mechanisms for various industrial applications i.e., robotic manipulator, tractor, crane etc. Many researchers have intently focused on this area and explained various processes of generating distinct kinematic chains which are laborious and complex. It is desirable to enumerate the kinematic chains systematically to know the inherent characteristics of a chain related to its structure so that all the distinct chains can be analyzed in depth, prior to the selection of a chain for a purpose. This paper proposes a novel and simple method with set of rules defined to eliminate isomorphic kinematic chains generating distinct kinematic chains. Also, this method simplifies the process of generating distinct kinematic chains even at higher levels i.e., 10-link, 11-link with single and multiple degree of freedom.

  4. An Adult Developmental Approach to Perceived Facial Attractiveness and Distinctiveness

    OpenAIRE

    Natalie C. Ebner; Natalie C. Ebner; Natalie C. Ebner; Joerg Luedicke; Manuel C. Voelkle; Manuel C. Voelkle; Michaela Riediger; Michaela Riediger; Tian Lin; Ulman Lindenberger; Ulman Lindenberger

    2018-01-01

    Attractiveness and distinctiveness constitute facial features with high biological and social relevance. Bringing a developmental perspective to research on social-cognitive face perception, we used a large set of faces taken from the FACES Lifespan Database to examine effects of face and perceiver characteristics on subjective evaluations of attractiveness and distinctiveness in young (20–31 years), middle-aged (44–55 years), and older (70–81 years) men and women. We report novel findings su...

  5. Identifying molecular subtypes in human colon cancer using gene expression and DNA methylation microarray data

    OpenAIRE

    REN, ZHONGLU; WANG, WENHUI; LI, JINMING

    2015-01-01

    Identifying colon cancer subtypes based on molecular signatures may allow for a more rational, patient-specific approach to therapy in the future. Classifications using gene expression data have been attempted before with little concordance between the different studies carried out. In this study we aimed to uncover subtypes of colon cancer that have distinct biological characteristics and identify a set of novel biomarkers which could best reflect the clinical and/or biological characteristi...

  6. QUANTATIVE SET COMPARISONS WITH COMPONENT MONEY IN MODERN RUSSIAN LANGUAGE CONTRASTED WITH SLAVIC LANGUAGES

    Directory of Open Access Journals (Sweden)

    Zinovieva, E.I.

    2016-06-01

    Full Text Available The article provides a detailed analysis of semantics and functioning of Russian set comparisons according to dictionaries, literary context, periodicals and the Internet and studies stereotypical perception of what is considered small or large amounts of money and the way it is reflected in consciousness of native speakers and the Russian language on the basis of survey. Set comparisons in Russian language are contrasted with other Slavic languages to identify their universal and distinctive features.

  7. Presidential address: distinction or extinction.

    Science.gov (United States)

    Pressman, Barry D

    2008-10-01

    Despite its continuing scientific successes in imaging, radiology as a specialty is faced with a very difficult and competitive environment. Nonradiologists are more and more interested in vertically integrating imaging into their practices, while teleradiology and picture archiving and communication systems are resulting in the greater isolation of radiologists. Commoditization is a realistic and devastating threat to the survival and professionalism of the specialty. To remain viable as a specialty, radiologists must elevate their practice by subspecializing, becoming more involved with clinical care, and actively interacting with patients and referring clinicians. Distinction will prevent extinction.

  8. Common and distinct brain networks underlying panic and social anxiety disorders.

    Science.gov (United States)

    Kim, Yong-Ku; Yoon, Ho-Kyoung

    2018-01-03

    Although panic disorder (PD) and phobic disorders are independent anxiety disorders with distinct sets of diagnostic criteria, there is a high level of overlap between them in terms of pathogenesis and neural underpinnings. Functional connectivity research using resting-state functional magnetic resonance imaging (rsfMRI) shows great potential in identifying the similarities and differences between PD and phobias. Understanding common and distinct networks between PD and phobic disorders is critical for identifying both specific and general neural characteristics of these disorders. We review recent rsfMRI studies and explore the clinical relevance of resting-state functional connectivity (rsFC) in PD and phobias. Although findings differ between studies, there are some meaningful, consistent findings. Social anxiety disorder (SAD) and PD share common default mode network alterations. Alterations within the sensorimotor network are observed primarily in PD. Increased connectivity in the salience network is consistently reported in SAD. This review supports hypotheses that PD and phobic disorders share common rsFC abnormalities and that the different clinical phenotypes between the disorders come from distinct brain functional network alterations. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. PERFECTED enhanced recovery (PERFECT-ER) care versus standard acute care for patients admitted to acute settings with hip fracture identified as experiencing confusion: study protocol for a feasibility cluster randomized controlled trial.

    Science.gov (United States)

    Hammond, Simon P; Cross, Jane L; Shepstone, Lee; Backhouse, Tamara; Henderson, Catherine; Poland, Fiona; Sims, Erika; MacLullich, Alasdair; Penhale, Bridget; Howard, Robert; Lambert, Nigel; Varley, Anna; Smith, Toby O; Sahota, Opinder; Donell, Simon; Patel, Martyn; Ballard, Clive; Young, John; Knapp, Martin; Jackson, Stephen; Waring, Justin; Leavey, Nick; Howard, Gregory; Fox, Chris

    2017-12-04

    Health and social care provision for an ageing population is a global priority. Provision for those with dementia and hip fracture has specific and growing importance. Older people who break their hip are recognised as exceptionally vulnerable to experiencing confusion (including but not exclusively, dementia and/or delirium and/or cognitive impairment(s)) before, during or after acute admissions. Older people experiencing hip fracture and confusion risk serious complications, linked to delayed recovery and higher mortality post-operatively. Specific care pathways acknowledging the differences in patient presentation and care needs are proposed to improve clinical and process outcomes. This protocol describes a multi-centre, feasibility, cluster-randomised, controlled trial (CRCT) to be undertaken across ten National Health Service hospital trusts in the UK. The trial will explore the feasibility of undertaking a CRCT comparing the multicomponent PERFECTED enhanced recovery intervention (PERFECT-ER), which acknowledges the differences in care needs of confused older patients experiencing hip fracture, with standard care. The trial will also have an integrated process evaluation to explore how PERFECT-ER is implemented and interacts with the local context. The study will recruit 400 hip fracture patients identified as experiencing confusion and will also recruit "suitable informants" (individuals in regular contact with participants who will complete proxy measures). We will also recruit NHS professionals for the process evaluation. This mixed methods design will produce data to inform a definitive evaluation of the intervention via a large-scale pragmatic randomised controlled trial (RCT). The trial will provide a preliminary estimate of potential efficacy of PERFECT-ER versus standard care; assess service delivery variation, inform primary and secondary outcome selection, generate estimates of recruitment and retention rates, data collection difficulties, and

  10. 10 distinct stellar populations in omega Centauri.

    Science.gov (United States)

    Bellini, Andrea; Anderson, Jay; Bedin, Luigi R.; Cool, Adrienne; King, Ivan R.; van der marel, roeland p.

    2015-08-01

    We are constructing the most comprehensive catalog of photometry and proper motions ever assembled for a globular cluster. The core of omega Centauri has been imaged over 600 times through WFC3’s UVIS and IR channels for the purposes of detector calibration. There exist ~30 exposures each for 26 filters, stretching uniformly from F225W in the UV to F160W in the infrared. Furthermore, the 12-year baseline between this data and a 2002 ACS survey will more than triple both the accuracy and the number of well-measured stars compared to previous studies.This totally unprecedented complete spectral coverage for over 400,000 stars, from the red-giant branch down to the white dwarfs, provides the best chance yet to understand the multiple-population phenomenon in any globular cluster. A preliminary analysis of the color-magnitude diagrams in different bands already allows us to identify 10 distinct sequences.

  11. The evolution of compositionally and functionally distinct actin filaments.

    Science.gov (United States)

    Gunning, Peter W; Ghoshdastider, Umesh; Whitaker, Shane; Popp, David; Robinson, Robert C

    2015-06-01

    The actin filament is astonishingly well conserved across a diverse set of eukaryotic species. It has essentially remained unchanged in the billion years that separate yeast, Arabidopsis and man. In contrast, bacterial actin-like proteins have diverged to the extreme, and many of them are not readily identified from sequence-based homology searches. Here, we present phylogenetic analyses that point to an evolutionary drive to diversify actin filament composition across kingdoms. Bacteria use a one-filament-one-function system to create distinct filament systems within a single cell. In contrast, eukaryotic actin is a universal force provider in a wide range of processes. In plants, there has been an expansion of the number of closely related actin genes, whereas in fungi and metazoa diversification in tropomyosins has increased the compositional variety in actin filament systems. Both mechanisms dictate the subset of actin-binding proteins that interact with each filament type, leading to specialization in function. In this Hypothesis, we thus propose that different mechanisms were selected in bacteria, plants and metazoa, which achieved actin filament compositional variation leading to the expansion of their functional diversity. © 2015. Published by The Company of Biologists Ltd.

  12. Set discrimination of quantum states

    International Nuclear Information System (INIS)

    Zhang Shengyu; Ying Mingsheng

    2002-01-01

    We introduce a notion of set discrimination, which is an interesting extension of quantum state discrimination. A state is secretly chosen from a number of quantum states, which are partitioned into some disjoint sets. A set discrimination is required to identify which set the given state belongs to. Several essential problems are addressed in this paper, including the condition of perfect set discrimination, unambiguous set discrimination, and in the latter case, the efficiency of the discrimination. This generalizes some important results on quantum state discrimination in the literature. A combination of state and set discrimination and the efficiency are also studied

  13. Identifying mental health services in clinical genetic settings.

    Science.gov (United States)

    Cappelli, M; Esplen, M J; Wilson, B J; Dorval, M; Bottorff, J L; Ly, M; Carroll, J C; Allanson, J; Humphreys, E; Rayson, D

    2009-10-01

    The purpose of this study was to examine the mental health needs of individuals at risk for adult onset hereditary disorder (AOHD) from the perspective of their genetic service providers, as it is unknown to what extent psychosocial services are required and being met. A mail-out survey was sent to 281 providers on the membership lists of the Canadian Association of Genetic Counsellors and the Canadian College of Medical Geneticists. The survey assessed psychosocial issues that were most commonly observed by geneticists, genetic counsellors (GCs), and nurses as well as availability and types of psychosocial services offered. Of the 129 respondents, half of genetic service providers reported observing signs of depression and anxiety, while 44% noted patients' concerns regarding relationships with family and friends. In terms of providing counselling to patients, as the level of psychological risk increased, confidence in dealing with these issues decreased. In addition, significantly more GCs reported that further training in psychosocial issues would be most beneficial to them if resources were available. As a feature of patient care, it is recommended that gene-based predictive testing include an integrative model of psychosocial services as well as training for genetic service providers in specific areas of AOHD mental health.

  14. A linguistic representation of the regulation of transcription initiation. I. An ordered array of complex symbols with distinctive features.

    Science.gov (United States)

    Collado-Vides, J

    1993-01-01

    The inadequacy of context-free grammars in the description of regulatory information contained in DNA gave the formal justification for a linguistic approach to the study of gene regulation. Based on that result, we have initiated a linguistic formalization of the regulatory arrays of 107 sigma 70 E. coli promoters. The complete sequences of promoter (Pr), operator (Op) and activator binding sites (I) have previously been identified as the smallest elements, or categories, for a combinatorial analysis of the range of transcription initiation of sigma 70 promoters. These categories are conceptually equivalent to phonemes of natural language. Several features associated with these categories are required in a complete description of regulatory arrays of promoters. We have to select the best way to describe the properties that are pertinent for the description of such regulatory regions. In this paper we define distinctive features of regulatory regions based on the following criteria: identification of subclasses of substitutable elements, simplicity, selection of the most directly related information, and distinction of one array among the whole set of promoters. Alternative ways to represent distances in between regulatory sites are discussed, permitting, together with a principle of precedence, the identification of an ordered set of complex symbols as a unique representation for a promoter and its associated regulatory sites. In the accompanying paper additional distinctive features of promoters and regulatory sites are identified.

  15. Distinct signaling roles of ceramide species in yeast revealed through systematic perturbation and systems biology analyses.

    Science.gov (United States)

    Montefusco, David J; Chen, Lujia; Matmati, Nabil; Lu, Songjian; Newcomb, Benjamin; Cooper, Gregory F; Hannun, Yusuf A; Lu, Xinghua

    2013-10-29

    Ceramide, the central molecule of sphingolipid metabolism, is an important bioactive molecule that participates in various cellular regulatory events and that has been implicated in disease. Deciphering ceramide signaling is challenging because multiple ceramide species exist, and many of them may have distinct functions. We applied systems biology and molecular approaches to perturb ceramide metabolism in the yeast Saccharomyces cerevisiae and inferred causal relationships between ceramide species and their potential targets by combining lipidomic, genomic, and transcriptomic analyses. We found that during heat stress, distinct metabolic mechanisms controlled the abundance of different groups of ceramide species and provided experimental support for the importance of the dihydroceramidase Ydc1 in mediating the decrease in dihydroceramides during heat stress. Additionally, distinct groups of ceramide species, with different N-acyl chains and hydroxylations, regulated different sets of functionally related genes, indicating that the structural complexity of these lipids produces functional diversity. The transcriptional modules that we identified provide a resource to begin to dissect the specific functions of ceramides.

  16. Serum and urine metabolomics study reveals a distinct diagnostic model for cancer cachexia

    Science.gov (United States)

    Yang, Quan‐Jun; Zhao, Jiang‐Rong; Hao, Juan; Li, Bin; Huo, Yan; Han, Yong‐Long; Wan, Li‐Li; Li, Jie; Huang, Jinlu; Lu, Jin

    2017-01-01

    Abstract Background Cachexia is a multifactorial metabolic syndrome with high morbidity and mortality in patients with advanced cancer. The diagnosis of cancer cachexia depends on objective measures of clinical symptoms and a history of weight loss, which lag behind disease progression and have limited utility for the early diagnosis of cancer cachexia. In this study, we performed a nuclear magnetic resonance‐based metabolomics analysis to reveal the metabolic profile of cancer cachexia and establish a diagnostic model. Methods Eighty‐four cancer cachexia patients, 33 pre‐cachectic patients, 105 weight‐stable cancer patients, and 74 healthy controls were included in the training and validation sets. Comparative analysis was used to elucidate the distinct metabolites of cancer cachexia, while metabolic pathway analysis was employed to elucidate reprogramming pathways. Random forest, logistic regression, and receiver operating characteristic analyses were used to select and validate the biomarker metabolites and establish a diagnostic model. Results Forty‐six cancer cachexia patients, 22 pre‐cachectic patients, 68 weight‐stable cancer patients, and 48 healthy controls were included in the training set, and 38 cancer cachexia patients, 11 pre‐cachectic patients, 37 weight‐stable cancer patients, and 26 healthy controls were included in the validation set. All four groups were age‐matched and sex‐matched in the training set. Metabolomics analysis showed a clear separation of the four groups. Overall, 45 metabolites and 18 metabolic pathways were associated with cancer cachexia. Using random forest analysis, 15 of these metabolites were identified as highly discriminating between disease states. Logistic regression and receiver operating characteristic analyses were used to create a distinct diagnostic model with an area under the curve of 0.991 based on three metabolites. The diagnostic equation was Logit(P) = −400.53 – 481.88

  17. Near Identifiability of Dynamical Systems

    Science.gov (United States)

    Hadaegh, F. Y.; Bekey, G. A.

    1987-01-01

    Concepts regarding approximate mathematical models treated rigorously. Paper presents new results in analysis of structural identifiability, equivalence, and near equivalence between mathematical models and physical processes they represent. Helps establish rigorous mathematical basis for concepts related to structural identifiability and equivalence revealing fundamental requirements, tacit assumptions, and sources of error. "Structural identifiability," as used by workers in this field, loosely translates as meaning ability to specify unique mathematical model and set of model parameters that accurately predict behavior of corresponding physical system.

  18. CLT and CLS job responsibilities: current distinctions and updates.

    Science.gov (United States)

    Doig, K; Beck, S J; Kolenc, K

    2001-01-01

    This study was undertaken to address the following questions: 1. What tasks distinguish the job of a clinical laboratory scientist (CLS) from that of a clinical laboratory technician (CLT)? 2. What changes in role distinctions, have occurred for entry-level CLS and CLT practitioners over the five-year period 1993-98? 3. What tasks have been deleted from the CLT and CLS content outlines because they were not frequently performed or not considered entry-level? 4. What changes in practice are reflected in the current job analyses? A national job analysis of tasks constituting the job of clinical laboratory scientists (CLSs) and clinical laboratory technicians (CLTs) was conducted in 1998-99 as part of a standard setting process for the certifying examinations of the National Credentialing Agency for Laboratory Personnel (NCA). The job analyses relied upon mail surveys to 1200 individuals for each job level asking respondents to identify tasks significant to effective practice at job entry. The task lists resulting from statistical analysis of those surveys were examined to answer the study questions. The sample for each survey included 1200 practitioners, educators and laboratory managers selected at random from membership in professional organizations or from NCA certificant lists. Sampling was stratified to insure adequate practitioner representation. The mean rating on a four point scale for each item on the surveys was evaluated for overall significance as well as significance across geographic regions. The tasks meeting specified criteria were retained in the final task lists. Tasks were counted and their content evaluated to compare CLS and CLT job tasks. The response rates to the surveys were 33% for CLT and 21% for CLS. Reliability was judged based on average intraclass correlation coefficients of .86 and .82 for the CLT and CLS surveys, respectively. There were 952 tasks retained on the CLS content outline and 725 retained on the CLT content outline of the

  19. Liquidity spillover in international stock markets through distinct time scales.

    Science.gov (United States)

    Righi, Marcelo Brutti; Vieira, Kelmara Mendes

    2014-01-01

    This paper identifies liquidity spillovers through different time scales based on a wavelet multiscaling method. We decompose daily data from U.S., British, Brazilian and Hong Kong stock markets indices in order to calculate the scale correlation between their illiquidities. The sample is divided in order to consider non-crisis, sub-prime crisis and Eurozone crisis. We find that there are changes in correlations of distinct scales and different periods. Association in finest scales is smaller than in coarse scales. There is a rise on associations in periods of crisis. In frequencies, there is predominance for significant distinctions involving the coarsest scale, while for crises periods there is predominance for distinctions on the finest scale.

  20. Social conformity despite individual preferences for distinctiveness.

    Science.gov (United States)

    Smaldino, Paul E; Epstein, Joshua M

    2015-03-01

    We demonstrate that individual behaviours directed at the attainment of distinctiveness can in fact produce complete social conformity. We thus offer an unexpected generative mechanism for this central social phenomenon. Specifically, we establish that agents who have fixed needs to be distinct and adapt their positions to achieve distinctiveness goals, can nevertheless self-organize to a limiting state of absolute conformity. This seemingly paradoxical result is deduced formally from a small number of natural assumptions and is then explored at length computationally. Interesting departures from this conformity equilibrium are also possible, including divergence in positions. The effect of extremist minorities on these dynamics is discussed. A simple extension is then introduced, which allows the model to generate and maintain social diversity, including multimodal distinctiveness distributions. The paper contributes formal definitions, analytical deductions and counterintuitive findings to the literature on individual distinctiveness and social conformity.

  1. Distinctiveness of Initial Preform Properties in Renovation

    Directory of Open Access Journals (Sweden)

    V. M. Yaroslavtsev

    2015-01-01

    Full Text Available Technologies of renovation form a special group of resource-and energy saving technological processes as they are, by definition, already aimed either at increasing resource of the objects satisfying needs of the society life support and practical activities in different spheres, or at extension of their life cycle including a reuse of material from which they are made. Renovation is used where there is a material object, which does not meet requirements of standard or technical documentation.A characteristic feature of the renovation technologies is lack of procedure for a choice of the preform as in all cases an initial preform is the renovation object itself. Thus each object, acting as an initial preform, has the exclusively individual properties, including technological ones.Distinctiveness of renovation object properties is correlated, first of all, with the personified conditions of formation and (or change of condition of their properties in time at all stages of life cycle (production – transportation – warehousing – operation starting with a preform material when manufacturing under all types of loadings (technological and operational. As a result each object forms its "history" of loading and damages and, therefore, its information base which has to consider the phenomenon of “heredity of life cycle”. The term "heredity of life cycle" characterizes information support of object at any moment under review, including both information of technological inheritance, and data of operational heredity.As a result at every moment of time we have a product with a set of new, uncertain properties caused by the phenomena of heredity of life cycle. These properties are individual for each object to be renovated, which changed its status for the status of initial preform for different types of renovation technologies. This is one of the most important distinctions of renovation technology from the technology used to manufacture a new

  2. Particularidades de la medición de presión sonora y vibraciones en grupos electrógenos MAN 18 V48/60 B // Distinctive features for sound pressure level and vibration measurements over engine generator sets type MAN 18 v48/60 b

    Directory of Open Access Journals (Sweden)

    Yanexi Cepero‐Aguilera

    2011-01-01

    Full Text Available Como parte de las líneas de investigación del Centro de Estudios en Ingeniería de Mantenimiento, sedesarrolla un proyecto de investigación encaminado a establecer las pautas para la evaluación de lacondición de grupos electrógenos. El presente artículo muestra las particularidades de la mediciónde sonido y vibraciones sobre un Grupo Electrógeno MAN 18 V48/60 B. Se analiza lo indicado en elestándar ISO 3744 concluyéndose con la imposibilidad práctica de su aplicación en el entornoindustrial y para grandes máquinas como lo es el caso de los grupos electrógenos MAN 18 V48/60 B.El interés de esta investigación se enfoca al generador del grupo electrógeno y por ello no obstante,se efectuaron mediciones de presión sonora orientando el micrófono hacia los cojinetes de este,sobre los cuales también se registraron sus vibraciones siguiendo lo indicado en el estándar ISO8528-9. El análisis comparativo de los registros espectrales de presión sonora y de vibracionesobligó a convertir los espectros FFT en espectros de ancho de banda proporcional constante. Comoresultado fundamental se obtiene la no correlación de las frecuencias espectrales de presión sonoracon las de vibraciones y una evaluación preliminar del generador exhibiendo una condición normal.Palabras claves: nivel de presión sonora, medición de vibraciones, ancho de banda proporcionalconstante, grupos electrógenos._________________________________________________________________AbstractA research project for condition monitoring of engine generator sets is developed as part of mainresearches at Maintenance Engineering Research Center. Sound pressure level and vibrationmeasurements over an engine generator set MAN 18 V48/60 B are made with the goal of identifythose frequencies present in both, sound pressure level and vibration spectra which could give thepossibility to use sound pressure level as a symptom parameter because of the continuous feature ofthis kind of

  3. Distinction between epigenic and hypogenic maze caves

    Science.gov (United States)

    Palmer, Arthur N.

    2011-11-01

    Certain caves formed by dissolution of bedrock have maze patterns composed of closed loops in which many intersecting fractures or pores have enlarged simultaneously. Their origin can be epigenic (by shallow circulation of meteoric groundwater) or hypogenic (by rising groundwater or production of deep-seated solutional aggressiveness). Epigenic mazes form by diffuse infiltration through a permeable insoluble caprock or by floodwater supplied by sinking streams. Most hypogenic caves involve deep sources of aggressiveness. Transverse hypogenic cave origin is a recently proposed concept in which groundwater of mainly meteoric origin rises across strata in the distal portions of large flow systems, to form mazes in soluble rock sandwiched between permeable but insoluble strata. The distinction between maze types is debated and is usually based on examination of diagnostic cave features and relation of caves to their regional setting. In this paper, the principles of mass transfer are applied to clarify the limits of each model, to show how cave origin is related to groundwater discharge, dissolution rate, and time. The results show that diffuse infiltration and floodwater can each form maze caves at geologically feasible rates (typically within 500 ka). Transverse hypogenic mazes in limestone, to enlarge significantly within 1 Ma, require an unusually high permeability of the non-carbonate beds (generally ≥ 10-4 cm/s), large discharge, and calcite saturation no greater than 90%, which is rare in deep diffuse flow in sedimentary rocks. Deep sources of aggressiveness are usually required. The origin of caves by transverse hypogenic flow is much more favorable in evaporite rocks than in carbonate rocks.

  4. Two distinct origins for Archean greenstone belts

    Science.gov (United States)

    Smithies, R. Hugh; Ivanic, Tim J.; Lowrey, Jack R.; Morris, Paul A.; Barnes, Stephen J.; Wyche, Stephen; Lu, Yong-Jun

    2018-04-01

    Applying the Th/Yb-Nb/Yb plot of Pearce (2008) to the well-studied Archean greenstone sequences of Western Australia shows that individual volcanic sequences evolved through one of two distinct processes reflecting different modes of crust-mantle interaction. In the Yilgarn Craton, the volcanic stratigraphy of the 2.99-2.71 Ga Youanmi Terrane mainly evolved through processes leading to Th/Yb-Nb/Yb trends with a narrow range of Th/Nb ('constant-Th/Nb' greenstones). In contrast, the 2.71-2.66 Ga volcanic stratigraphy of the Eastern Goldfields Superterrane evolved through processes leading to Th/Yb-Nb/Yb trends showing a continuous range in Th/Nb ('variable-Th/Nb' greenstones). Greenstone sequences of the Pilbara Craton show a similar evolution, with constant-Th/Nb greenstone evolution between 3.13 and 2.95 Ga and variable-Th/Nb greenstone evolution between 3.49 and 3.23 Ga and between 2.77 and 2.68 Ga. The variable-Th/Nb trends dominate greenstone sequences in Australia and worldwide, and are temporally associated with peaks in granite magmatism, which promoted crustal preservation. The increasing Th/Nb in basalts correlates with decreasing εNd, reflecting variable amounts of crustal assimilation during emplacement of mantle-derived magmas. These greenstones are typically accompanied in the early stages by komatiite, and can probably be linked to mantle plume activity. Thus, regions such as the Eastern Goldfields Superterrane simply developed as plume-related rifts over existing granite-greenstone crust - in this case the Youanmi Terrane. Their Th/Nb trends are difficult to reconcile with modern-style subduction processes. The constant-Th/Nb trends may reflect derivation from a mantle source already with a high and constant Th/Nb ratio. This, and a lithological association including boninite-like lavas, basalts, and calc-alkaline andesites, all within a narrow Th/Nb range, resembles compositions typical of modern-style subduction settings. These greenstones are very

  5. Considerations and Algorithms for Compression of Sets

    DEFF Research Database (Denmark)

    Larsson, Jesper

    We consider compression of unordered sets of distinct elements. After a discus- sion of the general problem, we focus on compressing sets of fixed-length bitstrings in the presence of statistical information. We survey techniques from previous work, suggesting some adjustments, and propose a novel...... compression algorithm that allows transparent incorporation of various estimates for probability distribution. Our experimental results allow the conclusion that set compression can benefit from incorporat- ing statistics, using our method or variants of previously known techniques....

  6. Discovery-based protein expression profiling identifies distinct subgroups and pathways in leiomyosarcomas

    DEFF Research Database (Denmark)

    Kirik, Ufuk; Hansson, Karin; Krogh, Morten

    2014-01-01

    UNLABELLED: Soft tissue sarcomas (STS) are malignant tumors of mesenchymal origin. A substantial portion of these tumors exhibits complex karyotypes and lack characterized chromosomal aberrations. Owing to such properties, both histopathologic and molecular classification of these tumors has been...

  7. PUBLIC-PRIVATE DISTINCTIONS AND STRATEGIC MANAGEMENT

    Directory of Open Access Journals (Sweden)

    Ioan NICOLAE

    2007-01-01

    Full Text Available Public organizations are no longer synonymous with governmental agencies but include many for-profit service organizations as well as the third sector, which is made up of the private NPOs. Such diverse organizations. meet the publicness criterion to the extent that they cannot ignore publicness when dealing with development of strategy. Competitive models of strategic management have little use in organizations with significant degrees of publicness. Instead, a strategy should be sought which enhances cooperation and collaboration. Strategic management in public settings must identify the beliefs and demands of key stakeholders and deal with elaborate fictions held by these individuals to premise development and guide implementation. Strategic managers must carefully collaborate with their oversight body as they fashion a strategy.

  8. New Maximal Two-distance Sets

    DEFF Research Database (Denmark)

    Lisonek, Petr

    1996-01-01

    A two-distance set in E^d is a point set X inthe d-dimensional Euclidean spacesuch that the distances between distinct points in Xassume only two different non-zero values. Based on results from classical distance geometry, we developan algorithm to classify, for a given dimension, all maximal...... (largest possible)two-distance sets in E^d.Using this algorithm we have completed the full classificationfor all dimensions less than or equal to 7, andwe have found one set in E^8 whosemaximality follows from Blokhuis' upper bound on sizes of s-distance sets.While in the dimensions less than or equal to 6...

  9. Distinct genetic alterations in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Hassan Ashktorab

    Full Text Available BACKGROUND: Colon cancer (CRC development often includes chromosomal instability (CIN leading to amplifications and deletions of large DNA segments. Epidemiological, clinical, and cytogenetic studies showed that there are considerable differences between CRC tumors from African Americans (AAs and Caucasian patients. In this study, we determined genomic copy number aberrations in sporadic CRC tumors from AAs, in order to investigate possible explanations for the observed disparities. METHODOLOGY/PRINCIPAL FINDINGS: We applied genome-wide array comparative genome hybridization (aCGH using a 105k chip to identify copy number aberrations in samples from 15 AAs. In addition, we did a population comparative analysis with aCGH data in Caucasians as well as with a widely publicized list of colon cancer genes (CAN genes. There was an average of 20 aberrations per patient with more amplifications than deletions. Analysis of DNA copy number of frequently altered chromosomes revealed that deletions occurred primarily in chromosomes 4, 8 and 18. Chromosomal duplications occurred in more than 50% of cases on chromosomes 7, 8, 13, 20 and X. The CIN profile showed some differences when compared to Caucasian alterations. CONCLUSIONS/SIGNIFICANCE: Chromosome X amplification in male patients and chromosomes 4, 8 and 18 deletions were prominent aberrations in AAs. Some CAN genes were altered at high frequencies in AAs with EXOC4, EPHB6, GNAS, MLL3 and TBX22 as the most frequently deleted genes and HAPLN1, ADAM29, SMAD2 and SMAD4 as the most frequently amplified genes. The observed CIN may play a distinctive role in CRC in AAs.

  10. Municipal solid waste landfills harbor distinct microbiomes

    Science.gov (United States)

    Stamps, Blake W.; Lyles, Christopher N.; Suflita, Joseph M.; Masoner, Jason R.; Cozzarelli, Isabelle M.; Kolpin, Dana W.; Stevenson, Bradley S.

    2016-01-01

    Landfills are the final repository for most of the discarded material from human society and its “built environments.” Microorganisms subsequently degrade this discarded material in the landfill, releasing gases (largely CH4 and CO2) and a complex mixture of soluble chemical compounds in leachate. Characterization of “landfill microbiomes” and their comparison across several landfills should allow the identification of environmental or operational properties that influence the composition of these microbiomes and potentially their biodegradation capabilities. To this end, the composition of landfill microbiomes was characterized as part of an ongoing USGS national survey studying the chemical composition of leachates from 19 non-hazardous landfills across 16 states in the continental U.S. The landfills varied in parameters such as size, waste composition, management strategy, geography, and climate zone. The diversity and composition of bacterial and archaeal populations in leachate samples were characterized by 16S rRNA gene sequence analysis, and compared against a variety of physical and chemical parameters in an attempt to identify their impact on selection. Members of the Epsilonproteobacteria, Gammaproteobacteria, Clostridia, and candidate division OP3 were the most abundant. The distribution of the observed phylogenetic diversity could best be explained by a combination of variables and was correlated most strongly with the concentrations of chloride and barium, rate of evapotranspiration, age of waste, and the number of detected household chemicals. This study illustrates how leachate microbiomes are distinct from those of other natural or built environments, and sheds light on the major selective forces responsible for this microbial diversity.

  11. Municipal Solid Waste Landfills Harbor Distinct Microbiomes

    Directory of Open Access Journals (Sweden)

    Blake Warren Stamps

    2016-04-01

    Full Text Available Landfills are the final repository for most of the discarded material from human society and its built environments. Microorganisms subsequently degrade this discarded material in the landfill, releasing gases (largely CH4 and CO2 and a complex mixture of soluble chemical compounds in leachate. Characterization of landfill microbiomes and their comparison across several landfills should allow the identification of environmental or operational properties that influence the composition of these microbiomes and potentially their biodegradation capabilities. To this end, the composition of landfill microbiomes was characterized as part of an ongoing USGS national survey studying the chemical composition of leachates from 19 non-hazardous landfills across 16 states in the continental U.S. The landfills varied in parameters such as size, waste composition, management strategy, geography, and climate zone. The diversity and composition of bacterial and archaeal populations in leachate samples were characterized by 16S rRNA gene sequence analysis, and compared against a variety of physical and chemical parameters in an attempt to identify their impact on selection. Members of the Epsilonproteobacteria, Gammaproteobacteria, Clostridia, and candidate division OP3 were the most abundant. The distribution of the observed phylogenetic diversity could best be explained by a combination of variables and was correlated most strongly with the concentrations of chloride and barium, rate of evapotranspiration, age of waste, and the number of detected household chemicals. This study illustrates how leachate microbiomes are distinct from those of other natural or built environments, and sheds light on the major selective forces responsible for this microbial diversity.

