Sample records for identify specific aspects

  1. Task-specific Aspects of Goal-directed Word Generation Identified via Simultaneous EEG-fMRI.

    PubMed

    Shapira-Lichter, Irit; Klovatch, Ilana; Nathan, Dana; Oren, Noga; Hendler, Talma

    2016-09-01

    Generating words according to a given rule relies on retrieval-related search and postretrieval control processes. Using fMRI, we recently characterized neural patterns of word generation in response to episodic, semantic, and phonemic cues by comparing free recall of wordlists, category fluency, and letter fluency [Shapira-Lichter, I., Oren, N., Jacob, Y., Gruberger, M., & Hendler, T. Portraying the unique contribution of the default mode network to internally driven mnemonic processes. Proceedings of the National Academy of Sciences, U.S.A., 110, 4950-4955, 2013]. Distinct selectivity for each condition was evident, representing discrete aspects of word generation-related memory retrieval. For example, the precuneus, implicated in processing spatiotemporal information, emerged as a key contributor to the episodic condition, which uniquely requires this information. Gamma band is known to play a central role in memory, and increased gamma power has been observed before word generation. Yet, gamma modulation in response to task demands has not been investigated. To capture the task-specific modulation of gamma power, we analyzed the EEG data recorded simultaneously with the aforementioned fMRI, focusing on the activity locked to and immediately preceding word articulation. Transient increases in gamma power were identified in a parietal electrode immediately before episodic and semantic word generation, however, within a different time frame relative to articulation. Gamma increases were followed by an alpha-theta decrease in the episodic condition, a gamma decrease in the semantic condition. This pattern indicates a task-specific modulation of the gamma signal corresponding to the specific demands of each word generation task. The gamma power and fMRI signal from the precuneus were correlated during the episodic condition, implying the existence of a common cognitive construct uniquely required for this task, possibly the reactivation or processing of

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

    PubMed

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

    2014-04-01

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

  3. Comparative Transcriptional Profiling of the Axolotl Limb Identifies a Tripartite Regeneration-Specific Gene Program

    PubMed Central

    Knapp, Dunja; Schulz, Herbert; Rascon, Cynthia Alexander; Volkmer, Michael; Scholz, Juliane; Nacu, Eugen; Le, Mu; Novozhilov, Sergey; Tazaki, Akira; Protze, Stephanie; Jacob, Tina; Hubner, Norbert; Habermann, Bianca; Tanaka, Elly M.

    2013-01-01

    Understanding how the limb blastema is established after the initial wound healing response is an important aspect of regeneration research. Here we performed parallel expression profile time courses of healing lateral wounds versus amputated limbs in axolotl. This comparison between wound healing and regeneration allowed us to identify amputation-specific genes. By clustering the expression profiles of these samples, we could detect three distinguishable phases of gene expression – early wound healing followed by a transition-phase leading to establishment of the limb development program, which correspond to the three phases of limb regeneration that had been defined by morphological criteria. By focusing on the transition-phase, we identified 93 strictly amputation-associated genes many of which are implicated in oxidative-stress response, chromatin modification, epithelial development or limb development. We further classified the genes based on whether they were or were not significantly expressed in the developing limb bud. The specific localization of 53 selected candidates within the blastema was investigated by in situ hybridization. In summary, we identified a set of genes that are expressed specifically during regeneration and are therefore, likely candidates for the regulation of blastema formation. PMID:23658691

  4. Assessing a Critical Aspect of Construct Continuity when Test Specifications Change or Test Forms Deviate from Specifications

    ERIC Educational Resources Information Center

    Liu, Jinghua; Dorans, Neil J.

    2013-01-01

    We make a distinction between two types of test changes: inevitable deviations from specifications versus planned modifications of specifications. We describe how score equity assessment (SEA) can be used as a tool to assess a critical aspect of construct continuity, the equivalence of scores, whenever planned changes are introduced to testing…

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

    PubMed Central

    Büssing, Arndt; Hedtstück, Anemone; Khalsa, Sat Bir S.; Ostermann, Thomas; Heusser, Peter

    2012-01-01

    The majority of research on yoga focuses on its psychophysiological and therapeutic benefits, while the spiritual aspects are rarely addressed. Changes of specific aspects of spirituality were thus investigated among 160 individuals (91% women, mean age 40.9 ± 8.3 years; 57% Christians) starting a 2-year yoga teacher training. We used standardized questionnaires to measure aspects of spirituality (ASP), mindfulness (FMI—Freiburg Mindfulness Inventory), life satisfaction (BMLSS—Brief Multidimensional Life Satisfaction Scale), and positive mood (lightheartedness/relief). At the start of the course, scores of the respective ASP subscales for search for insight/wisdom, transcendence conviction, and conscious interactions/compassion were high, while those for religious orientation were low. Within the 6 month observation period, both conscious interactions/compassion (effect size, Cohen's d = .33), Religious orientation (d = .21), Lightheartedness/Relief (d = .75) and mindfulness (d = .53) increased significantly. Particularly non-religious/non-spiritual individuals showed moderate effects for an increase of conscious interactions/compassion. The results from this study suggest that an intensive yoga practice (1) may significantly increase specific aspects of practitioners' spirituality, mindfulness, and mood, (2) that these changes are dependent in part on their original spiritual/religious self-perception, and (3) that there are strong correlations amongst these constructs (i.e., conscious interactions/compassion, and mindfulness). PMID:22852023

  6. Japan-Specific Key Regulatory Aspects for Development of New Biopharmaceutical Drug Products.

    PubMed

    Desai, Kashappa Goud; Obayashi, Hirokazu; Colandene, James D; Nesta, Douglas P

    2018-03-28

    Japan represents the third largest pharmaceutical market in the world. Developing a new biopharmaceutical drug product for the Japanese market is a top business priority for global pharmaceutical companies while aligning with ethical drivers to treat more patients in need. Understanding Japan-specific key regulatory requirements is essential to achieve successful approvals. Understanding the full context of Japan-specific regulatory requirements/expectations is challenging to global pharmaceutical companies due to differences in language and culture. This article summarizes key Japan-specific regulatory aspects/requirements/expectations applicable to new drug development, approval, and postapproval phases. Formulation excipients should meet Japan compendial requirements with respect to the type of excipient, excipient grade, and excipient concentration. Preclinical safety assessments needed to support clinical phases I, II, and III development are summarized. Japanese regulatory authorities have taken appropriate steps to consider foreign clinical data, thereby enabling accelerated drug development and approval in Japan. Other important topics summarized in this article include: Japan new drug application-specific bracketing strategies for critical and noncritical aspects of the manufacturing process, regulatory requirements related to stability studies, release specifications and testing methods, standard processes involved in pre and postapproval inspections, management of postapproval changes, and Japan regulatory authority's consultation services available to global pharmaceutical companies. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

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

    PubMed

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

    2016-04-30

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

  8. Epistemic Uncertainty: Turkish Children with Specific Language Impairment and Their Comprehension of Tense and Aspect

    ERIC Educational Resources Information Center

    Yarbay Duman, Tuba; Topbas, Seyhun

    2016-01-01

    Background: Impairments in tense morphology are characteristic of English-speaking children with specific language impairment (SLI). Recent studies have investigated the role that aspect plays in the difficulties found in tense morphology. It has been suggested that children with SLI are less sensitive to aspect and its interaction with tense than…

  9. Aspect: A Formal Specification Language for Detecting Bugs

    DTIC Science & Technology

    1992-06-01

    the Aspect state from Chapter 6 and, below it, the definition of the approximating state used by the checker. The additional component Multilocs marks...stages. First, each collection object in Multilocs is expanded into a set of objects whose dependency and value sets are subsets of those of the... Multilocs x Prelocs Env = Var ý7 PLoc x PSource Store = Loc x Aspect F-k Val x PSource Vat = Unknown + PLoc Aspect = PlainAspect + Pointer + Collection

  10. Long-range correlations and burstiness in written texts: Universal and language-specific aspects

    NASA Astrophysics Data System (ADS)

    Constantoudis, Vassilios; Kalimeri, Maria; Diakonos, Fotis; Karamanos, Konstantinos; Papadimitriou, Constantinos; Chatzigeorgiou, Manolis; Papageorgiou, Harris

    2016-08-01

    Recently, methods from the statistical physics of complex systems have been applied successfully to identify universal features in the long-range correlations (LRCs) of written texts. However, in real texts, these universal features are being intermingled with language-specific influences. This paper aims at the characterization and further understanding of the interplay between universal and language-specific effects on the LRCs in texts. To this end, we apply the language-sensitive mapping of written texts to word-length series (wls) and analyse large parallel (of same content) corpora from 10 languages classified to four families (Romanic, Germanic, Greek and Uralic). The autocorrelation functions of the wls reveal tiny but persistent LRCs decaying at large scales following a power-law with a language-independent exponent ˜0.60-0.65. The impact of language is displayed in the amplitude of correlations where a relative standard deviation >40% among the analyzed languages is observed. The classification to language families seems to play a significant role since, the Finnish and Germanic languages exhibit more correlations than the Greek and Roman families. To reveal the origins of the LRCs, we focus on the long words and perform burst and correlation analysis in their positions along the corpora. We find that the universal features are linked more to the correlations of the inter-long word distances while the language-specific aspects are related more to their distributions.

  11. Inferring Gene Family Histories in Yeast Identifies Lineage Specific Expansions

    PubMed Central

    Ames, Ryan M.; Money, Daniel; Lovell, Simon C.

    2014-01-01

    The complement of genes found in the genome is a balance between gene gain and gene loss. Knowledge of the specific genes that are gained and lost over evolutionary time allows an understanding of the evolution of biological functions. Here we use new evolutionary models to infer gene family histories across complete yeast genomes; these models allow us to estimate the relative genome-wide rates of gene birth, death, innovation and extinction (loss of an entire family) for the first time. We show that the rates of gene family evolution vary both between gene families and between species. We are also able to identify those families that have experienced rapid lineage specific expansion/contraction and show that these families are enriched for specific functions. Moreover, we find that families with specific functions are repeatedly expanded in multiple species, suggesting the presence of common adaptations and that these family expansions/contractions are not random. Additionally, we identify potential specialisations, unique to specific species, in the functions of lineage specific expanded families. These results suggest that an important mechanism in the evolution of genome content is the presence of lineage-specific gene family changes. PMID:24921666

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

    ERIC Educational Resources Information Center

    Bradley, Robert H.; Gaa, John P.

    1977-01-01

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

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

    PubMed

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

    2017-01-01

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

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

    PubMed

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

    2005-05-01

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

  15. Method To Identify Specific Inhibiutors Of Imp Dehydrogenase

    DOEpatents

    Collart, Frank R.; Huberman, Eliezer

    2000-11-28

    This invention relates to methods to identify specific inhibitors of the purine nucleotide synthesis enzyme, IMP dehydrogenase (IMPDH). IMPDH is an essential enzyme found in all free-living organisms from humans to bacteria and is an important therapeutic target. The invention allows the identification of specific inhibitors of any IMPDH enzyme which can be expressed in a functional form in a recombinant host cell. A variety of eukaryotic or prokaryotic host systems commonly used for the expression of recombinant proteins are suitable for the practice of the invention. The methods are amenable to high throughput systems for the screening of inhibitors generated by combinatorial chemistry or other methods such as antisense molecule production. Utilization of exogenous guanosine as a control component of the methods allows for the identification of inhibitors specific for IMPDH rather than other causes of decreased cell proliferation.

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

    PubMed

    Taghizadeh, Rouzbeh; Noh, Minsoo; Huh, Yang Hoon; Ciusani, Emilio; Sigalotti, Luca; Maio, Michele; Arosio, Beatrice; Nicotra, Maria R; Natali, PierGiorgio; Sherley, James L; La Porta, Caterina A M

    2010-12-22

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

  17. Behavioural aspects of terrorism.

    PubMed

    Leistedt, Samuel J

    2013-05-10

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

  18. HES factors regulate specific aspects of chondrogenesis and chondrocyte hypertrophy during cartilage development

    PubMed Central

    Rutkowski, Timothy P.; Kohn, Anat; Sharma, Deepika; Ren, Yinshi; Mirando, Anthony J.

    2016-01-01

    ABSTRACT RBPjκ-dependent Notch signaling regulates multiple processes during cartilage development, including chondrogenesis, chondrocyte hypertrophy and cartilage matrix catabolism. Select members of the HES- and HEY-families of transcription factors are recognized Notch signaling targets that mediate specific aspects of Notch function during development. However, whether particular HES and HEY factors play any role(s) in the processes during cartilage development is unknown. Here, for the first time, we have developed unique in vivo genetic models and in vitro approaches demonstrating that the RBPjκ-dependent Notch targets HES1 and HES5 suppress chondrogenesis and promote the onset of chondrocyte hypertrophy. HES1 and HES5 might have some overlapping function in these processes, although only HES5 directly regulates Sox9 transcription to coordinate cartilage development. HEY1 and HEYL play no discernable role in regulating chondrogenesis or chondrocyte hypertrophy, whereas none of the HES or HEY factors appear to mediate Notch regulation of cartilage matrix catabolism. This work identifies important candidates that might function as downstream mediators of Notch signaling both during normal skeletal development and in Notch-related skeletal disorders. PMID:27160681

  19. Facial Shape Analysis Identifies Valid Cues to Aspects of Physiological Health in Caucasian, Asian, and African Populations.

    PubMed

    Stephen, Ian D; Hiew, Vivian; Coetzee, Vinet; Tiddeman, Bernard P; Perrett, David I

    2017-01-01

    Facial cues contribute to attractiveness, including shape cues such as symmetry, averageness, and sexual dimorphism. These cues may represent cues to objective aspects of physiological health, thereby conferring an evolutionary advantage to individuals who find them attractive. The link between facial cues and aspects of physiological health is therefore central to evolutionary explanations of attractiveness. Previously, studies linking facial cues to aspects of physiological health have been infrequent, have had mixed results, and have tended to focus on individual facial cues in isolation. Geometric morphometric methodology (GMM) allows a bottom-up approach to identifying shape correlates of aspects of physiological health. Here, we apply GMM to facial shape data, producing models that successfully predict aspects of physiological health in 272 Asian, African, and Caucasian faces - percentage body fat (21.0% of variance explained), body mass index (BMI; 31.9%) and blood pressure (BP; 21.3%). Models successfully predict percentage body fat and blood pressure even when controlling for BMI, suggesting that they are not simply measuring body size. Predicted values of BMI and BP, but not percentage body fat, correlate with health ratings. When asked to manipulate the shape of faces along the physiological health variable axes (as determined by the models), participants reduced predicted BMI, body fat and (marginally) BP, suggesting that facial shape provides a valid cue to aspects of physiological health.

  20. Facial Shape Analysis Identifies Valid Cues to Aspects of Physiological Health in Caucasian, Asian, and African Populations

    PubMed Central

    Stephen, Ian D.; Hiew, Vivian; Coetzee, Vinet; Tiddeman, Bernard P.; Perrett, David I.

    2017-01-01

    Facial cues contribute to attractiveness, including shape cues such as symmetry, averageness, and sexual dimorphism. These cues may represent cues to objective aspects of physiological health, thereby conferring an evolutionary advantage to individuals who find them attractive. The link between facial cues and aspects of physiological health is therefore central to evolutionary explanations of attractiveness. Previously, studies linking facial cues to aspects of physiological health have been infrequent, have had mixed results, and have tended to focus on individual facial cues in isolation. Geometric morphometric methodology (GMM) allows a bottom–up approach to identifying shape correlates of aspects of physiological health. Here, we apply GMM to facial shape data, producing models that successfully predict aspects of physiological health in 272 Asian, African, and Caucasian faces – percentage body fat (21.0% of variance explained), body mass index (BMI; 31.9%) and blood pressure (BP; 21.3%). Models successfully predict percentage body fat and blood pressure even when controlling for BMI, suggesting that they are not simply measuring body size. Predicted values of BMI and BP, but not percentage body fat, correlate with health ratings. When asked to manipulate the shape of faces along the physiological health variable axes (as determined by the models), participants reduced predicted BMI, body fat and (marginally) BP, suggesting that facial shape provides a valid cue to aspects of physiological health. PMID:29163270

  1. Are parents identifying positive aspects to parenting their child with an intellectual disability or are they just coping? A qualitative exploration

    PubMed Central

    Wills, Jane

    2017-01-01

    Although acknowledging the stress of raising their child with intellectual disabilities, parents also report that their child has brought about many positive changes in themselves and family. This study reports what parents perceive to be a positive aspect of parenting their child, as currently what constitutes a ‘positive’ is unclear. Seven key themes were identified; an increased sense of personal strength and confidence, changed priorities, greater appreciation of life, pleasure in the child’s accomplishments, increased faith/spirituality, more meaningful relationships and the positive effect that the child has on the wider community. Interpretive examination of the themes reveals that the positive aspects identified consist mostly of meaning-focused coping strategies. These enable parents to adapt successfully to the stressful experiences of raising their child and therefore could be amenable to meaning-focused therapeutic interventions for parents with newly diagnosed children or for those unable to identify any positive aspects of parenting their child. PMID:27352854

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

    PubMed

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

    2014-06-01

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

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

    PubMed

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

    2012-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  5. Aspects of Spirituality in Medical Doctors and Their Relation to Specific Views of Illness and Dealing with Their Patients' Individual Situation

    PubMed Central

    Büssing, Arndt; Hirdes, Almut Tabea; Baumann, Klaus; Hvidt, Niels Christian; Heusser, Peter

    2013-01-01

    We intended to analyse which aspects of spirituality are of relevance for medical doctors in a mostly secular society and how their spiritual/religious attitudes are related to specific views of illness, their dealing with patients' individual situation, and finally physicians' life satisfaction. Data from an anonymous survey enrolling 237 medical doctors from Germany (mean age 45.7 ± 9.6, 58% male, 42% female) indicated that secular forms of spirituality scored highest, while specific religious orientation had the lowest scores. Physicians with a specific specialization in complementary/alternative medicine (CAM) or anthroposophic medicine differed from their conventional counterparts with respect to specific aspects of spirituality; however, the specific views associated with these specialisations were only weakly to moderately correlated with physicians' view on the meaning of illness and how they assume that they would deal with their patients' individual situation. Of interest, the specific aspects of spirituality were negatively correlated with the view of “illness as a meaningless interruption” of life, indicating that physicians with a spiritual attitude would see illness also as a chance for an “individual development” and associated with a “biographical meaning” rather than just a “useless interruption” of life. PMID:23956779

  6. Identifying Group-Specific Sequences for Microbial Communities Using Long k-mer Sequence Signatures

    PubMed Central

    Wang, Ying; Fu, Lei; Ren, Jie; Yu, Zhaoxia; Chen, Ting; Sun, Fengzhu

    2018-01-01

    Comparing metagenomic samples is crucial for understanding microbial communities. For different groups of microbial communities, such as human gut metagenomic samples from patients with a certain disease and healthy controls, identifying group-specific sequences offers essential information for potential biomarker discovery. A sequence that is present, or rich, in one group, but absent, or scarce, in another group is considered “group-specific” in our study. Our main purpose is to discover group-specific sequence regions between control and case groups as disease-associated markers. We developed a long k-mer (k ≥ 30 bps)-based computational pipeline to detect group-specific sequences at strain resolution free from reference sequences, sequence alignments, and metagenome-wide de novo assembly. We called our method MetaGO: Group-specific oligonucleotide analysis for metagenomic samples. An open-source pipeline on Apache Spark was developed with parallel computing. We applied MetaGO to one simulated and three real metagenomic datasets to evaluate the discriminative capability of identified group-specific markers. In the simulated dataset, 99.11% of group-specific logical 40-mers covered 98.89% disease-specific regions from the disease-associated strain. In addition, 97.90% of group-specific numerical 40-mers covered 99.61 and 96.39% of differentially abundant genome and regions between two groups, respectively. For a large-scale metagenomic liver cirrhosis (LC)-associated dataset, we identified 37,647 group-specific 40-mer features. Any one of the features can predict disease status of the training samples with the average of sensitivity and specificity higher than 0.8. The random forests classification using the top 10 group-specific features yielded a higher AUC (from ∼0.8 to ∼0.9) than that of previous studies. All group-specific 40-mers were present in LC patients, but not healthy controls. All the assembled 11 LC-specific sequences can be mapped to two

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

    PubMed

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

    2015-10-01

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

  8. Aspects of Cognitive Functioning in Adults with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Perkins, Elizabeth A.; Small, Brent J.