  12. Distinct Evening Fatigue Profiles in Oncology Outpatients Receiving Chemotherapy

    Science.gov (United States)

    Wright, Fay; Cooper, Bruce A.; Conley, Yvette P.; Hammer, Marilyn J.; Chen, Lee-May; Paul, Steven M.; Levine, Jon D.; Miaskowski, Christine; Kober, Kord M.

    2018-01-01

    Background Fatigue is the most common and debilitating symptom experienced by oncology patients during chemotherapy (CTX). Fatigue severity demonstrates a large amount of inter-individual and diurnal variability. Purpose Study purposes were to evaluate for subgroups of patients with distinct evening fatigue profiles and evaluate how these subgroups differed on demographic, clinical, and symptom characteristics. Methods Outpatients with breast, gastrointestinal, gynecological, or lung cancer (n=1332) completed questionnaires six times over two cycles of CTX. Lee Fatigue Scale (LFS) evaluated evening fatigue severity. Latent profile analysis was used to identify distinct evening fatigue profiles. Results Four distinct evening fatigue classes (i.e., Low (14.0%), Moderate (17.2%), High (36.0%), Very High (32.8%)) were identified. Compared to the Low class, patients in the Very High evening fatigue class were: younger, female, had childcare responsibilities, had more years of education, had a lower functional status, had a higher comorbidity burden, and were diagnosed with breast cancer. Patients in the Very High class reported higher levels of depressive symptoms, sleep disturbance, and evening fatigue at enrollment. Conclusions Findings provide new insights into modifiable risk factors for higher levels of evening fatigue. Clinicians can use this information to identify higher risk patients and plan appropriate interventions. PMID:29725554

  13. Searching for biogeochemical hot spots in three dimensions: soil C and N cycling in hydropedologic settings in a northern hardwood forest

    Science.gov (United States)

    J.L. Morse; S.F. Werner; C.P. Gillin; C.L. Goodale; S.W. Bailey; K.J. McGuire; P.M. Groffman

    2014-01-01

    Understanding and predicting the extent, location, and function of biogeochemical hot spots at the watershed scale is a frontier in environmental science. We applied a hydropedologic approach to identify (1) biogeochemical differences among morphologically distinct hydropedologic settings and (2) hot spots of microbial carbon (C) and nitrogen (N) cycling activity in a...

  14. Translational analysis of mouse and human placental protein and mRNA reveals distinct molecular pathologies in human preeclampsia.

    Science.gov (United States)

    Cox, Brian; Sharma, Parveen; Evangelou, Andreas I; Whiteley, Kathie; Ignatchenko, Vladimir; Ignatchenko, Alex; Baczyk, Dora; Czikk, Marie; Kingdom, John; Rossant, Janet; Gramolini, Anthony O; Adamson, S Lee; Kislinger, Thomas

    2011-12-01

    Preeclampsia (PE) adversely impacts ~5% of pregnancies. Despite extensive research, no consistent biomarkers or cures have emerged, suggesting that different molecular mechanisms may cause clinically similar disease. To address this, we undertook a proteomics study with three main goals: (1) to identify a panel of cell surface markers that distinguish the trophoblast and endothelial cells of the placenta in the mouse; (2) to translate this marker set to human via the Human Protein Atlas database; and (3) to utilize the validated human trophoblast markers to identify subgroups of human preeclampsia. To achieve these goals, plasma membrane proteins at the blood tissue interfaces were extracted from placentas using intravascular silica-bead perfusion, and then identified using shotgun proteomics. We identified 1181 plasma membrane proteins, of which 171 were enriched at the maternal blood-trophoblast interface and 192 at the fetal endothelial interface with a 70% conservation of expression in humans. Three distinct molecular subgroups of human preeclampsia were identified in existing human microarray data by using expression patterns of trophoblast-enriched proteins. Analysis of all misexpressed genes revealed divergent dysfunctions including angiogenesis (subgroup 1), MAPK signaling (subgroup 2), and hormone biosynthesis and metabolism (subgroup 3). Subgroup 2 lacked expected changes in known preeclampsia markers (sFLT1, sENG) and uniquely overexpressed GNA12. In an independent set of 40 banked placental specimens, GNA12 was overexpressed during preeclampsia when co-incident with chronic hypertension. In the current study we used a novel translational analysis to integrate mouse and human trophoblast protein expression with human microarray data. This strategy identified distinct molecular pathologies in human preeclampsia. We conclude that clinically similar preeclampsia patients exhibit divergent placental gene expression profiles thus implicating divergent

  15. Validity of Sensory Systems as Distinct Constructs

    OpenAIRE

    Su, Chia-Ting; Parham, L. Diane

    2014-01-01

    Confirmatory factor analysis testing whether sensory questionnaire items represented distinct sensory system constructs found, using data from two age groups, that such constructs can be measured validly using questionnaire data.

  16. Visual distinctiveness can enhance recency effects.

    Science.gov (United States)

    Bornstein, B H; Neely, C B; LeCompte, D C

    1995-05-01

    Experimental efforts to meliorate the modality effect have included attempts to make the visual stimulus more distinctive. McDowd and Madigan (1991) failed to find an enhanced recency effect in serial recall when the last item was made more distinct in terms of its color. In an attempt to extend this finding, three experiments were conducted in which visual distinctiveness was manipulated in a different manner, by combining the dimensions of physical size and coloration (i.e., whether the stimuli were solid or outlined in relief). Contrary to previous findings, recency was enhanced when the size and coloration of the last item differed from the other items in the list, regardless of whether the "distinctive" item was larger or smaller than the remaining items. The findings are considered in light of other research that has failed to obtain a similar enhanced recency effect, and their implications for current theories of the modality effect are discussed.

  17. Two distinct classes of QTL determine rust resistance in sorghum.

    Science.gov (United States)

    Wang, Xuemin; Mace, Emma; Hunt, Colleen; Cruickshank, Alan; Henzell, Robert; Parkes, Heidi; Jordan, David

    2014-12-31

    Agriculture is facing enormous challenges to feed a growing population in the face of rapidly evolving pests and pathogens. The rusts, in particular, are a major pathogen of cereal crops with the potential to cause large reductions in yield. Improving stable disease resistance is an on-going major and challenging focus for many plant breeding programs, due to the rapidly evolving nature of the pathogen. Sorghum is a major summer cereal crop that is also a host for a rust pathogen Puccinia purpurea, which occurs in almost all sorghum growing areas of the world, causing direct and indirect yield losses in sorghum worldwide, however knowledge about its genetic control is still limited. In order to further investigate this issue, QTL and association mapping methods were implemented to study rust resistance in three bi-parental populations and an association mapping set of elite breeding lines in different environments. In total, 64 significant or highly significant QTL and 21 suggestive rust resistance QTL were identified representing 55 unique genomic regions. Comparisons across populations within the current study and with rust QTL identified previously in both sorghum and maize revealed a high degree of correspondence in QTL location. Negative phenotypic correlations were observed between rust, maturity and height, indicating a trend for both early maturing and shorter genotypes to be more susceptible to rust. The significant amount of QTL co-location across traits, in addition to the consistency in the direction of QTL allele effects, has provided evidence to support pleiotropic QTL action across rust, height, maturity and stay-green, supporting the role of carbon stress in susceptibility to rust. Classical rust resistance QTL regions that did not co-locate with height, maturity or stay-green QTL were found to be significantly enriched for the defence-related NBS-encoding gene family, in contrast to the lack of defence-related gene enrichment in multi-trait effect

  18. A microarray analysis of two distinct lymphatic endothelial cell populations

    Directory of Open Access Journals (Sweden)

    Bernhard Schweighofer

    2015-06-01

    Full Text Available We have recently identified lymphatic endothelial cells (LECs to form two morphologically different populations, exhibiting significantly different surface protein expression levels of podoplanin, a major surface marker for this cell type. In vitro shockwave treatment (IVSWT of LECs resulted in enrichment of the podoplaninhigh cell population and was accompanied by markedly increased cell proliferation, as well as 2D and 3D migration. Gene expression profiles of these distinct populations were established using Affymetrix microarray analyses. Here we provide additional details about our dataset (NCBI GEO accession number GSE62510 and describe how we analyzed the data to identify differently expressed genes in these two LEC populations.

  19. A 6-gene signature identifies four molecular subgroups of neuroblastoma

    Science.gov (United States)

    2011-01-01

    Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB); Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA) and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK) was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples). Four distinct clusters were identified by Principal Components Analysis (PCA) in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples) using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p INSS stage 4 and/or dead of disease, p < 0.05, Fisher's exact test). Conclusions Based on expression profiling we have identified four molecular subgroups of neuroblastoma, which can be distinguished by a 6-gene signature. The fourth subgroup has not been described elsewhere, and efforts are currently made to further investigate this group's specific characteristics. PMID:21492432

  20. A 6-gene signature identifies four molecular subgroups of neuroblastoma

    Directory of Open Access Journals (Sweden)

    Kogner Per

    2011-04-01

    Full Text Available Abstract Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB; Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples. Four distinct clusters were identified by Principal Components Analysis (PCA in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p ALK, BIRC5, and PHOX2B, and was significantly associated with higher tumour stage, poor outcome and poor survival compared to the Type 1-corresponding favourable group (INSS stage 4 and/or dead of disease, p Conclusions Based on expression profiling we have identified four molecular subgroups of neuroblastoma, which can be distinguished by a 6-gene signature. The fourth subgroup has not been described elsewhere, and efforts are currently made to further investigate this group's specific characteristics.

  1. An Adult Developmental Approach to Perceived Facial Attractiveness and Distinctiveness

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    Natalie C. Ebner

    2018-05-01

    Full Text Available Attractiveness and distinctiveness constitute facial features with high biological and social relevance. Bringing a developmental perspective to research on social-cognitive face perception, we used a large set of faces taken from the FACES Lifespan Database to examine effects of face and perceiver characteristics on subjective evaluations of attractiveness and distinctiveness in young (20–31 years, middle-aged (44–55 years, and older (70–81 years men and women. We report novel findings supporting variations by face and perceiver age, in interaction with gender and emotion: although older and middle-aged compared to young perceivers generally rated faces of all ages as more attractive, young perceivers gave relatively higher attractiveness ratings to young compared to middle-aged and older faces. Controlling for variations in attractiveness, older compared to young faces were viewed as more distinctive by young and middle-aged perceivers. Age affected attractiveness more negatively for female than male faces. Furthermore, happy faces were rated as most attractive, while disgusted faces were rated as least attractive, particularly so by middle-aged and older perceivers and for young and female faces. Perceivers largely agreed on distinctiveness ratings for neutral and happy emotions, but older and middle-aged compared to young perceivers rated faces displaying negative emotions as more distinctive. These findings underscore the importance of a lifespan perspective on perception of facial characteristics and suggest possible effects of age on goal-directed perception, social motivation, and in-group bias. This publication makes available picture-specific normative data for experimental stimulus selection.

  2. An overexpression screen of Toxoplasma gondii Rab-GTPases reveals distinct transport routes to the micronemes.

    Directory of Open Access Journals (Sweden)

    Katrin Kremer

    2013-03-01

    Full Text Available The basic organisation of the endomembrane system is conserved in all eukaryotes and comparative genome analyses provides compelling evidence that the endomembrane system of the last common eukaryotic ancestor (LCEA is complex with many genes required for regulated traffic being present. Although apicomplexan parasites, causative agents of severe human and animal diseases, appear to have only a basic set of trafficking factors such as Rab-GTPases, they evolved unique secretory organelles (micronemes, rhoptries and dense granules that are sequentially secreted during invasion of the host cell. In order to define the secretory pathway of apicomplexans, we performed an overexpression screen of Rabs in Toxoplasma gondii and identified Rab5A and Rab5C as important regulators of traffic to micronemes and rhoptries. Intriguingly, we found that not all microneme proteins traffic depends on functional Rab5A and Rab5C, indicating the existence of redundant microneme targeting pathways. Using two-colour super-resolution stimulated emission depletion (STED we verified distinct localisations of independent microneme proteins and demonstrate that micronemal organelles are organised in distinct subsets or subcompartments. Our results suggest that apicomplexan parasites modify classical regulators of the endocytic system to carryout essential parasite-specific roles in the biogenesis of their unique secretory organelles.

  3. Children and Young People-Mental Health Safety Assessment Tool (CYP-MH SAT) study: Protocol for the development and psychometric evaluation of an assessment tool to identify immediate risk of self-harm and suicide in children and young people (10–19 years) in acute paediatric hospital settings

    Science.gov (United States)

    Walker, Gemma M; Carter, Tim; Aubeeluck, Aimee; Witchell, Miranda; Coad, Jane

    2018-01-01

    Introduction Currently, no standardised, evidence-based assessment tool for assessing immediate self-harm and suicide in acute paediatric inpatient settings exists. Aim The aim of this study is to develop and test the psychometric properties of an assessment tool that identifies immediate risk of self-harm and suicide in children and young people (10–19 years) in acute paediatric hospital settings. Methods and analysis Development phase: This phase involved a scoping review of the literature to identify and extract items from previously published suicide and self-harm risk assessment scales. Using a modified electronic Delphi approach, these items will then be rated according to their relevance for assessment of immediate suicide or self-harm risk by expert professionals. Inclusion of items will be determined by 65%–70% consensus between raters. Subsequently, a panel of expert members will convene to determine the face validity, appropriate phrasing, item order and response format for the finalised items. Psychometric testing phase: The finalised items will be tested for validity and reliability through a multicentre, psychometric evaluation. Psychometric testing will be undertaken to determine the following: internal consistency, inter-rater reliability, convergent, divergent validity and concurrent validity. Ethics and dissemination Ethical approval was provided by the National Health Service East Midlands—Derby Research Ethics Committee (17/EM/0347) and full governance clearance received by the Health Research Authority and local participating sites. Findings from this study will be disseminated to professionals and the public via peer-reviewed journal publications, popular social media and conference presentations. PMID:29654046

  4. Distinct Neural Substrates for Maintaining Locations and Spatial Relations in Working Memory

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    Kara J Blacker

    2016-11-01

    Full Text Available Previous work has demonstrated a distinction between maintenance of two types of spatial information in working memory (WM: spatial locations and spatial relations. While a body of work has investigated the neural mechanisms of sensory-based information like spatial locations, little is known about how spatial relations are maintained in WM. In two experiments, we used fMRI to investigate the involvement of early visual cortex in the maintenance of spatial relations in WM. In both experiments, we found less quadrant-specific BOLD activity in visual cortex when a single spatial relation, compared to a single spatial location, was held in WM. Also across both experiments, we found a consistent set of brain regions that were differentially activated during maintenance of locations versus relations. Maintaining a location, compared to a relation, was associated with greater activity in typical spatial WM regions like posterior parietal cortex and prefrontal regions. Whereas maintaining a relation, compared to a location, was associated with greater activity in the parahippocampal gyrus and precuneus/retrosplenial cortex. Further, in Experiment 2 we manipulated WM load and included trials where participants had to maintain three spatial locations or relations. Under this high load condition, the regions sensitive to locations versus relations were somewhat different than under low load. We also identified regions that were sensitive to load specifically for location or relation maintenance, as well as overlapping regions sensitive to load more generally. These results suggest that the neural substrates underlying WM maintenance of spatial locations and relations are distinct from one another and that the neural representations of these distinct types of spatial information change with load.

  5. Identifying Patient Attitudinal Clusters Associated with Asthma Control: The European REALISE Survey.

    Science.gov (United States)

    van der Molen, Thys; Fletcher, Monica; Price, David

    Asthma is a highly heterogeneous disease that can be classified into different clinical phenotypes, and treatment may be tailored accordingly. However, factors beyond purely clinical traits, such as patient attitudes and behaviors, can also have a marked impact on treatment outcomes. The objective of this study was to further analyze data from the REcognise Asthma and LInk to Symptoms and Experience (REALISE) Europe survey, to identify distinct patient groups sharing common attitudes toward asthma and its management. Factor analysis of respondent data (N = 7,930) from the REALISE Europe survey consolidated the 34 attitudinal variables provided by the study population into a set of 8 summary factors. Cluster analyses were used to identify patient clusters that showed similar attitudes and behaviors toward each of the 8 summary factors. Five distinct patient clusters were identified and named according to the key characteristics comprising that cluster: "Confident and self-managing," "Confident and accepting of their asthma," "Confident but dependent on others," "Concerned but confident in their health care professional (HCP)," and "Not confident in themselves or their HCP." Clusters showed clear variability in attributes such as degree of confidence in managing their asthma, use of reliever and preventer medication, and level of asthma control. The 5 patient clusters identified in this analysis displayed distinctly different personal attitudes that would require different approaches in the consultation room certainly for asthma but probably also for other chronic diseases. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Distinctiveness of Saudi Arabian EFL Learners

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    Manssour Habbash

    2016-04-01

    Full Text Available In view of the increasing concern among English language teachers dealing with students from Saudi Arabia, as it manifests in TESOL community discussions, about the uniqueness of Saudi Arabian EFL learners, this paper attempts to document the outcome of a study of their distinctiveness from the perspective of expatriate teachers working for PYPs (Preparatory Year Programs in Saudi Arabia. This study examines the distinctiveness with regard to the learning attitudes of Saudi students that are often cultivated by the culture and academic environment in their homeland. Employing an emic approach for collecting the required data an analysis was carried out in light of the other studies on ‘education’ in Saudi Arabia that have particular reference to the factors that can positively influence student motivation, student success and the academic environment. The findings were used in constructing the rationale behind such distinctiveness. Assuming that the outcome of the discussion on the findings of this exploration can be helpful for teachers in adapting their teaching methodology and improving their teacher efficacy in dealing with students both from the kingdom and in the kingdom, some recommendations are made. Keywords: China Distinctiveness, Saudi Arabian University context, Expatriate teachers’ perspective, Distinctiveness Theory

  7. Healthcare priority setting in Kenya

    DEFF Research Database (Denmark)

    Bukachi, Salome A.; Onyango-Ouma, Washington; Siso, Jared Maaka

    2014-01-01

    In resource-poor settings, the accountability for reasonableness (A4R) has been identified as an important advance in priority setting that helps to operationalize fair priority setting in specific contexts. The four conditions of A4R are backed by theory, not evidence, that conformance with them...... improves the priority setting decisions. This paper describes the healthcare priority setting processes in Malindi district, Kenya, prior to the implementation of A4R in 2008 and evaluates the process for its conformance with the conditions for A4R. In-depth interviews and focus group discussions with key...... players in the Malindi district health system and a review of key policy documents and national guidelines show that the priority setting process in the district relies heavily on guidelines from the national level, making it more of a vertical, top-down orientation. Multilateral and donor agencies...

  8. A distinct bacterial dysbiosis associated skin inflammation in ovine footrot

    Science.gov (United States)

    Maboni, Grazieli; Blanchard, Adam; Frosth, Sara; Stewart, Ceri; Emes, Richard; Tötemeyer, Sabine

    2017-03-01

    Ovine footrot is a highly prevalent bacterial disease caused by Dichelobacter nodosus and characterised by the separation of the hoof horn from the underlying skin. The role of innate immune molecules and other bacterial communities in the development of footrot lesions remains unclear. This study shows a significant association between the high expression of IL1β and high D. nodosus load in footrot samples. Investigation of the microbial population identified distinct bacterial populations in the different disease stages and also depending on the level of inflammation. Treponema (34%), Mycoplasma (29%) and Porphyromonas (15%) were the most abundant genera associated with high levels of inflammation in footrot. In contrast, Acinetobacter (25%), Corynebacteria (17%) and Flavobacterium (17%) were the most abundant genera associated with high levels of inflammation in healthy feet. This demonstrates for the first time there is a distinct microbial community associated with footrot and high cytokine expression.

  9. Pseudomonas aeruginosa diversity in distinct paediatric patient groups

    DEFF Research Database (Denmark)

    Tramper-Stranders, G.A.; Ent, C.K. van der; Wolfs, T.F.

    2008-01-01

    the other groups. A group of clonal isolates was observed among patients from the CF-chronic and CF-1 groups. These or different clonal isolates were not encountered among the three other patient groups. No characteristic resistance pattern could be identified among isolates from the distinct patient groups......Pseudomonas aeruginosa is a pathogen that often infects patients who are either immunocompromised or have local defects in host defences. It is known that cystic fibrosis (CF) patients are sometimes infected with certain clonal isolates. It is not clear whether these clonal isolates also infect non......-CF patients and whether clonality of isolates occurs in other patient groups. The aim of this study was to investigate P. aeruginosa diversity and the occurrence of clones within five distinct paediatric patient groups susceptible to P. aeruginosa infection. P. aeruginosa isolates were cultured from 157...

  10. The True Self: A Psychological Concept Distinct From the Self.

    Science.gov (United States)

    Strohminger, Nina; Knobe, Joshua; Newman, George

    2017-07-01

    A long tradition of psychological research has explored the distinction between characteristics that are part of the self and those that lie outside of it. Recently, a surge of research has begun examining a further distinction. Even among characteristics that are internal to the self, people pick out a subset as belonging to the true self. These factors are judged as making people who they really are, deep down. In this paper, we introduce the concept of the true self and identify features that distinguish people's understanding of the true self from their understanding of the self more generally. In particular, we consider recent findings that the true self is perceived as positive and moral and that this tendency is actor-observer invariant and cross-culturally stable. We then explore possible explanations for these findings and discuss their implications for a variety of issues in psychology.

  11. On Hobbes’s distinction of accidents

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    Lupoli Agostino

    2012-06-01

    Full Text Available An interpolation introduced by K. Schuhmann in his critical edition of "De corpore" (chap. VI, § 13 diametrically overturns the meaning of Hobbes’s doctrine of distinction of accidents in comparison with all previous editions. The article focuses on the complexity of this crucial juncture in "De corpore" argument on which depends the interpretation of Hobbes’s whole conception of science. It discusses the reasons pro and contra Schuhmann’s interpolation and concludes against it, because it is not compatible with the rationale underlying the complex architecture of "De corpore", which involves a symmetry between the ‘logical’ distinction of accidents and the ‘metaphysical’ distinction of phantasms.

  12. Intergroup Leadership Across Distinct Subgroups and Identities.

    Science.gov (United States)

    Rast, David E; Hogg, Michael A; van Knippenberg, Daan

    2018-03-01

    Resolving intergroup conflict is a significant and often arduous leadership challenge, yet existing theory and research rarely, if ever, discuss or examine this situation. Leaders confront a significant challenge when they provide leadership across deep divisions between distinct subgroups defined by self-contained identities-The challenge is to avoid provoking subgroup identity distinctiveness threat. Drawing on intergroup leadership theory, three studies were conducted to test the core hypothesis that, where identity threat exists, leaders promoting an intergroup relational identity will be better evaluated and are more effective than leaders promoting a collective identity; in the absence of threat, leaders promoting a collective identity will prevail. Studies 1 and 2 ( N = 170; N = 120) supported this general proposition. Study 3 ( N = 136) extended these findings, showing that leaders promoting an intergroup relational identity, but not a collective identity, improved intergroup attitudes when participants experienced an identity distinctiveness threat.

  13. Distinct sets of locomotor modules control the speed and modes of human locomotion

    Science.gov (United States)

    Yokoyama, Hikaru; Ogawa, Tetsuya; Kawashima, Noritaka; Shinya, Masahiro; Nakazawa, Kimitaka

    2016-01-01

    Although recent vertebrate studies have revealed that different spinal networks are recruited in locomotor mode- and speed-dependent manners, it is unknown whether humans share similar neural mechanisms. Here, we tested whether speed- and mode-dependence in the recruitment of human locomotor networks exists or not by statistically extracting locomotor networks. From electromyographic activity during walking and running over a wide speed range, locomotor modules generating basic patterns of muscle activities were extracted using non-negative matrix factorization. The results showed that the number of modules changed depending on the modes and speeds. Different combinations of modules were extracted during walking and running, and at different speeds even during the same locomotor mode. These results strongly suggest that, in humans, different spinal locomotor networks are recruited while walking and running, and even in the same locomotor mode different networks are probably recruited at different speeds. PMID:27805015

  14. Fermionic bound states in distinct kinklike backgrounds

    Energy Technology Data Exchange (ETDEWEB)

    Bazeia, D. [Universidade Federal da Paraiba, Departamento de Fisica, Joao Pessoa, Paraiba (Brazil); Mohammadi, A. [Universidade Federal de Campina Grande, Departamento de Fisica, Caixa Postal 10071, Campina Grande, Paraiba (Brazil)

    2017-04-15

    This work deals with fermions in the background of distinct localized structures in the two-dimensional spacetime. Although the structures have a similar topological character, which is responsible for the appearance of fractionally charged excitations, we want to investigate how the geometric deformations that appear in the localized structures contribute to the change in the physical properties of the fermionic bound states. We investigate the two-kink and compact kinklike backgrounds, and we consider two distinct boson-fermion interactions, one motivated by supersymmetry and the other described by the standard Yukawa coupling. (orig.)

  15. Identifying flares in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Bykerk, Vivian P; Bingham, Clifton O; Choy, Ernest H

    2016-01-01

    to flare, with escalation planned in 61%. CONCLUSIONS: Flares are common in rheumatoid arthritis (RA) and are often preceded by treatment reductions. Patient/MD/DAS agreement of flare status is highest in patients worsening from R/LDA. OMERACT RA flare questions can discriminate between patients with...... Set. METHODS: Candidate flare questions and legacy measures were administered at consecutive visits to Canadian Early Arthritis Cohort (CATCH) patients between November 2011 and November 2014. The American College of Rheumatology (ACR) core set indicators were recorded. Concordance to identify flares...

  16. Organism versus mechanism: Losing our grip on the distinction

    Directory of Open Access Journals (Sweden)

    Henk Reitsema

    2013-11-01

    Full Text Available The distinction between organism and mechanism is often subtle or unclear and yet can prove to be fundamental to our understanding of the world. It has been tempting for many thinkers to seek to ‘understand’ all of reality through the lens of either the one or the other of these concepts rather than by giving both a place. This article sets out to argue that there is a substantial loss of understanding when either of these metaphors is absolutised to explain all causal processes and patterns in reality. Clarifying the distinction between the two may provide one more tool to grasp what is reductionist in many of the perspectives that have come to dominate public life and science today. This contention is tested on the quest for the design of self-replicating systems (i.e. synthetic organisms in the nanotech industry. It is common that the concepts of organic functioning and mechanism are used imprecisely and in an overlapping way. This is also true of much scientific debate, especially in the fields of biology, micro-biology and nano-science. This imprecise use signals a reductionist tendency both in the way that the organic is perceived and in terms of the distinctive nature of mechanisms.

  17. UpSet: Visualization of Intersecting Sets

    Science.gov (United States)

    Lex, Alexander; Gehlenborg, Nils; Strobelt, Hendrik; Vuillemot, Romain; Pfister, Hanspeter

    2016-01-01

    Understanding relationships between sets is an important analysis task that has received widespread attention in the visualization community. The major challenge in this context is the combinatorial explosion of the number of set intersections if the number of sets exceeds a trivial threshold. In this paper we introduce UpSet, a novel visualization technique for the quantitative analysis of sets, their intersections, and aggregates of intersections. UpSet is focused on creating task-driven aggregates, communicating the size and properties of aggregates and intersections, and a duality between the visualization of the elements in a dataset and their set membership. UpSet visualizes set intersections in a matrix layout and introduces aggregates based on groupings and queries. The matrix layout enables the effective representation of associated data, such as the number of elements in the aggregates and intersections, as well as additional summary statistics derived from subset or element attributes. Sorting according to various measures enables a task-driven analysis of relevant intersections and aggregates. The elements represented in the sets and their associated attributes are visualized in a separate view. Queries based on containment in specific intersections, aggregates or driven by attribute filters are propagated between both views. We also introduce several advanced visual encodings and interaction methods to overcome the problems of varying scales and to address scalability. UpSet is web-based and open source. We demonstrate its general utility in multiple use cases from various domains. PMID:26356912

  18. Distinctive characters of Nostoc genomes in cyanolichens.

    Science.gov (United States)

    Gagunashvili, Andrey N; Andrésson, Ólafur S

    2018-06-05

    Cyanobacteria of the genus Nostoc are capable of forming symbioses with a wide range of organism, including a diverse assemblage of cyanolichens. Only certain lineages of Nostoc appear to be able to form a close, stable symbiosis, raising the question whether symbiotic competence is determined by specific sets of genes and functionalities. We present the complete genome sequencing, annotation and analysis of two lichen Nostoc strains. Comparison with other Nostoc genomes allowed identification of genes potentially involved in symbioses with a broad range of partners including lichen mycobionts. The presence of additional genes necessary for symbiotic competence is likely reflected in larger genome sizes of symbiotic Nostoc strains. Some of the identified genes are presumably involved in the initial recognition and establishment of the symbiotic association, while others may confer advantage to cyanobionts during cohabitation with a mycobiont in the lichen symbiosis. Our study presents the first genome sequencing and genome-scale analysis of lichen-associated Nostoc strains. These data provide insight into the molecular nature of the cyanolichen symbiosis and pinpoint candidate genes for further studies aimed at deciphering the genetic mechanisms behind the symbiotic competence of Nostoc. Since many phylogenetic studies have shown that Nostoc is a polyphyletic group that includes several lineages, this work also provides an improved molecular basis for demarcation of a Nostoc clade with symbiotic competence.

  19. Distinct types of glial cells populate the Drosophila antenna

    Directory of Open Access Journals (Sweden)

    Jhaveri Dhanisha

    2005-11-01

    Full Text Available Abstract Background The development of nervous systems involves reciprocal interactions between neurons and glia. In the Drosophila olfactory system, peripheral glial cells arise from sensory lineages specified by the basic helix-loop-helix transcription factor, Atonal. These glia wrap around the developing olfactory axons early during development and pattern the three distinct fascicles as they exit the antenna. In the moth Manduca sexta, an additional set of central glia migrate to the base of the antennal nerve where axons sort to their glomerular targets. In this work, we have investigated whether similar types of cells exist in the Drosophila antenna. Results We have used different P(Gal4 lines to drive Green Fluorescent Protein (GFP in distinct populations of cells within the Drosophila antenna. Mz317::GFP, a marker for cell body and perineural glia, labels the majority of peripheral glia. An additional ~30 glial cells detected by GH146::GFP do not derive from any of the sensory lineages and appear to migrate into the antenna from the brain. Their appearance in the third antennal segment is regulated by normal function of the Epidermal Growth Factor receptor and small GTPases. We denote these distinct populations of cells as Mz317-glia and GH146-glia respectively. In the adult, processes of GH146-glial cells ensheath the olfactory receptor neurons directly, while those of the Mz317-glia form a peripheral layer. Ablation of GH146-glia does not result in any significant effects on the patterning of the olfactory receptor axons. Conclusion We have demonstrated the presence of at least two distinct populations of glial cells within the Drosophila antenna. GH146-glial cells originate in the brain and migrate to the antenna along the newly formed olfactory axons. The number of cells populating the third segment of the antenna is regulated by signaling through the Epidermal Growth Factor receptor. These glia share several features of the sorting

  20. Common and distinct components in data fusion

    DEFF Research Database (Denmark)

    Smilde, Age Klaas; Mage, Ingrid; Næs, Tormod

    2016-01-01

    and understanding their relative merits. This paper provides a unifying framework for this subfield of data fusion by using rigorous arguments from linear algebra. The most frequently used methods for distinguishing common and distinct components are explained in this framework and some practical examples are given...

  1. Knowledge Affords Distinctive Processing in Memory

    Science.gov (United States)

    Hunt, R. Reed; Rawson, Katherine A.