    2006-01-01

    Recently, more attention is being given to identifying aging-related and dementia-related pathological changes in performance and cognition among persons with intellectual disabilities (ID). This literature review examines age-related differences in specific aspects of cognitive functioning and cognitive performance of people with ID and…

  9. Language-Independent and Language-Specific Aspects of Early Literacy: An Evaluation of the Common Underlying Proficiency Model.

    PubMed

    Goodrich, J Marc; Lonigan, Christopher J

    2017-08-01

    According to the common underlying proficiency model (Cummins, 1981), as children acquire academic knowledge and skills in their first language, they also acquire language-independent information about those skills that can be applied when learning a second language. The purpose of this study was to evaluate the relevance of the common underlying proficiency model for the early literacy skills of Spanish-speaking language-minority children using confirmatory factor analysis. Eight hundred fifty-eight Spanish-speaking language-minority preschoolers (mean age = 60.83 months, 50.2% female) participated in this study. Results indicated that bifactor models that consisted of language-independent as well as language-specific early literacy factors provided the best fits to the data for children's phonological awareness and print knowledge skills. Correlated factors models that only included skills specific to Spanish and English provided the best fits to the data for children's oral language skills. Children's language-independent early literacy skills were significantly related across constructs and to language-specific aspects of early literacy. Language-specific aspects of early literacy skills were significantly related within but not across languages. These findings suggest that language-minority preschoolers have a common underlying proficiency for code-related skills but not language-related skills that may allow them to transfer knowledge across languages.

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

    PubMed

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

    2011-03-01

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

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

    NASA Astrophysics Data System (ADS)

    Bochet, Esther; García-Fayos, Patricio

    2017-04-01

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

  12. Epistemic uncertainty: Turkish children with specific language impairment and their comprehension of tense and aspect.

    PubMed

    Yarbay Duman, Tuba; Topbaş, Seyhun

    2016-11-01

    Impairments in tense morphology are characteristic of English-speaking children with specific language impairment (SLI). Recent studies have investigated the role that aspect plays in the difficulties found in tense morphology. It has been suggested that children with SLI are less sensitive to aspect and its interaction with tense than typically developing (TD) children. Profound impairment in past tense morphology compared with the present in this population was explained by a breakdown in the association between event completion information and past tense. To date, research on tense morphology in this population has not examined all three tense conditions in a single study. To examine whether monolingual Turkish-speaking children with SLI exhibit deficits in comprehending tense and aspect morphology, and, if so, whether these deficits are restricted to completed events (past tense) or also occur for incomplete non-past events (future and present tense). A sentence-picture matching task was administered to 36 monolingual Turkish-speaking children: 13 with SLI (mean age = 6;9 years) and 23 age-matched TD children (mean age = 6;5 years). Upon hearing a sentence, each child had to select between a target (past, present or future) and a distracter picture. Tense and aspect information could only be established from verb morphology. The SLI group had lower accuracy than the TD group on all test conditions. For both groups, present tense had the highest accuracy scores. Performance scores within the SLI group showed the following hierarchy from easy to difficult: present > future > past. Turkish children with SLI have deficits in comprehending tense and aspect morphology. Although comprehending past was more difficult than non-past (present and future), future was more difficult to comprehend than the present. This disassociation between two non-past incomplete events indicates that the underlying difficulties comprehending (past) tense-aspect is not restricted to event

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

    PubMed

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

    2014-06-01

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

  14. Genetic dissection of TrkB activated signalling pathways required for specific aspects of the taste system

    PubMed Central

    2014-01-01

    Background Neurotrophin-4 (NT-4) and brain derived neurotrophic factor (BDNF) bind to the same receptor, Ntrk2/TrkB, but play distinct roles in the development of the rodent gustatory system. However, the mechanisms underlying these processes are lacking. Results Here, we demonstrate, in vivo, that single or combined point mutations in major adaptor protein docking sites on TrkB receptor affect specific aspects of the mouse gustatory development, known to be dependent on BDNF or NT-4. In particular, mice with a mutation in the TrkB-SHC docking site had reduced gustatory neuron survival at both early and later stages of development, when survival is dependent on NT-4 and BDNF, respectively. In addition, lingual innervation and taste bud morphology, both BDNF-dependent functions, were altered in these mutants. In contrast, mutation of the TrkB-PLCγ docking site alone did not affect gustatory neuron survival. Moreover, innervation to the tongue was delayed in these mutants and taste receptor expression was altered. Conclusions We have genetically dissected pathways activated downstream of the TrkB receptor that are required for specific aspects of the taste system controlled by the two neurotrophins NT-4 and BDNF. In addition, our results indicate that TrkB also regulate the expression of specific taste receptors by distinct signalling pathways. These results advance our knowledge of the biology of the taste system, one of the fundamental sensory systems crucial for an organism to relate to the environment. PMID:25256039

  15. Griffonia simplicifolia Isolectin B4 Identifies a Specific Subpopulation of Angiogenic Blood Vessels Following Contusive Spinal Cord Injury in the Adult Mouse

    PubMed Central

    BENTON, RICHARD L.; MADDIE, MELISSA A.; MINNILLO, DANIELLE R.; HAGG, THEO; WHITTEMORE, SCOTT R.

    2009-01-01

    After traumatic spinal cord injury (SCI), disruption and plasticity of the microvasculature within injured spinal tissue contribute to the pathological cascades associated with the evolution of both primary and secondary injury. Conversely, preserved vascular function most likely results in tissue sparing and subsequent functional recovery. It has been difficult to identify subclasses of damaged or regenerating blood vessels at the cellular level. Here, adult mice received a single intravenous injection of the Griffonia simplicifolia isolectin B4 (IB4) at 1–28 days following a moderate thoracic (T9) contusion. Vascular binding of IB4 was maximally observed 7 days following injury, a time associated with multiple pathologic aspects of the intrinsic adaptive angiogenesis, with numbers of IB4 vascular profiles decreasing by 21 days postinjury. Quantitative assessment of IB4 binding shows that it occurs within the evolving lesion epicenter, with affected vessels expressing a temporally specific dysfunctional tight junctional phenotype as assessed by occludin, claudin-5, and ZO-1 immunoreactivities. Taken together, these results demonstrate that intravascular lectin delivery following SCI is a useful approach not only for observing the functional status of neovascular formation but also for definitively identifying specific subpopulations of reactive spinal microvascular elements. PMID:18092342

  16. 40 CFR 148.18 - Waste specific prohibitions-newly listed and identified wastes.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Waste specific prohibitions-newly listed and identified wastes. 148.18 Section 148.18 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) HAZARDOUS WASTE INJECTION RESTRICTIONS Prohibitions on...

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

    ERIC Educational Resources Information Center

    Reeder, Glenn D.; Mangiarcina, Janet

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

  18. Systematic Approaches for Identifying and Organizing Content for Training Programs.

    ERIC Educational Resources Information Center

    Ammerman, Harry L.

    This paper concentrates on two aspects in the development of curriculums for technical training: the identification of curriculum content for specific courses of study; and the organization of such content in training programs. Seven steps in the HumRRO procedure for systematic curriculum engineering are identified: determining the performance…

  19. Toward identifying specification requirements for digital bone-anchored prosthesis design incorporating substructure fabrication: a pilot study.

    PubMed

    Eggbeer, Dominic; Bibb, Richard; Evans, Peter

    2006-01-01

    This paper is the first in a series that aims to identify the specification requirements for advanced digital technologies that may be used to design and fabricate complex, soft tissue facial prostheses. Following a review of previously reported techniques, appropriate and currently available technologies were selected and applied in a pilot study. This study uses a range of optical surface scanning, computerized tomography, computer-aided design, and rapid prototyping technologies to capture, design, and fabricate a bone-anchored auricular prosthesis, including the retentive components. The techniques are assessed in terms of their effectiveness, and the results are used to identify future research and specification requirements to direct developments. The case study identifies that while digital technologies may be used to design implant-retained facial prostheses, many limitations need to be addressed to make the techniques clinically viable. It also identifies the need to develop a more robust specification that covers areas such as resolution, accuracy, materials, and design, against which potential technologies may be assessed. There is a need to develop a specification against which potential technologies may be assessed for their suitability in soft tissue facial prosthetics. The specification will be developed using further experimental research studies.

  20. Modeling Submarine Lava Flow with ASPECT

    NASA Astrophysics Data System (ADS)

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

    2017-12-01

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

  1. PD-1 identifies the patient-specific CD8+ tumor-reactive repertoire infiltrating human tumors

    PubMed Central

    Gros, Alena; Robbins, Paul F.; Yao, Xin; Li, Yong F.; Turcotte, Simon; Tran, Eric; Wunderlich, John R.; Mixon, Arnold; Farid, Shawn; Dudley, Mark E.; Hanada, Ken-ichi; Almeida, Jorge R.; Darko, Sam; Douek, Daniel C.; Yang, James C.; Rosenberg, Steven A.

    2014-01-01

    Adoptive transfer of tumor-infiltrating lymphocytes (TILs) can mediate regression of metastatic melanoma; however, TILs are a heterogeneous population, and there are no effective markers to specifically identify and select the repertoire of tumor-reactive and mutation-specific CD8+ lymphocytes. The lack of biomarkers limits the ability to study these cells and develop strategies to enhance clinical efficacy and extend this therapy to other malignancies. Here, we evaluated unique phenotypic traits of CD8+ TILs and TCR β chain (TCRβ) clonotypic frequency in melanoma tumors to identify patient-specific repertoires of tumor-reactive CD8+ lymphocytes. In all 6 tumors studied, expression of the inhibitory receptors programmed cell death 1 (PD-1; also known as CD279), lymphocyte-activation gene 3 (LAG-3; also known as CD223), and T cell immunoglobulin and mucin domain 3 (TIM-3) on CD8+ TILs identified the autologous tumor-reactive repertoire, including mutated neoantigen-specific CD8+ lymphocytes, whereas only a fraction of the tumor-reactive population expressed the costimulatory receptor 4-1BB (also known as CD137). TCRβ deep sequencing revealed oligoclonal expansion of specific TCRβ clonotypes in CD8+PD-1+ compared with CD8+PD-1– TIL populations. Furthermore, the most highly expanded TCRβ clonotypes in the CD8+ and the CD8+PD-1+ populations recognized the autologous tumor and included clonotypes targeting mutated antigens. Thus, in addition to the well-documented negative regulatory role of PD-1 in T cells, our findings demonstrate that PD-1 expression on CD8+ TILs also accurately identifies the repertoire of clonally expanded tumor-reactive cells and reveal a dual importance of PD-1 expression in the tumor microenvironment. PMID:24667641

  2. Identifying content for the glaucoma-specific item bank to measure quality-of-life parameters.

    PubMed

    Khadka, Jyoti; McAlinden, Colm; Craig, Jamie E; Fenwick, Eva K; Lamoureux, Ecosse L; Pesudovs, Konrad

    2015-01-01

    Patient-reported outcomes (PROs) have become essential clinical trial end points. However, a comprehensive, multidimensional, patient-relevant, and precise glaucoma-specific PRO instrument is not available. Therefore, the purpose of this study was to identify content for a new, glaucoma-specific, quality-of-life (QOL) item bank. Content identification was undertaken in 5 phases: (1) identification of extant items in glaucoma-specific instruments and the qualitative literature; (2) focus groups and interviews with glaucoma patients; (3) item classification and selection; (4) expert review and revision of items; and (5) cognitive interviews with patients. A total of 737 unique items (extant items from PRO instruments, 247; qualitative articles, 14 items; focus groups and semistructured interviews, 476 items) were identified. These items were classified into 10 QOL domains. Four criteria (item redundancy, item inconsistent with domain definition, item content too narrow to have wider applicability, and item clarity) were used to remove and refine the items. After the cognitive interviews, the final minimally representative item set had a total of 342 unique items belonging to 10 domains: activity limitation (88), mobility (20), visual symptoms (19), ocular surface symptoms (22), general symptoms (15), convenience (39), health concerns (45), emotional well-being (49), social issues (23), and economic issues (22). The systematic content identification process identified 10 QOL domains, which were important to patients with glaucoma. The majority of the items were identified from the patient-specific focus groups and semistructured interviews suggesting that the existing PRO instruments do not adequately address QOL issues relevant to individuals with glaucoma.

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

    PubMed

    Simanowski, Stefanie; Krajewski, Kristin

    2017-08-10

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

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

    PubMed

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

    2015-11-17

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

  5. Mining the Immune Cell Proteome to Identify Ovarian Cancer-Specific Biomarkers

    DTIC Science & Technology

    2012-03-01

    data and are in the process of identifying gene signatures that can be used as biomarkers for the identification of ovarian cancer-specific biomarkers...groups. The groups showed significant difference in age as well as gestational age, which is expected when considering the disease process . Isolation of...MUC4 in intracellular signaling.32 Oligosaccharides attached to the extracellular domains of mucins have also been shown to interact with different

  6. Hydrograph Separations can Identify Contaminant-Specific Pathways for Conservation Targeting in a Tile-Drained Watershed

    USDA-ARS?s Scientific Manuscript database

    Water quality issues continue to vex agriculture. Understanding contaminant-specific pathways could help clarify effective water quality management strategies in watersheds. Hypothesis: If conducted at nested scales, hydrograph separation techniques can identify contaminant-specific pathways that co...

  7. 40 CFR 148.18 - Waste specific prohibitions-newly listed and identified wastes.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    .... (e) On July 8, 1996, the wastes specified in 40 CFR 261.32 as EPA Hazardous waste numbers K156-K161... 40 Protection of Environment 24 2012-07-01 2012-07-01 false Waste specific prohibitions-newly listed and identified wastes. 148.18 Section 148.18 Protection of Environment ENVIRONMENTAL PROTECTION...

  8. 40 CFR 148.18 - Waste specific prohibitions-newly listed and identified wastes.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    .... (e) On July 8, 1996, the wastes specified in 40 CFR 261.32 as EPA Hazardous waste numbers K156-K161... 40 Protection of Environment 23 2011-07-01 2011-07-01 false Waste specific prohibitions-newly listed and identified wastes. 148.18 Section 148.18 Protection of Environment ENVIRONMENTAL PROTECTION...

  9. 40 CFR 148.18 - Waste specific prohibitions-newly listed and identified wastes.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    .... (e) On July 8, 1996, the wastes specified in 40 CFR 261.32 as EPA Hazardous waste numbers K156-K161... 40 Protection of Environment 24 2013-07-01 2013-07-01 false Waste specific prohibitions-newly listed and identified wastes. 148.18 Section 148.18 Protection of Environment ENVIRONMENTAL PROTECTION...

  10. 40 CFR 148.18 - Waste specific prohibitions-newly listed and identified wastes.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    .... (e) On July 8, 1996, the wastes specified in 40 CFR 261.32 as EPA Hazardous waste numbers K156-K161... 40 Protection of Environment 23 2014-07-01 2014-07-01 false Waste specific prohibitions-newly listed and identified wastes. 148.18 Section 148.18 Protection of Environment ENVIRONMENTAL PROTECTION...

  11. An Automated Method for Identifying Inconsistencies within Diagrammatic Software Requirements Specifications

    NASA Technical Reports Server (NTRS)

    Zhang, Zhong

    1997-01-01

    The development of large-scale, composite software in a geographically distributed environment is an evolutionary process. Often, in such evolving systems, striving for consistency is complicated by many factors, because development participants have various locations, skills, responsibilities, roles, opinions, languages, terminology and different degrees of abstraction they employ. This naturally leads to many partial specifications or viewpoints. These multiple views on the system being developed usually overlap. From another aspect, these multiple views give rise to the potential for inconsistency. Existing CASE tools do not efficiently manage inconsistencies in distributed development environment for a large-scale project. Based on the ViewPoints framework the WHERE (Web-Based Hypertext Environment for requirements Evolution) toolkit aims to tackle inconsistency management issues within geographically distributed software development projects. Consequently, WHERE project helps make more robust software and support software assurance process. The long term goal of WHERE tools aims to the inconsistency analysis and management in requirements specifications. A framework based on Graph Grammar theory and TCMJAVA toolkit is proposed to detect inconsistencies among viewpoints. This systematic approach uses three basic operations (UNION, DIFFERENCE, INTERSECTION) to study the static behaviors of graphic and tabular notations. From these operations, subgraphs Query, Selection, Merge, Replacement operations can be derived. This approach uses graph PRODUCTIONS (rewriting rules) to study the dynamic transformations of graphs. We discuss the feasibility of implementation these operations. Also, We present the process of porting original TCM (Toolkit for Conceptual Modeling) project from C++ to Java programming language in this thesis. A scenario based on NASA International Space Station Specification is discussed to show the applicability of our approach. Finally

  12. 40 CFR 268.38 - Waste specific prohibitions-newly identified organic toxicity characteristic wastes and newly...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... identified organic toxicity characteristic wastes and newly listed coke by-product and chlorotoluene... specific prohibitions—newly identified organic toxicity characteristic wastes and newly listed coke by-product and chlorotoluene production wastes. (a) Effective December 19, 1994, the wastes specified in 40...

  13. Signatures from Tissue-specific MPSS Libraries Identify Transcripts Preferentially Expressed in the Mouse Inner Ear

    PubMed Central

    Peters, Linda M.; Belyantseva, Inna A.; Lagziel, Ayala; Battey, James F.; Friedman, Thomas B.; Morell, Robert J.

    2007-01-01

    Specialization in cell function and morphology is influenced by the differential expression of mRNAs, many of which are expressed at low abundance and restricted to certain cell types. Detecting such transcripts in cDNA libraries may require sequencing millions of clones. Massively parallel signature sequencing (MPSS) is well-suited for identifying transcripts that are expressed in discrete cell types and in low abundance. We have made MPSS libraries from microdissections of three inner ear tissues. By comparing these MPSS libraries to those of 87 other tissues included in the Mouse Reference Transcriptome (MRT) online resource, we have identified genes that are highly enriched in, or specific to, the inner ear. We show by RT-PCR and in situ hybridization that signatures unique to the inner ear libraries identify transcripts with highly specific cell-type localizations. These transcripts serve to illustrate the utility of a resource that is available to the research community. Utilization of these resources will increase the number of known transcription units and expand our knowledge of the tissue-specific regulation of the transcriptome. PMID:17049805

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

    PubMed

    Kassir, Yona

    2017-01-01

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

  15. A computational approach to identify cellular heterogeneity and tissue-specific gene regulatory networks.

    PubMed

    Jambusaria, Ankit; Klomp, Jeff; Hong, Zhigang; Rafii, Shahin; Dai, Yang; Malik, Asrar B; Rehman, Jalees

    2018-06-07

    The heterogeneity of cells across tissue types represents a major challenge for studying biological mechanisms as well as for therapeutic targeting of distinct tissues. Computational prediction of tissue-specific gene regulatory networks may provide important insights into the mechanisms underlying the cellular heterogeneity of cells in distinct organs and tissues. Using three pathway analysis techniques, gene set enrichment analysis (GSEA), parametric analysis of gene set enrichment (PGSEA), alongside our novel model (HeteroPath), which assesses heterogeneously upregulated and downregulated genes within the context of pathways, we generated distinct tissue-specific gene regulatory networks. We analyzed gene expression data derived from freshly isolated heart, brain, and lung endothelial cells and populations of neurons in the hippocampus, cingulate cortex, and amygdala. In both datasets, we found that HeteroPath segregated the distinct cellular populations by identifying regulatory pathways that were not identified by GSEA or PGSEA. Using simulated datasets, HeteroPath demonstrated robustness that was comparable to what was seen using existing gene set enrichment methods. Furthermore, we generated tissue-specific gene regulatory networks involved in vascular heterogeneity and neuronal heterogeneity by performing motif enrichment of the heterogeneous genes identified by HeteroPath and linking the enriched motifs to regulatory transcription factors in the ENCODE database. HeteroPath assesses contextual bidirectional gene expression within pathways and thus allows for transcriptomic assessment of cellular heterogeneity. Unraveling tissue-specific heterogeneity of gene expression can lead to a better understanding of the molecular underpinnings of tissue-specific phenotypes.

  16. [Needs-based offers and gender-specific aspects in nursing homes : Results of a representative survey among directors of nursing homes].

    PubMed

    Teubner, Christian; Sulmann, Daniela; Lahmann, Nils; Suhr, Ralf

    2016-12-01

    Nursing and care that consider individual and biographically shaped impressions requires, among other things sensitivity for the specific needs of persons in need of care. A representative survey was conducted among directors of nursing homes to provide information about the importance of gender-specific aspects in nursing. In a written survey 516 directors of German resident care facilities were interviewed about their attitudes and perceptions regarding the subject, about information on general and gender-specific offers and about demographic information on the management of nursing homes. Activities specifically considering the needs of men and women (gender-specific 43.1 %) are not widespread in the nursing homes surveyed. Most respondents reasoned that there was no demand for such offers (57.1 %) or that they are dispensable due to the composition of residents (47.6 %). Of the respondents 36.4 % saw specific needs more with women than with men (18.4 %). Nevertheless, the need for male-specific activities is given a relatively high priority. The consideration of gender aspects in the planning of care processes (57.0 %) and the regular reflection of gender issues (20.7 %) are strongly correlated with the existence of gender-specific offers, while structural factors, such as the institution size and the education of nursing home directors are not. Currently, gender-specific activity offers in nursing facilities are not widespread. Existing offers are mostly based on traditional gender stereotypes; therefore, it would be desirable if the diversity in the reality of life and the individual needs of women and men would be recognized.

  17. Empirical Methods for Identifying Specific Peptide-protein Interactions for Smart Reagent Development

    DTIC Science & Technology

    2012-09-01

    orientated immobilization of proteins,” Biotechnology Progress, 22(2), 401-405 ( 2006 ). [26] J. M. Kogot, D. A. Sarkes , I. Val-Addo et al...Empirical Methods for Identifying Specific Peptide-protein Interactions for Smart Reagent Development by Joshua M. Kogot, Deborah A. Sarkes ...Peptide-protein Interactions for Smart Reagent Development Joshua M. Kogot, Deborah A. Sarkes , Dimitra N. Stratis-Cullum, and Paul M

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

    PubMed Central

    Johnston, Henry Richard; Hu, Yi-Juan; Gao, Jingjing; O’Connor, Timothy D.; Abecasis, Gonçalo R.; Wojcik, Genevieve L; Gignoux, Christopher R.; Gourraud, Pierre-Antoine; Lizee, Antoine; Hansen, Mark; Genuario, Rob; Bullis, Dave; Lawley, Cindy; Kenny, Eimear E.; Bustamante, Carlos; Beaty, Terri H.; Mathias, Rasika A.; Barnes, Kathleen C.; Qin, Zhaohui S.; Preethi Boorgula, Meher; Campbell, Monica; Chavan, Sameer; Ford, Jean G.; Foster, Cassandra; Gao, Li; Hansel, Nadia N.; Horowitz, Edward; Huang, Lili; Ortiz, Romina; Potee, Joseph; Rafaels, Nicholas; Ruczinski, Ingo; Scott, Alan F.; Taub, Margaret A.; Vergara, Candelaria; Levin, Albert M.; Padhukasahasram, Badri; Williams, L. Keoki; Dunston, Georgia M.; Faruque, Mezbah U.; Gietzen, Kimberly; Deshpande, Aniket; Grus, Wendy E.; Locke, Devin P.; Foreman, Marilyn G.; Avila, Pedro C.; Grammer, Leslie; Kim, Kwang-Youn A.; Kumar, Rajesh; Schleimer, Robert; De La Vega, Francisco M.; Shringarpure, Suyash S.; Musharoff, Shaila; Burchard, Esteban G.; Eng, Celeste; Hernandez, Ryan D.; Pino-Yanes, Maria; Torgerson, Dara G.; Szpiech, Zachary A.; Torres, Raul; Nicolae, Dan L.; Ober, Carole; Olopade, Christopher O; Olopade, Olufunmilayo; Oluwole, Oluwafemi; Arinola, Ganiyu; Song, Wei; Correa, Adolfo; Musani, Solomon; Wilson, James G.; Lange, Leslie A.; Akey, Joshua; Bamshad, Michael; Chong, Jessica; Fu, Wenqing; Nickerson, Deborah; Reiner, Alexander; Hartert, Tina; Ware, Lorraine B.; Bleecker, Eugene; Meyers, Deborah; Ortega, Victor E.; Maul, Pissamai; Maul, Trevor; Watson, Harold; Ilma Araujo, Maria; Riccio Oliveira, Ricardo; Caraballo, Luis; Marrugo, Javier; Martinez, Beatriz; Meza, Catherine; Ayestas, Gerardo; Francisco Herrera-Paz, Edwin; Landaverde-Torres, Pamela; Erazo, Said Omar Leiva; Martinez, Rosella; Mayorga, Alvaro; Mayorga, Luis F.; Mejia-Mejia, Delmy-Aracely; Ramos, Hector; Saenz, Allan; Varela, Gloria; Marina Vasquez, Olga; Ferguson, Trevor; Knight-Madden, Jennifer; Samms-Vaughan, Maureen; Wilks, Rainford J.; Adegnika, Akim; Ateba-Ngoa, Ulysse; Yazdanbakhsh, Maria

    2017-01-01

    A primary goal of The Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to develop an ‘African Diaspora Power Chip’ (ADPC), a genotyping array consisting of tagging SNPs, useful in comprehensively identifying African specific genetic variation. This array is designed based on the novel variation identified in 642 CAAPA samples of African ancestry with high coverage whole genome sequence data (~30× depth). This novel variation extends the pattern of variation catalogued in the 1000 Genomes and Exome Sequencing Projects to a spectrum of populations representing the wide range of West African genomic diversity. These individuals from CAAPA also comprise a large swath of the African Diaspora population and incorporate historical genetic diversity covering nearly the entire Atlantic coast of the Americas. Here we show the results of designing and producing such a microchip array. This novel array covers African specific variation far better than other commercially available arrays, and will enable better GWAS analyses for researchers with individuals of African descent in their study populations. A recent study cataloging variation in continental African populations suggests this type of African-specific genotyping array is both necessary and valuable for facilitating large-scale GWAS in populations of African ancestry. PMID:28429804

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

    NASA Astrophysics Data System (ADS)

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

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

  20. Comparative genome analysis identifies novel nucleic acid diagnostic targets for use in the specific detection of Haemophilus influenzae.

    PubMed

    Coughlan, Helena; Reddington, Kate; Tuite, Nina; Boo, Teck Wee; Cormican, Martin; Barrett, Louise; Smith, Terry J; Clancy, Eoin; Barry, Thomas

    2015-10-01

    Haemophilus influenzae is recognised as an important human pathogen associated with invasive infections, including bloodstream infection and meningitis. Currently used molecular-based diagnostic assays lack specificity in correctly detecting and identifying H. influenzae. As such, there is a need to develop novel diagnostic assays for the specific identification of H. influenzae. Whole genome comparative analysis was performed to identify putative diagnostic targets, which are unique in nucleotide sequence to H. influenzae. From this analysis, we identified 2H. influenzae putative diagnostic targets, phoB and pstA, for use in real-time PCR diagnostic assays. Real-time PCR diagnostic assays using these targets were designed and optimised to specifically detect and identify all 55H. influenzae strains tested. These novel rapid assays can be applied to the specific detection and identification of H. influenzae for use in epidemiological studies and could also enable improved monitoring of invasive disease caused by these bacteria. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Identifying Topics in Microblogs Using Wikipedia.

    PubMed

    Yıldırım, Ahmet; Üsküdarlı, Suzan; Özgür, Arzucan

    2016-01-01

    Twitter is an extremely high volume platform for user generated contributions regarding any topic. The wealth of content created at real-time in massive quantities calls for automated approaches to identify the topics of the contributions. Such topics can be utilized in numerous ways, such as public opinion mining, marketing, entertainment, and disaster management. Towards this end, approaches to relate single or partial posts to knowledge base items have been proposed. However, in microblogging systems like Twitter, topics emerge from the culmination of a large number of contributions. Therefore, identifying topics based on collections of posts, where individual posts contribute to some aspect of the greater topic is necessary. Models, such as Latent Dirichlet Allocation (LDA), propose algorithms for relating collections of posts to sets of keywords that represent underlying topics. In these approaches, figuring out what the specific topic(s) the keyword sets represent remains as a separate task. Another issue in topic detection is the scope, which is often limited to specific domain, such as health. This work proposes an approach for identifying domain-independent specific topics related to sets of posts. In this approach, individual posts are processed and then aggregated to identify key tokens, which are then mapped to specific topics. Wikipedia article titles are selected to represent topics, since they are up to date, user-generated, sophisticated articles that span topics of human interest. This paper describes the proposed approach, a prototype implementation, and a case study based on data gathered during the heavily contributed periods corresponding to the four US election debates in 2012. The manually evaluated results (0.96 precision) and other observations from the study are discussed in detail.

  2. Identifying Topics in Microblogs Using Wikipedia

    PubMed Central

    Yıldırım, Ahmet; Üsküdarlı, Suzan; Özgür, Arzucan

    2016-01-01

    Twitter is an extremely high volume platform for user generated contributions regarding any topic. The wealth of content created at real-time in massive quantities calls for automated approaches to identify the topics of the contributions. Such topics can be utilized in numerous ways, such as public opinion mining, marketing, entertainment, and disaster management. Towards this end, approaches to relate single or partial posts to knowledge base items have been proposed. However, in microblogging systems like Twitter, topics emerge from the culmination of a large number of contributions. Therefore, identifying topics based on collections of posts, where individual posts contribute to some aspect of the greater topic is necessary. Models, such as Latent Dirichlet Allocation (LDA), propose algorithms for relating collections of posts to sets of keywords that represent underlying topics. In these approaches, figuring out what the specific topic(s) the keyword sets represent remains as a separate task. Another issue in topic detection is the scope, which is often limited to specific domain, such as health. This work proposes an approach for identifying domain-independent specific topics related to sets of posts. In this approach, individual posts are processed and then aggregated to identify key tokens, which are then mapped to specific topics. Wikipedia article titles are selected to represent topics, since they are up to date, user-generated, sophisticated articles that span topics of human interest. This paper describes the proposed approach, a prototype implementation, and a case study based on data gathered during the heavily contributed periods corresponding to the four US election debates in 2012. The manually evaluated results (0.96 precision) and other observations from the study are discussed in detail. PMID:26991442

  3. A specific pathway can be identified between genetic characteristics and behaviour profiles in Prader-Willi syndrome via cognitive, environmental and physiological mechanisms.

    PubMed

    Woodcock, K A; Oliver, C; Humphreys, G W

    2009-06-01

    Behavioural phenotypes associated with genetic syndromes have been extensively investigated in order to generate rich descriptions of phenomenology, determine the degree of specificity of behaviours for a particular syndrome, and examine potential interactions between genetic predispositions for behaviour and environmental influences. However, relationships between different aspects of behavioural phenotypes have been less frequently researched and although recent interest in potential cognitive phenotypes or endophenotypes has increased, these are frequently studied independently of the behavioural phenotypes. Taking Prader-Willi syndrome (PWS) as an example, we discuss evidence suggesting specific relationships between apparently distinct aspects of the PWS behavioural phenotype and relate these to specific endophenotypic characteristics. The framework we describe progresses through biological, cognitive, physiological and behavioural levels to develop a pathway from genetic characteristics to behaviour with scope for interaction with the environment at any stage. We propose this multilevel approach as useful in setting out hypotheses in order to structure research that can more rapidly advance theory.

  4. 40 CFR 268.38 - Waste specific prohibitions-newly identified organic toxicity characteristic wastes and newly...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... identified organic toxicity characteristic wastes and newly listed coke by-product and chlorotoluene... specific prohibitions—newly identified organic toxicity characteristic wastes and newly listed coke by... numbers F037, F038, K107-K112, K117, K118, K123-K126, K131, K132, K136, U328, U353, U359, and soil and...

  5. 40 CFR 268.38 - Waste specific prohibitions-newly identified organic toxicity characteristic wastes and newly...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... identified organic toxicity characteristic wastes and newly listed coke by-product and chlorotoluene... specific prohibitions—newly identified organic toxicity characteristic wastes and newly listed coke by... numbers F037, F038, K107-K112, K117, K118, K123-K126, K131, K132, K136, U328, U353, U359, and soil and...

  6. 40 CFR 268.38 - Waste specific prohibitions-newly identified organic toxicity characteristic wastes and newly...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... identified organic toxicity characteristic wastes and newly listed coke by-product and chlorotoluene... specific prohibitions—newly identified organic toxicity characteristic wastes and newly listed coke by... numbers F037, F038, K107-K112, K117, K118, K123-K126, K131, K132, K136, U328, U353, U359, and soil and...

  7. 40 CFR 268.38 - Waste specific prohibitions-newly identified organic toxicity characteristic wastes and newly...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... identified organic toxicity characteristic wastes and newly listed coke by-product and chlorotoluene... specific prohibitions—newly identified organic toxicity characteristic wastes and newly listed coke by... numbers F037, F038, K107-K112, K117, K118, K123-K126, K131, K132, K136, U328, U353, U359, and soil and...

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

    PubMed

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

    2012-08-01

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

  9. Tense or Aspect?: Effects of L1 Tense/Aspect Prominence in L2 Acquisition

    ERIC Educational Resources Information Center

    Martinovic-Zic, Aida

    2009-01-01

    This study introduces a typological model of the "conceptual language-specific approach" to the L2 research on the acquisition of tense-aspect. The model is based on the typological notion of prominence, classifying languages into tense-prominent and aspect-prominent (Bhat 1999) and the L1 research proposal that language-specific…

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

    NASA Astrophysics Data System (ADS)

    Astuti, Laili Dwi; Subali, Bambang

    2017-08-01

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

  11. Efficacy of ACL injury risk screening methods in identifying high-risk landing patterns during a sport-specific task.

    PubMed

    Fox, A S; Bonacci, J; McLean, S G; Saunders, N

    2017-05-01

    Screening methods sensitive to movement strategies that increase anterior cruciate ligament (ACL) loads are likely to be effective in identifying athletes at-risk of ACL injury. Current ACL injury risk screening methods are yet to be evaluated for their ability to identify athletes' who exhibit high-risk lower limb mechanics during sport-specific maneuvers associated with ACL injury occurrences. The purpose of this study was to examine the efficacy of two ACL injury risk screening methods in identifying high-risk lower limb mechanics during a sport-specific landing task. Thirty-two female athletes were screened using the Landing Error Scoring System (LESS) and Tuck Jump Assessment. Participants' also completed a sport-specific landing task, during which three-dimensional kinematic and kinetic data were collected. One-dimensional statistical parametric mapping was used to examine the relationships between screening method scores, and the three-dimensional hip and knee joint rotation and moment data from the sport-specific landing. Higher LESS scores were associated with reduced knee flexion from 30 to 57 ms after initial contact (P = 0.003) during the sport-specific landing; however, no additional relationships were found. These findings suggest the LESS and Tuck Jump Assessment may have minimal applicability in identifying athletes' who exhibit high-risk landing postures in the sport-specific task examined. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Specific aspects of a combined approach to male face correction: botulinum toxin A and volumetric fillers.

    PubMed

    Scherer, Max-Adam

    2016-12-01

    Cosmetologists in the last decade face a permanently increasing number of male patients. The necessity of a gender-adjusted approach in treatment of this patient category is obvious. An adequate correction requires consideration of the anatomic and physiologic features of male faces together with a whole set of interrelated aspects of psychologic perception of the male face esthetics, socially formed understanding of masculine features and appropriate emotional expressions, also of the motivations and expectations of men coming to a cosmetologist. The author explains in detail the elaborated out of own vast experience methods of complex male face correction using the above-mentioned gender-specific approach to create a naturally looking and harmonic facial expression and appearance. The presented botulinum therapy specifics concern the injection point location and toxin doses for every point. As a result, a rather distinct smoothening of the skin profile without detriment to the facial expressiveness and gender-related features is achieved. The importance and methods of an extremely delicate approach to volumetric plasty with stabilized hyaluronic acid-based fillers in men for avoiding hypercorrection and retaining the gender-specific features are discussed. © 2016 Wiley Periodicals, Inc.

  13. Using patients’ experiences to identify priorities for quality improvement in breast cancer care: patient narratives, surveys or both?