    2011-01-01

    The effect of knowledge on memory generally is processing. However, both conceptual and empirical reasons exist to suspect that the organizational account is incomplete. Recently a revised version of that account has been proposed under the rubric of distinctiveness theory (Rawson & Van Overschelde, 2008). The goal of the experiments reported…

  2. Distinctiveness of Saudi Arabian EFL Learners

    Science.gov (United States)

    Habbash, Manssour; Idapalapati, Srinivasa Rao

    2016-01-01

    In view of the increasing concern among English language teachers dealing with students from Saudi Arabia, as it manifests in TESOL community discussions, about the uniqueness of Saudi Arabian EFL learners, this paper attempts to document the outcome of a study of their distinctiveness from the perspective of expatriate teachers working for PYPs…

  3. Suitability of public use secondary data sets to study multiple activities.

    Science.gov (United States)

    Putnam, Michelle; Morrow-Howell, Nancy; Inoue, Megumi; Greenfield, Jennifer C; Chen, Huajuan; Lee, YungSoo

    2014-10-01

    The aims of this study were to inventory activity items within and across U.S. public use data sets, to identify gaps in represented activity domains and challenges in interpreting domains, and to assess the potential for studying multiple activity engagement among older adults using existing data. We engaged in content analysis of activity measures of 5U.S. public use data sets with nationally representative samples of older adults. Data sets included the Health & Retirement Survey (HRS), Americans' Changing Lives Survey (ACL), Midlife in the United States Survey (MIDUS), the National Health Interview Survey (NHIS), and the Panel Study of Income Dynamics survey (PSID). Two waves of each data set were analyzed. We identified 13 distinct activity domains across the 5 data sets, with substantial differences in representation of those domains among the data sets, and variance in the number and type of activity measures included in each. Our findings indicate that although it is possible to study multiple activity engagement within existing data sets, fuller sets of activity measures need to be developed in order to evaluate the portfolio of activities older adults engage in and the relationship of these portfolios to health and wellness outcomes. Importantly, clearer conceptual models of activity broadly conceived are required to guide this work. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Puerto Rico and Florida manatees represent genetically distinct groups

    Science.gov (United States)

    Hunter, Margaret E.; Mignucci-Giannoni, Antonio A.; Tucker, Kimberly Pause; King, Timothy L.; Bonde, Robert K.; Gray, Brian A.; McGuire, Peter M.

    2012-01-01

    The West Indian manatee (Trichechus manatus) populations in Florida (T. m. latirostris) and Puerto Rico (T. m. manatus) are considered distinct subspecies and are listed together as endangered under the United States Endangered Species Act. Sustained management and conservation efforts for the Florida subspecies have led to the suggested reclassification of the species to a threatened or delisted status. However, the two populations are geographically distant, morphologically distinct, and habitat degradation and boat strikes continue to threaten the Puerto Rico population. Here, 15 microsatellite markers and mitochondrial control region sequences were used to determine the relatedness of the two populations and investigate the genetic diversity and phylogeographic organization of the Puerto Rico population. Highly divergent allele frequencies were identified between Florida and Puerto Rico using microsatellite (F ST = 0.16; R ST = 0.12 (P ST = 0.66; Φ ST = 0.50 (P E = 0.45; NA = 3.9), were similar, but lower than those previously identified in Florida (HE = 0.48, NA = 4.8). Within Puerto Rico, the mitochondrial genetic diversity values (π = 0.001; h = 0.49) were slightly lower than those previously reported (π = 0.002; h = 0.54) and strong phylogeographic structure was identified (F ST global = 0.82; Φ ST global = 0.78 (P population size (N = 250), and distinct threats and habitat emphasize the need for separate protections in Puerto Rico. Conservation efforts including threat mitigation, migration corridors, and protection of subpopulations could lead to improved genetic variation in the endangered Puerto Rico manatee population.

  5. Fuzzy sets, rough sets, multisets and clustering

    CERN Document Server

    Dahlbom, Anders; Narukawa, Yasuo

    2017-01-01

    This book is dedicated to Prof. Sadaaki Miyamoto and presents cutting-edge papers in some of the areas in which he contributed. Bringing together contributions by leading researchers in the field, it concretely addresses clustering, multisets, rough sets and fuzzy sets, as well as their applications in areas such as decision-making. The book is divided in four parts, the first of which focuses on clustering and classification. The second part puts the spotlight on multisets, bags, fuzzy bags and other fuzzy extensions, while the third deals with rough sets. Rounding out the coverage, the last part explores fuzzy sets and decision-making.

  6. Number of perceptually distinct surface colors in natural scenes.

    Science.gov (United States)

    Marín-Franch, Iván; Foster, David H

    2010-09-30

    The ability to perceptually identify distinct surfaces in natural scenes by virtue of their color depends not only on the relative frequency of surface colors but also on the probabilistic nature of observer judgments. Previous methods of estimating the number of discriminable surface colors, whether based on theoretical color gamuts or recorded from real scenes, have taken a deterministic approach. Thus, a three-dimensional representation of the gamut of colors is divided into elementary cells or points which are spaced at one discrimination-threshold unit intervals and which are then counted. In this study, information-theoretic methods were used to take into account both differing surface-color frequencies and observer response uncertainty. Spectral radiances were calculated from 50 hyperspectral images of natural scenes and were represented in a perceptually almost uniform color space. The average number of perceptually distinct surface colors was estimated as 7.3 × 10(3), much smaller than that based on counting methods. This number is also much smaller than the number of distinct points in a scene that are, in principle, available for reliable identification under illuminant changes, suggesting that color constancy, or the lack of it, does not generally determine the limit on the use of color for surface identification.

  7. Distinct termination morphologies for vertically aligned carbon nanotube forests

    International Nuclear Information System (INIS)

    Vinten, P; Marshall, P; Lefebvre, J; Finnie, P

    2010-01-01

    Vertically aligned carbon nanotube forests, including single-walled nanotubes, are imaged optically as they grow in situ from cobalt/alumina catalyst using water-assisted acetylene chemical vapor deposition. Three distinct termination morphologies are identified and investigated optically and via scanning electron microscopy. Quantitative growth dynamics are extracted and show gradual deceleration and sudden termination of growth. The termination morphology is discussed in terms of the balance of forces within the forest. We speculate that sudden termination is a collective effect arising from an imbalance in these forces.

  8. A 6-gene signature identifies four molecular subgroups of neuroblastoma

    LENUS (Irish Health Repository)

    Abel, Frida

    2011-04-14

    Abstract Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB); Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA) and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK) was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples). Four distinct clusters were identified by Principal Components Analysis (PCA) in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples) using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p < 0.05, one-way ANOVA test). PCA clusters p1, p2, and p3 were found to correspond well to the postulated subtypes 1, 2A, and 2B, respectively. Remarkably, a fourth novel cluster was detected in all three independent data sets. This cluster comprised mainly 11q-deleted MNA-negative tumours with low expression of ALK, BIRC5, and PHOX2B, and was significantly associated with higher tumour stage, poor outcome and poor survival compared to the Type 1-corresponding favourable group (INSS stage 4 and\\/or dead of disease, p < 0.05, Fisher\\'s exact test). Conclusions Based on expression profiling we have identified four molecular subgroups of neuroblastoma, which can be distinguished by a 6-gene signature. The fourth subgroup has not been described elsewhere, and efforts are currently made to further investigate this group\\'s specific characteristics.

  9. Large scale aggregate microarray analysis reveals three distinct molecular subclasses of human preeclampsia.

    Science.gov (United States)

    Leavey, Katherine; Bainbridge, Shannon A; Cox, Brian J

    2015-01-01

    Preeclampsia (PE) is a life-threatening hypertensive pathology of pregnancy affecting 3-5% of all pregnancies. To date, PE has no cure, early detection markers, or effective treatments short of the removal of what is thought to be the causative organ, the placenta, which may necessitate a preterm delivery. Additionally, numerous small placental microarray studies attempting to identify "PE-specific" genes have yielded inconsistent results. We therefore hypothesize that preeclampsia is a multifactorial disease encompassing several pathology subclasses, and that large cohort placental gene expression analysis will reveal these groups. To address our hypothesis, we utilized known bioinformatic methods to aggregate 7 microarray data sets across multiple platforms in order to generate a large data set of 173 patient samples, including 77 with preeclampsia. Unsupervised clustering of these patient samples revealed three distinct molecular subclasses of PE. This included a "canonical" PE subclass demonstrating elevated expression of known PE markers and genes associated with poor oxygenation and increased secretion, as well as two other subclasses potentially representing a poor maternal response to pregnancy and an immunological presentation of preeclampsia. Our analysis sheds new light on the heterogeneity of PE patients, and offers up additional avenues for future investigation. Hopefully, our subclassification of preeclampsia based on molecular diversity will finally lead to the development of robust diagnostics and patient-based treatments for this disorder.

  10. Common and distinct neural mechanisms of attentional switching and response conflict.

    Science.gov (United States)

    Kim, Chobok; Johnson, Nathan F; Gold, Brian T

    2012-08-21

    The human capacities for overcoming prepotent actions and flexibly switching between tasks represent cornerstones of cognitive control. Functional neuroimaging has implicated a diverse set of brain regions contributing to each of these cognitive control processes. However, the extent to which attentional switching and response conflict draw on shared or distinct neural mechanisms remains unclear. The current study examined the neural correlates of response conflict and attentional switching using event-related functional magnetic resonance imaging (fMRI) and a fully randomized 2×2 design. We manipulated an arrow-word version of the Stroop task to measure conflict and switching in the context of a single task decision, in response to a common set of stimuli. Under these common conditions, both behavioral and imaging data showed significant main effects of conflict and switching but no interaction. However, conjunction analyses identified frontal regions involved in both switching and response conflict, including the dorsal anterior cingulate cortex (dACC) and left inferior frontal junction. In addition, connectivity analyses demonstrated task-dependent functional connectivity patterns between dACC and inferior temporal cortex for attentional switching and between dACC and posterior parietal cortex for response conflict. These results suggest that the brain makes use of shared frontal regions, but can dynamically modulate the connectivity patterns of some of those regions, to deal with attentional switching and response conflict. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. New control system: the commands of the settings equipments

    International Nuclear Information System (INIS)

    David, L.; Maugeais, C.

    1992-01-01

    The equipments allowing the setting of the GANIL beam (motors, probes, supplies...) may be operated by three distinct ways: by dial (pseudo potentiometer), by menu or by slider. These processes are described. (A.B.)

  12. Embarrassment: its distinct form and appeasement functions.

    Science.gov (United States)

    Keltner, D; Buswell, B N

    1997-11-01

    The authors address 2 questions about embarrassment. First, Is embarrassment a distinct emotion? The evidence indicates that the antecedents, experience, and display of embarrassment, and to a limited extent its autonomic physiology, are distinct from shame, guilt, and amusement and share the dynamic, temporal characteristics of emotion. Second, What are the theoretical accounts of embarrassment? Three accounts focus on the causes of embarrassment, positioning that it follows the loss of self-esteem, concern for others' evaluations, or absence of scripts to guide interactions. A fourth account focuses on the effects of the remedial actions of embarrassment, which correct preceding transgressions. A fifth account focuses on the functional parallels between embarrassment and nonhuman appeasement. The discussion focuses on unanswered questions about embarrassment.

  13. Distinctive skeletal dysplasia in Cockayne syndrome

    International Nuclear Information System (INIS)

    Silengo, M.C.; Franceschini, P.; Bianco, R.; Biagioli, M.; Pastorin, L.; Vista, N.; Baldassar, A.; Benso, L.

    1986-01-01

    Cockayne syndrom is a well-known autosomal recessive form of dwarfism with senile-like appearance. Skeletal changes such as flattening of vertebral bodies, ivory epiphyses and thickening of cranial vault, have been observed in some patients with this condition. We describe here a 5.5-year-old girl with the typical clinical signs of Cockayne syndrome and a distinctive form of bone dysplasia with major involvment of the spine. (orig.)

  14. Distinctive skeletal dysplasia in Cockayne syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Silengo, M.C.; Franceschini, P.; Bianco, R.; Biagioli, M.; Pastorin, L.; Vista, N.; Baldassar, A.; Benso, L.

    1986-03-01

    Cockayne syndrome is a well-known autosomal recessive form of dwarfism with senile-like appearance. Skeletal changes such as flattening of vertebral bodies, ivory epiphyses and thickening of cranial vault, have been observed in some patients with this condition. We describe here a 5.5-year-old girl with the typical clinical signs of Cockayne syndrome and a distinctive form of bone dysplasia with major involvement of the spine.

  15. Army nurses in wartime: distinction and pride.

    Science.gov (United States)

    Higgins, L P

    1996-08-01

    Nurses have served with distinction in wartime since Florence Nightingale went to the Crimea. Women often accompanied their husbands to battle during the Revolutionary and Civil Wars, caring for the sick and wounded. Although not officially given officer status until 1920, Army nurses served in the Spanish-American War and World War I. As officers, thousands of nurses served in subsequent wars, distinguishing themselves by their heroism, devotion to duty, and sheer tenacity of spirit.

  16. Tools to identify the men with prostate cancer most appropriate for active surveillance?

    Directory of Open Access Journals (Sweden)

    Robert H Getzenberg

    2014-02-01

    Full Text Available A great deal of effort is underway in order to identify those men with prostate cancer felicitous for active surveillance with greater precision than that afforded to us today. In the manuscript by Irshad et al. the authors evaluate a novel set of genes associated with senescence and aging as tools that can provide guidance regarding the indolent nature of an individual's prostate cancer with validation using both mRNA and protein analyses. While additional studies are required to understand the full impact of these findings, the innovative approach taken enhances our understanding of distinct phenotypes of prostate cancer.

  17. A Conceptual Model to Identify Intent to Use Chemical-Biological Weapons

    Directory of Open Access Journals (Sweden)

    Mary Zalesny

    2017-10-01

    Full Text Available This paper describes a conceptual model to identify and interrelate indicators of intent of non-state actors to use chemical or biological weapons. The model expands on earlier efforts to understand intent to use weapons of mass destruction by building upon well-researched theories of intent and behavior and focusing on a sub-set of weapons of mass destruction (WMD to account for the distinct challenges of employing different types of WMD in violent acts. The conceptual model is presented as a first, critical step in developing a computational model for assessing the potential for groups to use chemical or biological weapons.

  18. Familiar ethical issues amplified: how members of research ethics committees describe ethical distinctions between disaster and non-disaster research.

    Science.gov (United States)

    Tansey, Catherine M; Anderson, James; Boulanger, Renaud F; Eckenwiler, Lisa; Pringle, John; Schwartz, Lisa; Hunt, Matthew

    2017-06-28

    The conduct of research in settings affected by disasters such as hurricanes, floods and earthquakes is challenging, particularly when infrastructures and resources were already limited pre-disaster. However, since post-disaster research is essential to the improvement of the humanitarian response, it is important that adequate research ethics oversight be available. We aim to answer the following questions: 1) what do research ethics committee (REC) members who have reviewed research protocols to be conducted following disasters in low- and middle-income countries (LMICs) perceive as the key ethical concerns associated with disaster research?, and 2) in what ways do REC members understand these concerns to be distinct from those arising in research conducted in non-crisis situations? This qualitative study was developed using interpretative description methodology; 15 interviews were conducted with REC members. Four key ethical issues were identified as presenting distinctive considerations for disaster research to be implemented in LMICs, and were described by participants as familiar research ethics issues that were amplified in these contexts. First, REC members viewed disaster research as having strong social value due to its potential for improving disaster response, but also as requiring a higher level of justification compared to other research settings. Second, they identified vulnerability as an overarching concern for disaster research ethics, and a feature that required careful and critical appraisal when assessing protocols. They noted that research participants' vulnerabilities frequently change in the aftermath of a disaster and often in unpredictable ways. Third, they identified concerns related to promoting and maintaining safety, confidentiality and data security in insecure or austere environments. Lastly, though REC members endorsed the need and usefulness of community engagement, they noted that there are significant challenges in a disaster

  19. [Cognition-Emotion Interactions and Psychopathic Personality: Distinct Pathways to Antisocial and Violent Behavior].

    Science.gov (United States)

    Verona, Edelyn

    Researchers have long acknowledged heterogeneity among persons who exhibit antisocial and violent behaviours. The study of psychopathic personality or psychopathy can help elucidate this heterogeneity through examination of the different facets that constitute this disorder. In particular, the distinct correlates of the interpersonal-affective traits (Factor 1) and the impulsive-antisocial traits (Factor 2) of psychopathy suggest at least two possible pathways to antisocial behaviours. Building on basic studies in cognitive and affective neuroscience, we provide a focused, non-comprehensive review of work identifying the biopsychological mechanisms involved in these two pathways, with special attention to studies using event-related potential (ERP) methods. In specific, a series of studies are discussed which examined affective and cognitive processes that may distinguish offenders high on psychopathic traits from other offenders, with emphasis on alterations in emotion-cognition interactions related to each factor of psychopathy. The set of findings reviewed highlight a central conclusion: Factor 1 represents a pathway involving reduced emotional responding, exacerbated by attentional abnormalities, that make for a more deliberate and emotionally insensitive offender profile. In contrast, Factor 2 characterizes a pathway marked by emotional and behavioural dysregulation and cognitive control dysfunctions, particularly in emotional contexts. Implications for identifying etiological processes and the further understanding of antisocial and violent behaviours are discussed.

  20. Parameter setting and input reduction

    NARCIS (Netherlands)

    Evers, A.; van Kampen, N.J.|info:eu-repo/dai/nl/126439737

    2008-01-01

    The language acquisition procedure identifies certain properties of the target grammar before others. The evidence from the input is processed in a stepwise order. Section 1 equates that order and its typical effects with an order of parameter setting. The question is how the acquisition procedure

  1. HEDIS Research Identifiable Files

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Healthcare Effectiveness Data and Information Set (HEDIS) is a tool used by more than 90 percent of Americas health plans to measure performance on important...

  2. Estimating climate resilience for conservation across geophysical settings.

    Science.gov (United States)

    Anderson, Mark G; Clark, Melissa; Sheldon, Arlene Olivero

    2014-08-01

    Conservationists need methods to conserve biological diversity while allowing species and communities to rearrange in response to a changing climate. We developed and tested such a method for northeastern North America that we based on physical features associated with ecological diversity and site resilience to climate change. We comprehensively mapped 30 distinct geophysical settings based on geology and elevation. Within each geophysical setting, we identified sites that were both connected by natural cover and that had relatively more microclimates indicated by diverse topography and elevation gradients. We did this by scoring every 405 ha hexagon in the region for these two characteristics and selecting those that scored >SD 0.5 above the mean combined score for each setting. We hypothesized that these high-scoring sites had the greatest resilience to climate change, and we compared them with sites selected by The Nature Conservancy for their high-quality rare species populations and natural community occurrences. High-scoring sites captured significantly more of the biodiversity sites than expected by chance (p < 0.0001): 75% of the 414 target species, 49% of the 4592 target species locations, and 53% of the 2170 target community locations. Calcareous bedrock, coarse sand, and fine silt settings scored markedly lower for estimated resilience and had low levels of permanent land protection (average 7%). Because our method identifies-for every geophysical setting-sites that are the most likely to retain species and functions longer under a changing climate, it reveals natural strongholds for future conservation that would also capture substantial existing biodiversity and correct the bias in current secured lands. © 2014 The Authors. Conservation Biology published by Wiley Periodicals, Inc., on behalf of the Society for Conservation Biology.

  3. Data from "Crossing to safety: Dispersal, colonization and mate choice in evolutionarily distinct populations of Steller sea lions, Eumetopias jubatus."

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Data sets used to support analysis published by O'Corry-Crowe et al (2014) Crossing to safety: Dispersal, colonization and mate choice in evolutionarily distinct...

  4. Temporomandibular joint formation requires two distinct hedgehog-dependent steps.

    Science.gov (United States)

    Purcell, Patricia; Joo, Brian W; Hu, Jimmy K; Tran, Pamela V; Calicchio, Monica L; O'Connell, Daniel J; Maas, Richard L; Tabin, Clifford J

    2009-10-27

    We conducted a genetic analysis of the developing temporo-mandibular or temporomandi-bular joint (TMJ), a highly specialized synovial joint that permits movement and function of the mammalian jaw. First, we used laser capture microdissection to perform a genome-wide expression analysis of each of its developing components. The expression patterns of genes identified in this screen were examined in the TMJ and compared with those of other synovial joints, including the shoulder and the hip joints. Striking differences were noted, indicating that the TMJ forms via a distinct molecular program. Several components of the hedgehog (Hh) signaling pathway are among the genes identified in the screen, including Gli2, which is expressed specifically in the condyle and in the disk of the developing TMJ. We found that mice deficient in Gli2 display aberrant TMJ development such that the condyle loses its growth-plate-like cellular organization and no disk is formed. In addition, we used a conditional strategy to remove Smo, a positive effector of the Hh signaling pathway, from chondrocyte progenitors. This cell autonomous loss of Hh signaling allows for disk formation, but the resulting structure fails to separate from the condyle. Thus, these experiments establish that Hh signaling acts at two distinct steps in disk morphogenesis, condyle initiation, and disk-condyle separation and provide a molecular framework for future studies of the TMJ.

  5. SETS reference manual

    International Nuclear Information System (INIS)

    Worrell, R.B.

    1985-05-01

    The Set Equation Transformation System (SETS) is used to achieve the symbolic manipulation of Boolean equations. Symbolic manipulation involves changing equations from their original forms into more useful forms - particularly by applying Boolean identities. The SETS program is an interpreter which reads, interprets, and executes SETS user programs. The user writes a SETS user program specifying the processing to be achieved and submits it, along with the required data, for execution by SETS. Because of the general nature of SETS, i.e., the capability to manipulate Boolean equations regardless of their origin, the program has been used for many different kinds of analysis

  6. Thoughts on identifiers

    CERN Multimedia

    CERN. Geneva

    2005-01-01

    As business processes and information transactions have become an inextricably intertwined with the Web, the importance of assignment, registration, discovery, and maintenance of identifiers has increased. In spite of this, integrated frameworks for managing identifiers have been slow to emerge. Instead, identification systems arise (quite naturally) from immediate business needs without consideration for how they fit into larger information architectures. In addition, many legacy identifier systems further complicate the landscape, making it difficult for content managers to select and deploy identifier systems that meet both the business case and long term information management objectives. This presentation will outline a model for evaluating identifier applications and the functional requirements of the systems necessary to support them. The model is based on a layered analysis of the characteristics of identifier systems, including: * Functional characteristics * Technology * Policy * Business * Social T...

  7. Identifiability in stochastic models

    CERN Document Server

    1992-01-01

    The problem of identifiability is basic to all statistical methods and data analysis, occurring in such diverse areas as Reliability Theory, Survival Analysis, and Econometrics, where stochastic modeling is widely used. Mathematics dealing with identifiability per se is closely related to the so-called branch of ""characterization problems"" in Probability Theory. This book brings together relevant material on identifiability as it occurs in these diverse fields.

  8. A distinction of two discourses concerning wellbeing

    DEFF Research Database (Denmark)

    Wistoft, Karen; Qvortrup, Lars

    2017-01-01

    and behavioral mental health interventions, while the latter defines wellbeing in positive terms with a focus on wellbeing as the result of learning and with pedagogical interventions that only indirectly can support the individual’s learning activity. The former sees wellbeing as the result of a “wellbeing cure......The article concerns the current discourses concerning well-being with the point that it is important to make a distinction between a healthcare oriented discourse and a learning oriented discourse. The former defines wellbeing in negative terms and looks at causally oriented aspects of wellbeing......”, while the latter sees wellbeing as the result of wellbeing learning processes....

  9. Approaching the Distinction between Intuition and Insight.

    Science.gov (United States)

    Zhang, Zhonglu; Lei, Yi; Li, Hong

    2016-01-01

    Intuition and insight share similar cognitive and neural basis. Though, there are still some essential differences between the two. Here in this short review, we discriminated between intuition, and insight in two aspects. First, intuition, and insight are toward different aspects of information processing. Whereas intuition involves judgment about "yes or no," insight is related to "what" is the solution. Second, tacit knowledge play different roles in between intuition and insight. On the one hand, tacit knowledge is conducive to intuitive judgment. On the other hand, tacit knowledge may first impede but later facilitate insight occurrence. Furthermore, we share theoretical, and methodological views on how to access the distinction between intuition and insight.

  10. Sets in Coq, Coq in Sets

    Directory of Open Access Journals (Sweden)

    Bruno Barras

    2010-01-01

    Full Text Available This work is about formalizing models of various type theories of the Calculus of Constructions family. Here we focus on set theoretical models. The long-term goal is to build a formal set theoretical model of the Calculus of Inductive Constructions, so we can be sure that Coq is consistent with the language used by most mathematicians.One aspect of this work is to axiomatize several set theories: ZF possibly with inaccessible cardinals, and HF, the theory of hereditarily finite sets. On top of these theories we have developped a piece of the usual set theoretical construction of functions, ordinals and fixpoint theory. We then proved sound several models of the Calculus of Constructions, its extension with an infinite hierarchy of universes, and its extension with the inductive type of natural numbers where recursion follows the type-based termination approach.The other aspect is to try and discharge (most of these assumptions. The goal here is rather to compare the theoretical strengths of all these formalisms. As already noticed by Werner, the replacement axiom of ZF in its general form seems to require a type-theoretical axiom of choice (TTAC.

  11. Distinctive striatal dopamine signaling after dieting and gastric bypass.

    Science.gov (United States)

    Hankir, Mohammed K; Ashrafian, Hutan; Hesse, Swen; Horstmann, Annette; Fenske, Wiebke K

    2015-05-01

    Highly palatable and/or calorically dense foods, such as those rich in fat, engage the striatum to govern and set complex behaviors. Striatal dopamine signaling has been implicated in hedonic feeding and the development of obesity. Dieting and bariatric surgery have markedly different outcomes on weight loss, yet how these interventions affect central homeostatic and food reward processing remains poorly understood. Here, we propose that dieting and gastric bypass produce distinct changes in peripheral factors with known roles in regulating energy homeostasis, resulting in differential modulation of nigrostriatal and mesolimbic dopaminergic reward circuits. Enhancement of intestinal fat metabolism after gastric bypass may also modify striatal dopamine signaling contributing to its unique long-term effects on feeding behavior and body weight in obese individuals. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Invariant sets for Windows

    CERN Document Server

    Morozov, Albert D; Dragunov, Timothy N; Malysheva, Olga V

    1999-01-01

    This book deals with the visualization and exploration of invariant sets (fractals, strange attractors, resonance structures, patterns etc.) for various kinds of nonlinear dynamical systems. The authors have created a special Windows 95 application called WInSet, which allows one to visualize the invariant sets. A WInSet installation disk is enclosed with the book.The book consists of two parts. Part I contains a description of WInSet and a list of the built-in invariant sets which can be plotted using the program. This part is intended for a wide audience with interests ranging from dynamical

  13. The neural signatures of distinct psychopathic traits.

    Science.gov (United States)

    Carré, Justin M; Hyde, Luke W; Neumann, Craig S; Viding, Essi; Hariri, Ahmad R

    2013-01-01

    Recent studies suggest that psychopathy may be associated with dysfunction in the neural circuitry supporting both threat- and reward-related processes. However, these studies have involved small samples and often focused on extreme groups. Thus, it is unclear to what extent current findings may generalize to psychopathic traits in the general population. Furthermore, no studies have systematically and simultaneously assessed associations between distinct psychopathy facets and both threat- and reward-related brain function in the same sample of participants. Here, we examined the relationship between threat-related amygdala reactivity and reward-related ventral striatum (VS) reactivity and variation in four facets of self-reported psychopathy in a sample of 200 young adults. Path models indicated that amygdala reactivity to fearful facial expressions is negatively associated with the interpersonal facet of psychopathy, whereas amygdala reactivity to angry facial expressions is positively associated with the lifestyle facet. Furthermore, these models revealed that differential VS reactivity to positive versus negative feedback is negatively associated with the lifestyle facet. There was suggestive evidence for gender-specific patterns of association between brain function and psychopathy facets. Our findings are the first to document differential associations between both threat- and reward-related neural processes and distinct facets of psychopathy and thus provide a more comprehensive picture of the pattern of neural vulnerabilities that may predispose to maladaptive outcomes associated with psychopathy.

  14. The Distinction Between Curative and Assistive Technology.

    Science.gov (United States)

    Stramondo, Joseph A

    2018-05-01

    Disability activists have sometimes claimed their disability has actually increased their well-being. Some even say they would reject a cure to keep these gains. Yet, these same activists often simultaneously propose improvements to the quality and accessibility of assistive technology. However, for any argument favoring assistive over curative technology (or vice versa) to work, there must be a coherent distinction between the two. This line is already vague and will become even less clear with the emergence of novel technologies. This paper asks and tries to answer the question: what is it about the paradigmatic examples of curative and assistive technologies that make them paradigmatic and how can these defining features help us clarify the hard cases? This analysis will begin with an argument that, while the common views of this distinction adequately explain the paradigmatic cases, they fail to accurately pick out the relevant features of those technologies that make them paradigmatic and to provide adequate guidance for parsing the hard cases. Instead, it will be claimed that these categories of curative or assistive technologies are defined by the role the technologies play in establishing a person's relational narrative identity as a member of one of two social groups: disabled people or non-disabled people.

  15. Corticosteroid receptors adopt distinct cyclical transcriptional signatures.

    Science.gov (United States)

    Le Billan, Florian; Amazit, Larbi; Bleakley, Kevin; Xue, Qiong-Yao; Pussard, Eric; Lhadj, Christophe; Kolkhof, Peter; Viengchareun, Say; Fagart, Jérôme; Lombès, Marc

    2018-05-07

    Mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) are two closely related hormone-activated transcription factors that regulate major pathophysiologic functions. High homology between these receptors accounts for the crossbinding of their corresponding ligands, MR being activated by both aldosterone and cortisol and GR essentially activated by cortisol. Their coexpression and ability to bind similar DNA motifs highlight the need to investigate their respective contributions to overall corticosteroid signaling. Here, we decipher the transcriptional regulatory mechanisms that underlie selective effects of MRs and GRs on shared genomic targets in a human renal cellular model. Kinetic, serial, and sequential chromatin immunoprecipitation approaches were performed on the period circadian protein 1 ( PER1) target gene, providing evidence that both receptors dynamically and cyclically interact at the same target promoter in a specific and distinct transcriptional signature. During this process, both receptors regulate PER1 gene by binding as homo- or heterodimers to the same promoter region. Our results suggest a novel level of MR-GR target gene regulation, which should be considered for a better and integrated understanding of corticosteroid-related pathophysiology.-Le Billan, F., Amazit, L., Bleakley, K., Xue, Q.-Y., Pussard, E., Lhadj, C., Kolkhof, P., Viengchareun, S., Fagart, J., Lombès, M. Corticosteroid receptors adopt distinct cyclical transcriptional signatures.

  16. Distinct types of eigenvector localization in networks

    Science.gov (United States)

    Pastor-Satorras, Romualdo; Castellano, Claudio

    2016-01-01

    The spectral properties of the adjacency matrix provide a trove of information about the structure and function of complex networks. In particular, the largest eigenvalue and its associated principal eigenvector are crucial in the understanding of nodes’ centrality and the unfolding of dynamical processes. Here we show that two distinct types of localization of the principal eigenvector may occur in heterogeneous networks. For synthetic networks with degree distribution P(q) ~ q-γ, localization occurs on the largest hub if γ > 5/2 for γ < 5/2 a new type of localization arises on a mesoscopic subgraph associated with the shell with the largest index in the K-core decomposition. Similar evidence for the existence of distinct localization modes is found in the analysis of real-world networks. Our results open a new perspective on dynamical processes on networks and on a recently proposed alternative measure of node centrality based on the non-backtracking matrix.

  17. Moderate Load Eccentric Exercise; A Distinct Novel Training Modality

    Science.gov (United States)

    Hoppeler, Hans

    2016-01-01

    Over the last 20 years a number of studies have been published using progressive eccentric exercise protocols on motorized ergometers or similar devices that allow for controlled application of eccentric loads. Exercise protocols ramp eccentric loads over an initial 3 weeks period in order to prevent muscle damage and delayed onset muscle soreness. Final training loads reach 400–500 W in rehabilitative settings and over 1200 W in elite athletes. Training is typically carried out three times per week for durations of 20–30 min. This type of training has been characterizes as moderate load eccentric exercise. It has also been denoted RENEW (Resistance Exercise via Negative Eccentric Work by LaStayo et al., 2014). It is distinct from plyometric exercises (i.e., drop jumps) that impose muscle loads of several thousand Watts on muscles and tendons. It is also distinct from eccentric overload training whereby loads in a conventional strength training setting are increased in the eccentric phase of the movement to match concentric loads. Moderate load eccentric exercise (or RENEW) has been shown to be similarly effective as conventional strength training in increasing muscle strength and muscle volume. However, as carried out at higher angular velocities of joint movement, it reduces joint loads. A hallmark of moderate load eccentric exercise is the fact that the energy requirements are typically 4-fold smaller than in concentric exercise of the same load. This makes moderate load eccentric exercise training the tool of choice in medical conditions with limitations in muscle energy supply. The use and effectiveness of moderate load eccentric exercise has been demonstrated mostly in small scale studies for cardiorespiratory conditions, sarcopenia of old age, cancer, diabetes type 2, and neurological conditions. It has also been used effectively in the prevention and rehabilitation of injuries of the locomotor system in particular the rehabilitation after anterior

  18. Sparse Linear Identifiable Multivariate Modeling

    DEFF Research Database (Denmark)

    Henao, Ricardo; Winther, Ole

    2011-01-01

    and bench-marked on artificial and real biological data sets. SLIM is closest in spirit to LiNGAM (Shimizu et al., 2006), but differs substantially in inference, Bayesian network structure learning and model comparison. Experimentally, SLIM performs equally well or better than LiNGAM with comparable......In this paper we consider sparse and identifiable linear latent variable (factor) and linear Bayesian network models for parsimonious analysis of multivariate data. We propose a computationally efficient method for joint parameter and model inference, and model comparison. It consists of a fully...