    PubMed Central

    2012-01-01

    Background Patients’ experiences have become central to assessing the performance of healthcare systems worldwide and are increasingly being used to inform quality improvement processes. This paper explores the relative value of surveys and detailed patient narratives in identifying priorities for improving breast cancer services as part of a quality improvement process. Methods One dataset was collected using a narrative interview approach, (n = 13) and the other using a postal survey (n = 82). Datasets were analyzed separately and then compared to determine whether similar priorities for improving patient experiences were identified. Results There were both similarities and differences in the improvement priorities arising from each approach. Day surgery was specifically identified as a priority in the narrative dataset but included in the survey recommendations only as part of a broader priority around improving inpatient experience. Both datasets identified appointment systems, patients spending enough time with staff, information about treatment and side effects and more information at the end of treatment as priorities. The specific priorities identified by the narrative interviews commonly related to ‘relational’ aspects of patient experience. Those identified by the survey typically related to more ‘functional’ aspects and were not always sufficiently detailed to identify specific improvement actions. Conclusions Our analysis suggests that whilst local survey data may act as a screening tool to identify potential problems within the breast cancer service, they do not always provide sufficient detail of what to do to improve that service. These findings may have wider applicability in other services. We recommend using an initial preliminary survey, with better use of survey open comments, followed by an in-depth qualitative analysis to help deliver improvements to relational and functional aspects of patient experience. PMID:22913525

  14. The Experiences of Parents with Adolescents Identified as Having a Specific Learning Disability

    ERIC Educational Resources Information Center

    Seals, Linda J.

    2010-01-01

    Of the 6.6 million children in the United States who were deemed in 2008 to have a disability that required special instruction, over 39% were classified as specific learning disabled (SLD). This figure translates into a high number of people who are parenting a child identified as having a SLD. Bronfenbrenner's theory of the ecology of human…

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

    EPA Science Inventory

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

  16. COMPETITIVE METAGENOMIC DNA HYBRIDIZATION IDENTIFIES HOST-SPECIFIC GENETIC MARKERS IN CATTLE FECAL SAMPLES - ABSTRACT

    EPA Science Inventory

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

  17. Terminological aspects of data elements

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Strehlow, R.A.; Kenworthey, W.H. Jr.; Schuldt, R.E.

    1991-01-01

    The creation and display of data comprise a process that involves a sequence of steps requiring both semantic and systems analysis. An essential early step in this process is the choice, definition, and naming of data element concepts and is followed by the specification of other needed data element concept attributes. The attributes and the values of data element concept remain associated with them from their birth as a concept to a generic data element that serves as a template for final application. Terminology is, therefore, centrally important to the entire data creation process. Smooth mapping from natural language tomore » a database is a critical aspect of database, and consequently, it requires terminology standardization from the outset of database work. In this paper the semantic aspects of data elements are analyzed and discussed. Seven kinds of data element concept information are considered and those that require terminological development and standardization are identified. The four terminological components of a data element are the hierarchical type of a concept, functional dependencies, schematas showing conceptual structures, and definition statements. These constitute the conventional role of terminology in database design. 12 refs., 8 figs., 1 tab.« less

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

    PubMed

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

    2017-10-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2014-11-01

    Abstract Background: Impulsivity is a complex trait often studied in substance abuse and overeating disorders, but the exact nature of impulsivity traits and their contribution to these disorders are still debated. Thus, understanding how to measure impulsivity is essential for comprehending addictive behaviors. Identify unique impulsivity traits specific to substance use and overeating. Impulsive Sensation Seeking (ImpSS) and Barratt's Impulsivity scales (BIS) Scales were analyzed with a non-parametric factor analytic technique (discriminant correspondence analysis) to identify group-specific traits on 297 individuals from five groups: Marijuana (n = 88), Nicotine (n = 82), Overeaters (n = 27), Marijuauna + Nicotine (n = 63), and CONTROLs (n = 37). A significant overall factor structure revealed three components of impulsivity that explained respectively 50.19% (pperm < 0.0005), 24.18% (pperm < 0.0005), and 15.98% (pperm < 0.0005) of the variance. All groups were significantly different from one another. When analyzed together, the BIS and ImpSS produce a multi-factorial structure that identified the impulsivity traits specific to these groups. The group specific traits are (1) CONTROL: low impulse, avoids thrill-seeking behaviors; (2) Marijuana: seeks mild sensation, is focused and attentive; (3) Marijuana + Nicotine: pursues thrill-seeking, lacks focus and attention; (4) Nicotine: lacks focus and planning; (5) Overeating: lacks focus, but plans (short and long term). Our results reveal impulsivity traits specific to each group. This may provide better criteria to define spectrums and trajectories - instead of categories - of symptoms for substance use and eating disorders. Defining symptomatic spectrums could be an important step forward in diagnostic strategies.

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

    PubMed Central

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

    2015-01-01

    Background Impulsivity is a complex trait often studied in substance abuse and overeating disorders, but the exact nature of impulsivity traits and their contribution to these disorders are still debated. Thus, understanding how to measure impulsivity is essential for comprehending addictive behaviors. Objectives Identify unique impulsivity traits specific to substance use and overeating. Methods Impulsive Sensation Seeking (ImpSS) and Barratt’s Impulsivity scales (BIS) Scales were analyzed with a non-parametric factor analytic technique (discriminant correspondence analysis) to identify group-specific traits on 297 individuals from five groups: Marijuana (n = 88), Nicotine (n = 82), Overeaters (n = 27), Marijuauna + Nicotine (n = 63), and Controls (n = 37). Results A significant overall factor structure revealed three components of impulsivity that explained respectively 50.19% (pperm<0.0005), 24.18% (pperm<0.0005), and 15.98% (pperm<0.0005) of the variance. All groups were significantly different from one another. When analyzed together, the BIS and ImpSS produce a multi-factorial structure that identified the impulsivity traits specific to these groups. The group specific traits are (1) Control: low impulse, avoids thrill-seeking behaviors; (2) Marijuana: seeks mild sensation, is focused and attentive; (3) Marijuana + Nicotine: pursues thrill-seeking, lacks focus and attention; (4) Nicotine: lacks focus and planning; (5) Overeating: lacks focus, but plans (short and long term). Conclusions Our results reveal impulsivity traits specific to each group. This may provide better criteria to define spectrums and trajectories – instead of categories – of symptoms for substance use and eating disorders. Defining symptomatic spectrums could be an important step forward in diagnostic strategies. PMID:25115831

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

    PubMed

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

    2016-01-19

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

  3. A microscopy-based screen employing multiplex genome sequencing identifies cargo-specific requirements for dynein velocity

    PubMed Central

    Tan, Kaeling; Roberts, Anthony J.; Chonofsky, Mark; Egan, Martin J.; Reck-Peterson, Samara L.

    2014-01-01

    The timely delivery of membranous organelles and macromolecules to specific locations within the majority of eukaryotic cells depends on microtubule-based transport. Here we describe a screening method to identify mutations that have a critical effect on intracellular transport and its regulation using mutagenesis, multicolor-fluorescence microscopy, and multiplex genome sequencing. This screen exploits the filamentous fungus Aspergillus nidulans, which has many of the advantages of yeast molecular genetics but uses long-range microtubule-based transport in a manner more similar to metazoan cells. Using this method, we identified seven mutants that represent novel alleles of components of the intracellular transport machinery: specifically, kinesin-1, cytoplasmic dynein, and the dynein regulators Lis1 and dynactin. The two dynein mutations identified in our screen map to dynein's AAA+ catalytic core. Single-molecule studies reveal that both mutations reduce dynein's velocity in vitro. In vivo these mutants severely impair the distribution and velocity of endosomes, a known dynein cargo. In contrast, another dynein cargo, the nucleus, is positioned normally in these mutants. These results reveal that different dynein functions have distinct stringencies for motor performance. PMID:24403603

  4. A nonmusical paradigm for identifying absolute pitch possessors

    NASA Astrophysics Data System (ADS)

    Ross, David A.; Olson, Ingrid R.; Marks, Lawrence E.; Gore, John C.

    2004-09-01

    The ability to identify and reproduce sounds of specific frequencies is remarkable and uncommon. The etiology and defining characteristics of this skill, absolute pitch (AP), have been very controversial. One theory suggests that AP requires a specific type of early musical training and that the ability to encode and remember tones depends on these learned musical associations. An alternate theory argues that AP may be strongly dependent on hereditary factors and relatively independent of musical experience. To date, it has been difficult to test these hypotheses because all previous paradigms for identifying AP have required subjects to employ knowledge of musical nomenclature. As such, these tests are insensitive to the possibility of discovering AP in either nonmusicians or musicians of non-Western training. Based on previous literature in pitch memory, a paradigm is presented that is intended to distinguish between AP possessors and nonpossessors independent of the subjects' musical experience. The efficacy of this method is then tested with 20 classically defined AP possessors and 22 nonpossessors. Data from these groups strongly support the validity of the paradigm. The use of a nonmusical paradigm to identify AP may facilitate research into many aspects of this phenomenon.

  5. A nonmusical paradigm for identifying absolute pitch possessors.

    PubMed

    Ross, David A; Olson, Ingrid R; Marks, Lawrence E; Gore, John C

    2004-09-01

    The ability to identify and reproduce sounds of specific frequencies is remarkable and uncommon. The etiology and defining characteristics of this skill, absolute pitch (AP), have been very controversial. One theory suggests that AP requires a specific type of early musical training and that the ability to encode and remember tones depends on these learned musical associations. An alternate theory argues that AP may be strongly dependent on hereditary factors and relatively independent of musical experience. To date, it has been difficult to test these hypotheses because all previous paradigms for identifying AP have required subjects to employ knowledge of musical nomenclature. As such, these tests are insensitive to the possibility of discovering AP in either nonmusicians or musicians of non-Western training. Based on previous literature in pitch memory, a paradigm is presented that is intended to distinguish between AP possessors and nonpossessors independent of the subjects' musical experience. The efficacy of this method is then tested with 20 classically defined AP possessors and 22 nonpossessors. Data from these groups strongly support the validity of the paradigm. The use of a nonmusical paradigm to identify AP may facilitate research into many aspects of this phenomenon.

  6. Structural aspects of denitrifying enzymes.

    PubMed

    Moura, I; Moura, J J

    2001-04-01

    The reduction of nitrate to nitrogen gas via nitrite, nitric oxide and nitrous oxide is the metabolic pathway usually known as denitrification, a key step in the nitrogen cycle. As observed for other elemental cycles, a battery of enzymes are utilized, namely the reductases for nitrate, nitrite, nitric oxide and nitrous oxide, as well as multiple electron donors that interact with these enzymes, in order to carry out the stepwise reactions that involve key intermediates. Because of the importance of this pathway (of parallel importance to the nitrogen-fixation pathway), efforts are underway to understand the structures of the participating enzymes and to uncover mechanistic aspects. Three-dimensional structures have been solved for the majority of these enzymes in the past few years, revealing the architecture of the active metal sites as well as global structural aspects, and possible mechanistic aspects. In addition, the recognition of specific electron-transfer partners raises important questions regarding specific electron-transfer pathways, partner recognition and control of metabolism.

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

    PubMed

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

    2017-11-01

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

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

    PubMed

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

    2013-12-01

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

  9. A forward chemical screen in zebrafish identifies a retinoic acid derivative with receptor specificity.

    PubMed

    Das, Bhaskar C; McCartin, Kellie; Liu, Ting-Chun; Peterson, Randall T; Evans, Todd

    2010-04-02

    Retinoids regulate key developmental pathways throughout life, and have potential uses for differentiation therapy. It should be possible to identify novel retinoids by coupling new chemical reactions with screens using the zebrafish embryonic model. We synthesized novel retinoid analogues and derivatives by amide coupling, obtaining 80-92% yields. A small library of these compounds was screened for bioactivity in living zebrafish embryos. We found that several structurally related compounds significantly affect development. Distinct phenotypes are generated depending on time of exposure, and we characterize one compound (BT10) that produces specific cardiovascular defects when added 1 day post fertilization. When compared to retinoic acid (ATRA), BT10 shows similar but not identical changes in the expression pattern of embryonic genes that are known targets of the retinoid pathway. Reporter assays determined that BT10 interacts with all three RAR receptor sub-types, but has no activity for RXR receptors, at all concentrations tested. Our screen has identified a novel retinoid with specificity for retinoid receptors. This lead compound may be useful for manipulating components of retinoid signaling networks, and may be further derivatized for enhanced activity.

  10. Automatically extracting the significant aspects evaluated in game reviews

    NASA Astrophysics Data System (ADS)

    Fong, Chiok Hoong; Ng, Yen Kaow

    2017-04-01

    Understanding the criteria (or "aspects") that reviewers use to evaluate games is important to game developers and publishers, since this will give them important input on how to improve their products. Techniques for the extraction of such aspects have been studied by others, albeit not specific to the gaming industry. In this paper we demonstrate an aspect extraction and analysis system specific to computer games. The system extracts game review texts from a list of known websites and automatically extracts candidate aspects from the review text using techniques from natural language processing and sentiment analysis. It then ranks the candidate aspects using the HITS algorithm. To evaluate the correctness of the extracted aspects, we used the system to calculate an overall score for each game by aggregating its highly-rated aspects, weighted by the importance of the respective aspects. The aggregated scores resulted in a ranking of games, which we compared to a known ranking from a popular website - the rankings showed overall consistency, which suggests that the system has extracted valuable aspects from the reviews. Using the extracted aspect, our system also facilitates the analysis of a game, by evaluating how review articles have rated its performance in these extracted aspects.

  11. Holistic aspects of children's ways of understanding in making sense of genetics

    NASA Astrophysics Data System (ADS)

    Huang, Hui-Ju

    The study examined the nature of how children make sense of phenomena in the area of genetics and inheritance. I proposed the phrase, way of understanding to capture a unified entity which children use to make sense of phenomena. The methodology was semi-structured probing interviews with six sixth grade students. Seven specific ways of understanding were discussed in the results section. Overall, the study described and discovered children's ways of understanding in terms of five aspects: cognitive aspects, affective aspects, social aspects, playfulness, and mode of awareness. Students' propositional knowledge, a holistic view of looking at how people resemble each other, syntactic knowledge, and an extension of rational explanations belonged to the cognitive aspects. Four categories of affective expressions were: an enjoyment of thinking and learning, a special feeling about the instructional activity, a deep personal involvement, and an anxiety in finding correct answers. Two types of social context were identified, one had somewhat of a connection to the science world, and the other did not have much of an scientific tie. The playfulness and the mode of awareness were two emerging aspects through the study. The playfulness represented the spontaneity, freedom, and sense of fun associated with the social interaction activity, such as the playfulness in expressing ideas to others. The modes of awareness included two types of metacognition, one was a conscious reflection on one's cognitive abilities, and the other was a continuous process of monitoring knowledge. In addition, the importance of considering language aspect in science learning was an emerging issue. Students' talking about genetics was embedded in the larger framework of social relationships and social institutions. Their social identify might influence the development of concepts, ways of talking and science learning. The study reflects the richness of children's sense-making processes

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

    PubMed Central

    Schulz, Peter J

    2017-01-01

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

  13. Disease Specific Aspects of Malnutrition in Neurogeriatric Patients

    PubMed Central

    Prell, Tino; Perner, Caroline

    2018-01-01

    Malnutrition in elderly patients is a common condition. Nevertheless, there is evidence on specific risk factors and problems of malnutrition in geriatric patients with neurological diseases. In this review, we summarize recent knowledge on malnutrition in different neurological diseases with a focus on elderly patients. This overview also provides strategies for a more specific and profound assessment of neurogeriatric patients to improve identification and treatment of malnutrition. Early and consequent treatment of malnutrition can lead to a decreased progression of the neurological disease and to a better quality of life in geriatric patients. PMID:29628887

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

    PubMed

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

    2018-03-22

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

  15. Genome-wide oxidative bisulfite sequencing identifies sex-specific methylation differences in the human placenta

    PubMed Central

    Johnson, Michelle D; Dopierala, Justyna

    2018-01-01

    ABSTRACT DNA methylation is an important regulator of gene function. Fetal sex is associated with the risk of several specific pregnancy complications related to placental function. However, the association between fetal sex and placental DNA methylation remains poorly understood. We carried out whole-genome oxidative bisulfite sequencing in the placentas of two healthy female and two healthy male pregnancies generating an average genome depth of coverage of 25x. Most highly ranked differentially methylated regions (DMRs) were located on the X chromosome but we identified a 225 kb sex-specific DMR in the body of the CUB and Sushi Multiple Domains 1 (CSMD1) gene on chromosome 8. The sex-specific differential methylation pattern observed in this region was validated in additional placentas using in-solution target capture. In a new RNA-seq data set from 64 female and 67 male placentas, CSMD1 mRNA was 1.8-fold higher in male than in female placentas (P value = 8.5 × 10−7, Mann-Whitney test). Exon-level quantification of CSMD1 mRNA from these 131 placentas suggested a likely placenta-specific CSMD1 isoform not detected in the 21 somatic tissues analyzed. We show that the gene body of an autosomal gene, CSMD1, is differentially methylated in a sex- and placental-specific manner, displaying sex-specific differences in placental transcript abundance. PMID:29376485

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

    PubMed

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

    2017-09-05

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

  17. A Bottom-Up Proteomic Approach to Identify Substrate Specificity of Outer-Membrane Protease OmpT.

    PubMed

    Wood, Sarah E; Sinsinbar, Gaurav; Gudlur, Sushanth; Nallani, Madhavan; Huang, Che-Fan; Liedberg, Bo; Mrksich, Milan

    2017-12-22

    Identifying peptide substrates that are efficiently cleaved by proteases gives insights into substrate recognition and specificity, guides development of inhibitors, and improves assay sensitivity. Peptide arrays and SAMDI mass spectrometry were used to identify a tetrapeptide substrate exhibiting high activity for the bacterial outer-membrane protease (OmpT). Analysis of protease activity for the preferred residues at the cleavage site (P1, P1') and nearest-neighbor positions (P2, P2') and their positional interdependence revealed FRRV as the optimal peptide with the highest OmpT activity. Substituting FRRV into a fragment of LL37, a natural substrate of OmpT, led to a greater than 400-fold improvement in OmpT catalytic efficiency, with a k cat /K m value of 6.1×10 6  L mol -1  s -1 . Wild-type and mutant OmpT displayed significant differences in their substrate specificities, demonstrating that even modest mutants may not be suitable substitutes for the native enzyme. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Tense-Aspect Processing in Second Language Learners

    ERIC Educational Resources Information Center

    Chan, Ho Leung

    2012-01-01

    This dissertation provides a language processing perspective on the study of second language acquisition (SLA) of tense and aspect. Of special interest are the universal vis-a-vis language-specific dimensions of temporal and aspectual semantics involved. According to the Aspect Hypothesis (AH, e.g. Andersen & Shirai, 1994), the initial…

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

    PubMed

    Gibson, Bradley S; Gondoli, Dawn M

    2018-04-01

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

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

    PubMed

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

    2016-09-07

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

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

    PubMed

    Rothenfluh, Fabia; Schulz, Peter J

    2017-05-01

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

  2. Identifying children with specific reading disabilities from listening and reading discrepancy scores.

    PubMed

    Spring, C; French, L

    1990-01-01

    A method of identifying children with specific reading disabilities by identifying discrepancies between their reading and listening comprehension scores was validated with disabled and nondisabled readers in Grades 4, 5, and 6. The method is based on a modification of the reading comprehension subtest of the Peabody Individual Achievement Test (Dunn & Markwardt, 1970). In this modification, even-numbered sentences are read by subjects, and odd-numbered sentences are read by the test administrator as subjects listen. The features of this test that reduce demands on working memory, thereby making it suitable for the detection of a discrepancy between reading and listening comprehension in readers with disabilities, are discussed. A significant group-by-modality interaction was obtained. Children with reading disabilities scored significantly lower on reading than on listening comprehension, while nondisabled readers scored slightly higher, but not significantly so, on reading than on listening comprehension. The appropriateness of this method as a substitute for the traditional method, which is based on the detection of a discrepancy between intelligence and reading and which has recently been proscribed in certain school districts, is discussed. Issues concerning the listening comprehension skills of disabled readers are also discussed.