  19. Device for identifying fuel assembly

    International Nuclear Information System (INIS)

    Imai, Tetsuo; Miyazawa, Tatsuo.

    1982-01-01

    Purpose: To accurately identify a symbol printed on a hanging tool at the upper part of a fuel assembly. Constitution: Optical fibers are bundled to prepare a detector which is disposed at a predetermined position on a hanging tool. This position is set by a guide. Thus, the light emitted from an illumination lamp arrives at the bottom of a groove printed on the upper surface of the tool, and is divided into a weak light reflected upwardly and a strong light reflected on the surface lower than the groove. When these lights are received by the optical fibers, the fibers corresponding to the grooved position become dark, and the fibers corresponding to the ungrooved position become bright. Since the fuel assembly is identified by the dark and bright of the optical fibers as symbols, different machining can be performed every fuel assembly on the upper surface of the tool. (Yoshihara, H.)

  20. Value Set Authority Center

    Data.gov (United States)

    U.S. Department of Health & Human Services — The VSAC provides downloadable access to all official versions of vocabulary value sets contained in the 2014 Clinical Quality Measures (CQMs). Each value set...

  1. Identifying Strategic Scientific Opportunities

    Science.gov (United States)

    As NCI's central scientific strategy office, CRS collaborates with the institute's divisions, offices, and centers to identify research opportunities to advance NCI's vision for the future of cancer research.

  2. Alternate superior Julia sets

    International Nuclear Information System (INIS)

    Yadav, Anju; Rani, Mamta

    2015-01-01

    Alternate Julia sets have been studied in Picard iterative procedures. The purpose of this paper is to study the quadratic and cubic maps using superior iterates to obtain Julia sets with different alternate structures. Analytically, graphically and computationally it has been shown that alternate superior Julia sets can be connected, disconnected and totally disconnected, and also fattier than the corresponding alternate Julia sets. A few examples have been studied by applying different type of alternate structures

  3. Identifying Breast Cancer Oncogenes

    Science.gov (United States)

    2011-10-01

    cells we observed that it promoted transformation of HMLE cells, suggesting a tumor suppressive role of Merlin in breast cancer (Figure 4B). A...08-1-0767 TITLE: Identifying Breast Cancer Oncogenes PRINCIPAL INVESTIGATOR: Yashaswi Shrestha...Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 W81XWH-08-1-0767 Identifying Breast Cancer Oncogenes Yashaswi Shrestha Dana-Farber

  4. STRUCTURAL IDENTIFICATION OF DISTINCT INVERSIONS OF PLANAR KINEMATIC CHAINS

    Directory of Open Access Journals (Sweden)

    Dr. Shubhashis Sanyal

    2011-12-01

    Full Text Available 0 0 1 171 979 International Islamic University 8 2 1148 14.0 Normal 0 false false false EN-US JA X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Times New Roman";} Inversions are various structural possibilities of a kinematic chain. The number of inversions depends on the number of links of a kinematic chain. At the stage of structural synthesis, identification of distinct structural inversions of a particular type of kinematic chain is necessary. Various researchers have proposed methods for identification of distinct inversions. Present method based on Link joint connectivity is proposed to identify the distinct inversions of a planar kinematic chain. Method is tested successfully on single degree and multiple degree of freedom planar kinematic chains. ABSTRAK: Penyonsangan merupakan kebarangkalian pelbagai struktur suatu rangkaian kinematik. Jumlah songsangan bergantung kepada jumlah hubungan suatu rangkaian kinematik. Pada peringkat sintesis struktur, pengenalan songsangan struktur yang berbeza untuk suatu jenis rangkaian kinematik adalah perlu. Ramai penyelidik telah mencadangkan pelbagai kaedah pengenalan songsangan yang berbeza. Kaedah terkini berdasarkan hubungan kesambungan bersama telah dicadangkan untuk mengenalpasti songsangan yang berbeza dalam suatu satah rangkaian kinematik.

  5. Rhinovirus infection induces distinct transcriptome profiles in polarized human macrophages.

    Science.gov (United States)

    Rajput, Charu; Walsh, Megan P; Eder, Breanna N; Metitiri, Ediri E; Popova, Antonia P; Hershenson, Marc B

    2018-05-01

    Infections with rhinovirus (RV) cause asthma exacerbations. Recent studies suggest that macrophages play a role in asthmatic airway inflammation and the innate immune response to RV infection. Macrophages exhibit phenotypes based on surface markers and gene expression. We hypothesized that macrophage polarization state alters gene expression in response to RV infection. Cells were derived from human peripheral blood derived monocytes. M1 and M2 polarization was carried out by using IFN-γ and IL-4, respectively, and RNA was extracted for Affymetrix Human Gene ST2.1 exon arrays. Selected genes were validated by quantitative (q)PCR. Treatment of nonactivated (M0) macrophages with IFN-γ and IL-4 induced the expression of 252 and 153 distinct genes, respectively, including previously-identified M1 and M2 markers. RV infection of M0 macrophages induced upregulation of 232 genes; pathway analysis showed significant overrepresentation of genes involved in IFN-α/β signaling and cytokine signaling in the immune system. RV infection induced differential expression of 195 distinct genes in M1-like macrophages but only seven distinct genes in M2-like-polarized cells. In a secondary analysis, comparison between M0-, RV-infected, and M1-like-polarized, RV-infected macrophages revealed differential expression of 227 genes including those associated with asthma and its exacerbation. qPCR demonstrated increased expression of CCL8, CXCL10, TNFSF10, TNFSF18, IL6, NOD2, and GSDMD and reduced expression of VNN1, AGO1, and AGO2. Together, these data show that, in contrast to M2-like-polarized macrophages, gene expression of M1-like macrophages is highly regulated by RV.

  6. Distinctive fingerprints of erosional regimes in terrestrial channel networks

    Science.gov (United States)

    Grau Galofre, A.; Jellinek, M.

    2017-12-01

    Satellite imagery and digital elevation maps capture the large scale morphology of channel networks attributed to long term erosional processes, such as fluvial, glacial, groundwater sapping and subglacial erosion. Characteristic morphologies associated with each of these styles of erosion have been studied in detail, but there exists a knowledge gap related to their parameterization and quantification. This knowledge gap prevents a rigorous analysis of the dominant processes that shaped a particular landscape, and a comparison across styles of erosion. To address this gap, we use previous morphological descriptions of glaciers, rivers, sapping valleys and tunnel valleys to identify and measure quantitative metrics diagnostic of these distinctive styles of erosion. From digital elevation models, we identify four geometric metrics: The minimum channel width, channel aspect ratio (longest length to channel width at the outlet), presence of undulating longitudinal profiles, and tributary junction angle. We also parameterize channel network complexity in terms of its stream order and fractal dimension. We then perform a statistical classification of the channel networks using a Principal Component Analysis on measurements of these six metrics on a dataset of 70 channelized systems. We show that rivers, glaciers, groundwater seepage and subglacial meltwater erode the landscape in rigorously distinguishable ways. Our methodology can more generally be applied to identify the contributions of different processes involved in carving a channel network. In particular, we are able to identify transitions from fluvial to glaciated landscapes or vice-versa.

  7. Sets, Planets, and Comets

    Science.gov (United States)

    Baker, Mark; Beltran, Jane; Buell, Jason; Conrey, Brian; Davis, Tom; Donaldson, Brianna; Detorre-Ozeki, Jeanne; Dibble, Leila; Freeman, Tom; Hammie, Robert; Montgomery, Julie; Pickford, Avery; Wong, Justine

    2013-01-01

    Sets in the game "Set" are lines in a certain four-dimensional space. Here we introduce planes into the game, leading to interesting mathematical questions, some of which we solve, and to a wonderful variation on the game "Set," in which every tableau of nine cards must contain at least one configuration for a player to pick up.

  8. Axiomatic set theory

    CERN Document Server

    Suppes, Patrick

    1972-01-01

    This clear and well-developed approach to axiomatic set theory is geared toward upper-level undergraduates and graduate students. It examines the basic paradoxes and history of set theory and advanced topics such as relations and functions, equipollence, finite sets and cardinal numbers, rational and real numbers, and other subjects. 1960 edition.

  9. Paired fuzzy sets

    DEFF Research Database (Denmark)

    Rodríguez, J. Tinguaro; Franco de los Ríos, Camilo; Gómez, Daniel

    2015-01-01

    In this paper we want to stress the relevance of paired fuzzy sets, as already proposed in previous works of the authors, as a family of fuzzy sets that offers a unifying view for different models based upon the opposition of two fuzzy sets, simply allowing the existence of different types...

  10. Keeping conceptual boundaries distinct between decision making and learning is necessary to understand social influence.

    Science.gov (United States)

    Le Mens, Gaël

    2014-02-01

    Bentley et al. make the deliberate choice to blur the distinction between learning and decision making. This obscures the social influence mechanisms that operate in the various empirical settings that their map aims to categorize. Useful policy prescriptions, however, require an accurate understanding of the social influence mechanisms that underlie the dynamics of popularity.

  11. Different risk-increasing drugs in recurrent versus single fallers: are recurrent fallers a distinct population?

    NARCIS (Netherlands)

    Askari, Marjan; Eslami, Saied; Scheffer, Alice C.; Medlock, Stephanie; de Rooij, Sophia E.; van der Velde, Nathalie; Abu-Hanna, Ameen

    2013-01-01

    Polypharmacy, and specifically the use of multiple fall-risk-increasing drugs (FRID), have been associated with increased risk of falling in older age. However, it is not yet clear whether the known set of FRIDs can be extrapolated to recurrent fallers, since they form a distinct group of more

  12. The relationship between information prioritization and visual distinctness in two progressive image transmission schemes

    NARCIS (Netherlands)

    Rodríguez-Sánchez, R.; Fdez-Valdivia, J.; Toet, A.; García, J.A.

    2004-01-01

    The goal of this paper is to analyze the relation between the visual distinctness and the priority assigned to the information in two di2erent progressive transmission schemes: the Set Partitioning in Hierarchical Trees (SPIHT) and the Rational Embedded Wavelet Image Coding (REWIC). SPIHT assigns

  13. Entrepreneurship research in Spain: developments and distinctiveness.

    Science.gov (United States)

    Sánchez, José C; Gutiérrez, Andrea

    2011-08-01

    This article presents a review of research on entrepreneurship in Spain, paying particular attention to its beginnings, nature and main focus of interest. We have developed a database based on the review of 471 works produced between 1977 and 2009, including articles published in national and international journals and dissertations (read in Spain) that allowed us to extract the following results. There is a preference for qualitative methods, conceptual contributions and the entrepreneurial process as the privileged research theme. There is also a strong focus of interest on micro and small enterprises. These characteristics of Spanish research in areas of entrepreneurship can make a distinctive contribution to international research. However, the dissemination of knowledge and inadequate strategies for international publication limit the diffusion of Spanish research in entrepreneurship. Lastly, we discuss the implications for future research.

  14. Elements of set theory

    CERN Document Server

    Enderton, Herbert B

    1977-01-01

    This is an introductory undergraduate textbook in set theory. In mathematics these days, essentially everything is a set. Some knowledge of set theory is necessary part of the background everyone needs for further study of mathematics. It is also possible to study set theory for its own interest--it is a subject with intruiging results anout simple objects. This book starts with material that nobody can do without. There is no end to what can be learned of set theory, but here is a beginning.

  15. Neurophysiological Distinction between Schizophrenia and Schizoaffective Disorder

    Science.gov (United States)

    Mathalon, Daniel H.; Hoffman, Ralph E.; Watson, Todd D.; Miller, Ryan M.; Roach, Brian J.; Ford, Judith M.

    2009-01-01

    Schizoaffective disorder (SA) is distinguished from schizophrenia (SZ) based on the presence of prominent mood symptoms over the illness course. Despite this clinical distinction, SA and SZ patients are often combined in research studies, in part because data supporting a distinct pathophysiological boundary between the disorders are lacking. Indeed, few studies have addressed whether neurobiological abnormalities associated with SZ, such as the widely replicated reduction and delay of the P300 event-related potential (ERP), are also present in SA. Scalp EEG was acquired from patients with DSM-IV SA (n = 15) or SZ (n = 22), as well as healthy controls (HC; n = 22) to assess the P300 elicited by infrequent target (15%) and task-irrelevant distractor (15%) stimuli in separate auditory and visual ”oddball” tasks. P300 amplitude was reduced and delayed in SZ, relative to HC, consistent with prior studies. These SZ abnormalities did not interact with stimulus type (target vs. task-irrelevant distractor) or modality (auditory vs. visual). Across sensory modality and stimulus type, SA patients exhibited normal P300 amplitudes (significantly larger than SZ patients and indistinguishable from HC). However, P300 latency and reaction time were both equivalently delayed in SZ and SA patients, relative to HC. P300 differences between SA and SZ patients could not be accounted for by variation in symptom severity, socio-economic status, education, or illness duration. Although both groups show similar deficits in processing speed, SA patients do not exhibit the P300 amplitude deficits evident in SZ, consistent with an underlying pathophysiological boundary between these disorders. PMID:20140266

  16. Distinctive personality profiles of fibromyalgia and chronic fatigue syndrome patients

    Directory of Open Access Journals (Sweden)

    Jacob N. Ablin

    2016-09-01

    Full Text Available Objective The current study is an innovative exploratory investigation, aiming at identifying differences in personality profiles within Fibromyalgia Syndrome (FMS and Chronic Fatigue Syndrome (CFS patients. Method In total, 344 participants (309 female, 35 male reported suffering from FMS and/or CFS and consented to participate in the study. Participants were recruited at an Israeli FM/CFS patient meeting held in May 2013, and through an announcement posted on several social networks. Participants were asked to complete a research questionnaire, which included FMS criteria and severity scales, and measures of personality, emotional functioning, positivity, social support and subjective assessment of general health. In total, 204 participants completed the research questionnaire (40.7% attrition rate. Results A cluster analysis produced two distinct clusters, which differed significantly on psychological variables, but did not differ on demographic variables or illness severity. As compared to cluster number 2 (N = 107, participants classified into cluster number 1 (N = 97 showed a less adaptive pattern, with higher levels of Harm Avoidance and Alexithymia; higher prevalence of Type D personality; and lower levels of Persistence (PS, Reward dependence (RD, Cooperation, Self-directedness (SD, social support and positivity. Conclusion The significant pattern of results indicates at least two distinct personality profiles of FM and CFS patients. Findings from this research may help improve the evaluation and treatment of FM and CFS patients, based on each patient’s unique needs, psychological resources and weaknesses, as proposed by the current trend of personalized medicine.

  17. Network analysis reveals distinct clinical syndromes underlying acute mountain sickness.

    Directory of Open Access Journals (Sweden)

    David P Hall

    Full Text Available Acute mountain sickness (AMS is a common problem among visitors at high altitude, and may progress to life-threatening pulmonary and cerebral oedema in a minority of cases. International consensus defines AMS as a constellation of subjective, non-specific symptoms. Specifically, headache, sleep disturbance, fatigue and dizziness are given equal diagnostic weighting. Different pathophysiological mechanisms are now thought to underlie headache and sleep disturbance during acute exposure to high altitude. Hence, these symptoms may not belong together as a single syndrome. Using a novel visual analogue scale (VAS, we sought to undertake a systematic exploration of the symptomatology of AMS using an unbiased, data-driven approach originally designed for analysis of gene expression. Symptom scores were collected from 292 subjects during 1110 subject-days at altitudes between 3650 m and 5200 m on Apex expeditions to Bolivia and Kilimanjaro. Three distinct patterns of symptoms were consistently identified. Although fatigue is a ubiquitous finding, sleep disturbance and headache are each commonly reported without the other. The commonest pattern of symptoms was sleep disturbance and fatigue, with little or no headache. In subjects reporting severe headache, 40% did not report sleep disturbance. Sleep disturbance correlates poorly with other symptoms of AMS (Mean Spearman correlation 0.25. These results challenge the accepted paradigm that AMS is a single disease process and describe at least two distinct syndromes following acute ascent to high altitude. This approach to analysing symptom patterns has potential utility in other clinical syndromes.

  18. Vertically distinct microbial communities in the Mariana and Kermadec trenches

    Science.gov (United States)

    Donaldson, Sierra; Osuntokun, Oladayo; Xia, Qing; Nelson, Alex; Blanton, Jessica; Allen, Eric E.; Church, Matthew J.; Bartlett, Douglas H.

    2018-01-01

    Hadal trenches, oceanic locations deeper than 6,000 m, are thought to have distinct microbial communities compared to those at shallower depths due to high hydrostatic pressures, topographical funneling of organic matter, and biogeographical isolation. Here we evaluate the hypothesis that hadal trenches contain unique microbial biodiversity through analyses of the communities present in the bottom waters of the Kermadec and Mariana trenches. Estimates of microbial protein production indicate active populations under in situ hydrostatic pressures and increasing adaptation to pressure with depth. Depth, trench of collection, and size fraction are important drivers of microbial community structure. Many putative hadal bathytypes, such as members related to the Marinimicrobia, Rhodobacteraceae, Rhodospirilliceae, and Aquibacter, are similar to members identified in other trenches. Most of the differences between the two trench microbiomes consists of taxa belonging to the Gammaproteobacteria whose distributions extend throughout the water column. Growth and survival estimates of representative isolates of these taxa under deep-sea conditions suggest that some members may descend from shallower depths and exist as a potentially inactive fraction of the hadal zone. We conclude that the distinct pelagic communities residing in these two trenches, and perhaps by extension other trenches, reflect both cosmopolitan hadal bathytypes and ubiquitous genera found throughout the water column. PMID:29621268

  19. The mechanism of the emergence of distinct overstretched DNA states

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, You-Liang; Sun, Zhao-Yan, E-mail: zysun@ciac.ac.cn [State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Lu, Zhong-Yuan [State Key Laboratory of Supramolecular Structure and Materials, Institute of Theoretical Chemistry, Jilin University, Changchun 130023 (China)

    2016-01-14

    Although multiple overstretched DNA states were identified in experiments, the mechanism of the emergence of distinct states is still unclear. Molecular dynamics simulation is an ideal tool to clarify the mechanism, but the force loading rates in stretching achieved by conventional all-atom DNA models are much faster, which essentially affect overstretching states. We employed a modified coarse-grained DNA model with an unprecedented low loading rate in simulations to study the overstretching transitions of end-opened double-stranded DNA. We observed two-strand peeling off for DNA with low stability and the S-DNA with high stability under tension. By introducing a melting-forbidden model which prevents base-pair breaking, we still observed the overstretching transition induced by the formation of S-DNA due to the change of dihedral angle. Hence, we confirmed that the competition between the two strain-softening manners, i.e., base-pair breaking and dihedral angle variation, results in the emergence of distinct overstretched DNA states.

  20. Sets of Mutually Orthogonal Sudoku Latin Squares

    Science.gov (United States)

    Vis, Timothy; Petersen, Ryan M.

    2009-01-01

    A Latin square of order "n" is an "n" x "n" array using n symbols, such that each symbol appears exactly once in each row and column. A set of Latin squares is c ordered pairs of symbols appearing in the cells of the array are distinct. The popular puzzle Sudoku involves Latin squares with n = 9, along with the added condition that each of the 9…

  1. Social Set Analysis

    DEFF Research Database (Denmark)

    Vatrapu, Ravi; Mukkamala, Raghava Rao; Hussain, Abid

    2016-01-01

    , conceptual and formal models of social data, and an analytical framework for combining big social data sets with organizational and societal data sets. Three empirical studies of big social data are presented to illustrate and demonstrate social set analysis in terms of fuzzy set-theoretical sentiment...... automata and agent-based modeling). However, when it comes to organizational and societal units of analysis, there exists no approach to conceptualize, model, analyze, explain, and predict social media interactions as individuals' associations with ideas, values, identities, and so on. To address...... analysis, crisp set-theoretical interaction analysis, and event-studies-oriented set-theoretical visualizations. Implications for big data analytics, current limitations of the set-theoretical approach, and future directions are outlined....

  2. Identifying Knowledge and Communication

    Directory of Open Access Journals (Sweden)

    Eduardo Coutinho Lourenço de Lima

    2006-12-01

    Full Text Available In this paper, I discuss how the principle of identifying knowledge which Strawson advances in ‘Singular Terms and Predication’ (1961, and in ‘Identifying Reference and Truth-Values’ (1964 turns out to constrain communication. The principle states that a speaker’s use of a referring expression should invoke identifying knowledge on the part of the hearer, if the hearer is to understand what the speaker is saying, and also that, in so referring, speakers are attentive to hearers’ epistemic states. In contrasting it with Russell’s Principle (Evans 1982, as well as with the principle of identifying descriptions (Donnellan 1970, I try to show that the principle of identifying knowledge, ultimately a condition for understanding, makes sense only in a situation of conversation. This allows me to conclude that the cooperative feature of communication (Grice 1975 and reference (Clark andWilkes-Gibbs 1986 holds also at the understanding level. Finally, I discuss where Strawson’s views seem to be unsatisfactory, and suggest how they might be improved.

  3. Parameter identifiability of linear dynamical systems

    Science.gov (United States)

    Glover, K.; Willems, J. C.

    1974-01-01

    It is assumed that the system matrices of a stationary linear dynamical system were parametrized by a set of unknown parameters. The question considered here is, when can such a set of unknown parameters be identified from the observed data? Conditions for the local identifiability of a parametrization are derived in three situations: (1) when input/output observations are made, (2) when there exists an unknown feedback matrix in the system and (3) when the system is assumed to be driven by white noise and only output observations are made. Also a sufficient condition for global identifiability is derived.

  4. The pursuit of optimal distinctiveness and consumer preferences.

    Science.gov (United States)

    He, Lingnan; Cong, Feng; Liu, Yanping; Zhou, Xinyue

    2010-10-01

    This article investigates the effect of optimal distinctiveness on consumer product consumption. The authors argue that consumers acquire and display material possessions to restore their optimal levels of distinctiveness. Results showed that placing consumers in a state of low distinctiveness increased desire to acquire distinctive products, whereas perceptions of high distinctiveness reduced desire to acquire such products. Consumers' desire for distinctiveness-related products held true for various consumer choices, including willingness to pay more for limited-edition products and preference for unpopular gifts. This finding has implications for understanding consumer choice in expressing identity. © 2010 The Authors. Scandinavian Journal of Psychology © 2010 The Scandinavian Psychological Associations.

  5. A systematic review of team-building interventions in non-acute healthcare settings.

    Science.gov (United States)

    Miller, Christopher J; Kim, Bo; Silverman, Allie; Bauer, Mark S

    2018-03-01

    Healthcare is increasingly delivered in a team-based format emphasizing interdisciplinary coordination. While recent reviews have investigated team-building interventions primarily in acute healthcare settings (e.g. emergency or surgery departments), we aimed to systematically review the evidence base for team-building interventions in non-acute settings (e.g. primary care or rehabilitation clinics). We conducted a systematic review in PubMed and Embase to identify team-building interventions, and conducted follow-up literature searches to identify articles describing empirical studies of those interventions. This process identified 14 team-building interventions for non-acute healthcare settings, and 25 manuscripts describing empirical studies of these interventions. We evaluated outcomes in four domains: trainee evaluations, teamwork attitudes/knowledge, team functioning, and patient impact. Trainee evaluations for team-building interventions were generally positive, but only one study associated team-building with statistically significant improvement in teamwork attitudes/knowledge. Similarly mixed results emerged for team functioning and patient impact. The evidence base for healthcare team-building interventions in non-acute healthcare settings is much less developed than the parallel literature for short-term team function in acute care settings. Only one intervention we identified has been tested in multiple non-acute settings by distinct research teams. Positive findings regarding the utility of team-building interventions are tempered by a lack of control conditions, inconsistency in outcome measures, and high probability of bias. Considering these results alongside the well-recognized costs of poor healthcare teamwork suggests that additional research is sorely needed to develop the evidence base for team-building in non-acute settings.

  6. A Canonical Approach to the Argument/Adjunct Distinction

    Directory of Open Access Journals (Sweden)

    Diana Forker

    2014-01-01

    Full Text Available This paper provides an account of the argument/adjunct distinction implementing the 'canonical approach'. I identify five criteria (obligatoriness, latency, co-occurrence restrictions, grammatical relations, and iterability and seven diagnostic tendencies that can be used to distinguish canonical arguments from canonical adjuncts. I then apply the criteria and tendencies to data from the Nakh-Daghestanian language Hinuq. Hinuq makes extensive use of spatial cases for marking adjunct-like and argument-like NPs. By means of the criteria and tendencies it is possible to distinguish spatial NPs that come close to canonical arguments from those that are canonical adjuncts, and to place the remaining NPs bearing spatial cases within the argument-adjunct continuum.

  7. Distinct facial processing in schizophrenia and schizoaffective disorders

    Science.gov (United States)

    Chen, Yue; Cataldo, Andrea; Norton, Daniel J; Ongur, Dost

    2011-01-01

    Although schizophrenia and schizoaffective disorders have both similar and differing clinical features, it is not well understood whether similar or differing pathophysiological processes mediate patients’ cognitive functions. Using psychophysical methods, this study compared the performances of schizophrenia (SZ) patients, patients with schizoaffective disorder (SA), and a healthy control group in two face-related cognitive tasks: emotion discrimination, which tested perception of facial affect, and identity discrimination, which tested perception of non-affective facial features. Compared to healthy controls, SZ patients, but not SA patients, exhibited deficient performance in both fear and happiness discrimination, as well as identity discrimination. SZ patients, but not SA patients, also showed impaired performance in a theory-of-mind task for which emotional expressions are identified based upon the eye regions of face images. This pattern of results suggests distinct processing of face information in schizophrenia and schizoaffective disorders. PMID:21868199

  8. Continental smokers couple mantle degassing and distinctive microbiology within continents

    Science.gov (United States)

    Crossey, Laura J.; Karlstrom, Karl E.; Schmandt, Brandon; Crow, Ryan R.; Colman, Daniel R.; Cron, Brandi; Takacs-Vesbach, Cristina D.; Dahm, Clifford N.; Northup, Diana E.; Hilton, David R.; Ricketts, Jason W.; Lowry, Anthony R.

    2016-02-01

    The discovery of oceanic black (and white) smokers revolutionized our understanding of mid-ocean ridges and led to the recognition of new organisms and ecosystems. Continental smokers, defined here to include a broad range of carbonic springs, hot springs, and fumaroles that vent mantle-derived fluids in continental settings, exhibit many of the same processes of heat and mass transfer and ecosystem niche differentiation. Helium isotope (3He/4He) analyses indicate that widespread mantle degassing is taking place in the western U.S.A., and that variations in mantle helium values correlate best with low seismic-velocity domains in the mantle and lateral contrasts in mantle velocity rather than crustal parameters such as GPS, proximity to volcanoes, crustal velocity, or composition. Microbial community analyses indicate that these springs can host novel microorganisms. A targeted analysis of four springs in New Mexico yield the first published occurrence of chemolithoautotrophic Zetaproteobacteria in a continental setting. These observations lead to two linked hypotheses: that mantle-derived volatiles transit through conduits in extending continental lithosphere preferentially above and at the edges of mantle low velocity domains. High CO2 and other constituents ultimately derived from mantle volatiles drive water-rock interactions and heterogeneous fluid mixing that help structure diverse and distinctive microbial communities.

  9. Comprehensive benchmarking reveals H2BK20 acetylation as a distinctive signature of cell-state-specific enhancers and promoters.

    Science.gov (United States)

    Kumar, Vibhor; Rayan, Nirmala Arul; Muratani, Masafumi; Lim, Stefan; Elanggovan, Bavani; Xin, Lixia; Lu, Tess; Makhija, Harshyaa; Poschmann, Jeremie; Lufkin, Thomas; Ng, Huck Hui; Prabhakar, Shyam

    2016-05-01

    Although over 35 different histone acetylation marks have been described, the overwhelming majority of regulatory genomics studies focus exclusively on H3K27ac and H3K9ac. In order to identify novel epigenomic traits of regulatory elements, we constructed a benchmark set of validated enhancers by performing 140 enhancer assays in human T cells. We tested 40 chromatin signatures on this unbiased enhancer set and identified H2BK20ac, a little-studied histone modification, as the most predictive mark of active enhancers. Notably, we detected a novel class of functionally distinct enhancers enriched in H2BK20ac but lacking H3K27ac, which was present in all examined cell lines and also in embryonic forebrain tissue. H2BK20ac was also unique in highlighting cell-type-specific promoters. In contrast, other acetylation marks were present in all active promoters, regardless of cell-type specificity. In stimulated microglial cells, H2BK20ac was more correlated with cell-state-specific expression changes than H3K27ac, with TGF-beta signaling decoupling the two acetylation marks at a subset of regulatory elements. In summary, our study reveals a previously unknown connection between histone acetylation and cell-type-specific gene regulation and indicates that H2BK20ac profiling can be used to uncover new dimensions of gene regulation. © 2016 Kumar et al.; Published by Cold Spring Harbor Laboratory Press.

  10. Identifying and Managing Risk.

    Science.gov (United States)

    Abraham, Janice M.

    1999-01-01

    The role of the college or university chief financial officer in institutional risk management is (1) to identify risk (physical, casualty, fiscal, business, reputational, workplace safety, legal liability, employment practices, general liability), (2) to develop a campus plan to reduce and control risk, (3) to transfer risk, and (4) to track and…

  11. Loss of Dnmt3a induces CLL and PTCL with distinct methylomes and transcriptomes in mice.

    Science.gov (United States)

    Haney, Staci L; Upchurch, Garland M; Opavska, Jana; Klinkebiel, David; Appiah, Adams Kusi; Smith, Lynette M; Heavican, Tayla B; Iqbal, Javeed; Joshi, Shantaram; Opavsky, Rene

    2016-09-28

    Cytosine methylation of DNA is an epigenetic modification involved in the repression of genes that affect biological processes including hematopoiesis. It is catalyzed by DNA methyltransferases, one of which -DNMT3A- is frequently mutated in human hematologic malignancies. We have previously reported that Dnmt3a inactivation in hematopoietic stem cells results in chronic lymphocytic leukemia (CLL) and CD8-positive peripheral T cell lymphomas (PTCL) in EμSRα-tTA;Teto-Cre;Dnmt3a fl/fl ; Rosa26LOXP EGFP/EGFP (Dnmt3a Δ/Δ ) mice. The extent to which molecular changes overlap between these diseases is not clear. Using high resolution global methylation and expression analysis we show that whereas patterns of methylation and transcription in normal B-1a cells and CD8-positive T cells are similar, methylomes and transcriptomes in malignant B-1a and CD8+ T cells are remarkably distinct, suggesting a cell-type specific function for Dnmt3a in cellular transformation. Promoter hypomethylation in tumors was 10 times more frequent than hypermethylation, three times more frequent in CLL than PTCL and correlated better with gene expression than hypermethylation. Cross-species molecular comparison of mouse and human CLL and PTCL reveals significant overlaps and identifies putative oncogenic drivers of disease. Thus, Dnmt3a Δ/Δ mice can serve as a new mouse model to study CLL and PTCL in relevant physiological settings.

  12. Asymptomatic hyperthyroidism in older adults: is it a distinct clinical and laboratory entity?

    Science.gov (United States)

    Mooradian, Arshag D

    2008-01-01

    Hyperthyroidism is the result of increased serum free thyroid hormone levels and is associated with a well recognized set of clinical signs and symptoms. However, older patients who develop hyperthyroidism tend to have fewer hyperadrenergic signs and an increased incidence of weight loss, cardiac arrhythmias and, occasionally, apathetic mood. This article highlights the paucity of clinical signs and symptoms of hyperthyroidism in older people and reviews the potential biochemical changes in thyroid hormone physiology that may account for an altered clinical presentation in older people with hyperthyroidism. First, a brief vignette from our own clinical practice is described to highlight an unusual presentation of hyperthyroidism in an older woman. The subject is then reviewed on the basis of relevant articles identified through a MEDLINE search of the English literature, using the key words 'hyperthyroidism' and 'aging'. The available evidence indicates that the clinical syndrome of asymptomatic hyperthyroidism in older adults appears to be distinct from the more widely recognized syndromes of apathetic hyperthyroidism or thyroid hormone resistance. Age-related changes in thyroid hormone economy and reduced cellular uptake of thyroid hormone as well as changes in thyroid hormone regulation of gene expression may account for reduced manifestations of hyperthyroidism in older adults. Thus, in addition to the well known changes in thyroid gland anatomy and function with aging, there may be an age-related resistance to thyroid hormone action. Asymptomatic hyperthyroidism may well be a syndrome that is currently under-diagnosed.

  13. GenomeRunner web server: regulatory similarity and differences define the functional impact of SNP sets.

    Science.gov (United States)

    Dozmorov, Mikhail G; Cara, Lukas R; Giles, Cory B; Wren, Jonathan D

    2016-08-01

    The growing amount of regulatory data from the ENCODE, Roadmap Epigenomics and other consortia provides a wealth of opportunities to investigate the functional impact of single nucleotide polymorphisms (SNPs). Yet, given the large number of regulatory datasets, researchers are posed with a challenge of how to efficiently utilize them to interpret the functional impact of SNP sets. We developed the GenomeRunner web server to automate systematic statistical analysis of SNP sets within a regulatory context. Besides defining the functional impact of SNP sets, GenomeRunner implements novel regulatory similarity/differential analyses, and cell type-specific regulatory enrichment analysis. Validated against literature- and disease ontology-based approaches, analysis of 39 disease/trait-associated SNP sets demonstrated that the functional impact of SNP sets corresponds to known disease relationships. We identified a group of autoimmune diseases with SNPs distinctly enriched in the enhancers of T helper cell subpopulations, and demonstrated relevant cell type-specificity of the functional impact of other SNP sets. In summary, we show how systematic analysis of genomic data within a regulatory context can help interpreting the functional impact of SNP sets. GenomeRunner web server is freely available at http://www.integrativegenomics.org/ mikhail.dozmorov@gmail.com Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Protein-energy malnutrition in the rehabilitation setting: Evidence to improve identification.

    Science.gov (United States)

    Marshall, Skye

    2016-04-01

    Methods of identifying malnutrition in the rehabilitation setting require further examination so that patient outcomes may be improved. The purpose of this narrative review was to: (1) examine the defining characteristics of malnutrition, starvation, sarcopenia and cachexia; (2) review the validity of nutrition screening tools and nutrition assessment tools in the rehabilitation setting; and (3) determine the prevalence of malnutrition in the rehabilitation setting by geographical region and method of diagnosis. A narrative review was conducted drawing upon international literature. Starvation represents one form of malnutrition. Inadequate energy and protein intake are the critical factor in the aetiology of malnutrition, which is distinct from sarcopenia and cachexia. Eight nutrition screening tools and two nutrition assessment tools have been evaluated for criterion validity in the rehabilitation setting, and consideration must be given to the resources of the facility and the patient group in order to select the appropriate tool. The prevalence of malnutrition in the rehabilitation setting ranges from 14-65% worldwide with the highest prevalence reported in rural, European and Australian settings. Malnutrition is highly prevalent in the rehabilitation setting, and consideration must be given to the patient group when determining the most appropriate method of identification so that resources may be used efficaciously and the chance of misdiagnosis minimised. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Comparative linkage meta-analysis reveals regionally-distinct, disparate genetic architectures: application to bipolar disorder and schizophrenia.

    Directory of Open Access Journals (Sweden)

    Brady Tang

    2011-04-01

    Full Text Available New high-throughput, population-based methods and next-generation sequencing capabilities hold great promise in the quest for common and rare variant discovery and in the search for "missing heritability." However, the optimal analytic strategies for approaching such data are still actively debated, representing the latest rate-limiting step in genetic progress. Since it is likely a majority of common variants of modest effect have been identified through the application of tagSNP-based microarray platforms (i.e., GWAS, alternative approaches robust to detection of low-frequency (1-5% MAF and rare (<1% variants are of great importance. Of direct relevance, we have available an accumulated wealth of linkage data collected through traditional genetic methods over several decades, the full value of which has not been exhausted. To that end, we compare results from two different linkage meta-analysis methods--GSMA and MSP--applied to the same set of 13 bipolar disorder and 16 schizophrenia GWLS datasets. Interestingly, we find that the two methods implicate distinct, largely non-overlapping, genomic regions. Furthermore, based on the statistical methods themselves and our contextualization of these results within the larger genetic literatures, our findings suggest, for each disorder, distinct genetic architectures may reside within disparate genomic regions. Thus, comparative linkage meta-analysis (CLMA may be used to optimize low-frequency and rare variant discovery in the modern genomic era.

  16. Variation in chick-a-dee calls of tufted titmice, Baeolophus bicolor: note type and individual distinctiveness.

    Science.gov (United States)

    Owens, Jessica L; Freeberg, Todd M

    2007-08-01

    The chick-a-dee call of chickadee species (genus Poecile) has been the focus of much research. A great deal is known about the structural complexity and the meaning of variation in notes making up calls in these species. However, little is known about the likely homologous "chick-a-dee" call of the closely related tufted titmouse, Baeolophus bicolor. Tufted titmice are a prime candidate for comparative analyses of the call, because their vocal and social systems share many characteristics with those of chickadees. To address the paucity of data on the structure of chick-a-dee calls of tufted titmice, we recorded birds in field and aviary settings. Four main note types were identified in the call: Z, A, D(h), and D notes. Several acoustic parameters of each note type were measured, and statistical analyses revealed that the note types are acoustically distinct from one another. Furthermore, note types vary in the extent of individual distinctiveness reflected in their acoustic parameters. This first step towards understanding the chick-a-dee call of tufted titmice indicates that the call is comparable in structure and complexity to the calls of chickadees.

  17. Mycobacterial secretion systems ESX-1 and ESX-5 play distinct roles in host cell death and inflammasome activation

    KAUST Repository

    Abdallah, Abdallah

    2011-09-28

    During infection of humans and animals, pathogenic mycobacteria manipulate the host cell causing severe diseases such as tuberculosis and leprosy. To understand the basis of mycobacterial pathogenicity, it is crucial to identify the molecular virulence mechanisms. In this study, we address the contribution of ESX-1 and ESX-5 - two homologous type VII secretion systems of mycobacteria that secrete distinct sets of immune modulators - during the macrophage infection cycle. Using wild-type, ESX-1- and ESX-5-deficient mycobacterial strains, we demonstrate that these secretion systems differentially affect subcellular localization and macrophage cell responses. We show that in contrast to ESX-1, the effector proteins secreted by ESX-5 are not required for the translocation of Mycobacterium tuberculosis or Mycobacterium marinum to the cytosol of host cells. However, the M. marinum ESX-5 mutant does not induce inflammasome activation and IL-1b activation. The ESX-5 system also induces a caspase-independent cell death after translocation has taken place. Importantly, by means of inhibitory agents and small interfering RNA experiments, we reveal that cathepsin B is involved in both the induction of cell death and inflammasome activation upon infection with wild-type mycobacteria. These results reveal distinct roles for two different type VII secretion systems during infection and shed light on how virulent mycobacteria manipulate the host cell in various ways to replicate and spread. Copyright © 2011 by The American Association of Immunologists, Inc.

  18. Peptidomic and transcriptomic profiling of four distinct spider venoms.

    Directory of Open Access Journals (Sweden)

    Vera Oldrati

    Full Text Available Venom based research is exploited to find novel candidates for the development of innovative pharmacological tools, drug candidates and new ingredients for cosmetic and agrochemical industries. Moreover, venomics, as a well-established approach in systems biology, helps to elucidate the genetic mechanisms of the production of such a great molecular biodiversity. Today the advances made in the proteomics, transcriptomics and bioinformatics fields, favor venomics, allowing the in depth study of complex matrices and the elucidation even of minor compounds present in minute biological samples. The present study illustrates a rapid and efficient method developed for the elucidation of venom composition based on NextGen mRNA sequencing of venom glands and LC-MS/MS venom proteome profiling. The analysis of the comprehensive data obtained was focused on cysteine rich peptide toxins from four spider species originating from phylogenetically distant families for comparison purposes. The studied species were Heteropoda davidbowie (Sparassidae, Poecilotheria formosa (Theraphosidae, Viridasius fasciatus (Viridasiidae and Latrodectus mactans (Theridiidae. This led to a high resolution profiling of 284 characterized cysteine rich peptides, 111 of which belong to the Inhibitor Cysteine Knot (ICK structural motif. The analysis of H. davidbowie venom revealed a high richness in term of venom diversity: 95 peptide sequences were identified; out of these, 32 peptides presented the ICK structural motif and could be classified in six distinct families. The profiling of P. formosa venom highlighted the presence of 126 peptide sequences, with 52 ICK toxins belonging to three structural distinct families. V. fasciatus venom was shown to contain 49 peptide sequences, out of which 22 presented the ICK structural motif and were attributed to five families. The venom of L. mactans, until now studied for its large neurotoxins (Latrotoxins, revealed the presence of 14

  19. Maximal Abelian sets of roots

    CERN Document Server

    Lawther, R

    2018-01-01

    In this work the author lets \\Phi be an irreducible root system, with Coxeter group W. He considers subsets of \\Phi which are abelian, meaning that no two roots in the set have sum in \\Phi \\cup \\{ 0 \\}. He classifies all maximal abelian sets (i.e., abelian sets properly contained in no other) up to the action of W: for each W-orbit of maximal abelian sets we provide an explicit representative X, identify the (setwise) stabilizer W_X of X in W, and decompose X into W_X-orbits. Abelian sets of roots are closely related to abelian unipotent subgroups of simple algebraic groups, and thus to abelian p-subgroups of finite groups of Lie type over fields of characteristic p. Parts of the work presented here have been used to confirm the p-rank of E_8(p^n), and (somewhat unexpectedly) to obtain for the first time the 2-ranks of the Monster and Baby Monster sporadic groups, together with the double cover of the latter. Root systems of classical type are dealt with quickly here; the vast majority of the present work con...

  20. Endpoint distinctiveness facilitates analogical mapping in pigeons.

    Science.gov (United States)

    Hagmann, Carl Erick; Cook, Robert G

    2015-03-01

    Analogical thinking necessitates mapping shared relations across two separate domains. We investigated whether pigeons could learn faster with ordinal mapping of relations across two physical dimensions (circle size & choice spatial position) relative to random mapping of these relations. Pigeons were trained to relate six circular samples of different sizes to horizontally positioned choice locations in a six alternative matching-to-sample task. Three pigeons were trained in a mapped condition in which circle size mapped directly onto choice spatial position. Three other pigeons were trained in a random condition in which the relations between size and choice position were arbitrarily assigned. The mapped group showed an advantage over the random group in acquiring this task. In a subsequent second phase, relations between the dimensions were ordinally reversed for the mapped group and re-randomized for the random group. There was no difference in how quickly matching accuracy re-emerged in the two groups, although the mapped group eventually performed more accurately. Analyses suggested this mapped advantage was likely due to endpoint distinctiveness and the benefits of proximity errors during choice responding rather than a conceptual or relational advantage attributable to the common or ordinal mapping of the two dimensions. This potential difficulty in mapping relations across dimensions may limit the pigeons' capacity for more advanced types of analogical reasoning. This article is part of a Special Issue entitled: Tribute to Tom Zentall. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Endpoint Distinctiveness Facilitates Analogical Mapping in Pigeons

    Science.gov (United States)

    Hagmann, Carl Erick; Cook, Robert G.

    2015-01-01

    Analogical thinking necessitates mapping shared relations across two separate domains. We investigated whether pigeons could learn faster with ordinal mapping of relations across two physical dimensions (circle size & choice spatial position) relative to random mapping of these relations. Pigeons were trained to relate six circular samples of different sizes to horizontally positioned choice locations in a six alternative matching-to-sample task. Three pigeons were trained in a mapped condition in which circle size mapped directly onto choice spatial position. Three other pigeons were trained in a random condition in which the relations between size and choice position were arbitrarily assigned. The mapped group showed an advantage over the random group in acquiring this task. In a subsequent second phase, reassignment, relations between the dimensions were ordinally reversed for the mapped group and re-randomized for the random group. There was no difference in how quickly matching accuracy re-emerged in the two groups, although the mapped group eventually performed more accurately. Analyses suggested this mapped advantage was likely due endpoint distinctiveness and the benefits of proximity errors during choice responding rather than a conceptual or relational advantage attributable to the common or ordinal map of the two dimensions. This potential difficulty in mapping relations across dimensions may limit the pigeons’ capacity for more advanced types of analogical reasoning. PMID:25447511

  2. Reservoir floodplains support distinct fish assemblages

    Science.gov (United States)

    Miranda, Leandro E.; Wigen, S. L.; Dagel, Jonah D.

    2014-01-01

    Reservoirs constructed on floodplain rivers are unique because the upper reaches of the impoundment may include extensive floodplain environments. Moreover, reservoirs that experience large periodic water level fluctuations as part of their operational objectives seasonally inundate and dewater floodplains in their upper reaches, partly mimicking natural inundations of river floodplains. In four flood control reservoirs in Mississippi, USA, we explored the dynamics of connectivity between reservoirs and adjacent floodplains and the characteristics of fish assemblages that develop in reservoir floodplains relative to those that develop in reservoir bays. Although fish species richness in floodplains and bays were similar, species composition differed. Floodplains emphasized fish species largely associated with backwater shallow environments, often resistant to harsh environmental conditions. Conversely, dominant species in bays represented mainly generalists that benefit from the continuous connectivity between the bay and the main reservoir. Floodplains in the study reservoirs provided desirable vegetated habitats at lower water level elevations, earlier in the year, and more frequently than in bays. Inundating dense vegetation in bays requires raising reservoir water levels above the levels required to reach floodplains. Therefore, aside from promoting distinct fish assemblages within reservoirs and helping promote diversity in regulated rivers, reservoir floodplains are valued because they can provide suitable vegetated habitats for fish species at elevations below the normal pool, precluding the need to annually flood upland vegetation that would inevitably be impaired by regular flooding. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

  3. Health and morality: two conceptually distinct categories?

    Science.gov (United States)

    Tengland, Per-Anders

    2012-03-01

    When seeing immoral actions, criminal or not, we sometimes deem the people who perform them unhealthy. This is especially so if the actions are of a serious nature, e.g. involving murder, assault, or rape. We turn our moral evaluation into an evaluation about health and illness. This tendency is partly supported by some diagnoses found in the DMS-IV, such as Antisocial personality disorder, and the ICD-10, such as Dissocial personality disorder. The aim of the paper is to answer the question: How analytically sound is the inclusion of morality into a theory of health? The holistic theory of Lennart Nordenfelt is used as a starting point, and it is used as an example of a theory where morality and health are conceptually distinct categories. Several versions of a pluralistic holistic theory are then discussed in order to see if, and if so, how, morality can be conceptually related to health. It is concluded that moral abilities (and dispositions) can be seen as being part of the individual's health. It is harder to incorporate moral virtues and moral actions into such a theory. However, if immoral actions "cluster" in an individual, and are of a severe kind, causing serious harm to other people, it is more likely that the person, for those reasons only, be deemed unhealthy.

  4. Are empathy and concern psychologically distinct?

    Science.gov (United States)

    Jordan, Matthew R; Amir, Dorsa; Bloom, Paul

    2016-12-01

    Researchers have long been interested in the relationship between feeling what you believe others feel-often described as empathy-and caring about the welfare of others-often described as compassion or concern. Many propose that empathy is a prerequisite for concern and is therefore the ultimate motivator of prosocial actions. To assess this hypothesis, the authors developed the Empathy Index, which consists of 2 novel scales, and explored their relationship to a measure of concern as well as to measures of cooperative and altruistic behavior. A series of factor analyses reveal that empathy and concern consistently load on different factors. Furthermore, they show that empathy and concern motivate different behaviors: concern for others is a uniquely positive predictor of prosocial action whereas empathy is either not predictive or negatively predictive of prosocial actions. Together these studies suggest that empathy and concern are psychologically distinct and empathy plays a more limited role in our moral lives than many believe. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  5. Medical student empathy: interpersonal distinctions and correlates.

    Science.gov (United States)

    Jordan, Kevin D; Foster, Penni Smith

    2016-12-01

    Attention to interpersonal behaviors, communication, and relational factors is taking on increasing importance in medical education. Medical student empathy is one aspect of the physician-patient relationship that is often involved in beneficial interactions leading to improved clinical outcomes and patient satisfaction. As an interpersonal quality, empathy is a social behavior well-suited to be examined from an interpersonal perspective. The present study used the interpersonal theory of clinical, personality, and social psychology to examine the construct of empathy and theorize about likely interpersonal correlates. One hundred and sixty-three students from an academic health center in the southeastern United States participated in this study. The medical student version of the Jefferson Scale of Empathy was used to assess empathy and its factors: Perspective taking, compassionate care, and walking in the patient's shoes. Interpersonal assessments included the International Personality Item Pool-Interpersonal Circumplex, the Interpersonal Support Evaluation List, and the UCLA Loneliness Scale. Distinct interpersonal styles and correlates emerged among empathy and its factors. While all factors of empathy were related to interpersonal warmth, perspective taking and compassionate care were also associated with submissiveness. Of note, only walking in the patient's shoes was correlated with both social support and less loneliness. These findings are discussed in light of interpersonal theory with particular attention paid to the implications for medical education and professional development.

  6. Internally readable identifying tag

    International Nuclear Information System (INIS)

    Jefferts, K.B.; Jefferts, E.R.

    1980-01-01

    A method of identifying non-metallic objects by means of X-ray equipment is described in detail. A small metal pin with a number of grooves cut in a pre-determined equi-spaced pattern is implanted into the non-metallic object and by decoding the groove patterns using X-ray equipment, the object is uniquely identified. A specific example of such an application is in studying the migratory habits of fish. The pin inserted into the snout of the fish is 0.010 inch in diameter, 0.040 inch in length with 8 possible positions for grooves if spaced 0.005 inch apart. With 6 of the groove positions available for data, the capacity is 2 6 or 64 combinations; clearly longer pins would increase the data capacity. This method of identification is a major advance over previous techniques which necessitated destruction of the fish in order to recover the identification tag. (UK)

  7. Identifying Breast Cancer Oncogenes

    Science.gov (United States)

    2010-10-01

    tyrosine kinases with an SH3, SH2 and catalytic domain, it lacks a native myristylation signal shared by most members of this class [14], [38]. The...therapeutics and consequently, improve clinical outcomes. We aim to identify novel drivers of breast oncogenesis. We hypothesize that a kinase gain-of...human mammary epithelial cells. A pBabe-Puro-Myr-Flag kinase open reading frame (ORF) library was screened in immortalized human mammary epithelial

  8. Rock disposal problems identified

    Energy Technology Data Exchange (ETDEWEB)

    Knox, R

    1978-06-01

    Mathematical models are the only way of examining the return of radioactivity from nuclear waste to the environment over long periods of time. Work in Britain has helped identify areas where more basic data is required, but initial results look very promising for final disposal of high level waste in hard rock repositories. A report by the National Radiological Protection Board of a recent study, is examined.

  9. Distinct taxonomic and functional composition of soil microbiomes along the gradient forest-restinga-mangrove in southeastern Brazil.

    Science.gov (United States)

    Mendes, Lucas William; Tsai, Siu Mui

    2018-01-01

    Soil microorganisms play crucial roles in ecosystem functioning, and the central goal in microbial ecology studies is to elucidate which factors shape community structure. A better understanding of the relationship between microbial diversity, functions and environmental parameters would increase our ability to set conservation priorities. Here, the bacterial and archaeal community structure in Atlantic Forest, restinga and mangrove soils was described and compared based on shotgun metagenomics. We hypothesized that each distinct site would harbor a distinct taxonomic and functional soil community, which is influenced by environmental parameters. Our data showed that the microbiome is shaped by soil properties, with pH, base saturation, boron and iron content significantly correlated to overall community structure. When data of specific phyla were correlated to specific soil properties, we demonstrated that parameters such as boron, copper, sulfur, potassium and aluminum presented significant correlation with the most number of bacterial groups. Mangrove soil was the most distinct site and presented the highest taxonomic and functional diversity in comparison with forest and restinga soils. From the total 34 microbial phyla identified, 14 were overrepresented in mangrove soils, including several archaeal groups. Mangrove soils hosted a high abundance of sequences related to replication, survival and adaptation; forest soils included high numbers of sequences related to the metabolism of nutrients and other composts; while restinga soils included abundant genes related to the metabolism of carbohydrates. Overall, our finds show that the microbial community structure and functional potential were clearly different across the environmental gradient, followed by functional adaptation and both were related to the soil properties.

  10. Mammalian odorant receptor tuning breadth persists across distinct odorant panels.

    Directory of Open Access Journals (Sweden)

    Devin Kepchia

    Full Text Available The molecular receptive range (MRR of a mammalian odorant receptor (OR is the set of odorant structures that activate the OR, while the distribution of these odorant structures across odor space is the tuning breadth of the OR. Variation in tuning breadth is thought to be an important property of ORs, with the MRRs of these receptors varying from narrowly to broadly tuned. However, defining the tuning breadth of an OR is a technical challenge. For practical reasons, a screening panel that broadly covers odor space must be limited to sparse coverage of the many potential structures in that space. When screened with such a panel, ORs with different odorant specificities, but equal tuning breadths, might appear to have different tuning breadths due to chance. We hypothesized that ORs would maintain their tuning breadths across distinct odorant panels. We constructed a new screening panel that was broadly distributed across an estimated odor space and contained compounds distinct from previous panels. We used this new screening panel to test several murine ORs that were previously characterized as having different tuning breadths. ORs were expressed in Xenopus laevis oocytes and assayed by two-electrode voltage clamp electrophysiology. MOR256-17, an OR previously characterized as broadly tuned, responded to nine novel compounds from our new screening panel that were structurally diverse and broadly dispersed across an estimated odor space. MOR256-22, an OR previously characterized as narrowly tuned, responded to a single novel compound that was structurally similar to a previously known ligand for this receptor. MOR174-9, a well-characterized receptor with a narrowly tuned MRR, did not respond to any novel compounds in our new panel. These results support the idea that variation in tuning breadth among these three ORs is not an artifact of the screening protocol, but is an intrinsic property of the receptors.

  11. Distinct cardiac transcriptional profiles defining pregnancy and exercise.

    Directory of Open Access Journals (Sweden)

    Eunhee Chung

    Full Text Available BACKGROUND: Although the hypertrophic responses of the heart to pregnancy and exercise are both considered to be physiological processes, they occur in quite different hormonal and temporal settings. In this study, we have compared the global transcriptional profiles of left ventricular tissues at various time points during the progression of hypertrophy in exercise and pregnancy. METHODOLOGY/PRINCIPAL FINDINGS: The following groups of female mice were analyzed: non-pregnant diestrus cycle sedentary control, mid-pregnant, late-pregnant, and immediate-postpartum, and animals subjected to 7 and 21 days of voluntary wheel running. Hierarchical clustering analysis shows that while mid-pregnancy and both exercise groups share the closest relationship and similar gene ontology categories, late pregnancy and immediate post-partum are quite different with high representation of secreted/extracellular matrix-related genes. Moreover, pathway-oriented ontological analysis shows that metabolism regulated by cytochrome P450 and chemokine pathways are the most significant signaling pathways regulated in late pregnancy and immediate-postpartum, respectively. Finally, increases in expression of components of the proteasome observed in both mid-pregnancy and immediate-postpartum also result in enhanced proteasome activity. Interestingly, the gene expression profiles did not correlate with the degree of cardiac hypertrophy observed in the animal groups, suggesting that distinct pathways are employed to achieve similar amounts of cardiac hypertrophy. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that cardiac adaptation to the later stages of pregnancy is quite distinct from both mid-pregnancy and exercise. Furthermore, it is very dynamic since, by 12 hours post-partum, the heart has already initiated regression of cardiac growth, and 50 genes have changed expression significantly in the immediate-postpartum compared to late-pregnancy. Thus, pregnancy

  12. Haar meager sets revisited

    Czech Academy of Sciences Publication Activity Database

    Doležal, Martin; Rmoutil, M.; Vejnar, B.; Vlasák, V.

    2016-01-01

    Roč. 440, č. 2 (2016), s. 922-939 ISSN 0022-247X Institutional support: RVO:67985840 Keywords : Haar meager set * Haar null set * Polish group Subject RIV: BA - General Mathematics Impact factor: 1.064, year: 2016 http://www.sciencedirect.com/science/article/pii/S0022247X1600305X

  13. Setting goals in psychotherapy

    DEFF Research Database (Denmark)

    Emiliussen, Jakob; Wagoner, Brady

    2013-01-01

    The present study is concerned with the ethical dilemmas of setting goals in therapy. The main questions that it aims to answer are: who is to set the goals for therapy and who is to decide when they have been reached? The study is based on four semi-­‐structured, phenomenological interviews...

  14. Pseudo-set framing.

    Science.gov (United States)

    Barasz, Kate; John, Leslie K; Keenan, Elizabeth A; Norton, Michael I

    2017-10-01

    Pseudo-set framing-arbitrarily grouping items or tasks together as part of an apparent "set"-motivates people to reach perceived completion points. Pseudo-set framing changes gambling choices (Study 1), effort (Studies 2 and 3), giving behavior (Field Data and Study 4), and purchase decisions (Study 5). These effects persist in the absence of any reward, when a cost must be incurred, and after participants are explicitly informed of the arbitrariness of the set. Drawing on Gestalt psychology, we develop a conceptual account that predicts what will-and will not-act as a pseudo-set, and defines the psychological process through which these pseudo-sets affect behavior: over and above typical reference points, pseudo-set framing alters perceptions of (in)completeness, making intermediate progress seem less complete. In turn, these feelings of incompleteness motivate people to persist until the pseudo-set has been fulfilled. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  15. Descriptive set theory

    CERN Document Server

    Moschovakis, YN

    1987-01-01

    Now available in paperback, this monograph is a self-contained exposition of the main results and methods of descriptive set theory. It develops all the necessary background material from logic and recursion theory, and treats both classical descriptive set theory and the effective theory developed by logicians.

  16. Possibility Fuzzy Soft Set

    Directory of Open Access Journals (Sweden)

    Shawkat Alkhazaleh

    2011-01-01

    Full Text Available We introduce the concept of possibility fuzzy soft set and its operation and study some of its properties. We give applications of this theory in solving a decision-making problem. We also introduce a similarity measure of two possibility fuzzy soft sets and discuss their application in a medical diagnosis problem.

  17. Archaeological predictive model set.

    Science.gov (United States)

    2015-03-01

    This report is the documentation for Task 7 of the Statewide Archaeological Predictive Model Set. The goal of this project is to : develop a set of statewide predictive models to assist the planning of transportation projects. PennDOT is developing t...

  18. Large Data Set Mining

    NARCIS (Netherlands)

    Leemans, I.B.; Broomhall, Susan

    2017-01-01

    Digital emotion research has yet to make history. Until now large data set mining has not been a very active field of research in early modern emotion studies. This is indeed surprising since first, the early modern field has such rich, copyright-free, digitized data sets and second, emotion studies

  19. "Ready, Set, FLOW!"

    Science.gov (United States)

    Stroud, Wesley

    2018-01-01

    All educators want their classrooms to be inviting areas that support investigations. However, a common mistake is to fill learning spaces with items or objects that are set up by the teacher or are simply "for show." This type of setting, although it may create a comfortable space for students, fails to stimulate investigations and…

  20. Some notes on tetrahedrally closed spherical sets in Euclidean spaces

    Indian Academy of Sciences (India)

    47

    is a relation between these sets. P is called the point set, L the line set and I the incidence relation. A point-line geometry S = (P,L,I) is called a near polygon if every two distinct points are incident with at most one line and if for every point x and every line L, there exists a unique point on L that is nearest to x with respect to ...

  1. Identifying molecular subtypes in human colon cancer using gene expression and DNA methylation microarray data.

    Science.gov (United States)

    Ren, Zhonglu; Wang, Wenhui; Li, Jinming

    2016-02-01

    Identifying colon cancer subtypes based on molecular signatures may allow for a more rational, patient-specific approach to therapy in the future. Classifications using gene expression data have been attempted before with little concordance between the different studies carried out. In this study we aimed to uncover subtypes of colon cancer that have distinct biological characteristics and identify a set of novel biomarkers which could best reflect the clinical and/or biological characteristics of each subtype. Clustering analysis and discriminant analysis were utilized to discover the subtypes in two different molecular levels on 153 colon cancer samples from The Cancer Genome Atlas (TCGA) Data Portal. At gene expression level, we identified two major subtypes, ECL1 (expression cluster 1) and ECL2 (expression cluster 2) and a list of signature genes. Due to the heterogeneity of colon cancer, the subtype ECL1 can be further subdivided into three nested subclasses, and HOTAIR were found upregulated in subclass 2. At DNA methylation level, we uncovered three major subtypes, MCL1 (methylation cluster 1), MCL2 (methylation cluster 2) and MCL3 (methylation cluster 3). We found only three subtypes of CpG island methylator phenotype (CIMP) in colon cancer instead of the four subtypes in the previous reports, and we found no sufficient evidence to subdivide MCL3 into two distinct subgroups.

  2. Economic communication model set

    Science.gov (United States)

    Zvereva, Olga M.; Berg, Dmitry B.

    2017-06-01

    This paper details findings from the research work targeted at economic communications investigation with agent-based models usage. The agent-based model set was engineered to simulate economic communications. Money in the form of internal and external currencies was introduced into the models to support exchanges in communications. Every model, being based on the general concept, has its own peculiarities in algorithm and input data set since it was engineered to solve the specific problem. Several and different origin data sets were used in experiments: theoretic sets were estimated on the basis of static Leontief's equilibrium equation and the real set was constructed on the basis of statistical data. While simulation experiments, communication process was observed in dynamics, and system macroparameters were estimated. This research approved that combination of an agent-based and mathematical model can cause a synergetic effect.

  3. Theory of random sets

    CERN Document Server

    Molchanov, Ilya

    2017-01-01

    This monograph, now in a thoroughly revised second edition, offers the latest research on random sets. It has been extended to include substantial developments achieved since 2005, some of them motivated by applications of random sets to econometrics and finance. The present volume builds on the foundations laid by Matheron and others, including the vast advances in stochastic geometry, probability theory, set-valued analysis, and statistical inference. It shows the various interdisciplinary relationships of random set theory within other parts of mathematics, and at the same time fixes terminology and notation that often vary in the literature, establishing it as a natural part of modern probability theory and providing a platform for future development. It is completely self-contained, systematic and exhaustive, with the full proofs that are necessary to gain insight. Aimed at research level, Theory of Random Sets will be an invaluable reference for probabilists; mathematicians working in convex and integ...

  4. ORGANIZATION MANAGEMENT TODAY: SETTING THE HUMAN ...

    African Journals Online (AJOL)

    CIU

    ... paper attempted to articulate the new roles by outlining the basic ingredients for setting an agenda for the ... The removal of traditional restrictive rules has opened up .... The human resource is identified as the most critical factor in the work.

  5. Two distinct neural mechanisms underlying indirect reciprocity.

    Science.gov (United States)

    Watanabe, Takamitsu; Takezawa, Masanori; Nakawake, Yo; Kunimatsu, Akira; Yamasue, Hidenori; Nakamura, Mitsuhiro; Miyashita, Yasushi; Masuda, Naoki

    2014-03-18

    Cooperation is a hallmark of human society. Humans often cooperate with strangers even if they will not meet each other again. This so-called indirect reciprocity enables large-scale cooperation among nonkin and can occur based on a reputation mechanism or as a succession of pay-it-forward behavior. Here, we provide the functional and anatomical neural evidence for two distinct mechanisms governing the two types of indirect reciprocity. Cooperation occurring as reputation-based reciprocity specifically recruited the precuneus, a region associated with self-centered cognition. During such cooperative behavior, the precuneus was functionally connected with the caudate, a region linking rewards to behavior. Furthermore, the precuneus of a cooperative subject had a strong resting-state functional connectivity (rsFC) with the caudate and a large gray matter volume. In contrast, pay-it-forward reciprocity recruited the anterior insula (AI), a brain region associated with affective empathy. The AI was functionally connected with the caudate during cooperation occurring as pay-it-forward reciprocity, and its gray matter volume and rsFC with the caudate predicted the tendency of such cooperation. The revealed difference is consistent with the existing results of evolutionary game theory: although reputation-based indirect reciprocity robustly evolves as a self-interested behavior in theory, pay-it-forward indirect reciprocity does not on its own. The present study provides neural mechanisms underlying indirect reciprocity and suggests that pay-it-forward reciprocity may not occur as myopic profit maximization but elicit emotional rewards.