  3. Male specific genes from dioecious white campion identified by fluorescent differential display.

    PubMed

    Scutt, Charles P; Jenkins, Tom; Furuya, Masaki; Gilmartin, Philip M

    2002-05-01

    Fluorescent differential display (FDD) has been used to screen for cDNAs that are differentially up-regulated in male flowers of the dioecious plant Silene latifolia in which an X/Y chromosome system of sex determination operates. To adapt FDD to the cloning of large numbers of differential cDNAs, a novel method of confirming the differential expression of these has been devised. FDD gels were Southern electro-blotted and probed with mixtures of individual cDNA clones derived from different FDD product ligation reactions. These Southern blots were then stripped and re-probed with further mixtures of individual cloned FDD products to identify the maximum number of recombinant clones carrying the true differential amplification products. Of 135 differential bands identified by FDD, 56 differential amplification products were confirmed; these represent 23 unique differentially expressed genes as determined by virtual Northern analysis and two genes expressed at or below the level of detection by virtual Northern analysis. These two low expressed genes show bands of hybridization on genomic Southern blots that are specific to male plants, indicating that they are derived from, or closely related to, Y chromosome genes.

  4. Sensitivity and specificity of administrative mortality data for identifying prescription opioid–related deaths

    PubMed Central

    Gladstone, Emilie; Smolina, Kate; Morgan, Steven G.; Fernandes, Kimberly A.; Martins, Diana; Gomes, Tara

    2016-01-01

    Background: Comprehensive systems for surveilling prescription opioid–related harms provide clear evidence that deaths from prescription opioids have increased dramatically in the United States. However, these harms are not systematically monitored in Canada. In light of a growing public health crisis, accessible, nationwide data sources to examine prescription opioid–related harms in Canada are needed. We sought to examine the performance of 5 algorithms to identify prescription opioid–related deaths from vital statistics data against data abstracted from the Office of the Chief Coroner of Ontario as a gold standard. Methods: We identified all prescription opioid–related deaths from Ontario coroners’ data that occurred between Jan. 31, 2003, and Dec. 31, 2010. We then used 5 different algorithms to identify prescription opioid–related deaths from vital statistics death data in 2010. We selected the algorithm with the highest sensitivity and a positive predictive value of more than 80% as the optimal algorithm for identifying prescription opioid–related deaths. Results: Four of the 5 algorithms had positive predictive values of more than 80%. The algorithm with the highest sensitivity (75%) in 2010 improved slightly in its predictive performance from 2003 to 2010. Interpretation: In the absence of specific systems for monitoring prescription opioid–related deaths in Canada, readily available national vital statistics data can be used to study prescription opioid–related mortality with considerable accuracy. Despite some limitations, these data may facilitate the implementation of national surveillance and monitoring strategies. PMID:26622006

  5. Sensitivity and specificity of administrative mortality data for identifying prescription opioid-related deaths.

    PubMed

    Gladstone, Emilie; Smolina, Kate; Morgan, Steven G; Fernandes, Kimberly A; Martins, Diana; Gomes, Tara

    2016-03-01

    Comprehensive systems for surveilling prescription opioid-related harms provide clear evidence that deaths from prescription opioids have increased dramatically in the United States. However, these harms are not systematically monitored in Canada. In light of a growing public health crisis, accessible, nationwide data sources to examine prescription opioid-related harms in Canada are needed. We sought to examine the performance of 5 algorithms to identify prescription opioid-related deaths from vital statistics data against data abstracted from the Office of the Chief Coroner of Ontario as a gold standard. We identified all prescription opioid-related deaths from Ontario coroners' data that occurred between Jan. 31, 2003, and Dec. 31, 2010. We then used 5 different algorithms to identify prescription opioid-related deaths from vital statistics death data in 2010. We selected the algorithm with the highest sensitivity and a positive predictive value of more than 80% as the optimal algorithm for identifying prescription opioid-related deaths. Four of the 5 algorithms had positive predictive values of more than 80%. The algorithm with the highest sensitivity (75%) in 2010 improved slightly in its predictive performance from 2003 to 2010. In the absence of specific systems for monitoring prescription opioid-related deaths in Canada, readily available national vital statistics data can be used to study prescription opioid-related mortality with considerable accuracy. Despite some limitations, these data may facilitate the implementation of national surveillance and monitoring strategies. © 2016 Canadian Medical Association or its licensors.

  6. Earth Observatory Satellite system definition study. Report 5: System design and specifications. Volume 6: Specification for EOS Central Data Processing Facility (CDPF)

    NASA Technical Reports Server (NTRS)

    1974-01-01

    The specifications and functions of the Central Data Processing (CDPF) Facility which supports the Earth Observatory Satellite (EOS) are discussed. The CDPF will receive the EOS sensor data and spacecraft data through the Spaceflight Tracking and Data Network (STDN) and the Operations Control Center (OCC). The CDPF will process the data and produce high density digital tapes, computer compatible tapes, film and paper print images, and other data products. The specific aspects of data inputs and data processing are identified. A block diagram of the CDPF to show the data flow and interfaces of the subsystems is provided.

  7. Aspects of Marine Ecology.

    ERIC Educational Resources Information Center

    Awkerman, Gary L.

    This publication is designed for use in standard science curricula to develop oceanologic manifestations of certain science topics. Included are teacher guides, student activities, and demonstrations to impart ocean science understanding, specifically, aspects of marine ecology, to high school students. The course objectives include the ability of…

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

    PubMed

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

    2008-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Hadi, Ria Fitriyani; Subali, Bambang

    2017-08-01

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

  10. Identifying Military and Combat-Specific Risk Factors for Child Adjustment: Comparing High and Low Risk Military Families and Civilian Families

    DTIC Science & Technology

    2016-08-01

    Award Number: W81XWH-12-2-0034 TITLE: Identifying Military and Combat-Specific Risk Factors for Child Adjustment: Comparing High and Low Risk...2. REPORT TYPE Final 3. DATES COVERED (From - To) 15May2012 - 31Aug2016 Identifying Military and Combat-Specific Risk Factors for Child Adjustment...deployment and has a child between the age of 3 and 7 and comparison groups of civilain single parent families (N=200) and civilian dual parent

  11. Cross-cultural aspects of anxiety disorders.

    PubMed

    Hofmann, Stefan G; Hinton, Devon E

    2014-06-01

    A person's cultural background influences the experience and expression of emotions. In reviewing the recent literature on cross-cultural aspects of anxiety disorders, we identified some culturally related ethnopsychology/ethnophysiology factors (the culture's conceptualizations of how the mind and body function) and contextual factors that influence anxiety disorders. Ethnopsychology/ethnophysiology factors include the person's ideas about the mental and bodily processes (and their interaction), whereas contextual factors are associated with the social norms and rules that may contribute to anxiety, including individualism vs. collectivism and self-construals. From the perspective of ethnopsychology/ethnophysiology and contextual factors, we will discuss "khyâl cap" ("wind attacks"), taijin kyofusho, and ataques de nervios, three prominent examples of culture-specific expressions of anxiety disorders that have all been included in the DSM-5 list of cultural concepts of distress.

  12. Cross-Cultural Aspects of Anxiety Disorders

    PubMed Central

    Hofmann, Stefan G.; Hinton, Devon E.

    2014-01-01

    A person’s cultural background influences the experience and expression of emotions. In reviewing the recent literature on cross-cultural aspects of anxiety disorders, we identified some culturally related ethnopsychology/ethnophysiology factors (the culture’s conceptualizations of how the mind and body function) and contextual factors that influence anxiety disorders. Ethnopsychology/ethnophysiology factors include the person’s ideas about the mental and bodily processes (and their interaction), whereas contextual factors are associated with the social norms and rules that may contribute to anxiety, including individualism vs. collectivism and self-construals. From the perspective of ethnopsychology/ethnophysiology and contextual factors, we will discuss “khyâl cap” (“wind attacks”), taijin kyofusho, and ataques de nervios, three prominent examples of culture-specific expressions of anxiety disorders that have all been included in the DSM-5 list of cultural concepts of distress, PMID:24744049

  13. Aspects Psychosociaux de la Toxicomanie Juvenile (Psychosocial Aspects of the Juvenile Addict).

    ERIC Educational Resources Information Center

    Tremblay, Yolande; And Others

    1992-01-01

    This paper reviews literature on the psychosocial aspects of drug addiction in youth, with specific reference to youth in Quebec, Canada. It notes trends in drug use and discusses three factors in drug usage: availability of the drug, the environment in which the drug use occurs, and the personality of the adolescent. (JDD)

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

    PubMed

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

    2012-10-01

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

  15. AIDS-MEDICOLEGAL ASPECTS.

    PubMed

    Kotabagi, R B; Pathak, P R; Apte, V V

    1999-04-01

    AIDS/HIV Positivity has been the most widely debated disease of this century. Reasons for this are manifold, viz-the non-availability of cure and consequent 100% mortality of a full blown case; its mode of transmission-homosexual and heterosexual activities; widespread occurrence amongst 'main liners'; and patients receiving blood and blood products etc. These aspects have created a dreaded halo around AIDS as well as social stigma. Even the medical community is not exempt from these problems. Unfortunately, legislatures around the world, more so in India, have lagged behind in clarifying many legal issues involved by not enacting specific laws pertaining to AIDS. Consequently many legal & ethical doubts arise in the minds of doctors when confronted with a case of AIDS either in a live patient or in a dead body. In addition, the disease being incurable & 100% fatal, makes it essential to adopt effective preventive measures which in turn need thorough knowledge of social aspects of the epidemic. Certain medicolegal, and ethical aspects of the problem of AIDS are recapitulated in this article for the benefit of the medical community.

  16. Identifying Military and Combat Specific Risk Factors for Child Adjustment: Comparing High and Low Risk Military Families and Civilian Families

    DTIC Science & Technology

    2016-06-01

    Award Number: W81XWH-12-2-0034 TITLE: Identifying Military and Combat-Specific Risk Factors for Child Adjustment: Comparing High and Low Risk...2. REPORT TYPE Annual 3. DATES COVERED (From - To) 15 May - 2013 - 14 May 2014. Identifying Military and Combat-Specific Risk Factors for Child ...parents (N=200) whose spouse/partner is currently in a “low perceived risk” deployment and has a child between the age of 3 and 7 and comparison

  17. Sexual Aspects of Multilateral Relations

    ERIC Educational Resources Information Center

    Constantine, Joan M.; Constantine, Larry L.

    1971-01-01

    This study involved a variety of data gathering techniques focusing on almost every aspect of multilateral marriages. Specific topics covered included sex as motivation, group sex, sleeping arrangements, cohesion, sexual problems, jealousy, roles and sex differences. (Author/CG)

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

    PubMed

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

    2017-10-01

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

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

    PubMed

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

    2002-01-01

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

  20. Exercise based interventions for alcohol use disorder: A comment on motivational aspects of participation.

    PubMed

    Roessler, Kirsten K; Bramsen, Rikke Holm; Dervisevic, Ajla; Bilberg, Randi

    2017-02-01

    Exercise based treatment for alcohol use disorders have shown an impact on mental health (e.g., depression or anxiety), and alcohol outcomes (e.g., craving or abstinence). However, there is a lack of information on the role of motivational aspects of participation in the process of designing exercise interventions for alcohol use disorder. This study aims to examine: (1) whether motivational aspects are taken into account when the type and delivery method of exercise interventions are chosen; (2) whether motivational aspects are taken into account post intervention; and (3) whether there are different traditions regarding payment for participants. A systematic search was conducted to identify eligible studies in order to investigate the impact of motivational aspects including payment for participation. Twelve samples including ten to 620 participants were investigated. Participants were predominantly male and in their 40s, ranging from 20 to 69 years. Aerobic exercise (running, walking, fitness) either in a group or individual condition is the most frequently used exercise form. Two studies included ball games or cycling, while only one study offered the opportunity to choose between a wide range of sports. Motivational aspects are mentioned explicitly in half of the studies, mostly with regard to adherence to participation and social integration as the reason for using a group condition. Achievement is mentioned in two studies but not explicitly with regard to planning the intervention design. Five studies include payment for participation in exercise. Findings of the present study identify that motivational aspects for participation are rarely involved in the planning of an exercise intervention. With regard to the specific psychosocial vulnerability of an alcohol use disorder population, this should be an important aspect of further research studies. © 2016 The Authors. Scandinavian Journal of Psychology published by Scandinavian Psychological Associations

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

    PubMed

    Ahn, Woo-Young; Vassileva, Jasmin

    2016-04-01

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

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

    PubMed Central

    Ahn, Woo-Young; Vassileva, Jasmin

    2016-01-01

    Background Recent animal and human studies reveal distinct cognitive and neurobiological differences between opiate and stimulant addictions; however, our understanding of the common and specific effects of these two classes of drugs remains limited due to the high rates of polysubstance-dependence among drug users. Methods The goal of the current study was to identify multivariate substance-specific markers classifying heroin dependence (HD) and amphetamine dependence (AD), by using machine-learning approaches. Participants included 39 amphetamine mono-dependent, 44 heroin mono-dependent, 58 polysubstance dependent, and 81 non-substance dependent individuals. The majority of substance dependent participants were in protracted abstinence. We used demographic, personality (trait impulsivity, trait psychopathy, aggression, sensation seeking), psychiatric (attention deficit hyperactivity disorder, conduct disorder, antisocial personality disorder, psychopathy, anxiety, depression), and neurocognitive impulsivity measures (Delay Discounting, Go/No-Go, Stop Signal, Immediate Memory, Balloon Analogue Risk, Cambridge Gambling, and Iowa Gambling tasks) as predictors in a machine-learning algorithm. Results The machine-learning approach revealed substance-specific multivariate profiles that classified HD and AD in new samples with high degree of accuracy. Out of 54 predictors, psychopathy was the only classifier common to both types of addiction. Important dissociations emerged between factors classifying HD and AD, which often showed opposite patterns among individuals with HD and AD. Conclusions These results suggest that different mechanisms may underlie HD and AD, challenging the unitary account of drug addiction. This line of work may shed light on the development of standardized and cost-efficient clinical diagnostic tests and facilitate the development of individualized prevention and intervention programs for HD and AD. PMID:26905209

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

    PubMed

    Donaldson, Alex; Finch, Caroline F

    2012-08-01

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

  4. MONKEY: Identifying conserved transcription-factor binding sitesin multiple alignments using a binding site-specific evolutionarymodel

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Moses, Alan M.; Chiang, Derek Y.; Pollard, Daniel A.

    2004-10-28

    We introduce a method (MONKEY) to identify conserved transcription-factor binding sites in multispecies alignments. MONKEY employs probabilistic models of factor specificity and binding site evolution, on which basis we compute the likelihood that putative sites are conserved and assign statistical significance to each hit. Using genomes from the genus Saccharomyces, we illustrate how the significance of real sites increases with evolutionary distance and explore the relationship between conservation and function.

  5. Genome-wide meta-analysis identifies novel gender specific loci associated with thyroid antibodies level in Croatians.

    PubMed

    Matana, Antonela; Popović, Marijana; Boutin, Thibaud; Torlak, Vesela; Brdar, Dubravka; Gunjača, Ivana; Kolčić, Ivana; Boraska Perica, Vesna; Punda, Ante; Polašek, Ozren; Hayward, Caroline; Barbalić, Maja; Zemunik, Tatijana

    2018-04-18

    Autoimmune thyroid diseases (AITD) are multifactorial endocrine diseases most frequently accompanied by Tg and TPO autoantibodies. Both antibodies have a higher prevalence in females and act under a strong genetic influence. To identify novel variants underlying thyroid antibody levels, we performed GWAS meta-analysis on the plasma levels of TgAb and TPOAb in three Croatian cohorts, as well as gender specific GWAS and a bivariate analysis. No significant association was detected with the level of TgAb and TPOAb in the meta-analysis of GWAS or bivariate results for all individuals. The bivariate analysis in females only revealed a genome-wide significant association for the locus near GRIN3A (rs4457391, P = 7.76 × 10 -9 ). The same locus had borderline association with TPOAb levels in females (rs1935377, P = 8.58 × 10 -8 ). In conclusion, we identified a novel gender specific locus associated with TgAb and TPOAb levels. Our findings provide a novel insight into genetic and gender differences associated with thyroid antibodies. Copyright © 2018 Elsevier Inc. All rights reserved.

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

    PubMed

    Labib, A

    1987-06-01

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

  7. GSHSite: Exploiting an Iteratively Statistical Method to Identify S-Glutathionylation Sites with Substrate Specificity

    PubMed Central

    Chen, Yi-Ju; Lu, Cheng-Tsung; Huang, Kai-Yao; Wu, Hsin-Yi; Chen, Yu-Ju; Lee, Tzong-Yi

    2015-01-01

    S-glutathionylation, the covalent attachment of a glutathione (GSH) to the sulfur atom of cysteine, is a selective and reversible protein post-translational modification (PTM) that regulates protein activity, localization, and stability. Despite its implication in the regulation of protein functions and cell signaling, the substrate specificity of cysteine S-glutathionylation remains unknown. Based on a total of 1783 experimentally identified S-glutathionylation sites from mouse macrophages, this work presents an informatics investigation on S-glutathionylation sites including structural factors such as the flanking amino acids composition and the accessible surface area (ASA). TwoSampleLogo presents that positively charged amino acids flanking the S-glutathionylated cysteine may influence the formation of S-glutathionylation in closed three-dimensional environment. A statistical method is further applied to iteratively detect the conserved substrate motifs with statistical significance. Support vector machine (SVM) is then applied to generate predictive model considering the substrate motifs. According to five-fold cross-validation, the SVMs trained with substrate motifs could achieve an enhanced sensitivity, specificity, and accuracy, and provides a promising performance in an independent test set. The effectiveness of the proposed method is demonstrated by the correct identification of previously reported S-glutathionylation sites of mouse thioredoxin (TXN) and human protein tyrosine phosphatase 1b (PTP1B). Finally, the constructed models are adopted to implement an effective web-based tool, named GSHSite (http://csb.cse.yzu.edu.tw/GSHSite/), for identifying uncharacterized GSH substrate sites on the protein sequences. PMID:25849935

  8. Use of mass spectrometry fingerprinting to identify urinary metabolites after consumption of specific foods.

    PubMed

    Lloyd, Amanda J; Favé, Gaëlle; Beckmann, Manfred; Lin, Wanchang; Tailliart, Kathleen; Xie, Long; Mathers, John C; Draper, John

    2011-10-01

    The lack of robust biological markers of dietary exposure hinders the quantitative understanding of causal relations between diet and health. We aimed to develop an efficient procedure to discover metabolites in urine that may have future potential as biomarkers of acute exposure to foods of high public health importance. Twenty-four participants were provided with a test breakfast in which the cereal component of a standardized breakfast was replaced by 1 of 4 foods of high public health importance; 1.5-, 3-, and 4.5-h postprandial urine samples were collected. Flow infusion electrospray-ionization mass spectrometry followed by supervised multivariate data analysis was used to discover signals resulting from consumption of each test food. Fasted-state urine samples provided a universal comparator for food biomarker lead discovery in postprandial urine. The filtering of data features associated with consumption of the common components of the standardized breakfast improved discrimination models and readily identified metabolites that showed consumption of specific test foods. A combination of trimethylamine-N-oxide and 1-methylhistidine was associated with salmon consumption. Novel ascorbate derivatives were discovered in urine after consumption of either broccoli or raspberries. Sulphonated caffeic acid and sulphonated methyl-epicatechin concentrations increased dramatically after consumption of raspberries. This biomarker lead discovery strategy can identify urinary metabolites associated with acute exposure to individual foods. Future studies are required to validate the specificity and utility of potential biomarkers in an epidemiologic context.