  6. Identifying phenomenal consciousness.

    Science.gov (United States)

    Schier, Elizabeth

    2009-03-01

    This paper examines the possibility of finding evidence that phenomenal consciousness is independent of access. The suggestion reviewed is that we should look for isomorphisms between phenomenal and neural activation spaces. It is argued that the fact that phenomenal spaces are mapped via verbal report is no problem for this methodology. The fact that activation and phenomenal space are mapped via different means does not mean that they cannot be identified. The paper finishes by examining how data addressing this theoretical question could be obtained.

  7. Distinct DNA methylomes of newborns and centenarians

    DEFF Research Database (Denmark)

    Heyn, Holger; Li, Ning; Ferreira, Humberto J.

    2012-01-01

    Human aging cannot be fully understood in terms of the constrained genetic setting. Epigenetic drift is an alternative means of explaining age-associated alterations. To address this issue, we performed whole-genome bisulfite sequencing (WGBS) of newborn and centenarian genomes. The centenarian DNA......-age individuals demonstrated DNA methylomes in the crossroad between the newborn and the nonagenarian/centenarian groups. Our study constitutes a unique DNA methylation analysis of the extreme points of human life at a single-nucleotide resolution level....

  8. Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: evidence from voxel-based meta-analysis.

    Science.gov (United States)

    Wise, T; Radua, J; Via, E; Cardoner, N; Abe, O; Adams, T M; Amico, F; Cheng, Y; Cole, J H; de Azevedo Marques Périco, C; Dickstein, D P; Farrow, T F D; Frodl, T; Wagner, G; Gotlib, I H; Gruber, O; Ham, B J; Job, D E; Kempton, M J; Kim, M J; Koolschijn, P C M P; Malhi, G S; Mataix-Cols, D; McIntosh, A M; Nugent, A C; O'Brien, J T; Pezzoli, S; Phillips, M L; Sachdev, P S; Salvadore, G; Selvaraj, S; Stanfield, A C; Thomas, A J; van Tol, M J; van der Wee, N J A; Veltman, D J; Young, A H; Fu, C H; Cleare, A J; Arnone, D

    2017-10-01

    Finding robust brain substrates of mood disorders is an important target for research. The degree to which major depression (MDD) and bipolar disorder (BD) are associated with common and/or distinct patterns of volumetric changes is nevertheless unclear. Furthermore, the extant literature is heterogeneous with respect to the nature of these changes. We report a meta-analysis of voxel-based morphometry (VBM) studies in MDD and BD. We identified studies published up to January 2015 that compared grey matter in MDD (50 data sets including 4101 individuals) and BD (36 data sets including 2407 individuals) using whole-brain VBM. We used statistical maps from the studies included where available and reported peak coordinates otherwise. Group comparisons and conjunction analyses identified regions in which the disorders showed common and distinct patterns of volumetric alteration. Both disorders were associated with lower grey-matter volume relative to healthy individuals in a number of areas. Conjunction analysis showed smaller volumes in both disorders in clusters in the dorsomedial and ventromedial prefrontal cortex, including the anterior cingulate cortex and bilateral insula. Group comparisons indicated that findings of smaller grey-matter volumes relative to controls in the right dorsolateral prefrontal cortex and left hippocampus, along with cerebellar, temporal and parietal regions were more substantial in major depression. These results suggest that MDD and BD are characterised by both common and distinct patterns of grey-matter volume changes. This combination of differences and similarities has the potential to inform the development of diagnostic biomarkers for these conditions.

  9. Scientometric methods for identifying emerging technologies

    Science.gov (United States)

    Abercrombie, Robert K; Schlicher, Bob G; Sheldon, Frederick T

    2015-11-03

    Provided is a method of generating a scientometric model that tracks the emergence of an identified technology from initial discovery (via original scientific and conference literature), through critical discoveries (via original scientific, conference literature and patents), transitioning through Technology Readiness Levels (TRLs) and ultimately on to commercial application. During the period of innovation and technology transfer, the impact of scholarly works, patents and on-line web news sources are identified. As trends develop, currency of citations, collaboration indicators, and on-line news patterns are identified. The combinations of four distinct and separate searchable on-line networked sources (i.e., scholarly publications and citation, worldwide patents, news archives, and on-line mapping networks) are assembled to become one collective network (a dataset for analysis of relations). This established network becomes the basis from which to quickly analyze the temporal flow of activity (searchable events) for the example subject domain.

  10. Quantitative expression profile of distinct functional regions in the adult mouse brain.

    Directory of Open Access Journals (Sweden)

    Takeya Kasukawa

    Full Text Available The adult mammalian brain is composed of distinct regions with specialized roles including regulation of circadian clocks, feeding, sleep/awake, and seasonal rhythms. To find quantitative differences of expression among such various brain regions, we conducted the BrainStars (B* project, in which we profiled the genome-wide expression of ∼50 small brain regions, including sensory centers, and centers for motion, time, memory, fear, and feeding. To avoid confounds from temporal differences in gene expression, we sampled each region every 4 hours for 24 hours, and pooled the samples for DNA-microarray assays. Therefore, we focused on spatial differences in gene expression. We used informatics to identify candidate genes with expression changes showing high or low expression in specific regions. We also identified candidate genes with stable expression across brain regions that can be used as new internal control genes, and ligand-receptor interactions of neurohormones and neurotransmitters. Through these analyses, we found 8,159 multi-state genes, 2,212 regional marker gene candidates for 44 small brain regions, 915 internal control gene candidates, and 23,864 inferred ligand-receptor interactions. We also found that these sets include well-known genes as well as novel candidate genes that might be related to specific functions in brain regions. We used our findings to develop an integrated database (http://brainstars.org/ for exploring genome-wide expression in the adult mouse brain, and have made this database openly accessible. These new resources will help accelerate the functional analysis of the mammalian brain and the elucidation of its regulatory network systems.

  11. Gene expression profiling of two distinct neuronal populations in the rodent spinal cord

    DEFF Research Database (Denmark)

    Ryge, Jesper; Westerdahl, Ann Charlotte; Alstøm, Preben

    2008-01-01

    Background: In the field of neuroscience microarray gene expression profiles on anatomically defined brain structures are being used increasingly to study both normal brain functions as well as pathological states. Fluorescent tracing techniques in brain tissue that identifies distinct neuronal p...

  12. Distinct trajectories of positive and negative affect after colorectal cancer diagnosis

    NARCIS (Netherlands)

    Ciere, Yvette; Janse, Moniek; Almansa, Josué; Visser, Annemieke; Sanderman, Robbert; Sprangers, Mirjam A.G.; Ranchor, Adelita V.; Fleer, Joke

    2017-01-01

    Objective: Insight into trajectories of positive affect (PA) and negative affect (NA) across the cancer continuum may improve understanding of the nature of adjustment problems. The primary aim of this study was to identify subgroups of patients with distinct trajectories of PA and NA following

  13. Distinct Trajectories of Positive and Negative Affect After Colorectal Cancer Diagnosis

    NARCIS (Netherlands)

    Ciere, Yvette; Janse, Moniek; Almansa, Josué; Visser, Annemieke; Sanderman, Robbert; Sprangers, Mirjam A G; Ranchor, Adelita V; Fleer, Joke

    OBJECTIVE: Insight into trajectories of positive affect (PA) and negative affect (NA) across the cancer continuum may improve understanding of the nature of adjustment problems. The primary aim of this study was to identify subgroups of patients with distinct trajectories of PA and NA following

  14. Distribution of Disease-Associated Copy Number Variants across Distinct Disorders of Cognitive Development

    Science.gov (United States)

    Pescosolido, Matthew F.; Gamsiz, Ece D.; Nagpal, Shailender; Morrow, Eric M.

    2013-01-01

    Objective: The purpose of the present study was to discover the extent to which distinct "DSM" disorders share large, highly recurrent copy number variants (CNVs) as susceptibility factors. We also sought to identify gene mechanisms common to groups of diagnoses and/or specific to a given diagnosis based on associations with CNVs. Method:…

  15. Papillary haemangioma. A distinctive cutaneous haemangioma of the head and neck area containing eosinophilic hyaline globules

    NARCIS (Netherlands)

    Suurmeijer, A. J. H.; Fletcher, C. D. M.

    2007-01-01

    Aims: To investigate and define a morphologically distinctive group of cutaneous papillary haemangiomas. Methods and results: Eleven patients (seven male, four female, age range 1-77 years, median 57) were identified with a solitary bluish cutaneous papule (median size 11 mm) arising in the head and

  16. Neurobiological Correlates and Predictors of Two Distinct Personality Trait Pathways to Escalated Alcohol Use

    Directory of Open Access Journals (Sweden)

    Malak Abu Shakra

    2018-01-01

    Interpretation: This double dissociation provides evidence of distinct neurobiological profiles in a priori identified personality trait-based risk groups for AUDs, and links these signatures to clinically relevant substance use outcomes at follow-up. AUD subtypes might benefit from motivationally and personality-specific ameliorative and preventative interventions.

  17. 76 FR 58867 - Endangered and Threatened Species; Determination of Nine Distinct Population Segments of...

    Science.gov (United States)

    2011-09-22

    ... Northern District of California modified the February 19, 2010, deadline to March 8, 2010. On March 16... markedly separated from other populations of the same taxon (an organism or group of organisms) as a... to identify two genetically distinct nesting populations in the Pacific--a northern hemisphere...

  18. Maintaining a Distinction Between Possible and Impossible Topics of Conversation in the Outpatient Respiratory Medical Clinic

    DEFF Research Database (Denmark)

    Birgitte Skov Jensen, Lone; Larsen, Kristian; Konradsen, Hanne

    2016-01-01

    by maintaining a distinction between possible and impossible topics to counseling. Three subcategories explaining the effort that maintain the impossible and possible topics separated were identified: (a) an effort to maintain the diseased lungs as the main task in counseling, (b) navigating interactions...

  19. Basic set theory

    CERN Document Server

    Levy, Azriel

    2002-01-01

    An advanced-level treatment of the basics of set theory, this text offers students a firm foundation, stopping just short of the areas employing model-theoretic methods. Geared toward upper-level undergraduate and graduate students, it consists of two parts: the first covers pure set theory, including the basic motions, order and well-foundedness, cardinal numbers, the ordinals, and the axiom of choice and some of it consequences; the second deals with applications and advanced topics such as point set topology, real spaces, Boolean algebras, and infinite combinatorics and large cardinals. An

  20. Set theory essentials

    CERN Document Server

    Milewski, Emil G

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Set Theory includes elementary logic, sets, relations, functions, denumerable and non-denumerable sets, cardinal numbers, Cantor's theorem, axiom of choice, and order relations.

  1. Technology Entrepreneurship: Overview, Definition, and Distinctive Aspects

    OpenAIRE

    Tony Bailetti

    2012-01-01

    Technology entrepreneurship lies at the heart of many important debates, including those around launching and growing firms, regional economic development, selecting the appropriate stakeholders to take ideas to markets, and educating managers, engineers, and scientists. Unless a generally accepted definition of technology entrepreneurship is established, however, these debates lose their focus. The purpose of this article is to identify the themes that dominate the technology entrepreneurshi...

  2. Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma.

    Directory of Open Access Journals (Sweden)

    Francesco Abate

    2015-10-01

    Full Text Available Endemic Burkitt lymphoma (eBL is primarily found in children in equatorial regions and represents the first historical example of a virus-associated human malignancy. Although Epstein-Barr virus (EBV infection and MYC translocations are hallmarks of the disease, it is unclear whether other factors may contribute to its development. We performed RNA-Seq on 20 eBL cases from Uganda and showed that the mutational and viral landscape of eBL is more complex than previously reported. First, we found the presence of other herpesviridae family members in 8 cases (40%, in particular human herpesvirus 5 and human herpesvirus 8 and confirmed their presence by immunohistochemistry in the adjacent non-neoplastic tissue. Second, we identified a distinct latency program in EBV involving lytic genes in association with TCF3 activity. Third, by comparing the eBL mutational landscape with published data on sporadic Burkitt lymphoma (sBL, we detected lower frequencies of mutations in MYC, ID3, TCF3 and TP53, and a higher frequency of mutation in ARID1A in eBL samples. Recurrent mutations in two genes not previously associated with eBL were identified in 20% of tumors: RHOA and cyclin F (CCNF. We also observed that polyviral samples showed lower numbers of somatic mutations in common altered genes in comparison to sBL specimens, suggesting dual mechanisms of transformation, mutation versus virus driven in sBL and eBL respectively.

  3. Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma.

    Science.gov (United States)

    Abate, Francesco; Ambrosio, Maria Raffaella; Mundo, Lucia; Laginestra, Maria Antonella; Fuligni, Fabio; Rossi, Maura; Zairis, Sakellarios; Gazaneo, Sara; De Falco, Giulia; Lazzi, Stefano; Bellan, Cristiana; Rocca, Bruno Jim; Amato, Teresa; Marasco, Elena; Etebari, Maryam; Ogwang, Martin; Calbi, Valeria; Ndede, Isaac; Patel, Kirtika; Chumba, David; Piccaluga, Pier Paolo; Pileri, Stefano; Leoncini, Lorenzo; Rabadan, Raul

    2015-10-01

    Endemic Burkitt lymphoma (eBL) is primarily found in children in equatorial regions and represents the first historical example of a virus-associated human malignancy. Although Epstein-Barr virus (EBV) infection and MYC translocations are hallmarks of the disease, it is unclear whether other factors may contribute to its development. We performed RNA-Seq on 20 eBL cases from Uganda and showed that the mutational and viral landscape of eBL is more complex than previously reported. First, we found the presence of other herpesviridae family members in 8 cases (40%), in particular human herpesvirus 5 and human herpesvirus 8 and confirmed their presence by immunohistochemistry in the adjacent non-neoplastic tissue. Second, we identified a distinct latency program in EBV involving lytic genes in association with TCF3 activity. Third, by comparing the eBL mutational landscape with published data on sporadic Burkitt lymphoma (sBL), we detected lower frequencies of mutations in MYC, ID3, TCF3 and TP53, and a higher frequency of mutation in ARID1A in eBL samples. Recurrent mutations in two genes not previously associated with eBL were identified in 20% of tumors: RHOA and cyclin F (CCNF). We also observed that polyviral samples showed lower numbers of somatic mutations in common altered genes in comparison to sBL specimens, suggesting dual mechanisms of transformation, mutation versus virus driven in sBL and eBL respectively.

  4. SOX2 co-occupies distal enhancer elements with distinct POU factors in ESCs and NPCs to specify cell state.

    Directory of Open Access Journals (Sweden)

    Michael A Lodato

    Full Text Available SOX2 is a master regulator of both pluripotent embryonic stem cells (ESCs and multipotent neural progenitor cells (NPCs; however, we currently lack a detailed understanding of how SOX2 controls these distinct stem cell populations. Here we show by genome-wide analysis that, while SOX2 bound to a distinct set of gene promoters in ESCs and NPCs, the majority of regions coincided with unique distal enhancer elements, important cis-acting regulators of tissue-specific gene expression programs. Notably, SOX2 bound the same consensus DNA motif in both cell types, suggesting that additional factors contribute to target specificity. We found that, similar to its association with OCT4 (Pou5f1 in ESCs, the related POU family member BRN2 (Pou3f2 co-occupied a large set of putative distal enhancers with SOX2 in NPCs. Forced expression of BRN2 in ESCs led to functional recruitment of SOX2 to a subset of NPC-specific targets and to precocious differentiation toward a neural-like state. Further analysis of the bound sequences revealed differences in the distances of SOX and POU peaks in the two cell types and identified motifs for additional transcription factors. Together, these data suggest that SOX2 controls a larger network of genes than previously anticipated through binding of distal enhancers and that transitions in POU partner factors may control tissue-specific transcriptional programs. Our findings have important implications for understanding lineage specification and somatic cell reprogramming, where SOX2, OCT4, and BRN2 have been shown to be key factors.

  5. Identifying and Assessing Effective Mechanisms for Technology Transfer

    Science.gov (United States)

    2007-03-01

    There is a distinct manner in which civilian technology is protected; even though secrecy is one option, as is the case with the Coca - Cola formula...done with the appropriate dedicated resources. They also placed heavy emphasis on acquiring early sponsorship for the technology and be able to set

  6. Goal-setting in clinical medicine.

    Science.gov (United States)

    Bradley, E H; Bogardus, S T; Tinetti, M E; Inouye, S K

    1999-07-01

    The process of setting goals for medical care in the context of chronic disease has received little attention in the medical literature, despite the importance of goal-setting in the achievement of desired outcomes. Using qualitative research methods, this paper develops a theory of goal-setting in the care of patients with dementia. The theory posits several propositions. First, goals are generated from embedded values but are distinct from values. Goals vary based on specific circumstances and alternatives whereas values are person-specific and relatively stable in the face of changing circumstances. Second, goals are hierarchical in nature, with complex mappings between general and specific goals. Third, there are a number of factors that modify the goal-setting process, by affecting the generation of goals from values or the translation of general goals to specific goals. Modifying factors related to individuals include their degree of risk-taking, perceived self-efficacy, and acceptance of the disease. Disease factors that modify the goal-setting process include the urgency and irreversibility of the medical condition. Pertinent characteristics of the patient-family-clinician interaction include the level of participation, control, and trust among patients, family members, and clinicians. The research suggests that the goal-setting process in clinical medicine is complex, and the potential for disagreements regarding goals substantial. The nature of the goal-setting process suggests that explicit discussion of goals for care may be necessary to promote effective patient-family-clinician communication and adequate care planning.

  7. List identifies threatened ecosystems

    Science.gov (United States)

    Showstack, Randy

    2012-09-01

    The International Union for Conservation of Nature (IUCN) announced on 9 September that it will develop a new Red List of Ecosystems that will identify which ecosystems are vulnerable or endangered. The list, which is modeled on the group's Red List of Threatened Species™, could help to guide conservation activities and influence policy processes such as the Convention on Biological Diversity, according to the group. “We will assess the status of marine, terrestrial, freshwater, and subterranean ecosystems at local, regional, and global levels,” stated Jon Paul Rodriguez, leader of IUCN's Ecosystems Red List Thematic Group. “The assessment can then form the basis for concerted implementation action so that we can manage them sustainably if their risk of collapse is low or restore them if they are threatened and then monitor their recovery.”

  8. Global Microbial Identifier

    DEFF Research Database (Denmark)

    Wielinga, Peter; Hendriksen, Rene S.; Aarestrup, Frank Møller

    2017-01-01

    ) will likely also enable a much better understanding of the pathogenesis of the infection and the molecular basis of the host response to infection. But the full potential of these advances will only transpire if the data in this area become transferable and thereby comparable, preferably in open-source...... of microorganisms, for the identification of relevant genes and for the comparison of genomes to detect outbreaks and emerging pathogens. To harness the full potential of WGS, a shared global database of genomes linked to relevant metadata and the necessary software tools needs to be generated, hence the global...... microbial identifier (GMI) initiative. This tool will ideally be used in amongst others in the diagnosis of infectious diseases in humans and animals, in the identification of microorganisms in food and environment, and to track and trace microbial agents in all arenas globally. This will require...

  9. Lebesgue Sets Immeasurable Existence

    Directory of Open Access Journals (Sweden)

    Diana Marginean Petrovai

    2012-12-01

    Full Text Available It is well known that the notion of measure and integral were released early enough in close connection with practical problems of measuring of geometric figures. Notion of measure was outlined in the early 20th century through H. Lebesgue’s research, founder of the modern theory of measure and integral. It was developed concurrently a technique of integration of functions. Gradually it was formed a specific area todaycalled the measure and integral theory. Essential contributions to building this theory was made by a large number of mathematicians: C. Carathodory, J. Radon, O. Nikodym, S. Bochner, J. Pettis, P. Halmos and many others. In the following we present several abstract sets, classes of sets. There exists the sets which are not Lebesgue measurable and the sets which are Lebesgue measurable but are not Borel measurable. Hence B ⊂ L ⊂ P(X.

  10. Leadership set-up

    DEFF Research Database (Denmark)

    Thude, Bettina Ravnborg; Stenager, Egon; von Plessen, Christian

    2018-01-01

    . Findings: The study found that the leadership set-up did not have any clear influence on interdisciplinary cooperation, as all wards had a high degree of interdisciplinary cooperation independent of which leadership set-up they had. Instead, the authors found a relation between leadership set-up and leader...... could influence legitimacy. Originality/value: The study shows that leadership set-up is not the predominant factor that creates interdisciplinary cooperation; but rather, leader legitimacy also should be considered. Additionally, the study shows that leader legitimacy can be difficult to establish...... and that it cannot be taken for granted. This is something chief executive officers should bear in mind when they plan and implement new leadership structures. Therefore, it would also be useful to look more closely at how to achieve legitimacy in cases where the leader is from a different profession to the staff....

  11. General Paleoclimatology Data Sets

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Data of past climate and environment derived from unusual proxy evidence. Parameter keywords describe what was measured in this data set. Additional summary...

  12. HEDIS Limited Data Set

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Healthcare Effectiveness Data and Information Set (HEDIS) is a tool used by more than 90 percent of Americas health plans to measure performance on important...

  13. The Delivery of Health Promotion and Environmental Health Services; Public Health or Primary Care Settings?

    Directory of Open Access Journals (Sweden)

    Lene Bjørn Jensen

    2018-05-01

    Full Text Available The WHO Regional Office for Europe developed a set of public health functions resulting in the ten Essential Public Health Operations (EPHO. Public health or primary care settings seem to be favorable to embrace all actions included into EPHOs. The presented paper aims to guide readers on how to assign individual health promotion and environmental health services to public health or primary care settings. Survey tools were developed based on EPHO 2, 3 and 4; there were six key informant surveys out of 18 contacted completed via e-mails by informants working in Denmark on health promotion and five face-to-face interviews were conducted in Australia (Melbourne and Victoria state with experts from environmental health, public health and a physician. Based on interviews, we developed a set of indicators to support the assignment process. Population or individual focus, a system approach or one-to-one approach, dealing with hazards or dealing with effects, being proactive or reactive were identified as main element of the decision tool. Assignment of public health services to one of two settings proved to be possible in some cases, whereas in many there is no clear distinction between the two settings. National context might be the one which guides delivery of public health services.

  14. The Delivery of Health Promotion and Environmental Health Services; Public Health or Primary Care Settings?

    Science.gov (United States)

    Bjørn Jensen, Lene; Lukic, Irena; Gulis, Gabriel

    2018-05-07

    The WHO Regional Office for Europe developed a set of public health functions resulting in the ten Essential Public Health Operations (EPHO). Public health or primary care settings seem to be favorable to embrace all actions included into EPHOs. The presented paper aims to guide readers on how to assign individual health promotion and environmental health services to public health or primary care settings. Survey tools were developed based on EPHO 2, 3 and 4; there were six key informant surveys out of 18 contacted completed via e-mails by informants working in Denmark on health promotion and five face-to-face interviews were conducted in Australia (Melbourne and Victoria state) with experts from environmental health, public health and a physician. Based on interviews, we developed a set of indicators to support the assignment process. Population or individual focus, a system approach or one-to-one approach, dealing with hazards or dealing with effects, being proactive or reactive were identified as main element of the decision tool. Assignment of public health services to one of two settings proved to be possible in some cases, whereas in many there is no clear distinction between the two settings. National context might be the one which guides delivery of public health services.

  15. Overcoming Barriers in Unhealthy Settings

    Directory of Open Access Journals (Sweden)

    Michael K. Lemke

    2016-03-01

    Full Text Available We investigated the phenomenon of sustained health-supportive behaviors among long-haul commercial truck drivers, who belong to an occupational segment with extreme health disparities. With a focus on setting-level factors, this study sought to discover ways in which individuals exhibit resiliency while immersed in endemically obesogenic environments, as well as understand setting-level barriers to engaging in health-supportive behaviors. Using a transcendental phenomenological research design, 12 long-haul truck drivers who met screening criteria were selected using purposeful maximum sampling. Seven broad themes were identified: access to health resources, barriers to health behaviors, recommended alternative settings, constituents of health behavior, motivation for health behaviors, attitude toward health behaviors, and trucking culture. We suggest applying ecological theories of health behavior and settings approaches to improve driver health. We also propose the Integrative and Dynamic Healthy Commercial Driving (IDHCD paradigm, grounded in complexity science, as a new theoretical framework for improving driver health outcomes.

  16. Set theory and physics

    Energy Technology Data Exchange (ETDEWEB)

    Svozil, K. [Univ. of Technology, Vienna (Austria)

    1995-11-01

    Inasmuch as physical theories are formalizable, set theory provides a framework for theoretical physics. Four speculations about the relevance of set theoretical modeling for physics are presented: the role of transcendental set theory (i) in chaos theory, (ii) for paradoxical decompositions of solid three-dimensional objects, (iii) in the theory of effective computability (Church-Turing thesis) related to the possible {open_quotes}solution of supertasks,{close_quotes} and (iv) for weak solutions. Several approaches to set theory and their advantages and disadvantages for physical applications are discussed: Cantorian {open_quotes}naive{close_quotes} (i.e., nonaxiomatic) set theory, contructivism, and operationalism. In the author`s opinion, an attitude, of {open_quotes}suspended attention{close_quotes} (a term borrowed from psychoanalysis) seems most promising for progress. Physical and set theoretical entities must be operationalized wherever possible. At the same time, physicists should be open to {open_quotes}bizarre{close_quotes} or {open_quotes}mindboggling{close_quotes} new formalisms, which need not be operationalizable or testable at the time of their creation, but which may successfully lead to novel fields of phenomenology and technology.

  17. Setting conservation priorities.

    Science.gov (United States)

    Wilson, Kerrie A; Carwardine, Josie; Possingham, Hugh P

    2009-04-01

    A generic framework for setting conservation priorities based on the principles of classic decision theory is provided. This framework encapsulates the key elements of any problem, including the objective, the constraints, and knowledge of the system. Within the context of this framework the broad array of approaches for setting conservation priorities are reviewed. While some approaches prioritize assets or locations for conservation investment, it is concluded here that prioritization is incomplete without consideration of the conservation actions required to conserve the assets at particular locations. The challenges associated with prioritizing investments through time in the face of threats (and also spatially and temporally heterogeneous costs) can be aided by proper problem definition. Using the authors' general framework for setting conservation priorities, multiple criteria can be rationally integrated and where, how, and when to invest conservation resources can be scheduled. Trade-offs are unavoidable in priority setting when there are multiple considerations, and budgets are almost always finite. The authors discuss how trade-offs, risks, uncertainty, feedbacks, and learning can be explicitly evaluated within their generic framework for setting conservation priorities. Finally, they suggest ways that current priority-setting approaches may be improved.

  18. Inference of boundaries in causal sets

    Science.gov (United States)

    Cunningham, William J.

    2018-05-01

    We investigate the extrinsic geometry of causal sets in (1+1) -dimensional Minkowski spacetime. The properties of boundaries in an embedding space can be used not only to measure observables, but also to supplement the discrete action in the partition function via discretized Gibbons–Hawking–York boundary terms. We define several ways to represent a causal set using overlapping subsets, which then allows us to distinguish between null and non-null bounding hypersurfaces in an embedding space. We discuss algorithms to differentiate between different types of regions, consider when these distinctions are possible, and then apply the algorithms to several spacetime regions. Numerical results indicate the volumes of timelike boundaries can be measured to within 0.5% accuracy for flat boundaries and within 10% accuracy for highly curved boundaries for medium-sized causal sets with N  =  214 spacetime elements.

  19. Occasion setting, inhibition, and the contextual control of extinction in Pavlovian and instrumental (operant) learning.

    Science.gov (United States)

    Trask, Sydney; Thrailkill, Eric A; Bouton, Mark E

    2017-04-01

    An occasion setter is a stimulus that modulates the ability of another stimulus to control behavior. A rich history of experimental investigation has identified several important properties that define occasion setters and the conditions that give rise to occasion setting. In this paper, we first consider the basic hallmarks of occasion setting in Pavlovian conditioning. We then review research that has examined the mechanisms underlying the crucial role of context in Pavlovian and instrumental extinction. In Pavlovian extinction, evidence suggests that the extinction context can function as a negative occasion setter whose role is to disambiguate the current meaning of the conditioned stimulus; the conditioning context can also function as a positive occasion setter. In operant extinction, in contrast, the extinction context may directly inhibit the response, and the conditioning context can directly excite it. We outline and discuss the key results supporting these distinctions. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Distinct Profiling of Antimicrobial Peptide Families

    KAUST Repository

    Khamis, Abdullah M.

    2014-11-10

    Motivation: The increased prevalence of multi-drug resistant (MDR) pathogens heightens the need to design new antimicrobial agents. Antimicrobial peptides (AMPs) exhibit broad-spectrum potent activity against MDR pathogens and kills rapidly, thus giving rise to AMPs being recognized as a potential substitute for conventional antibiotics. Designing new AMPs using current in-silico approaches is, however, challenging due to the absence of suitable models, large number of design parameters, testing cycles, production time and cost. To date, AMPs have merely been categorized into families according to their primary sequences, structures and functions. The ability to computationally determine the properties that discriminate AMP families from each other could help in exploring the key characteristics of these families and facilitate the in-silico design of synthetic AMPs. Results: Here we studied 14 AMP families and sub-families. We selected a specific description of AMP amino acid sequence and identified compositional and physicochemical properties of amino acids that accurately distinguish each AMP family from all other AMPs with an average sensitivity, specificity and precision of 92.88%, 99.86% and 95.96%, respectively. Many of our identified discriminative properties have been shown to be compositional or functional characteristics of the corresponding AMP family in literature. We suggest that these properties could serve as guides for in-silico methods in design of novel synthetic AMPs. The methodology we developed is generic and has a potential to be applied for characterization of any protein family.

  1. Technology Entrepreneurship: Overview, Definition, and Distinctive Aspects

    Directory of Open Access Journals (Sweden)

    Tony Bailetti

    2012-02-01

    Full Text Available Technology entrepreneurship lies at the heart of many important debates, including those around launching and growing firms, regional economic development, selecting the appropriate stakeholders to take ideas to markets, and educating managers, engineers, and scientists. Unless a generally accepted definition of technology entrepreneurship is established, however, these debates lose their focus. The purpose of this article is to identify the themes that dominate the technology entrepreneurship literature, provide a definition of technology entrepreneurship, and identify its distinguishing aspects relative to economics, entrepreneurship, and management. The author argues that technology entrepreneurship is an investment in a project that assembles and deploys specialized individuals and heterogeneous assets to create and capture value for the firm. What distinguishes technology entrepreneurship from other entrepreneurship types (e.g., social entrepreneurship, small business management, and self-employment is the collaborative experimentation and production of new products, assets, and their attributes, which are intricately related to advances in scientific and technological knowledge and the firm’s asset ownership rights.

  2. Distinct Profiling of Antimicrobial Peptide Families

    KAUST Repository

    Khamis, Abdullah M.; Essack, Magbubah; Gao, Xin; Bajic, Vladimir B.

    2014-01-01

    Motivation: The increased prevalence of multi-drug resistant (MDR) pathogens heightens the need to design new antimicrobial agents. Antimicrobial peptides (AMPs) exhibit broad-spectrum potent activity against MDR pathogens and kills rapidly, thus giving rise to AMPs being recognized as a potential substitute for conventional antibiotics. Designing new AMPs using current in-silico approaches is, however, challenging due to the absence of suitable models, large number of design parameters, testing cycles, production time and cost. To date, AMPs have merely been categorized into families according to their primary sequences, structures and functions. The ability to computationally determine the properties that discriminate AMP families from each other could help in exploring the key characteristics of these families and facilitate the in-silico design of synthetic AMPs. Results: Here we studied 14 AMP families and sub-families. We selected a specific description of AMP amino acid sequence and identified compositional and physicochemical properties of amino acids that accurately distinguish each AMP family from all other AMPs with an average sensitivity, specificity and precision of 92.88%, 99.86% and 95.96%, respectively. Many of our identified discriminative properties have been shown to be compositional or functional characteristics of the corresponding AMP family in literature. We suggest that these properties could serve as guides for in-silico methods in design of novel synthetic AMPs. The methodology we developed is generic and has a potential to be applied for characterization of any protein family.

  3. Radiograph identifying means

    International Nuclear Information System (INIS)

    Sheldon, A.D.