  9. Asteroid Secular Dynamics: Ceres’ Fingerprint Identified

    NASA Astrophysics Data System (ADS)

    Novaković, Bojan; Maurel, Clara; Tsirvoulis, Georgios; Knežević, Zoran

    2015-07-01

    Here we report on the significant role of a so far overlooked dynamical aspect, namely, a secular resonance between the dwarf planet Ceres and other asteroids. We demonstrate that this type of secular resonance can be the dominant dynamical factor in certain regions of the main asteroid belt. Specifically, we performed a dynamical analysis of the asteroids belonging to the (1726) Hoffmeister family. To identify which dynamical mechanisms are actually at work in this part of the main asteroid belt, i.e., to isolate the main perturber(s), we study the evolution of this family in time. The study is accomplished using numerical integrations of test particles performed within different dynamical models. The obtained results reveal that the post-impact evolution of the Hoffmeister asteroid family is a direct consequence of the nodal secular resonance with Ceres. This leads us to the conclusion that similar effects must exist in other parts of the asteroid belt. In this respect, the obtained results shed light on an important and entirely new aspect of the long-term dynamics of small bodies. Ceres’ fingerprint in asteroid dynamics, expressed through the discovered secular resonance effect, completely changes our understanding of the way in which perturbations by Ceres-like objects affect the orbits of nearby bodies.

  10. The Development of a Nystagmus-Specific Quality-of-Life Questionnaire.

    PubMed

    McLean, Rebecca J; Maconachie, Gail D E; Gottlob, Irene; Maltby, John

    2016-09-01

    To develop a nystagmus-specific quality-of-life (QOL) questionnaire derived from patient concerns based on eudaimonic aspects of well-being. Cross-sectional study. A total of 206 participants with nystagmus for factor analysis phase and an additional 42 participants with nystagmus for construct validity phase. Questionnaire items were written on the basis of the 6 domains of everyday living affected by nystagmus that were elicited by previous semistructured interviews conducted with 21 people with nystagmus. After consultation with 8 nystagmus experts, 37 items were administered to 206 people with nystagmus. Factor analysis was used to identify latent factors among the items and identify items to propose new nystagmus QOL scales. Cronbach's alpha was used to assess the internal reliability of the new scales. To assess for discriminate and concurrent validity between the new nystagmus scales and an existing vision-related QOL tool, the Visual Function Questionnaire-25 (VFQ-25) was administered to 42 additional participants. Questionnaire response scores on nystagmus-specific QOL items. The factor analysis revealed the retention of 29 items to form a measure comprising 2 distinct subscales reflecting "personal and social" and "physical and environmental" functioning as relating to nystagmus-specific QOL. The Cronbach's alpha coefficients for the "personal and social" functioning scale and "physical and environmental" functioning were 0.95 and 0.93, respectively. Tests for validity of the measure, consistent with a priori predictions, when compared with the VFQ-25, revealed the "physical and environmental" subscale showed concurrent validity (0.88), whereas the "personal and social" subscale was demonstrated to have discriminative validity (0.81). We have developed a 29-item, nystagmus-specific QOL questionnaire (NYS-29) based on eudaimonic aspects of well-being with subscales that address not only physical functioning but also psycho-social issues. The NYS-29 is

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

    PubMed Central

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

    2008-01-01

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

  12. Joint-specific DNA methylation and transcriptome signatures in rheumatoid arthritis identify distinct pathogenic processes

    PubMed Central

    Ai, Rizi; Hammaker, Deepa; Boyle, David L.; Morgan, Rachel; Walsh, Alice M.; Fan, Shicai; Firestein, Gary S.; Wang, Wei

    2016-01-01

    Stratifying patients on the basis of molecular signatures could facilitate development of therapeutics that target pathways specific to a particular disease or tissue location. Previous studies suggest that pathogenesis of rheumatoid arthritis (RA) is similar in all affected joints. Here we show that distinct DNA methylation and transcriptome signatures not only discriminate RA fibroblast-like synoviocytes (FLS) from osteoarthritis FLS, but also distinguish RA FLS isolated from knees and hips. Using genome-wide methods, we show differences between RA knee and hip FLS in the methylation of genes encoding biological pathways, such as IL-6 signalling via JAK-STAT pathway. Furthermore, differentially expressed genes are identified between knee and hip FLS using RNA-sequencing. Double-evidenced genes that are both differentially methylated and expressed include multiple HOX genes. Joint-specific DNA signatures suggest that RA disease mechanisms might vary from joint to joint, thus potentially explaining some of the diversity of drug responses in RA patients. PMID:27282753

  13. Specification Reformulation During Specification Validation

    NASA Technical Reports Server (NTRS)

    Benner, Kevin M.

    1992-01-01

    The goal of the ARIES Simulation Component (ASC) is to uncover behavioral errors by 'running' a specification at the earliest possible points during the specification development process. The problems to be overcome are the obvious ones the specification may be large, incomplete, underconstrained, and/or uncompilable. This paper describes how specification reformulation is used to mitigate these problems. ASC begins by decomposing validation into specific validation questions. Next, the specification is reformulated to abstract out all those features unrelated to the identified validation question thus creating a new specialized specification. ASC relies on a precise statement of the validation question and a careful application of transformations so as to preserve the essential specification semantics in the resulting specialized specification. This technique is a win if the resulting specialized specification is small enough so the user my easily handle any remaining obstacles to execution. This paper will: (1) describe what a validation question is; (2) outline analysis techniques for identifying what concepts are and are not relevant to a validation question; and (3) identify and apply transformations which remove these less relevant concepts while preserving those which are relevant.

  14. A novel assay to identify the trafficking proteins that bind to specific vesicle populations

    PubMed Central

    Bentley, Marvin; Banker, Gary

    2016-01-01

    Here we describe a method capable of identifying interactions between candidate trafficking proteins and a defined vesicle population in intact cells. The assay involves the expression of an FKBP12-rapamycin–binding domain (FRB)–tagged candidate vesicle-binding protein that can be inducibly linked to an FKBP-tagged molecular motor. If the FRB-tagged candidate protein binds the labeled vesicles, then linking the FRB and FKBP domains recruits motors to the vesicles and causes a predictable, highly distinctive change in vesicle trafficking. We describe two versions of the assay: a general protocol for use in cells with a typical microtubule-organizing center and a specialized protocol designed to detect protein-vesicle interactions in cultured neurons. We have successfully used this assay to identify kinesins and Rabs that bind to a variety of different vesicle populations. In principle, this assay could be used to investigate interactions between any category of vesicle trafficking proteins and any vesicle population that can be specifically labeled. PMID:26621371

  15. Beta Atomic Contacts: Identifying Critical Specific Contacts in Protein Binding Interfaces

    PubMed Central

    Liu, Qian; Kwoh, Chee Keong; Hoi, Steven C. H.

    2013-01-01

    Specific binding between proteins plays a crucial role in molecular functions and biological processes. Protein binding interfaces and their atomic contacts are typically defined by simple criteria, such as distance-based definitions that only use some threshold of spatial distance in previous studies. These definitions neglect the nearby atomic organization of contact atoms, and thus detect predominant contacts which are interrupted by other atoms. It is questionable whether such kinds of interrupted contacts are as important as other contacts in protein binding. To tackle this challenge, we propose a new definition called beta (β) atomic contacts. Our definition, founded on the β-skeletons in computational geometry, requires that there is no other atom in the contact spheres defined by two contact atoms; this sphere is similar to the van der Waals spheres of atoms. The statistical analysis on a large dataset shows that β contacts are only a small fraction of conventional distance-based contacts. To empirically quantify the importance of β contacts, we design βACV, an SVM classifier with β contacts as input, to classify homodimers from crystal packing. We found that our βACV is able to achieve the state-of-the-art classification performance superior to SVM classifiers with distance-based contacts as input. Our βACV also outperforms several existing methods when being evaluated on several datasets in previous works. The promising empirical performance suggests that β contacts can truly identify critical specific contacts in protein binding interfaces. β contacts thus provide a new model for more precise description of atomic organization in protein quaternary structures than distance-based contacts. PMID:23630569

  16. Lung transplantation in children. Specific aspects.

    PubMed

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

    2013-12-01

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

  17. Ethical and legal aspects in medically assisted human reproduction in Romania.

    PubMed

    Ioan, Beatrice; Astarastoae, Vasile

    2008-01-01

    Up to the present, there have not been any specific norms regarding medically assisted human reproduction in Romanian legislation. Due to this situation the general legislation regarding medical assistance (law no. 95/2006, regarding the Reform in Health Care System), the Penal and Civil law and the provisions of the Code of Deontology of the Romanian College of Physicians are applied to the field of medically assisted human reproduction. By analysing the ethical and legal conflicts regarding medically assisted human reproduction in Romania, some characteristics cannot be set apart because they derive from religious, cultural and socio-economic aspects. In this article the authors identify the development stages of medically assisted human reproduction in Romania, beginning from these characteristics and insisting upon the failure of the legal system in this specific field. The authors consider that the law regarding medically assisted human reproduction cannot be effective because it did not take into account the ethical and cultural aspects that might appear. Furthermore, in this framework of the legal process, no public debate involving the representatives of civil society was undertaken although the Council of Europe Oviedo Convention approved by our country according to law no. 17/2001 stipulated exactly this working method.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-05-15

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

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

    PubMed Central

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

    2011-01-01

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

  1. Profiling Synaptic Proteins Identifies Regulators of Insulin Secretion and Lifespan

    PubMed Central

    Kaplan, Joshua M.

    2008-01-01

    Cells are organized into distinct compartments to perform specific tasks with spatial precision. In neurons, presynaptic specializations are biochemically complex subcellular structures dedicated to neurotransmitter secretion. Activity-dependent changes in the abundance of presynaptic proteins are thought to endow synapses with different functional states; however, relatively little is known about the rules that govern changes in the composition of presynaptic terminals. We describe a genetic strategy to systematically analyze protein localization at Caenorhabditis elegans presynaptic specializations. Nine presynaptic proteins were GFP-tagged, allowing visualization of multiple presynaptic structures. Changes in the distribution and abundance of these proteins were quantified in 25 mutants that alter different aspects of neurotransmission. Global analysis of these data identified novel relationships between particular presynaptic components and provides a new method to compare gene functions by identifying shared protein localization phenotypes. Using this strategy, we identified several genes that regulate secretion of insulin-like growth factors (IGFs) and influence lifespan in a manner dependent on insulin/IGF signaling. PMID:19043554

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

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

  4. Sensitivity and Specificity of Cetuximab-IRDye800CW to Identify Regional Metastatic Disease in Head and Neck Cancer.

    PubMed

    Rosenthal, Eben L; Moore, Lindsay S; Tipirneni, Kiranya; de Boer, Esther; Stevens, Todd M; Hartman, Yolanda E; Carroll, William R; Zinn, Kurt R; Warram, Jason M

    2017-08-15

    Purpose: Comprehensive cervical lymphadenectomy can be associated with significant morbidity and poor quality of life. This study evaluated the sensitivity and specificity of cetuximab-IRDye800CW to identify metastatic disease in patients with head and neck cancer. Experimental Design: Consenting patients scheduled for curative resection were enrolled in a clinical trial to evaluate the safety and specificity of cetuximab-IRDye800CW. Patients ( n = 12) received escalating doses of the study drug. Where indicated, cervical lymphadenectomy accompanied primary tumor resection, which occurred 3 to 7 days following intravenous infusion of cetuximab-IRDye800CW. All 471 dissected lymph nodes were imaged with a closed-field, near-infrared imaging device during gross processing of the fresh specimens. Intraoperative imaging of exposed neck levels was performed with an open-field fluorescence imaging device. Blinded assessments of the fluorescence data were compared to histopathology to calculate sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). Results: Of the 35 nodes diagnosed pathologically positive, 34 were correctly identified with fluorescence imaging, yielding a sensitivity of 97.2%. Of the 435 pathologically negative nodes, 401 were correctly assessed using fluorescence imaging, yielding a specificity of 92.7%. The NPV was determined to be 99.7%, and the PPV was 50.7%. When 37 fluorescently false-positive nodes were sectioned deeper (1 mm) into their respective blocks, metastatic cancer was found in 8.1% of the recut nodal specimens, which altered staging in two of those cases. Conclusions: Fluorescence imaging of lymph nodes after systemic cetuximab-IRDye800CW administration demonstrated high sensitivity and was capable of identifying additional positive nodes on deep sectioning. Clin Cancer Res; 23(16); 4744-52. ©2017 AACR . ©2017 American Association for Cancer Research.

  5. The Relationship Between Approach to Activity Engagement, Specific Aspects of Physical Function, and Pain Duration in Chronic Pain.

    PubMed

    Andrews, Nicole E; Strong, Jenny; Meredith, Pamela J

    2016-01-01

    To examine: (1) the relationships between habitual approach to activity engagement and specific aspects of physical functioning in chronic pain; and (2) whether or not these relationships differ according to pain duration. Outpatients (N=169) with generalized chronic pain completed a set of written questionnaires. Categories of "approach to activity engagement" were created using the confronting and avoidance subscales of the Pain and Activity Relations Questionnaire. An interaction term between "approach to activity engagement" categories and pain duration was entered into analysis with age, sex, pain intensity, the categorical "approach to activity engagement" variable, and pain duration, in 9 ordinal regression models investigating functioning in a variety of daily activities. The "approach to activity engagement" category predicted the personal care, lifting, sleeping, social life, and traveling aspects of physical functioning but, interestingly, not the performance skills used during these activities, that is, walking, sitting, and standing. The interaction term was significant in 2 models; however, the effect of pain duration on associations was the inverse of that theorized, with the relationship between variables becoming less pronounced with increasing duration of pain. The results of this study do not support the commonly held notion that avoidance and/or overactivity behavior leads to deconditioning and reduced physical capacity over time. Findings do, however, suggest that a relationship exists between avoidance and/or overactivity behavior and reduced participation in activities. Implications for the clinical management of chronic pain and directions for further research are discussed.

  6. Specifications for updating USGS land use and land cover maps

    USGS Publications Warehouse

    Milazzo, Valerie A.

    1983-01-01

    To meet the increasing demands for up-to-date land use and land cover information, a primary goal of the U.S. Geological Survey's (USGS) national land use and land cover mapping program is to provide for periodic updating of maps and data in a timely and uniform manner. The technical specifications for updating existing USGS land use and land cover maps that are presented here cover both the interpretive aspects of detecting and identifying land use and land cover changes and the cartographic aspects of mapping and presenting the change data in conventional map format. They provide the map compiler with the procedures and techniques necessary to then use these change data to update existing land use and land cover maps in a manner that is both standardized and repeatable. Included are specifications for the acquisition of remotely sensed source materials, selection of compilation map bases, handling of data base corrections, editing and quality control operations, generation of map update products for USGS open file, and the reproduction and distribution of open file materials. These specifications are planned to become part of the National Mapping Division's Technical Instructions.

  7. Specific aspects of gastro-intestinal transit in children for drug delivery design.

    PubMed

    Bowles, Alexandra; Keane, Joanne; Ernest, Terry; Clapham, David; Tuleu, Catherine

    2010-08-16

    This mini-review discusses relevant aspects of gastro-intestinal transit in different ages of paediatric patients with an attempt to highlight factors which should be considered in oral dosage form design, in particular multi-particulate dosage forms. This emphasis is due to multi-particulates possessing many of the benefits of liquid oral formulations (such as ease of swallowing and dose adaptability) without many of their drawbacks (such as stability issues and lack of enteric or modified release functionalities). It is commonly stated that children are not merely small adults with regards to medicines. However, there has been very little research regarding how different dosage forms transit through the gastro-intestinal tract in children compared to adults, due to both ethical and practical hurdles. Due to this lack of studies on dosage form transit in children, information which was available on the transit of food, milk and liquids (often dependent upon the age of the patient) has been used to look at how various aspects of transit vary with age and, where possible, when they reach adult values and how these may affect the fate of dosage forms in vivo: swallowability, oesophageal transit, gastric emptying and pH, intestinal and colonic transit are discussed. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  8. Parallel RNAi screens across different cell lines identify generic and cell type-specific regulators of actin organization and cell morphology.

    PubMed

    Liu, Tao; Sims, David; Baum, Buzz

    2009-01-01

    In recent years RNAi screening has proven a powerful tool for dissecting gene functions in animal cells in culture. However, to date, most RNAi screens have been performed in a single cell line, and results then extrapolated across cell types and systems. Here, to dissect generic and cell type-specific mechanisms underlying cell morphology, we have performed identical kinome RNAi screens in six different Drosophila cell lines, derived from two distinct tissues of origin. This analysis identified a core set of kinases required for normal cell morphology in all lines tested, together with a number of kinases with cell type-specific functions. Most significantly, the screen identified a role for minibrain (mnb/DYRK1A), a kinase associated with Down's syndrome, in the regulation of actin-based protrusions in CNS-derived cell lines. This cell type-specific requirement was not due to the peculiarities in the morphology of CNS-derived cells and could not be attributed to differences in mnb expression. Instead, it likely reflects differences in gene expression that constitute the cell type-specific functional context in which mnb/DYRK1A acts. Using parallel RNAi screens and gene expression analyses across cell types we have identified generic and cell type-specific regulators of cell morphology, which include mnb/DYRK1A in the regulation of protrusion morphology in CNS-derived cell lines. This analysis reveals the importance of using different cell types to gain a thorough understanding of gene function across the genome and, in the case of kinases, the difficulties of using the differential gene expression to predict function.

  9. TargetLink, a new method for identifying the endogenous target set of a specific microRNA in intact living cells.

    PubMed

    Xu, Yan; Chen, Yan; Li, Daliang; Liu, Qing; Xuan, Zhenyu; Li, Wen-Hong

    2017-02-01

    MicroRNAs are small non-coding RNAs acting as posttranscriptional repressors of gene expression. Identifying mRNA targets of a given miRNA remains an outstanding challenge in the field. We have developed a new experimental approach, TargetLink, that applied locked nucleic acid (LNA) as the affinity probe to enrich target genes of a specific microRNA in intact cells. TargetLink also consists a rigorous and systematic data analysis pipeline to identify target genes by comparing LNA-enriched sequences between experimental and control samples. Using miR-21 as a test microRNA, we identified 12 target genes of miR-21 in a human colorectal cancer cell by this approach. The majority of the identified targets interacted with miR-21 via imperfect seed pairing. Target validation confirmed that miR-21 repressed the expression of the identified targets. The cellular abundance of the identified miR-21 target transcripts varied over a wide range, with some targets expressed at a rather low level, confirming that both abundant and rare transcripts are susceptible to regulation by microRNAs, and that TargetLink is an efficient approach for identifying the target set of a specific microRNA in intact cells. C20orf111, one of the novel targets identified by TargetLink, was found to reside in the nuclear speckle and to be reliably repressed by miR-21 through the interaction at its coding sequence.

  10. Tissue-enriched expression profiles in Aedes aegypti identify hemocyte-specific transcriptome responses to infection

    PubMed Central

    Choi, Young-Jun; Fuchs, Jeremy F.; Mayhew, George F.; Yu, Helen E.; Christensen, Bruce M.

    2012-01-01

    Hemocytes are integral components of mosquito immune mechanisms such as phagocytosis, melanization, and production of antimicrobial peptides. However, our understanding of hemocyte-specific molecular processes and their contribution to shaping the host immune response remains limited. To better understand the immunophysiological features distinctive of hemocytes, we conducted genome-wide analysis of hemocyte-enriched transcripts, and examined how tissue-enriched expression patterns change with the immune status of the host. Our microarray data indicate that the hemocyte-enriched trascriptome is dynamic and context-dependent. Analysis of transcripts enriched after bacterial challenge in circulating hemocytes with respect to carcass added a dimension to evaluating infection-responsive genes and immune-related gene families. We resolved patterns of transcriptional change unique to hemocytes from those that are likely shared by other immune responsive tissues, and identified clusters of genes preferentially induced in hemocytes, likely reflecting their involvement in cell type specific functions. In addition, the study revealed conserved hemocyte-enriched molecular repertoires which might be implicated in core hemocyte function by cross-species meta-analysis of microarray expression data from Anopheles gambiae and Drosophila melanogaster. PMID:22796331

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

    PubMed

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

    2015-01-01

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

  12. Nano-material aspects of shock absorption in bone joints.

    PubMed

    Tributsch, H; Copf, F; Copf, P; Hindenlang, U; Niethard, F U; Schneider, R

    2010-01-01

    This theoretical study is based on a nano-technological evaluation of the effect of pressure on the composite bone fine structure. It turned out, that the well known macroscopic mechano-elastic performance of bones in combination with muscles and tendons is just one functional aspect which is critically supported by additional micro- and nano- shock damping technology aimed at minimising local bone material damage within the joints and supporting spongy bone material. The identified mechanisms comprise essentially three phenomena localised within the three-dimensional spongy structure with channels and so called perforated flexible tensulae membranes of different dimensions intersecting and linking them. Kinetic energy of a mechanical shock may be dissipated within the solid-liquid composite bone structure into heat via the generation of quasi-chaotic hydromechanic micro-turbulence. It may generate electro-kinetic energy in terms of electric currents and potentials. And the resulting specific structural and surface electrochemical changes may induce the compressible intra-osseal liquid to build up pressure dependent free chemical energy. Innovative bone joint prostheses will have to consider and to be adapted to the nano-material aspects of shock absorption in the operated bones.

  13. Nano-Material Aspects of Shock Absorption in Bone Joints

    PubMed Central

    Tributsch, H; Copf, F; Copf, p; Hindenlang, U; Niethard, F.U; Schneider, R

    2010-01-01

    This theoretical study is based on a nano-technological evaluation of the effect of pressure on the composite bone fine structure. It turned out, that the well known macroscopic mechano-elastic performance of bones in combination with muscles and tendons is just one functional aspect which is critically supported by additional micro- and nano- shock damping technology aimed at minimising local bone material damage within the joints and supporting spongy bone material. The identified mechanisms comprise essentially three phenomena localised within the three–dimensional spongy structure with channels and so called perforated flexible tensulae membranes of different dimensions intersecting and linking them. Kinetic energy of a mechanical shock may be dissipated within the solid-liquid composite bone structure into heat via the generation of quasi-chaotic hydromechanic micro-turbulence. It may generate electro-kinetic energy in terms of electric currents and potentials. And the resulting specific structural and surface electrochemical changes may induce the compressible intra-osseal liquid to build up pressure dependent free chemical energy. Innovative bone joint prostheses will have to consider and to be adapted to the nano-material aspects of shock absorption in the operated bones. PMID:21625375

  14. The Self in Movement: Being Identified and Identifying Oneself in the Process of Migration and Asylum Seeking.

    PubMed

    Watzlawik, Meike; Brescó de Luna, Ignacio

    2017-06-01

    How migration influences the processes of identity development has been under longstanding scrutiny in the social sciences. Usually, stage models have been suggested, and different strategies for acculturation (e.g., integration, assimilation, separation, and marginalization) have been considered as ways to make sense of the psychological transformations of migrants as a group. On an individual level, however, identity development is a more complex endeavor: Identity does not just develop by itself, but is constructed as an ongoing process. To capture these processes, we will look at different aspects of migration and asylum seeking; for example, the cultural-specific values and expectations of the hosting (European) countries (e.g., as identifier), but also of the arriving individuals/groups (e.g., identified as refugees). Since the two may contradict each other, negotiations between identities claims and identity assignments become necessary. Ways to solve these contradictions are discussed, with a special focus on the experienced (and often missing) agency in different settings upon arrival in a new country. In addition, it will be shown how sudden events (e.g., 9/11, the Charlie Hebdo attack) may challenge identity processes in different ways.

  15. The emotional eyewitness: the effects of emotion on specific aspects of eyewitness recall and recognition performance.

    PubMed

    Houston, Kate A; Clifford, Brian R; Phillips, Louise H; Memon, Amina

    2013-02-01

    The present set of experiments aimed to investigate the effects of negative emotion on specific aspects of eyewitness recall and recognition performance. The experience of emotion was manipulated between subjects, with participants either viewing a crime scenario (a mugging) or a neutral scenario (a conversation). Eyewitness recall was categorized into descriptions of the perpetrator, critical incident, victim, and environmental details. The completeness and accuracy of eyewitness recall across categories of detail were measured in Experiment 1. A significant main effect of negative emotion was found for the completeness of recall. Furthermore, a significant main effect of the completeness of eyewitness statements was found, but not for their accuracy. However, these main effects were qualified by a significant interaction between emotion and category of detail recalled. Specifically, emotional participants provided a more complete description of the perpetrator than neutral participants; however, they were less able than their neutral counterparts to describe what the perpetrator did to the victim. In light of these findings, Experiment 2 investigated whether enhanced completeness of perpetrator descriptions during recall translated into an enhanced ability to recognize the perpetrator from a photographic lineup by emotional compared with neutral participants. Results from Experiment 2 suggest that while emotional participants again provide a more complete description of the perpetrator, they are less able than their neutral counterparts to recognize the perpetrator from a photographic lineup. Results are discussed in terms of a retrieval motivation hypothesis of negative emotional experience and the possible consequences for eyewitness testimony. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  16. Sparse Feature Selection Identifies H2A.Z as a Novel, Pattern-Specific Biomarker for Asymmetrically Self-Renewing Distributed Stem Cells

    PubMed Central

    Huh, Yang Hoon; Noh, Minsoo; Burden, Frank R.; Chen, Jennifer C.; Winkler, David A.; Sherley, James L.

    2015-01-01

    There is a long-standing unmet clinical need for biomarkers with high specificity for distributed stem cells (DSCs) in tissues, or for use in diagnostic and therapeutic cell preparations (e.g., bone marrow). Although DSCs are essential for tissue maintenance and repair, accurate determination of their numbers for medical applications has been problematic. Previous searches for biomarkers expressed specifically in DSCs were hampered by difficulty obtaining pure DSCs and by the challenges in mining complex molecular expression data. To identify DSC such useful and specific biomarkers, we combined a novel sparse feature selection method with combinatorial molecular expression data focused on asymmetric self-renewal, a conspicuous property of DSCs. The analysis identified reduced expression of the histone H2A variant H2A.Z as a superior molecular discriminator for DSC asymmetric self-renewal. Subsequent molecular expression studies showed H2A.Z to be a novel “pattern-specific biomarker” for asymmetrically self-renewing cells with sufficient specificity to count asymmetrically self-renewing DSCs in vitro and potentially in situ. PMID:25636161

  17. Specific aspects of cognitive and language proficiency account for variability in neural indices of semantic and syntactic processing in children.

    PubMed

    Hampton Wray, Amanda; Weber-Fox, Christine

    2013-07-01

    The neural activity mediating language processing in young children is characterized by large individual variability that is likely related in part to individual strengths and weakness across various cognitive abilities. The current study addresses the following question: How does proficiency in specific cognitive and language functions impact neural indices mediating language processing in children? Thirty typically developing seven- and eight-year-olds were divided into high-normal and low-normal proficiency groups based on performance on nonverbal IQ, auditory word recall, and grammatical morphology tests. Event-related brain potentials (ERPs) were elicited by semantic anomalies and phrase structure violations in naturally spoken sentences. The proficiency for each of the specific cognitive and language tasks uniquely contributed to specific aspects (e.g., timing and/or resource allocation) of neural indices underlying semantic (N400) and syntactic (P600) processing. These results suggest that distinct aptitudes within broader domains of cognition and language, even within the normal range, influence the neural signatures of semantic and syntactic processing. Furthermore, the current findings have important implications for the design and interpretation of developmental studies of ERPs indexing language processing, and they highlight the need to take into account cognitive abilities both within and outside the classic language domain. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Sex-Specific Genetic Loci for Femoral Neck Bone Mass and Strength Identified in Inbred COP and DA Rats

    PubMed Central

    Alam, Imranul; Sun, Qiwei; Liu, Lixiang; Koller, Daniel L; Carr, Lucinda G; Econs, Michael J; Foroud, Tatiana; Turner, Charles H

    2008-01-01

    Introduction Hip fracture is the most devastating osteoporotic fracture type with significant morbidity and mortality. Several studies in humans identified chromosomal regions linked to hip size and bone mass. Animal models, particularly the inbred rat, serve as complementary approaches for studying the genetic influence on hip fragility. The purpose of this study is to identify sex-independent and sex-specific quantitative trait loci (QTLs) for femoral neck density, structure, and strength in inbred Copenhagen 2331 (COP) and Dark Agouti (DA) rats. Materials and Methods A total of 828 (405 males and 423 females) F2 progeny derived from the inbred COP and DA strains of rats were phenotyped for femoral neck volumetric BMD (vBMD), cross-sectional area, polar moment of inertia (Ip), neck width, ultimate force, and energy to break. A whole genome screen was performed using 93 microsatellite markers with an average intermarker distance of 20 cM. Recombination-based marker maps were generated using MAPMAKER/EXP from the COP × DA F2 data and compared with published Rat Genome Database (RGD) maps. These maps were used for genome-wide linkage analyses to detect sex-independent and sex-specific QTLs. Results Significant evidence of linkage (p < 0.01) for sex-independent QTLs were detected for (1) femoral neck vBMD on chromosomes (Chrs) 1, 6, 10, and 12, (2) femoral neck structure on Chrs 5, 7, 10, and 18, and (3) biomechanical properties on Chrs 1 and 4. Male-specific QTLs were discovered on Chrs 2, 9, and 18 for total vBMD, on Chr 17 for trabecular vBMD, on Chr 9 for total bone area, and on Chr 15 for ultimate force. A female-specific QTL was discovered on Chr 2 for ultimate force. The effect size of the individual QTL varied between 1% and 4%. Conclusions We detected evidence that sex-independent and sex-specific QTLs contribute to hip fragility in the inbred rat. Several QTLs regions identified in this study are homologous to human chromosomal regions previously linked to

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

    PubMed Central

    Lu, Xiangfeng; Peloso, Gina M; Liu, Dajiang J.; Wu, Ying; Zhang, He; Zhou, Wei; Li, Jun; Tang, Clara Sze-man; Dorajoo, Rajkumar; Li, Huaixing; Long, Jirong; Guo, Xiuqing; Xu, Ming; Spracklen, Cassandra N.; Chen, Yang; Liu, Xuezhen; Zhang, Yan; Khor, Chiea Chuen; Liu, Jianjun; Sun, Liang; Wang, Laiyuan; Gao, Yu-Tang; Hu, Yao; Yu, Kuai; Wang, Yiqin; Cheung, Chloe Yu Yan; Wang, Feijie; Huang, Jianfeng; Fan, Qiao; Cai, Qiuyin; Chen, Shufeng; Shi, Jinxiu; Yang, Xueli; Zhao, Wanting; Sheu, Wayne H.-H.; Cherny, Stacey Shawn; He, Meian; Feranil, Alan B.; Adair, Linda S.; Gordon-Larsen, Penny; Du, Shufa; Varma, Rohit; da Chen, Yii-Der I; Shu, XiaoOu; Lam, Karen Siu Ling; Wong, Tien Yin; Ganesh, Santhi K.; Mo, Zengnan; Hveem, Kristian; Fritsche, Lars; Nielsen, Jonas Bille; Tse, Hung-fat; Huo, Yong; Cheng, Ching-Yu; Chen, Y. Eugene; Zheng, Wei; Tai, E Shyong; Gao, Wei; Lin, Xu; Huang, Wei; Abecasis, Goncalo; Consortium, GLGC; Kathiresan, Sekar; Mohlke, Karen L.; Wu, Tangchun; Sham, Pak Chung; Gu, Dongfeng; Willer, Cristen J

    2017-01-01

    Most genome-wide association studies have been conducted in European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we examined protein-coding genetic variants in 47,532 East Asian individuals using an exome array. We identified 255 variants at 41 loci reaching chip-wide significance, including 3 novel loci and 14 East Asian-specific coding variant associations. After meta-analysis with > 300,000 European samples, we identified an additional 9 novel loci. The same 16 genes were identified by the protein-altering variants in both East Asians and Europeans, likely pointing to the functional genes. Our data demonstrate that most of the low-frequency or rare coding variants associated with lipids are population-specific, and that examining genomic data across diverse ancestries may facilitate the identification of functional genes at associated loci. PMID:29083407

  20. Ranking product aspects through sentiment analysis of online reviews

    NASA Astrophysics Data System (ADS)

    Wang, Wei; Wang, Hongwei; Song, Yuan

    2017-03-01

    The electronic word-of-mouth (e-WOM) is one of the most important among all the factors affecting consumers' behaviours. Opinions towards a product through online reviews will influence purchase decisions of other online consumers by changing their perceptions on the product quality. Furthermore, each product aspect may impact consumers' intentions differently. Thus, sentiment analysis and econometric models are incorporated to examine the relationship between purchase intentions and aspect-opinion pairs, which enable the weight estimation for each product aspect. We first identify product aspects and reduce dimensions to extract aspect-opinion pairs. Next the information gain is calculated for each aspect through entropy theory. Based on sentiment polarity and sentiment strength, we formulate an econometric model by integrating the information gain to measure the aspect's weight. In the experiment, we track 386 digital cameras on Amazon for 39 months, and results show that the aspect weight for digital cameras is detected more precisely than TF-ID and HAC algorithms. The results will bridge product aspects and consumption intention to facilitate e-WOM-based marketing.

  1. Biomarkers of systemic lupus erythematosus identified using mass spectrometry-based proteomics: a systematic review.

    PubMed

    Nicolaou, Orthodoxia; Kousios, Andreas; Hadjisavvas, Andreas; Lauwerys, Bernard; Sokratous, Kleitos; Kyriacou, Kyriacos

    2017-05-01

    Advances in mass spectrometry technologies have created new opportunities for discovering novel protein biomarkers in systemic lupus erythematosus (SLE). We performed a systematic review of published reports on proteomic biomarkers identified in SLE patients using mass spectrometry-based proteomics and highlight their potential disease association and clinical utility. Two electronic databases, MEDLINE and EMBASE, were systematically searched up to July 2015. The methodological quality of studies included in the review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Twenty-five studies were included in the review, identifying 241 SLE candidate proteomic biomarkers related to various aspects of the disease including disease diagnosis and activity or pinpointing specific organ involvement. Furthermore, 13 of the 25 studies validated their results for a selected number of biomarkers in an independent cohort, resulting in the validation of 28 candidate biomarkers. It is noteworthy that 11 candidate biomarkers were identified in more than one study. A significant number of potential proteomic biomarkers that are related to a number of aspects of SLE have been identified using mass spectrometry proteomic approaches. However, further studies are required to assess the utility of these biomarkers in routine clinical practice. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  2. Public clonotype usage identifies protective Gag-specific CD8+ T cell responses in SIV infection

    PubMed Central

    Asher, Tedi E.; Wilson, Nancy A.; Nason, Martha C.; Brenchley, Jason M.; Metzler, Ian S.; Venturi, Vanessa; Gostick, Emma; Chattopadhyay, Pratip K.; Roederer, Mario; Davenport, Miles P.; Watkins, David I.; Douek, Daniel C.

    2009-01-01

    Despite the pressing need for an AIDS vaccine, the determinants of protective immunity to HIV remain concealed within the complexity of adaptive immune responses. We dissected immunodominant virus-specific CD8+ T cell populations in Mamu-A*01+ rhesus macaques with primary SIV infection to elucidate the hallmarks of effective immunity at the level of individual constituent clonotypes, which were identified according to the expression of distinct T cell receptors (TCRs). The number of public clonotypes, defined as those that expressed identical TCR β-chain amino acid sequences and recurred in multiple individuals, contained within the acute phase CD8+ T cell population specific for the biologically constrained Gag CM9 (CTPYDINQM; residues 181–189) epitope correlated negatively with the virus load set point. This independent molecular signature of protection was confirmed in a prospective vaccine trial, in which clonotype engagement was governed by the nature of the antigen rather than the context of exposure and public clonotype usage was associated with enhanced recognition of epitope variants. Thus, the pattern of antigen-specific clonotype recruitment within a protective CD8+ T cell population is a prognostic indicator of vaccine efficacy and biological outcome in an AIDS virus infection. PMID:19349463

  3. [Preclinical evaluation of the safety of biotechnology products: specific aspects].