    1983-01-01

    A flexible character-indentable plastics embossing tape is backed by and bonded to a lead strip, not more than 0.025 inches thick, to form a tape suitable for identifying radiographs. The lead strip is itself backed by a relatively thin and flimsy plastics or fabric strip which, when removed, allows the lead plastic tape to be pressure-bonded to the surface to be radiographed. A conventional tape-embossing gun is used to indent the desired characters in succession into the lead-backed tape, without necessarily severing the lead; and then the backing strip is peeled away to expose the layer of adhesive which pressure-bonds the indented tape to the object to be radiographed. X-rays incident on the embossed tape will cause the raised characters to show up dark on the subsequently-developed film, whilst the raised side areas will show up white. Each character will thus stand out on the developed film. (author)

  4. Distinct timing mechanisms produce discrete and continuous movements.

    Directory of Open Access Journals (Sweden)

    Raoul Huys

    2008-04-01

    Full Text Available The differentiation of discrete and continuous movement is one of the pillars of motor behavior classification. Discrete movements have a definite beginning and end, whereas continuous movements do not have such discriminable end points. In the past decade there has been vigorous debate whether this classification implies different control processes. This debate up until the present has been empirically based. Here, we present an unambiguous non-empirical classification based on theorems in dynamical system theory that sets discrete and continuous movements apart. Through computational simulations of representative modes of each class and topological analysis of the flow in state space, we show that distinct control mechanisms underwrite discrete and fast rhythmic movements. In particular, we demonstrate that discrete movements require a time keeper while fast rhythmic movements do not. We validate our computational findings experimentally using a behavioral paradigm in which human participants performed finger flexion-extension movements at various movement paces and under different instructions. Our results demonstrate that the human motor system employs different timing control mechanisms (presumably via differential recruitment of neural subsystems to accomplish varying behavioral functions such as speed constraints.

  5. Uniform and Complementary Social Interaction: Distinct Pathways to Solidarity.

    Science.gov (United States)

    Koudenburg, Namkje; Postmes, Tom; Gordijn, Ernestine H; van Mourik Broekman, Aafke

    2015-01-01

    We examine how different forms of co-action give rise to feelings of solidarity. We propose that (a) coordinated action elicits a sense of solidarity, and (b) the process through which such solidarity emerges differs for different forms of co-action. We suggest that whether solidarity within groups emerges from uniform action (e.g. synchronizing, as when people speak in unison) or from more complementary forms of action (e.g. alternating, when speaking in turns) has important consequences for the emergent position of individuals within the group. Uniform action relies on commonality, leaving little scope for individuality. In complementary action each individual makes a distinctive contribution to the group, thereby increasing a sense of personal value to the group, which should contribute to the emergence of solidarity. The predictions receive support from five studies, in which we study groups in laboratory and field settings. Results show that both complementary and uniform co-action increase a sense of solidarity compared to control conditions. However, in the complementary action condition, but not in the uniform action (or synchrony) condition, the effect on feelings of solidarity is mediated by a sense of personal value to the group.

  6. Excitations Partition into Two Distinct Populations in Bulk Perovskites

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Lili [Department of Chemistry, The James Franck Institute, The Institute for Biophysical Dynamics, The University of Chicago, Chicago IL 60637 USA; Brawand, Nicholas P. [The Institute for Molecular Engineering, The University of Chicago, Chicago IL 60637 USA; Vörös, Márton [Materials Science Division, Argonne National Laboratory, Lemont IL 60439 USA; Dahlberg, Peter D. [Department of Chemistry, The James Franck Institute, The Institute for Biophysical Dynamics, The University of Chicago, Chicago IL 60637 USA; Chemical Sciences and Engineering Division, Argonne National Laboratory, Lemont IL 60439 USA; Otto, John P. [Department of Chemistry, The James Franck Institute, The Institute for Biophysical Dynamics, The University of Chicago, Chicago IL 60637 USA; Williams, Nicholas E. [Department of Chemistry, The James Franck Institute, The Institute for Biophysical Dynamics, The University of Chicago, Chicago IL 60637 USA; Tiede, David M. [Chemical Sciences and Engineering Division, Argonne National Laboratory, Lemont IL 60439 USA; Galli, Giulia [The Institute for Molecular Engineering, The University of Chicago, Chicago IL 60637 USA; Materials Science Division, Argonne National Laboratory, Lemont IL 60439 USA; Engel, Gregory S. [Department of Chemistry, The James Franck Institute, The Institute for Biophysical Dynamics, The University of Chicago, Chicago IL 60637 USA

    2018-01-09

    Organolead halide perovskites convert optical excitations to charge carriers with remarkable efficiency in optoelectronic devices. Previous research predominantly documents dynamics in perovskite thin films; however, extensive disorder in this platform may obscure the observed carrier dynamics. Here, carrier dynamics in perovskite single-domain single crystals is examined by performing transient absorption spectroscopy in a transmissive geometry. Two distinct sets of carrier populations that coexist at the same radiation fluence, but display different decay dynamics, are observed: one dominated by second-order recombination and the other by third-order recombination. Based on ab initio simulations, this observation is found to be most consistent with the hypothesis that free carriers and localized carriers coexist due to polaron formation. The calculations suggest that polarons will form in both CH3NH3PbBr3 and CH3NH3PbI3 crystals, but that they are more pronounced in CH3NH3PbBr3. Single-crystal CH3NH3PbBr3 could represent the key to understanding the impact of polarons on the transport properties of perovskite optoelectronic devices.

  7. Quantum mechanics over sets

    Science.gov (United States)

    Ellerman, David

    2014-03-01

    In models of QM over finite fields (e.g., Schumacher's ``modal quantum theory'' MQT), one finite field stands out, Z2, since Z2 vectors represent sets. QM (finite-dimensional) mathematics can be transported to sets resulting in quantum mechanics over sets or QM/sets. This gives a full probability calculus (unlike MQT with only zero-one modalities) that leads to a fulsome theory of QM/sets including ``logical'' models of the double-slit experiment, Bell's Theorem, QIT, and QC. In QC over Z2 (where gates are non-singular matrices as in MQT), a simple quantum algorithm (one gate plus one function evaluation) solves the Parity SAT problem (finding the parity of the sum of all values of an n-ary Boolean function). Classically, the Parity SAT problem requires 2n function evaluations in contrast to the one function evaluation required in the quantum algorithm. This is quantum speedup but with all the calculations over Z2 just like classical computing. This shows definitively that the source of quantum speedup is not in the greater power of computing over the complex numbers, and confirms the idea that the source is in superposition.

  8. Parameter identifiability and redundancy: theoretical considerations.

    Directory of Open Access Journals (Sweden)

    Mark P Little

    Full Text Available BACKGROUND: Models for complex biological systems may involve a large number of parameters. It may well be that some of these parameters cannot be derived from observed data via regression techniques. Such parameters are said to be unidentifiable, the remaining parameters being identifiable. Closely related to this idea is that of redundancy, that a set of parameters can be expressed in terms of some smaller set. Before data is analysed it is critical to determine which model parameters are identifiable or redundant to avoid ill-defined and poorly convergent regression. METHODOLOGY/PRINCIPAL FINDINGS: In this paper we outline general considerations on parameter identifiability, and introduce the notion of weak local identifiability and gradient weak local identifiability. These are based on local properties of the likelihood, in particular the rank of the Hessian matrix. We relate these to the notions of parameter identifiability and redundancy previously introduced by Rothenberg (Econometrica 39 (1971 577-591 and Catchpole and Morgan (Biometrika 84 (1997 187-196. Within the widely used exponential family, parameter irredundancy, local identifiability, gradient weak local identifiability and weak local identifiability are shown to be largely equivalent. We consider applications to a recently developed class of cancer models of Little and Wright (Math Biosciences 183 (2003 111-134 and Little et al. (J Theoret Biol 254 (2008 229-238 that generalize a large number of other recently used quasi-biological cancer models. CONCLUSIONS/SIGNIFICANCE: We have shown that the previously developed concepts of parameter local identifiability and redundancy are closely related to the apparently weaker properties of weak local identifiability and gradient weak local identifiability--within the widely used exponential family these concepts largely coincide.

  9. Identifying shortcomings in the measurement of service quality.

    Science.gov (United States)

    Fogarty, G; Catts, R; Forlin, C

    2000-01-01

    SERVPEFR, the performance component of the Service Quality Scale (SERVQUAL), has been shown to measure five underlying dimensions corresponding to Tangibles, Reliability, Responsiveness, Assurance, and Empathy (Parasuraman, Zeithaml, & Berry, 1988). This paper describes three separate studies employing SERVPERF in an Australian context. In the first of these studies (N = 113), a shortened 15-item version of the SERVPERF scale (SERVPERF-R) was found to be suitable for use in an Australian small business setting. A five-factor structure was identifiable but the factors were highly correlated, suggesting that they were not clearly distinct. The tendency for marked negative skewness observed by other researchers was also noted here. A follow-up study involving three other small businesses (N = 212) used Rasch analysis to test assumptions about the spread of items on the underlying continuum. These analyses indicated that there is an even, though narrow, spread of items across the continuum. The Rasch analysis suggested that the items in both SERVPERF and SERVPERF-R are too easy to rate highly and that more "difficult" items need to be added to the scale. The third study (N = 122) was conducted using a version of SERVPERF-R that included seven new items intended to extend the range of the scale. The new items, however, did not achieve this desirable outcome. The implications for service quality assessment are discussed.

  10. NSAID gastropathy and enteropathy: distinct pathogenesis likely necessitates distinct prevention strategies.

    Science.gov (United States)

    Wallace, John L

    2012-01-01

    The mechanisms underlying the ability of nonsteroidal anti-inflammatory drugs (NSAIDs) to cause ulceration in the stomach and proximal duodenum are well understood, and this injury can largely be prevented through suppression of gastric acid secretion (mainly with proton pump inhibitors). In contrast, the pathogenesis of small intestinal injury induced by NSAIDs is less well understood, involving more complex mechanisms than those in the stomach and proximal duodenum. There is clear evidence for important contributions to NSAID enteropathy of enteric bacteria, bile and enterohepatic recirculation of the NSAID. There is no evidence that suppression of gastric acid secretion will reduce the incidence or severity of NSAID enteropathy. Indeed, clinical data suggest little, if any, benefit. Animal studies suggest a significant exacerbation of NSAID enteropathy when proton pump inhibitors are co-administered with the NSAID. This worsening of damage appears to be linked to changes in the number and types of bacteria in the small intestine during proton pump inhibitor therapy. The distinct mechanisms of NSAID-induced injury in the stomach/proximal duodenum versus the more distal small intestine likely dictate distinct strategies for prevention. © 2011 The Author. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  11. The Model Confidence Set

    DEFF Research Database (Denmark)

    Hansen, Peter Reinhard; Lunde, Asger; Nason, James M.

    The paper introduces the model confidence set (MCS) and applies it to the selection of models. A MCS is a set of models that is constructed such that it will contain the best model with a given level of confidence. The MCS is in this sense analogous to a confidence interval for a parameter. The MCS......, beyond the comparison of models. We apply the MCS procedure to two empirical problems. First, we revisit the inflation forecasting problem posed by Stock and Watson (1999), and compute the MCS for their set of inflation forecasts. Second, we compare a number of Taylor rule regressions and determine...... the MCS of the best in terms of in-sample likelihood criteria....

  12. Revitalizing the setting approach

    DEFF Research Database (Denmark)

    Bloch, Paul; Toft, Ulla; Reinbach, Helene Christine

    2014-01-01

    BackgroundThe concept of health promotion rests on aspirations aiming at enabling people to increase control over and improve their health. Health promotion action is facilitated in settings such as schools, homes and work places. As a contribution to the promotion of healthy lifestyles, we have ...... approach is based on ecological and whole-systems thinking, and stipulates important principles and values of integration, participation, empowerment, context and knowledge-based development....... further developed the setting approach in an effort to harmonise it with contemporary realities (and complexities) of health promotion and public health action. The paper introduces a modified concept, the supersetting approach, which builds on the optimised use of diverse and valuable resources embedded...... in local community settings and on the strengths of social interaction and local ownership as drivers of change processes. Interventions based on a supersetting approach are first and foremost characterised by being integrated, but also participatory, empowering, context-sensitive and knowledge...

  13. Set theory and logic

    CERN Document Server

    Stoll, Robert R

    1979-01-01

    Set Theory and Logic is the result of a course of lectures for advanced undergraduates, developed at Oberlin College for the purpose of introducing students to the conceptual foundations of mathematics. Mathematics, specifically the real number system, is approached as a unity whose operations can be logically ordered through axioms. One of the most complex and essential of modern mathematical innovations, the theory of sets (crucial to quantum mechanics and other sciences), is introduced in a most careful concept manner, aiming for the maximum in clarity and stimulation for further study in

  14. Nonmeasurable sets and functions

    CERN Document Server

    Kharazishvili, Alexander

    2004-01-01

    The book is devoted to various constructions of sets which are nonmeasurable with respect to invariant (more generally, quasi-invariant) measures. Our starting point is the classical Vitali theorem stating the existence of subsets of the real line which are not measurable in the Lebesgue sense. This theorem stimulated the development of the following interesting topics in mathematics:1. Paradoxical decompositions of sets in finite-dimensional Euclidean spaces;2. The theory of non-real-valued-measurable cardinals;3. The theory of invariant (quasi-invariant)extensions of invariant (quasi-invaria

  15. Why quasi-sets?

    Directory of Open Access Journals (Sweden)

    Décio Krause

    2002-11-01

    Full Text Available Quasi-set theory was developed to deal with collections of indistinguishable objects. In standard mathematics, there are no such kind of entities, for indistinguishability (agreement with respect to all properties entails numerical identity. The main motivation underlying such a theory is of course quantum physics, for collections of indistinguishable (’identical’ in the physicists’ jargon particles cannot be regarded as ’sets’ of standard set theories, which are collections of distinguishable objects. In this paper, a rationale for the development of such a theory is presented, motivated by Heinz Post’s claim that indistinguishability ofquantum entities should be attributed ’right at the start’.

  16. Combinatorics of finite sets

    CERN Document Server

    Anderson, Ian

    2011-01-01

    Coherent treatment provides comprehensive view of basic methods and results of the combinatorial study of finite set systems. The Clements-Lindstrom extension of the Kruskal-Katona theorem to multisets is explored, as is the Greene-Kleitman result concerning k-saturated chain partitions of general partially ordered sets. Connections with Dilworth's theorem, the marriage problem, and probability are also discussed. Each chapter ends with a helpful series of exercises and outline solutions appear at the end. ""An excellent text for a topics course in discrete mathematics."" - Bulletin of the Ame

  17. Creating fair lineups for suspects with distinctive features

    OpenAIRE

    Zarkadi, Theodora; Wade, Kimberley A.; Stewart, Neil

    2009-01-01

    In their descriptions, eyewitnesses often refer to a culprit's distinctive facial features. However, in a police lineup, selecting the only member with the described distinctive feature is unfair to the suspect and provides the police with little further information. For fair and informative lineups, the distinctive feature should be either replicated across foils or concealed on the target. In the present experiments, replication produced more correct identifications in target-present lineup...

  18. The Amish: A Distinctive Cosmos Serving Well For A Philological Dualism

    OpenAIRE

    Erbay, Şakire

    2016-01-01

    The success of the Amish in maintaining their ancestral language until now has been well-documented in the related literature, and the arguments about this maintenance sound not to dry up any time soon. At the heart of the existing discussions stand the questions of how and to what extent they have managed to protect their language. The present theoretical commentary serves as an explanatory account of this distinctive issue. To that end, without going into much detail , the author first sets...

  19. Distinctive identity claims in federal systems: Judicial policing of subnational variance

    DEFF Research Database (Denmark)

    Abat Ninet, Antoni; Gardner, James A.

    2016-01-01

    nationally imposed limits on their power typically have at their disposal many tools with which to press against formal boundaries. Federal systems, moreover, frequently display a surprising degree of tolerance for subnational obstruction, disobedience, and other behaviors intended to expand subnational...... authority and influence, even over national objection. This tolerance, however, has limits. In this article, we examine a set of rulings by national constitutional courts invalidating formalized claims by subnational units to a distinctive subnational identity. The emphatically negative reactions...

  20. The distinct proteome of placental malaria parasites.

    Energy Technology Data Exchange (ETDEWEB)

    Fried, Michal; Hixson, Kim K.; Anderson, Lori; Ogata, Yuko; Mutabingwa, Theonest K.; Duffy, Patrick E.

    2007-09-01

    Malaria proteins expressed on the surface of Plasmodium falciparum infected erythrocytes (IE) mediate adhesion and are targeted by protective immune responses. During pregnancy, IE sequester in the placenta. Placental IE bind to the molecule chondroitin sulfate A (CSA) and preferentially transcribe the gene that encodes VAR2CSA, a member of the PfEMP1 variant surface antigen family. Over successive pregnancies women develop specific immunity to CSA-binding IE and antibodies to VAR2CSA. We used tandem mass spectrometry together with accurate mass and time tag technology to study IE membrane fractions of placental parasites. VAR2CSA peptides were detected in placental IE and in IE from children, but the MC variant of VAR2CSA was specifically associated with placental IE. We identified six conserved hypothetical proteins with putative TM or signal peptides that were exclusively expressed by the placental IE, and 11 such proteins that were significantly more abundant in placental IE. One of these hypothetical proteins, PFI1785w, is a 42kDa molecule detected by Western blot in parasites infecting pregnant women but not those infecting children.

  1. Prices and Price Setting

    NARCIS (Netherlands)

    R.P. Faber (Riemer)

    2010-01-01

    textabstractThis thesis studies price data and tries to unravel the underlying economic processes of why firms have chosen these prices. It focuses on three aspects of price setting. First, it studies whether the existence of a suggested price has a coordinating effect on the prices of firms.

  2. Cobham recursive set functions

    Czech Academy of Sciences Publication Activity Database

    Beckmann, A.; Buss, S.; Friedman, S.-D.; Müller, M.; Thapen, Neil

    2016-01-01

    Roč. 167, č. 3 (2016), s. 335-369 ISSN 0168-0072 R&D Projects: GA ČR GBP202/12/G061 Institutional support: RVO:67985840 Keywords : set function * polynomial time * Cobham recursion Subject RIV: BA - General Mathematics Impact factor: 0.647, year: 2016 http://www.sciencedirect.com/science/article/pii/S0168007215001293

  3. SET-Routes programme

    CERN Multimedia

    Marietta Schupp, EMBL Photolab

    2008-01-01

    Dr Sabine Hentze, specialist in human genetics, giving an Insight Lecture entitled "Human Genetics – Diagnostics, Indications and Ethical Issues" on 23 September 2008 at EMBL Heidelberg. Activities in a achool in Budapest during a visit of Angela Bekesi, Ambassadors for the SET-Routes programme.

  4. The Crystal Set

    Science.gov (United States)

    Greenslade, Thomas B., Jr.

    2014-01-01

    In past issues of this journal, the late H. R. Crane wrote a long series of articles under the running title of "How Things Work." In them, Dick dealt with many questions that physics teachers asked themselves, but did not have the time to answer. This article is my attempt to work through the physics of the crystal set, which I thought…

  5. State-set branching

    DEFF Research Database (Denmark)

    Jensen, Rune Møller; Veloso, Manuela M.; Bryant, Randal E.

    2008-01-01

    In this article, we present a framework called state-set branching that combines symbolic search based on reduced ordered Binary Decision Diagrams (BDDs) with best-first search, such as A* and greedy best-first search. The framework relies on an extension of these algorithms from expanding a sing...

  6. Generalized rough sets

    International Nuclear Information System (INIS)

    Rady, E.A.; Kozae, A.M.; Abd El-Monsef, M.M.E.

    2004-01-01

    The process of analyzing data under uncertainty is a main goal for many real life problems. Statistical analysis for such data is an interested area for research. The aim of this paper is to introduce a new method concerning the generalization and modification of the rough set theory introduced early by Pawlak [Int. J. Comput. Inform. Sci. 11 (1982) 314

  7. Therapists in Oncology Settings

    Science.gov (United States)

    Hendrick, Susan S.

    2013-01-01

    This article describes the author's experiences of working with cancer patients/survivors both individually and in support groups for many years, across several settings. It also documents current best-practice guidelines for the psychosocial treatment of cancer patients/survivors and their families. The author's view of the important qualities…

  8. Probabilistic Open Set Recognition

    Science.gov (United States)

    Jain, Lalit Prithviraj

    Real-world tasks in computer vision, pattern recognition and machine learning often touch upon the open set recognition problem: multi-class recognition with incomplete knowledge of the world and many unknown inputs. An obvious way to approach such problems is to develop a recognition system that thresholds probabilities to reject unknown classes. Traditional rejection techniques are not about the unknown; they are about the uncertain boundary and rejection around that boundary. Thus traditional techniques only represent the "known unknowns". However, a proper open set recognition algorithm is needed to reduce the risk from the "unknown unknowns". This dissertation examines this concept and finds existing probabilistic multi-class recognition approaches are ineffective for true open set recognition. We hypothesize the cause is due to weak adhoc assumptions combined with closed-world assumptions made by existing calibration techniques. Intuitively, if we could accurately model just the positive data for any known class without overfitting, we could reject the large set of unknown classes even under this assumption of incomplete class knowledge. For this, we formulate the problem as one of modeling positive training data by invoking statistical extreme value theory (EVT) near the decision boundary of positive data with respect to negative data. We provide a new algorithm called the PI-SVM for estimating the unnormalized posterior probability of class inclusion. This dissertation also introduces a new open set recognition model called Compact Abating Probability (CAP), where the probability of class membership decreases in value (abates) as points move from known data toward open space. We show that CAP models improve open set recognition for multiple algorithms. Leveraging the CAP formulation, we go on to describe the novel Weibull-calibrated SVM (W-SVM) algorithm, which combines the useful properties of statistical EVT for score calibration with one-class and binary

  9. The Honolulu posttraumatic stress disorder stimulus set.

    Science.gov (United States)

    Chemtob, C M; Roitblat, H L; Hamada, R S; Carlson, J G; Muraoka, M Y; Bauer, G B

    1997-04-01

    We present word and picture stimuli constituting a validated stimulus set appropriate for cognitive investigations of posttraumatic stress disorder (PTSD). Combat related and neutral words and pictures were rated by Vietnam veterans with PTSD and by three comparison groups along four dimensions: unpleasantness, Vietnam relevance, stressfulness, and memorability. There were distinctive patterns of responses by the PTSD group which efficiently discriminated the individuals in this group from those in the control groups. These stimuli have the potential to be developed as a diagnostic instrument.

  10. Identifiability of PBPK Models with Applications to ...

    Science.gov (United States)

    Any statistical model should be identifiable in order for estimates and tests using it to be meaningful. We consider statistical analysis of physiologically-based pharmacokinetic (PBPK) models in which parameters cannot be estimated precisely from available data, and discuss different types of identifiability that occur in PBPK models and give reasons why they occur. We particularly focus on how the mathematical structure of a PBPK model and lack of appropriate data can lead to statistical models in which it is impossible to estimate at least some parameters precisely. Methods are reviewed which can determine whether a purely linear PBPK model is globally identifiable. We propose a theorem which determines when identifiability at a set of finite and specific values of the mathematical PBPK model (global discrete identifiability) implies identifiability of the statistical model. However, we are unable to establish conditions that imply global discrete identifiability, and conclude that the only safe approach to analysis of PBPK models involves Bayesian analysis with truncated priors. Finally, computational issues regarding posterior simulations of PBPK models are discussed. The methodology is very general and can be applied to numerous PBPK models which can be expressed as linear time-invariant systems. A real data set of a PBPK model for exposure to dimethyl arsinic acid (DMA(V)) is presented to illustrate the proposed methodology. We consider statistical analy

  11. Setting priorities for safeguards upgrades

    International Nuclear Information System (INIS)

    Al-Ayat, R.A.; Judd, B.R.; Patenaude, C.J.; Sicherman, A.

    1987-01-01

    This paper describes an analytic approach and a computer program for setting priorities among safeguards upgrades. The approach provides safeguards decision makers with a systematic method for allocating their limited upgrade resources. The priorities are set based on the upgrades cost and their contribution to safeguards effectiveness. Safeguards effectiveness is measured by the probability of defeat for a spectrum of potential insider and outsider adversaries. The computer program, MI$ER, can be used alone or as a companion to ET and SAVI, programs designed to evaluate safeguards effectiveness against insider and outsider threats, respectively. Setting the priority required judgments about the relative importance (threat likelihoods and consequences) of insider and outsider threats. Although these judgments are inherently subjective, MI$ER can analyze the sensitivity of the upgrade priorities to these weights and determine whether or not they are critical to the priority ranking. MI$ER produces tabular and graphical results for comparing benefits and identifying the most cost-effective upgrades for a given expenditure. This framework provides decision makers with an explicit and consistent analysis to support their upgrades decisions and to allocate the safeguards resources in a cost-effective manner

  12. Distinct growth of the nasomaxillary complex in Au. sediba.

    Science.gov (United States)

    Lacruz, Rodrigo S; Bromage, Timothy G; O'Higgins, Paul; Toro-Ibacache, Viviana; Warshaw, Johanna; Berger, Lee R

    2015-10-15

    Studies of facial ontogeny in immature hominins have contributed significantly to understanding the evolution of human growth and development. The recently discovered hominin species Autralopithecus sediba is represented by a well-preserved and nearly complete facial skeleton of a juvenile (MH1) which shows a derived facial anatomy. We examined MH1 using high radiation synchrotron to interpret features of the oronasal complex pertinent to facial growth. We also analyzed bone surface microanatomy to identify and map fields of bone deposition and bone resorption, which affect the development of the facial skeleton. The oronasal anatomy (premaxilla-palate-vomer architecture) is similar to other Australopithecus species. However surface growth remodeling of the midface (nasomaxillary complex) differs markedly from Australopithecus, Paranthropus, early Homo and from KNM-WT 15000 (H. erectus/ergaster) showing a distinct distribution of vertically disposed alternating depository and resorptive fields in relation to anterior dental roots and the subnasal region. The ontogeny of the MH1 midface superficially resembles some H. sapiens in the distribution of remodeling fields. The facial growth of MH1 appears unique among early hominins representing an evolutionary modification in facial ontogeny at 1.9 my, or to changes in masticatory system loading associated with diet.

  13. Differentiating intolerance of uncertainty from three related but distinct constructs.

    Science.gov (United States)

    Rosen, Natalie O; Ivanova, Elena; Knäuper, Bärbel

    2014-01-01

    Individual differences in uncertainty have been associated with heightened anxiety, stress and approach-oriented coping. Intolerance of uncertainty (IU) is a trait characteristic that arises from negative beliefs about uncertainty and its consequences. Researchers have established the central role of IU in the development of problematic worry and maladaptive coping, highlighting the importance of this construct to anxiety disorders. However, there is a need to improve our understanding of the phenomenology of IU. The goal of this paper was to present hypotheses regarding the similarities and differences between IU and three related constructs--intolerance of ambiguity, uncertainty orientation, and need for cognitive closure--and to call for future empirical studies to substantiate these hypotheses. To assist with achieving this goal, we conducted a systematic review of the literature, which also served to identify current gaps in knowledge. This paper differentiates these constructs by outlining each definition and general approaches to assessment, reviewing the existing empirical relations, and proposing theoretical similarities and distinctions. Findings may assist researchers in selecting the appropriate construct to address their research questions. Future research directions for the application of these constructs, particularly within the field of clinical and health psychology, are discussed.

  14. Distinct neutrophil subpopulations phenotype by flow cytometry in myelodysplastic syndromes.

    Science.gov (United States)

    Vikentiou, Myrofora; Psarra, Katerina; Kapsimali, Violetta; Liapis, Konstantinos; Michael, Michalis; Tsionos, Konstantinos; Lianidou, Evi; Papasteriades, Chryssa

    2009-03-01

    The cardinal feature of myelodysplastic syndromes (MDS) is dysplasia involving one or more myeloid cell lineages. In the present study, we used 4-color flow cytometric analysis to investigate dysgranulopoiesis in bone marrow specimens from 65 patients with MDS. The antigen expression patterns of total neutrophil granulocytes (TNG) and of the two distinct neutrophil granulocytic subpopulations (NGSs), NGS-1 (dimmer CD45 expression) and NGS-2 (stronger CD45 expression) identified on the side scatter (SS) vs. CD45-intensity plot, were studied. The neutrophil granulocytes from patients with MDS showed characteristic antigen expression aberrancies which were more pronounced in NGS-2 subpopulation. Studying separately the NGS-2 subpopulation with the CD16/MPO/LF combination, the low CD16(+)/MPO(+) and low CD16(+)/LF(+) percentages seemed to discriminate between lower-risk and higher-risk patients with MDS in most occasions. Furthermore, a detailed assessment of the NGS-1 and NGS-2 immunophenotypic patterns revealed early dysplastic changes, not otherwise observed by standard TNG analysis, especially in cases of lower-risk MDS.

  15. Pyrosequencing Analysis of Subgingival Microbiota in Distinct Periodontal Conditions.

    Science.gov (United States)

    Park, O-J; Yi, H; Jeon, J H; Kang, S-S; Koo, K-T; Kum, K-Y; Chun, J; Yun, C-H; Han, S H

    2015-07-01

    Subgingival microorganisms are potentially associated with periodontal diseases. However, changes in the subgingival microbiota during the progress of periodontal diseases are poorly understood. In this study, we analyzed bacterial communities in the subgingival paper point samples from 32 Korean individuals with no sign of disease, gingivitis, or periodontitis using 454 FLX Titanium pyrosequencing. A total of 256,113 reads representing 26 phyla, 433 genera, and 1,016 species were detected. Bacteroidetes, Fusobacteria, Synergistetes, and Spirochaetes were the abundant phyla in periodontitis subjects, whereas Firmicutes and Proteobacteria were identified as the dominant phyla in the gingivitis and healthy subjects, respectively. Although high levels of Porphyromonas, Fusobacterium, Fretibacterium, Rothia, Filifactor, and Treponema genera were observed in the periodontitis subjects, Streptococcus, Capnocytophaga, Leptotrichia, and Haemophilus genera were found at high frequency in the gingivitis subjects. Species including Porphyromonas gingivalis, Fusobacterium nucleatum, and Fretibacterium fastidiosum were significantly increased in periodontitis subjects. On the other hand, Streptococcus pseudopneumoniae, Haemophilus parainfluenzae, and Leptotrichia hongkongensis were preferentially observed in the gingivitis subjects. Intriguingly, the halophile Halomonas hamiltonii was revealed as a predominant species in the healthy subjects. Based on Fast UniFrac analysis, distinctive bacterial clusters were classified for the healthy, gingivitis, and periodontitis state. The current findings might be useful for understanding the pathogenesis, diagnosis, and treatment of periodontal diseases. © International & American Associations for Dental Research 2015.

  16. Astragalus polysaccharides lowers plasma cholesterol through mechanisms distinct from statins.

    Directory of Open Access Journals (Sweden)

    Yunjiu Cheng

    Full Text Available To determine the efficacy and underlying mechanism of Astragalus polysaccharides (APS on plasma lipids in hypercholesterolemia hamsters. The effect of APS (0.25 g/kg/d on plasma and liver lipids, fecal bile acids and neutral sterol, cholesterol absorption and synthesis, HMG-CoA reductase activity, and gene and protein expressions in the liver and small intestine was investigated in twenty-four hypercholesterolemia hamsters. Treatment periods lasted for three months. APS significantly lowered plasma total cholesterol by 45.8%, triglycerides by 30%, and low-density lipoprotein-cholesterol by 47.4%, comparable to simvastatin. Further examinations revealed that APS reduced total cholesterol and triglycerides in the liver, increased fecal bile acid and neutral sterol excretion, inhibited cholesterol absorption, and by contrast, increased hepatic cholesterol synthesis and HMG-CoA reductase activity. Plasma total cholesterol or low-density lipoprotein-cholesterol levels were significantly correlated with cholesterol absorption rates. APS up-regulated cholesterol-7α-hydroxylase and LDL-receptor gene expressions. These new findings identify APS as a potential natural cholesterol lowering agent, working through mechanisms distinct from statins.

  17. Functional Analysis of Dishevelled-3 Phosphorylation Identifies Distinct Mechanisms Driven by Casein Kinase 1 epsilon and Frizzled5

    Czech Academy of Sciences Publication Activity Database

    Bernatík, Ondřej; Šedová, K.; Schille, C.; Ganji, R.S.; Červenka, I.; Trantírek, L.; Schambony, A.; Zdráhal, Z.; Bryja, Vítězslav

    2014-01-01

    Roč. 289, č. 34 (2014), s. 23520-23533 ISSN 0021-9258 R&D Projects: GA ČR(CZ) GP13-31488P Institutional support: RVO:68081707 Keywords : Cell Signaling * Mass Spectrometry * Phosphorylation Subject RIV: BO - Biophysics Impact factor: 4.573, year: 2014

  18. Differential Lectin Binding Patterns Identify Distinct Heart Regions in Giant Danio (Devario aequipinnatus) and Zebrafish (Danio rerio) Hearts

    Science.gov (United States)

    Manalo, Trina; May, Adam; Quinn, Joshua; Lafontant, Dominique S.; Shifatu, Olubusola; He, Wei; Gonzalez-Rosa, Juan M.; Burns, Geoffrey C.; Burns, Caroline E.; Burns, Alan R.; Lafontant, Pascal J.

    2016-01-01

    Lectins are carbohydrate-binding proteins commonly used as biochemical and histochemical tools to study glycoconjugate (glycoproteins, glycolipids) expression patterns in cells, tissues, including mammalian hearts. However, lectins have received little attention in zebrafish (Danio rerio) and giant danio (Devario aequipinnatus) heart studies. Here, we sought to determine the binding patterns of six commonly used lectins—wheat germ agglutinin (WGA), Ulex europaeus agglutinin, Bandeiraea simplicifolia lectin (BS lectin), concanavalin A (Con A), Ricinus communis agglutinin I (RCA I), and Lycopersicon esculentum agglutinin (tomato lectin)—in these hearts. Con A showed broad staining in the myocardium. WGA stained cardiac myocyte borders, with binding markedly stronger in the compact heart and bulbus. BS lectin, which stained giant danio coronaries, was used to measure vascular reconstruction during regeneration. However, BS lectin reacted poorly in zebrafish. RCA I stained the compact heart of both fish. Tomato lectin stained the giant danio, and while low reactivity was seen in the zebrafish ventricle, staining was observed in their transitional cardiac myocytes. In addition, we observed unique staining patterns in the developing zebrafish heart. Lectins’ ability to reveal differential glycoconjugate expression in giant danio and zebrafish hearts suggests they can serve as simple but important tools in studies of developing, adult, and regenerating fish hearts. PMID:27680670

  19. An Exploration of Strategic Planning Perspectives and Processes within Community Colleges Identified as Being Distinctive in Their Strategic Planning Practices

    Science.gov (United States)

    Augustyniak, Lisa J.

    2015-01-01

    Community college leaders face unprecedented change, and some have begun reexamining their institutional strategic planning processes. Yet, studies in higher education strategic planning spend little time examining how community colleges formulate their strategic plans. This mixed-method qualitative study used an expert sampling method to identify…

  20. A Functional Magnetic Resonance Imaging Paradigm to Identify Distinct Cortical Areas of Facial Function : A Reliable Localizer

    NARCIS (Netherlands)

    Romeo, Marco; Vizioli, Luca; Breukink, Myrte; Aganloo, Kiomars; Lao, Junpeng; Cotrufo, Stefano; Caldara, Roberto; Morley, Stephen

    Background: Irreversible facial paralysis can be surgically treated by importing both a new neural and a new motor muscle supply. Various donor nerves can be used. If a nerve supply other than the facial nerve is used, the patient has to adapt to generate a smile. If branches of the fifth cranial

  1. MM2-Thalamic Creutzfeldt-Jacob Disease: Neuropathological, Biochemical and Transmission Studies Identify a Distinctive Prion Strain

    NARCIS (Netherlands)

    Moda, F.; Suardi, S.; Fede, Di G.; Indaco, A.; Limido, L.; Vimercati, C.; Ruggerone, M.; Campagnani, I.; Langeveld, J.P.M.; Terruzzi, A.; Brambilla, A.; Zerbi, P.; Fociani, P.; Bishop, T.; Will, G.W.; Manson, J.C.; Giaccone, G.; Tagliavini, F.

    2012-01-01

    In CreutzfeldtJakob disease (CJD), molecular typing based on the size of the protease resistant core of the disease-associated prion protein (PrPSc) and the M/V polymorphism at codon 129 of the PRNP gene correlates with the clinico-pathologic subtypes. Approximately 95% of the sporadic 129MM CJD

  2. Identity-specific motivation: How distinct identities direct self-regulation across distinct situations.

    Science.gov (United States)

    Browman, Alexander S; Destin, Mesmin; Molden, Daniel C

    2017-12-01

    Research on self-regulation has traditionally emphasized that people's thoughts and actions are guided by either (a) domain-general motivations that emerge from a cumulative history of life experiences, or (b) situation-specific motivations that emerge in immediate response to the incentives present in a particular context. However, more recent studies have illustrated the importance of understanding the interplay between such domain-general and situation-specific motivations across the types of contexts people regularly encounter. The present research, therefore, expands existing perspectives on self-regulation by investigating how people's identities -the internalized roles, relationships, and social group memberships that define who they are-systemically guide when and how different domain-general motivations are activated within specific types of situations. Using the motivational framework described by regulatory focus theory (Higgins, 1997), Studies 1 and 2 demonstrate that people indeed have distinct, identity-specific motivations that uniquely influence their current self-regulation when such identities are active. Studies 3-5 then begin to explore how identity-specific motivations are situated within people's larger self-concept. Studies 3a and 3b demonstrate that the less compatible people's specific identities, the more distinct are the motivations connected to those identities. Studies 4-5 then provide some initial, suggestive evidence that identity-specific motivations are not a separate, superordinate feature of people's identities that then alter how they pursue any subordinate, identity-relevant traits, but instead that such motivations emerge from the cumulative motivational significance of the subordinate traits to which the identities themselves become attached. Implications for understanding the role of the self-concept in self-regulation are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  3. Women with preterm birth have a distinct cervicovaginal metabolome.

    Science.gov (United States)

    Ghartey, Jeny; Bastek, Jamie A; Brown, Amy G; Anglim, Laura; Elovitz, Michal A

    2015-06-01

    Metabolomics has the potential to reveal novel pathways involved in the pathogenesis of preterm birth (PTB). The objective of this study was to investigate whether the cervicovaginal (CV) metabolome was different in asymptomatic women destined to have a PTB compared with term birth. A nested case-control study was performed using CV fluid collected from a larger prospective cohort. The CV fluid was collected between 20-24 weeks (V1) and 24-28 weeks (V2). The metabolome was compared between women with a spontaneous PTB (n = 10) to women who delivered at term (n = 10). Samples were extracted and prepared for analysis using a standard extraction solvent method. Global biochemical profiles were determined using gas chromatography/mass spectrometry and ultra-performance liquid chromatography/tandem mass spectrometry. An ANOVA was used to detect differences in biochemical compounds between the groups. A false discovery rate was estimated to account for multiple comparisons. A total of 313 biochemicals were identified in CV fluid. Eighty-two biochemicals were different in the CV fluid at V1 in those destined to have a PTB compared with term birth, whereas 48 were different at V2. Amino acid, carbohydrate, and peptide metabolites were distinct between women with and without PTB. These data suggest that the CV space is metabolically active during pregnancy. Changes in the CV metabolome may be observed weeks, if not months, prior to any clinical symptoms. Understanding the CV metabolome may hold promise for unraveling the pathogenesis of PTB and may provide novel biomarkers to identify women most at risk. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Spatiotemporal Dynamics of Ammonia-Oxidizing Thaumarchaeota in Distinct Arctic Water Masses

    Directory of Open Access Journals (Sweden)

    Oliver Müller

    2018-01-01

    Full Text Available One of the most abundant archaeal groups on Earth is the Thaumarchaeota. They are recognized as major contributors to marine ammonia oxidation, a crucial step in the biogeochemical cycling of nitrogen. Their universal success is attributed to a high genomic flexibility and niche adaptability. Based on differences in the gene coding for ammonia monooxygenase subunit A (amoA, two different ecotypes with distinct distribution patterns in the water column have been identified. We used high-throughput sequencing of 16S rRNA genes combined with archaeal amoA functional gene clone libraries to investigate which environmental factors are driving the distribution of Thaumarchaeota ecotypes in the Atlantic gateway to the Arctic Ocean through an annual cycle in 2014. We observed the characteristic vertical pattern of Thaumarchaeota abundance with high values in the mesopelagic (>200 m water throughout the entire year, but also in the epipelagic (<200 m water during the dark winter months (January, March and November. The Thaumarchaeota community was dominated by three OTUs which on average comprised 76% ± 11 and varied in relative abundance according to water mass characteristics and not to depth or ammonium concentration, as suggested in previous studies. The ratios of the abundance of the different OTU types were similar to that of the functional amoA water cluster types. Together, this suggests a strong selection of ecotypes within different water masses, supporting the general idea of water mass characteristics as an important factor in defining microbial community structure. If indeed, as suggested in this study, Thaumarchaeota population dynamics are controlled by a set of factors, described here as water mass characteristics and not just depth alone, then changes in water mass flow will inevitably affect the distribution of the different ecotypes.

  5. Hesitant fuzzy sets theory

    CERN Document Server

    Xu, Zeshui

    2014-01-01

    This book provides the readers with a thorough and systematic introduction to hesitant fuzzy theory. It presents the most recent research results and advanced methods in the field. These includes: hesitant fuzzy aggregation techniques, hesitant fuzzy preference relations, hesitant fuzzy measures, hesitant fuzzy clustering algorithms and hesitant fuzzy multi-attribute decision making methods. Since its introduction by Torra and Narukawa in 2009, hesitant fuzzy sets have become more and more popular and have been used for a wide range of applications, from decision-making problems to cluster analysis, from medical diagnosis to personnel appraisal and information retrieval. This book offers a comprehensive report on the state-of-the-art in hesitant fuzzy sets theory and applications, aiming at becoming a reference guide for both researchers and practitioners in the area of fuzzy mathematics and other applied research fields (e.g. operations research, information science, management science and engineering) chara...

  6. Distinctiveness of Encoding and Memory for Learning Tasks.

    Science.gov (United States)

    Glover, John A.; And Others

    1982-01-01

    A distinctiveness of encoding hypothesis, as applied to the facilitative effects that higher order objectives have on readers' prose recall, was evaluated in three experiments. Results suggest that distinctiveness of encoding may offer a theoretical basis for the effects of adjunct aids as well as a guide to their construction. (Author/GK)

  7. Frame scaling function sets and frame wavelet sets in Rd

    International Nuclear Information System (INIS)

    Liu Zhanwei; Hu Guoen; Wu Guochang

    2009-01-01

    In this paper, we classify frame wavelet sets and frame scaling function sets in higher dimensions. Firstly, we obtain a necessary condition for a set to be the frame wavelet sets. Then, we present a necessary and sufficient condition for a set to be a frame scaling function set. We give a property of frame scaling function sets, too. Some corresponding examples are given to prove our theory in each section.

  8. Blood Pressure Loci Identified with a Gene-Centric Array

    NARCIS (Netherlands)

    Johnson, Toby; Gaunt, Tom R.; Newhouse, Stephen J.; Padmanabhan, Sandosh; Tomaszewski, Maciej; Kumari, Meena; Morris, Richard W.; Tzoulaki, Ioanna; O'Brien, Eoin T.; Poulter, Neil R.; Sever, Peter; Shields, Denis C.; Thom, Simon; Wannamethee, Sasiwarang G.; Whincup, Peter H.; Brown, Morris J.; Connell, John M.; Dobson, Richard J.; Howard, Philip J.; Mein, Charles A.; Onipinla, Abiodun; Shaw-Hawkins, Sue; Zhang, Yun; Smith, George Davey; Day, Ian N. M.; Lawlor, Debbie A.; Goodall, Alison H.; Fowkes, F. Gerald; Abecasis, Goncalo R.; Elliott, Paul; Gateva, Vesela; Braund, Peter S.; Burton, Paul R.; Nelson, Christopher P.; Tobin, Martin D.; van der Harst, Pim; Glorioso, Nicola; Neuvrith, Hani; Salvi, Erika; Staessen, Jan A.; Stucchi, Andrea; Devos, Nabila; Jeunemaitre, Xavier; Plouin, Pierre-Francois; Tichet, Jean; Juhanson, Peeter; Org, Elin; Westra, Harm-Jan; Wolfs, Marcel G. M.; Franke, Lude

    2011-01-01

    Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a

  9. Improving the functionality of dictionary definitions for lexical sets ...

    African Journals Online (AJOL)

    2008) approach to the design of lexicographic definitions for members of lexical sets. The questions raised are how to define and identify lexical sets, how lexical conceptual models (LCMs) can support definitional consistency and coherence in ...

  10. Tagging like Humans: Diverse and Distinct Image Annotation

    KAUST Repository

    Wu, Baoyuan

    2018-03-31

    In this work we propose a new automatic image annotation model, dubbed {\\\\bf diverse and distinct image annotation} (D2IA). The generative model D2IA is inspired by the ensemble of human annotations, which create semantically relevant, yet distinct and diverse tags. In D2IA, we generate a relevant and distinct tag subset, in which the tags are relevant to the image contents and semantically distinct to each other, using sequential sampling from a determinantal point process (DPP) model. Multiple such tag subsets that cover diverse semantic aspects or diverse semantic levels of the image contents are generated by randomly perturbing the DPP sampling process. We leverage a generative adversarial network (GAN) model to train D2IA. Extensive experiments including quantitative and qualitative comparisons, as well as human subject studies, on two benchmark datasets demonstrate that the proposed model can produce more diverse and distinct tags than the state-of-the-arts.

  11. Replicating distinctive facial features in lineups: identification performance in young versus older adults.

    Science.gov (United States)

    Badham, Stephen P; Wade, Kimberley A; Watts, Hannah J E; Woods, Natalie G; Maylor, Elizabeth A

    2013-04-01

    Criminal suspects with distinctive facial features, such as tattoos or bruising, may stand out in a police lineup. To prevent suspects from being unfairly identified on the basis of their distinctive feature, the police often manipulate lineup images to ensure that all of the members appear similar. Recent research shows that replicating a distinctive feature across lineup members enhances eyewitness identification performance, relative to removing that feature on the target. In line with this finding, the present study demonstrated that with young adults (n = 60; mean age = 20), replication resulted in more target identifications than did removal in target-present lineups and that replication did not impair performance, relative to removal, in target-absent lineups. Older adults (n = 90; mean age = 74) performed significantly worse than young adults, identifying fewer targets and more foils; moreover, older adults showed a minimal benefit from replication over removal. This pattern is consistent with the associative deficit hypothesis of aging, such that older adults form weaker links between faces and their distinctive features. Although replication did not produce much benefit over removal for older adults, it was not detrimental to their performance. Therefore, the results suggest that replication may not be as beneficial to older adults as it is to young adults and demonstrate a new practical implication of age-related associative deficits in memory.

  12. Long-term future risk of severe exacerbations: Distinct 5-year trajectories of problematic asthma.

    Science.gov (United States)

    Yii, A C A; Tan, J H Y; Lapperre, T S; Chan, A K W; Low, S Y; Ong, T H; Tan, K L; Chotirmall, S H; Sterk, P J; Koh, M S

    2017-09-01

    Assessing future risk of exacerbations is an important component of asthma management. Existing studies have investigated short- but not long-term risk. Problematic asthma patients with unfavorable long-term disease trajectory and persistently frequent severe exacerbations need to be identified early to guide treatment. To identify distinct trajectories of severe exacerbation rates among "problematic asthma" patients and develop a risk score to predict the most unfavorable trajectory. Severe exacerbation rates over five years for 177 "problematic asthma" patients presenting to a specialist asthma clinic were tracked. Distinct trajectories of severe exacerbation rates were identified using group-based trajectory modeling. Baseline predictors of trajectory were identified and used to develop a clinical risk score for predicting the most unfavorable trajectory. Three distinct trajectories were found: 58.5% had rare intermittent severe exacerbations ("infrequent"), 32.0% had frequent severe exacerbations at baseline but improved subsequently ("nonpersistently frequent"), and 9.5% exhibited persistently frequent severe exacerbations, with the highest incidence of near-fatal asthma ("persistently frequent"). A clinical risk score composed of ≥2 severe exacerbations in the past year (+2 points), history of near-fatal asthma (+1 point), body mass index ≥25kg/m 2 (+1 point), obstructive sleep apnea (+1 point), gastroesophageal reflux (+1 point), and depression (+1 point) was predictive of the "persistently frequent" trajectory (area under the receiver operating characteristic curve: 0.84, sensitivity 72.2%, specificity 81.1% using cutoff ≥3 points). The trajectories and clinical risk score had excellent performance in an independent validation cohort. Patients with problematic asthma follow distinct illness trajectories over a period of five years. We have derived and validated a clinical risk score that accurately identifies patients who will have persistently

  13. Part-set cueing impairment & facilitation in semantic memory.

    Science.gov (United States)

    Kelley, Matthew R; Parihar, Sushmeena A

    2018-01-19

    The present study explored the influence of part-set cues in semantic memory using tests of "free" recall, reconstruction of order, and serial recall. Nine distinct categories of information were used (e.g., Zodiac signs, Harry Potter books, Star Wars films, planets). The results showed part-set cueing impairment for all three "free" recall sets, whereas part-set cueing facilitation was evident for five of the six ordered sets. Generally, the present results parallel those often observed across episodic tasks, which could indicate that similar mechanisms contribute to part-set cueing effects in both episodic and semantic memory. A novel anchoring explanation of part-set cueing facilitation in order and spatial tasks is provided.

  14. SPARQL-enabled identifier conversion with Identifiers.org

    Science.gov (United States)

    Wimalaratne, Sarala M.; Bolleman, Jerven; Juty, Nick; Katayama, Toshiaki; Dumontier, Michel; Redaschi, Nicole; Le Novère, Nicolas; Hermjakob, Henning; Laibe, Camille

    2015-01-01

    Motivation: On the semantic web, in life sciences in particular, data is often distributed via multiple resources. Each of these sources is likely to use their own International Resource Identifier for conceptually the same resource or database record. The lack of correspondence between identifiers introduces a barrier when executing federated SPARQL queries across life science data. Results: We introduce a novel SPARQL-based service to enable on-the-fly integration of life science data. This service uses the identifier patterns defined in the Identifiers.org Registry to generate a plurality of identifier variants, which can then be used to match source identifiers with target identifiers. We demonstrate the utility of this identifier integration approach by answering queries across major producers of life science Linked Data. Availability and implementation: The SPARQL-based identifier conversion service is available without restriction at http://identifiers.org/services/sparql. Contact: sarala@ebi.ac.uk PMID:25638809

  15. SPARQL-enabled identifier conversion with Identifiers.org.

    Science.gov (United States)

    Wimalaratne, Sarala M; Bolleman, Jerven; Juty, Nick; Katayama, Toshiaki; Dumontier, Michel; Redaschi, Nicole; Le Novère, Nicolas; Hermjakob, Henning; Laibe, Camille

    2015-06-01

    On the semantic web, in life sciences in particular, data is often distributed via multiple resources. Each of these sources is likely to use their own International Resource Identifier for conceptually the same resource or database record. The lack of correspondence between identifiers introduces a barrier when executing federated SPARQL queries across life science data. We introduce a novel SPARQL-based service to enable on-the-fly integration of life science data. This service uses the identifier patterns defined in the Identifiers.org Registry to generate a plurality of identifier variants, which can then be used to match source identifiers with target identifiers. We demonstrate the utility of this identifier integration approach by answering queries across major producers of life science Linked Data. The SPARQL-based identifier conversion service is available without restriction at http://identifiers.org/services/sparql. © The Author 2015. Published by Oxford University Press.

  16. Comparing sociocultural features of cholera in three endemic African settings

    Science.gov (United States)

    2013-01-01

    and class. In contrast, in western Kenya, gender differentiation was pronounced, and children and the poor were regarded as most vulnerable to cholera. Conclusions This comprehensive review identified common and distinctive features of local understandings of cholera. Classical treatment (that is, rehydration) was highlighted as a priority for control in the three African study settings and is likely to be identified in the region beyond. Findings indicate the value of insight from community studies to guide local program planning for cholera control and elimination. PMID:24047241

  17. Setting Goals for Achievement in Physical Education Settings

    Science.gov (United States)

    Baghurst, Timothy; Tapps, Tyler; Kensinger, Weston

    2015-01-01

    Goal setting has been shown to improve student performance, motivation, and task completion in academic settings. Although goal setting is utilized by many education professionals to help students set realistic and proper goals, physical educators may not be using goal setting effectively. Without incorporating all three types of goals and…

  18. Towards a typology of business process management professionals: identifying patterns of competences through latent semantic analysis

    Science.gov (United States)

    Müller, Oliver; Schmiedel, Theresa; Gorbacheva, Elena; vom Brocke, Jan

    2016-01-01

    While researchers have analysed the organisational competences that are required for successful Business Process Management (BPM) initiatives, individual BPM competences have not yet been studied in detail. In this study, latent semantic analysis is used to examine a collection of 1507 BPM-related job advertisements in order to develop a typology of BPM professionals. This empirical analysis reveals distinct ideal types and profiles of BPM professionals on several levels of abstraction. A closer look at these ideal types and profiles confirms that BPM is a boundary-spanning field that requires interdisciplinary sets of competence that range from technical competences to business and systems competences. Based on the study's findings, it is posited that individual and organisational alignment with the identified ideal types and profiles is likely to result in high employability and organisational BPM success.

  19. Social Set Visualizer

    DEFF Research Database (Denmark)

    Flesch, Benjamin; Hussain, Abid; Vatrapu, Ravi

    2015-01-01

    -edge open source visual analytics libraries from D3.js and creation of new visualizations (ac-tor mobility across time, conversational comets etc). Evaluation of the dashboard consisting of technical testing, usability testing, and domain-specific testing with CSR students and yielded positive results.......This paper presents a state-of-the art visual analytics dash-board, Social Set Visualizer (SoSeVi), of approximately 90 million Facebook actions from 11 different companies that have been mentioned in the traditional media in relation to garment factory accidents in Bangladesh. The enterprise...

  20. Social Set Analysis

    DEFF Research Database (Denmark)

    Vatrapu, Ravi; Hussain, Abid; Buus Lassen, Niels

    2015-01-01

    of Facebook or Twitter data. However, there exist no other holistic computational social science approach beyond the relational sociology and graph theory of SNA. To address this limitation, this paper presents an alternative holistic approach to Big Social Data analytics called Social Set Analysis (SSA......This paper argues that the basic premise of Social Network Analysis (SNA) -- namely that social reality is constituted by dyadic relations and that social interactions are determined by structural properties of networks-- is neither necessary nor sufficient, for Big Social Data analytics...

  1. Markov set-chains

    CERN Document Server

    Hartfiel, Darald J

    1998-01-01

    In this study extending classical Markov chain theory to handle fluctuating transition matrices, the author develops a theory of Markov set-chains and provides numerous examples showing how that theory can be applied. Chapters are concluded with a discussion of related research. Readers who can benefit from this monograph are those interested in, or involved with, systems whose data is imprecise or that fluctuate with time. A background equivalent to a course in linear algebra and one in probability theory should be sufficient.

  2. The influence of distinct types of aquatic vegetation on the flow field

    Science.gov (United States)

    Valyrakis, Manousos; Barcroft, Stephen; Yagci, Oral

    2014-05-01

    The Sustainable management of fluvial systems dealing with flood prevention, erosion protection and restoration of rivers and estuaries requires implementation of soft/green-engineering methods. In-stream aquatic vegetation can be regarded as one of these as it plays an important role for both river ecology (function) and geomorphology (form). The goal of this research is to offer insight gained from pilot experimental studies on the effects of a number of different elements modeling instream, aquatic vegetation on the local flow field. It is hypothesized that elements of the same effective "blockage" area but of distinct characteristics (structure, porosity and flexibility), will affect both the mean and fluctuating levels of the turbulent flow to a different degree. The above hypothesis is investigated through a set of rigorous set of experimental runs which are appropriately designed to assess the variability between the interaction of aquatic elements and flow, both quantitatively and qualitatively. In this investigation three elements are employed to model aquatic vegetation, namely a rigid cylinder, a porous but rigid structure and a flexible live plant (Cupressus Macrocarpa). Firstly, the flow field downstream each of the mentioned elements was measured under steady uniform flow conditions employing acoustic Doppler velocimetry. Three-dimensional flow velocities downstream the vegetation element are acquired along a measurement grid extending about five-fold the element's diameter. These measurements are analyzed to develop mean velocity and turbulent intensity profiles for all velocity components. A detailed comparison between the obtained results is demonstrative of the validity of the above hypothesis as each of the employed elements affects in a different manner and degree the flow field. Then a flow visualization technique, during which fluorescent dye is injected upstream of the element and images are captured for further analysis and comparison, was

  3. Identifying ELIXIR Core Data Resources.

    Science.gov (United States)

    Durinx, Christine; McEntyre, Jo; Appel, Ron; Apweiler, Rolf; Barlow, Mary; Blomberg, Niklas; Cook, Chuck; Gasteiger, Elisabeth; Kim, Jee-Hyub; Lopez, Rodrigo; Redaschi, Nicole; Stockinger, Heinz; Teixeira, Daniel; Valencia, Alfonso

    2016-01-01

    The core mission of ELIXIR is to build a stable and sustainable infrastructure for biological information across Europe. At the heart of this are the data resources, tools and services that ELIXIR offers to the life-sciences community, providing stable and sustainable access to biological data. ELIXIR aims to ensure that these resources are available long-term and that the life-cycles of these resources are managed such that they support the scientific needs of the life-sciences, including biological research. ELIXIR Core Data Resources are defined as a set of European data resources that are of fundamental importance to the wider life-science community and the long-term preservation of biological data. They are complete collections of generic value to life-science, are considered an authority in their field with respect to one or more characteristics, and show high levels of scientific quality and service. Thus, ELIXIR Core Data Resources are of wide applicability and usage. This paper describes the structures, governance and processes that support the identification and evaluation of ELIXIR Core Data Resources. It identifies key indicators which reflect the essence of the definition of an ELIXIR Core Data Resource and support the promotion of excellence in resource development and operation. It describes the specific indicators in more detail and explains their application within ELIXIR's sustainability strategy and science policy actions, and in capacity building, life-cycle management and technical actions. The identification process is currently being implemented and tested for the first time. The findings and outcome will be evaluated by the ELIXIR Scientific Advisory Board in March 2017. Establishing the portfolio of ELIXIR Core Data Resources and ELIXIR Services is a key priority for ELIXIR and publicly marks the transition towards a cohesive infrastructure.

  4. Topological setting of Bessel functions

    International Nuclear Information System (INIS)

    Mekhfi, M.

    1995-11-01

    We start from the topology of the punctured plane encoded within its homotopy group which is isomorphic to the set of integers Z. We then realize group elements Π(n), n is an element of Z as differential operators on the space of analytic functions. Using plausible physical arguments we select a subset of functions which we identify with integer orders reduced Bessel functions. On the other hand we propose a unifying new formula of topological origin, generating real orders Bessel functions out of integers orders ones, the generator being an operator built entirely out of the Π s . We thus have shown that the topology (of the puntured plane) is underlying the inner structure of Bessel functions, in addition it unifies them independently of the orders being integers or reals. (author). 4 refs

  5. Analysis of successive data sets

    NARCIS (Netherlands)

    Spreeuwers, Lieuwe Jan; Breeuwer, Marcel; Haselhoff, Eltjo Hans

    2008-01-01

    The invention relates to the analysis of successive data sets. A local intensity variation is formed from such successive data sets, that is, from data values in successive data sets at corresponding positions in each of the data sets. A region of interest is localized in the individual data sets on

  6. Analysis of successive data sets

    NARCIS (Netherlands)

    Spreeuwers, Lieuwe Jan; Breeuwer, Marcel; Haselhoff, Eltjo Hans

    2002-01-01

    The invention relates to the analysis of successive data sets. A local intensity variation is formed from such successive data sets, that is, from data values in successive data sets at corresponding positions in each of the data sets. A region of interest is localized in the individual data sets on

  7. Many-Objective Distinct Candidates Optimization using Differential Evolution

    DEFF Research Database (Denmark)

    Justesen, Peter; Ursem, Rasmus Kjær

    2010-01-01

    for each objective. The Many-Objective Distinct Candidates Optimization using Differential Evolution (MODCODE) algorithm takes a novel approach by focusing search using a user-defined number of subpopulations each returning a distinct optimal solution within the preferred region of interest. In this paper......, we present the novel MODCODE algorithm incorporating the ROD measure to measure and control candidate distinctiveness. MODCODE is tested against GDE3 on three real world centrifugal pump design problems supplied by Grundfos. Our algorithm outperforms GDE3 on all problems with respect to all...

  8. Creating fair lineups for suspects with distinctive features.

    Science.gov (United States)

    Zarkadi, Theodora; Wade, Kimberley A; Stewart, Neil

    2009-12-01

    In their descriptions, eyewitnesses often refer to a culprit's distinctive facial features. However, in a police lineup, selecting the only member with the described distinctive feature is unfair to the suspect and provides the police with little further information. For fair and informative lineups, the distinctive feature should be either replicated across foils or concealed on the target. In the present experiments, replication produced more correct identifications in target-present lineups--without increasing the incorrect identification of foils in target-absent lineups--than did concealment. This pattern, and only this pattern, is predicted by the hybrid-similarity model of recognition.

  9. Comparative analysis of distinct phenotypes in gambling disorder based on gambling preferences

    OpenAIRE

    Moragas, Laura; Granero, Roser; Stinchfield, Randy; Fern?ndez-Aranda, Fernando; Fr?berg, Frida; Aymam?, Neus; G?mez-Pe?a, M?nica; Fagundo, Ana B; Islam, Mohammed A; del Pino-Guti?rrez, Amparo; Ag?era, Zaida; Savvidou, Lamprini G; Arcelus, Jon; Witcomb, Gemma L; Sauchelli, Sarah

    2015-01-01

    Background: studies examining gambling preferences have identified the importance of the type of gambling practiced on distinct individual profiles. The objectives were to compare clinical, psychopathological and personality variables between two different groups of individuals with a gambling disorder (strategic and non-strategic gamblers) and to evaluate the statistical prediction capacity of these preferences with respect to the severity of the disorder. Method: a total sample of 2010 trea...

  10. Grade-related differences in strategy use in multidigit division in two instructional settings.

    Science.gov (United States)

    Hickendorff, Marian; Torbeyns, Joke; Verschaffel, Lieven

    2017-11-23

    We aimed to investigate upper elementary children's strategy use in the domain of multidigit division in two instructional settings: the Netherlands and Flanders (Belgium). A cross-sectional sample of 119 Dutch and 122 Flemish fourth to sixth graders solved a varied set of multidigit division problems. With latent class analysis, three distinct strategy profiles were identified: children consistently using number-based strategies, children combining the use of column-based and number-based strategies, and children combining the use of digit-based and number-based strategies. The relation between children's strategy profiles and their instructional setting (country) and grade were generally in line with instructional differences, but large individual differences remained. Furthermore, Dutch children more frequently made adaptive strategy choices and realistic solutions than their Flemish peers. These results complement and refine previous findings on children's strategy use in relation to mathematics instruction. Statement of contribution What is already known? Mathematics education reform emphasizes variety, adaptivity, and insight in arithmetic strategies. Countries have different instructional trajectories for multidigit division. Mixed results on the impact of instruction on children's strategy use in multidigit division. What does this study add? Latent class analysis identified three meaningful strategy profiles in children from grades 4-6. These strategy profiles substantially differed between children. Dutch and Flemish children's strategy use is related to their instructional trajectory. © 2017 The Authors. British Journal of Developmental Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.

  11. Using choice architecture to exploit a university Distinct Urban Mine.

    Science.gov (United States)

    Pierron, Xavier; Williams, Ian D; Shaw, Peter J; Cleaver, Victoria

    2017-10-01

    There are widespread concerns regarding the potential future scarcity of ferrous and non-ferrous materials. However, there are already potentially rich reserves of secondary materials via high ownership of Electrical and Electronic Equipment (EEE) in economically-developed nations. Young people are particularly high consumers of EEE, thus university students and campuses may present an opportunity to harness this potential. University Distinct Urban Mines (DUM) may be used to exemplify how potential reserves of secondary metals may be exploited, and could contribute to the transition from a linear to a circular economy. This study aimed to evaluate small household appliances (SHA) DUM from a UK university, with the objectives to identify and quantify student households' SHA ownership, WEEE recycling, stockpiling and discarding habits amongst student households, assess and evaluate the monetary potential of SHA DUM at UK level, and propose methods to exploit DUM for universities in the UK. To this purpose, a quantitative survey was undertaken to measure students' ownership and discarding behaviour with respect to SHA. The amounts of ferrous and non-ferrous materials were then estimated and converted to monetary values from secondary materials market data to appraise the SHA DUM overall value. Thirty-five per cent of SHA are discarded in the general refuse. Broken personal care appliances (PCA) tend to be discarded due to hygiene and small size factors. When in working order, SHA tend to be equally reused, recycled or stockpiled. We conclude that a total of 189 tonnes of ferrous and non-ferrous materials were available via discarding or being stockpiled at the University of Southampton. Extrapolated to UK higher education level, discarded and stockpiled SHA