    PubMed

    Descotes, Jacques; Ravel, Guillaume; Vial, Thierry

    2003-01-01

    Biotechnology-derived products represent a class of increasingly numerous drugs. One of their major characteristics is extreme diversity, which requires specific approaches for the preclinical evaluation of their safety. The selection of relevant animal species is not easy, as most of these products are human-specific. Thus, only one species will often be used, i.e. primates. As most of these products are large molecules, they can be directly immunogenic. When they are human-specific, no animal model is available to predict the risk. Many biotechnology-derived products have an expected influence on the immune system. This must be taken into account in the preclinical strategy of immunotoxicity evaluation that is now required for every new drug. As conventional toxicity testing is generally limited, safety pharmacology studies should include more than the core battery of assays required by current guidelines in order to complement missing data as much as possible. Because of these particularities, a comprehensive investigation of metabolism and pharmacokinetics is not usually needed. Some products can cross-react with cellular components not intended as therapeutic targets. It is, therefore, essential to rule out the risk of possible cross-reactions that can result in adverse effects. Finally, viral safety is a crucial component of the preclinical safety evaluation of these products. Overall, biotechnology-derived products raise specific issues because of their innovative and original characteristics, and it is difficult to address all these issues if not by using a case-by-case approach.

  4. Single measure and gated screening approaches for identifying students at-risk for academic problems: Implications for sensitivity and specificity.

    PubMed

    Van Norman, Ethan R; Nelson, Peter M; Klingbeil, David A

    2017-09-01

    Educators need recommendations to improve screening practices without limiting students' instructional opportunities. Repurposing previous years' state test scores has shown promise in identifying at-risk students within multitiered systems of support. However, researchers have not directly compared the diagnostic accuracy of previous years' state test scores with data collected during fall screening periods to identify at-risk students. In addition, the benefit of using previous state test scores in conjunction with data from a separate measure to identify at-risk students has not been explored. The diagnostic accuracy of 3 types of screening approaches were tested to predict proficiency on end-of-year high-stakes assessments: state test data obtained during the previous year, data from a different measure administered in the fall, and both measures combined (i.e., a gated model). Extant reading and math data (N = 2,996) from 10 schools in the Midwest were analyzed. When used alone, both measures yielded similar sensitivity and specificity values. The gated model yielded superior specificity values compared with using either measure alone, at the expense of sensitivity. Implications, limitations, and ideas for future research are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  5. Some Legal Aspects of Campus Housing.

    ERIC Educational Resources Information Center

    Moore, Donald R.

    Legal aspects and implications affecting college and university housing administration are unpredictable, unsettled, and subject to change. The complete practical guide to the everyday legal answers for campus housing simply does not exist. This document presents some specific legal considerations involved in housing that may affect the management…

  6. Comprehensive Aspectual UML approach to support AspectJ.

    PubMed

    Magableh, Aws; Shukur, Zarina; Ali, Noorazean Mohd

    2014-01-01

    Unified Modeling Language is the most popular and widely used Object-Oriented modelling language in the IT industry. This study focuses on investigating the ability to expand UML to some extent to model crosscutting concerns (Aspects) to support AspectJ. Through a comprehensive literature review, we identify and extensively examine all the available Aspect-Oriented UML modelling approaches and find that the existing Aspect-Oriented Design Modelling approaches using UML cannot be considered to provide a framework for a comprehensive Aspectual UML modelling approach and also that there is a lack of adequate Aspect-Oriented tool support. This study also proposes a set of Aspectual UML semantic rules and attempts to generate AspectJ pseudocode from UML diagrams. The proposed Aspectual UML modelling approach is formally evaluated using a focus group to test six hypotheses regarding performance; a "good design" criteria-based evaluation to assess the quality of the design; and an AspectJ-based evaluation as a reference measurement-based evaluation. The results of the focus group evaluation confirm all the hypotheses put forward regarding the proposed approach. The proposed approach provides a comprehensive set of Aspectual UML structural and behavioral diagrams, which are designed and implemented based on a comprehensive and detailed set of AspectJ programming constructs.

  7. Comprehensive Aspectual UML Approach to Support AspectJ

    PubMed Central

    Magableh, Aws; Shukur, Zarina; Mohd. Ali, Noorazean

    2014-01-01

    Unified Modeling Language is the most popular and widely used Object-Oriented modelling language in the IT industry. This study focuses on investigating the ability to expand UML to some extent to model crosscutting concerns (Aspects) to support AspectJ. Through a comprehensive literature review, we identify and extensively examine all the available Aspect-Oriented UML modelling approaches and find that the existing Aspect-Oriented Design Modelling approaches using UML cannot be considered to provide a framework for a comprehensive Aspectual UML modelling approach and also that there is a lack of adequate Aspect-Oriented tool support. This study also proposes a set of Aspectual UML semantic rules and attempts to generate AspectJ pseudocode from UML diagrams. The proposed Aspectual UML modelling approach is formally evaluated using a focus group to test six hypotheses regarding performance; a “good design” criteria-based evaluation to assess the quality of the design; and an AspectJ-based evaluation as a reference measurement-based evaluation. The results of the focus group evaluation confirm all the hypotheses put forward regarding the proposed approach. The proposed approach provides a comprehensive set of Aspectual UML structural and behavioral diagrams, which are designed and implemented based on a comprehensive and detailed set of AspectJ programming constructs. PMID:25136656

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

    PubMed

    Condie, Brian G; Urbanski, William M

    2014-01-01

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

  9. [Genetic aspects of pancreatic cancer].

    PubMed

    Grigor'eva, I N; Efimova, O V; Suvorova, T S; Tov, N L

    2014-01-01

    The purpose of the review--to analyze the basic data on modifiable and genetic risk factors of pancreatic cancer (PC). PC is the most fatal disease that kills about 95% of patients. Among the known risk factors for PC only for smoking, obesity, and family history a positive association with the PC risk in meta-analyzes confirmed. The PC etiology remains unclear, more than 90% of patients acquire it sporadically. Currently, the most significant genes for PC include KRAS2, p16/CDKN2, TP53, SMAD4/DPC4. Mutations in the KRAS noted in 90% of cases of pancreatic ducts adenocarcinoma. p16/CDKN2A mutation is accompanied by a 38-fold increased risk of PC compared with the general population. TP53 mutations are associated not only with carcinogenesis but also PC metastasis, as well as SMAD4/DPC4 mutations. Study of the role of genetic aspects in the PC development is necessary both to identify individuals with high PC risk, as well as for the development of gene-specific treatments, such as inhibitors of proteins, histone deacetylase, and histone acetyltransferase (vorinostat, belinostat, entinostat, panobinostat, curcumin) are in clinical trials.

  10. Behavioral aspects of children's sports.

    PubMed

    Pratt, Helen D; Patel, Dilip R; Greydanus, Donald E

    2003-08-01

    This article considers some of the numerous behavioral aspects that are related to children's sports. The pediatrician, during various encounters with the athlete and his or her parents in the office, or on the field, can positively influence the sport participation experience of the athlete, by screening and identifying potential problem areas as well as providing anticipatory guidance on various issues.

  11. Ancestry-specific and sex-specific risk alleles identified in a genome-wide gene-by-alcohol dependence interaction study of risky sexual behaviors.

    PubMed

    Polimanti, Renato; Zhao, Hongyu; Farrer, Lindsay A; Kranzler, Henry R; Gelernter, Joel

    2017-12-01

    We previously mapped loci for the genome-wide association studies (GWAS) and genome-wide gene-by-alcohol dependence interaction (GW-GxAD) analyses of risky sexual behaviors (RSB). This study extends those findings by analyzing the ancestry- and sex-specific AD-stratified effects on RSB. We examined the concordance of findings for the AD-stratified GWAS and the GW-GxAD analysis of RSB, with concordance defined as genome-wide significance in one analysis and at least nominal significance in the second analysis. A total of 2,173 African-American (AA) and 1,751 European-American (EA) subjects were investigated. Information regarding RSB (lifetime experiences of unprotected sex and multiple sexual partners) and DSM-IV diagnosis of lifetime AD were derived from the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA). In our ancestry- and sex-specific analyses, we identified four independent genome-wide significant (GWS) loci (p < 5*10 -8 ) and one suggestive locus (p < 6*10 -8 ). In men, we observed a GWS signal in FAM162A (rs2002594, p = 4.96*10 -8 ). In women, there was a suggestive locus in PLGRKT (rs3824435, p = 5.52*10 -8 ). In AAs, there was a GWS signal in GRK5 (rs1316543, p = 1.25*10 -9 ). In AA men, we observed an intergenic GWS signal (rs12898370, p = 4.49*10 -8 ) near LINGO1. In EA men, there was a GWS signal in CCSER1 (rs62313897; p = 7.93*10 -10 ). The loci identified in this GWAS implicate molecular mechanisms related to psychiatric illness and personality features, suggesting that the interplay between AD and RSB is mediated by alleles associated with behavioral traits. © 2017 Wiley Periodicals, Inc.

  12. Copy Number Variation Is a Fundamental Aspect of the Placental Genome

    PubMed Central

    Hannibal, Roberta L.; Chuong, Edward B.; Rivera-Mulia, Juan Carlos; Gilbert, David M.; Valouev, Anton; Baker, Julie C.

    2014-01-01

    Discovery of lineage-specific somatic copy number variation (CNV) in mammals has led to debate over whether CNVs are mutations that propagate disease or whether they are a normal, and even essential, aspect of cell biology. We show that 1,000N polyploid trophoblast giant cells (TGCs) of the mouse placenta contain 47 regions, totaling 138 Megabases, where genomic copies are underrepresented (UR). UR domains originate from a subset of late-replicating heterochromatic regions containing gene deserts and genes involved in cell adhesion and neurogenesis. While lineage-specific CNVs have been identified in mammalian cells, classically in the immune system where V(D)J recombination occurs, we demonstrate that CNVs form during gestation in the placenta by an underreplication mechanism, not by recombination nor deletion. Our results reveal that large scale CNVs are a normal feature of the mammalian placental genome, which are regulated systematically during embryogenesis and are propagated by a mechanism of underreplication. PMID:24785991

  13. Copy number variation is a fundamental aspect of the placental genome.

    PubMed

    Hannibal, Roberta L; Chuong, Edward B; Rivera-Mulia, Juan Carlos; Gilbert, David M; Valouev, Anton; Baker, Julie C

    2014-05-01

    Discovery of lineage-specific somatic copy number variation (CNV) in mammals has led to debate over whether CNVs are mutations that propagate disease or whether they are a normal, and even essential, aspect of cell biology. We show that 1,000 N polyploid trophoblast giant cells (TGCs) of the mouse placenta contain 47 regions, totaling 138 Megabases, where genomic copies are underrepresented (UR). UR domains originate from a subset of late-replicating heterochromatic regions containing gene deserts and genes involved in cell adhesion and neurogenesis. While lineage-specific CNVs have been identified in mammalian cells, classically in the immune system where V(D)J recombination occurs, we demonstrate that CNVs form during gestation in the placenta by an underreplication mechanism, not by recombination nor deletion. Our results reveal that large scale CNVs are a normal feature of the mammalian placental genome, which are regulated systematically during embryogenesis and are propagated by a mechanism of underreplication.

  14. Identifying decohering paths in closed quantum systems

    NASA Technical Reports Server (NTRS)

    Albrecht, Andreas

    1990-01-01

    A specific proposal is discussed for how to identify decohering paths in a wavefunction of the universe. The emphasis is on determining the correlations among subsystems and then considering how these correlations evolve. The proposal is similar to earlier ideas of Schroedinger and of Zeh, but in other ways it is closer to the decoherence functional of Griffiths, Omnes, and Gell-Mann and Hartle. There are interesting differences with each of these which are discussed. Once a given coarse-graining is chosen, the candidate paths are fixed in this scheme, and a single well defined number measures the degree of decoherence for each path. The normal probability sum rules are exactly obeyed (instantaneously) by these paths regardless of the level of decoherence. Also briefly discussed is how one might quantify some other aspects of classicality. The important role that concrete calculations play in testing this and other proposals is stressed.

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

    PubMed

    Lu, Xiangfeng; Peloso, Gina M; Liu, Dajiang J; Wu, Ying; Zhang, He; Zhou, Wei; Li, Jun; Tang, Clara Sze-Man; Dorajoo, Rajkumar; Li, Huaixing; Long, Jirong; Guo, Xiuqing; Xu, Ming; Spracklen, Cassandra N; Chen, Yang; Liu, Xuezhen; Zhang, Yan; Khor, Chiea Chuen; Liu, Jianjun; Sun, Liang; Wang, Laiyuan; Gao, Yu-Tang; Hu, Yao; Yu, Kuai; Wang, Yiqin; Cheung, Chloe Yu Yan; Wang, Feijie; Huang, Jianfeng; Fan, Qiao; Cai, Qiuyin; Chen, Shufeng; Shi, Jinxiu; Yang, Xueli; Zhao, Wanting; Sheu, Wayne H-H; Cherny, Stacey Shawn; He, Meian; Feranil, Alan B; Adair, Linda S; Gordon-Larsen, Penny; Du, Shufa; Varma, Rohit; Chen, Yii-Der Ida; Shu, Xiao-Ou; Lam, Karen Siu Ling; Wong, Tien Yin; Ganesh, Santhi K; Mo, Zengnan; Hveem, Kristian; Fritsche, Lars G; Nielsen, Jonas Bille; Tse, Hung-Fat; Huo, Yong; Cheng, Ching-Yu; Chen, Y Eugene; Zheng, Wei; Tai, E Shyong; Gao, Wei; Lin, Xu; Huang, Wei; Abecasis, Goncalo; Kathiresan, Sekar; Mohlke, Karen L; Wu, Tangchun; Sham, Pak Chung; Gu, Dongfeng; Willer, Cristen J

    2017-12-01

    Most genome-wide association studies have been of European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we used an exome array to examine protein-coding genetic variants in 47,532 East Asian individuals. We identified 255 variants at 41 loci that reached chip-wide significance, including 3 novel loci and 14 East Asian-specific coding variant associations. After a meta-analysis including >300,000 European samples, we identified an additional nine novel loci. Sixteen genes were identified by protein-altering variants in both East Asians and Europeans, and thus are likely to be functional genes. Our data demonstrate that most of the low-frequency or rare coding variants associated with lipids are population specific, and that examining genomic data across diverse ancestries may facilitate the identification of functional genes at associated loci.

  16. Genome-wide Association Study Identifies African-Specific Susceptibility Loci in African Americans with Inflammatory Bowel Disease

    PubMed Central

    Brant, Steven R.; Okou, David T.; Simpson, Claire L.; Cutler, David J.; Haritunians, Talin; Bradfield, Jonathan P.; Chopra, Pankaj; Prince, Jarod; Begum, Ferdouse; Kumar, Archana; Huang, Chengrui; Venkateswaran, Suresh; Datta, Lisa W.; Wei, Zhi; Thomas, Kelly; Herrinton, Lisa J.; Klapproth, Jan-Micheal A.; Quiros, Antonio J.; Seminerio, Jenifer; Liu, Zhenqiu; Alexander, Jonathan S.; Baldassano, Robert N.; Dudley-Brown, Sharon; Cross, Raymond K.; Dassopoulos, Themistocles; Denson, Lee A.; Dhere, Tanvi A.; Dryden, Gerald W.; Hanson, John S.; Hou, Jason K.; Hussain, Sunny Z.; Hyams, Jeffrey S.; Isaacs, Kim L.; Kader, Howard; Kappelman, Michael D.; Katz, Jeffry; Kellermayer, Richard; Kirschner, Barbara S.; Kuemmerle, John F.; Kwon, John H.; Lazarev, Mark; Li, Ellen; Mack, David; Mannon, Peter; Moulton, Dedrick E.; Newberry, Rodney D.; Osuntokun, Bankole O.; Patel, Ashish S.; Saeed, Shehzad A.; Targan, Stephan R.; Valentine, John F.; Wang, Ming-Hsi; Zonca, Martin; Rioux, John D.; Duerr, Richard H.; Silverberg, Mark S.; Cho, Judy H.; Hakonarson, Hakon; Zwick, Michael E.; McGovern, Dermot P.B.; Kugathasan, Subra

    2016-01-01

    Background & Aims The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn’s disease (CD) cause significant morbidity and are increasing in prevalence among all populations, including African Americans. More than 200 susceptibility loci have been identified in populations of predominantly European ancestry, but few loci have been associated with IBD in other ethnicities. Methods We performed 2 high-density, genome-wide scans comprising 2345 cases of African Americans with IBD (1646 with CD, 583 with UC, and 116 inflammatory bowel disease unclassified [IBD-U]) and 5002 individuals without IBD (controls, identified from the Health Retirement Study and Kaiser Permanente database). Single-nucleotide polymorphisms (SNPs) associated at P<5.0×10−8 in meta-analysis with a nominal evidence (P<.05) in each scan were considered to have genome-wide significance. Results We detected SNPs at HLA-DRB1, and African-specific SNPs at ZNF649 and LSAMP, with associations of genome-wide significance for UC. We detected SNPs at USP25 with associations of genome-wide significance associations for IBD. No associations of genome-wide significance were detected for CD. In addition, 9 genes previously associated with IBD contained SNPs with significant evidence for replication (P<1.6×10−6): ADCY3, CXCR6, HLA-DRB1 to HLA-DQA1 (genome-wide significance on conditioning), IL12B, PTGER4, and TNC for IBD; IL23R, PTGER4, and SNX20 (in strong linkage disequilibrium with NOD2) for CD; and KCNQ2 (near TNFRSF6B) for UC. Several of these genes, such as TNC (near TNFSF15), CXCR6, and genes associated with IBD at the HLA locus, contained SNPs with unique association patterns with African-specific alleles. Conclusions We performed a genome-wide association study of African Americans with IBD and identified loci associated with CD and UC in only this population; we also replicated loci identified in European populations. The detection of variants associated with IBD risk in only

  17. Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in African Americans With Inflammatory Bowel Disease.

    PubMed

    Brant, Steven R; Okou, David T; Simpson, Claire L; Cutler, David J; Haritunians, Talin; Bradfield, Jonathan P; Chopra, Pankaj; Prince, Jarod; Begum, Ferdouse; Kumar, Archana; Huang, Chengrui; Venkateswaran, Suresh; Datta, Lisa W; Wei, Zhi; Thomas, Kelly; Herrinton, Lisa J; Klapproth, Jan-Micheal A; Quiros, Antonio J; Seminerio, Jenifer; Liu, Zhenqiu; Alexander, Jonathan S; Baldassano, Robert N; Dudley-Brown, Sharon; Cross, Raymond K; Dassopoulos, Themistocles; Denson, Lee A; Dhere, Tanvi A; Dryden, Gerald W; Hanson, John S; Hou, Jason K; Hussain, Sunny Z; Hyams, Jeffrey S; Isaacs, Kim L; Kader, Howard; Kappelman, Michael D; Katz, Jeffry; Kellermayer, Richard; Kirschner, Barbara S; Kuemmerle, John F; Kwon, John H; Lazarev, Mark; Li, Ellen; Mack, David; Mannon, Peter; Moulton, Dedrick E; Newberry, Rodney D; Osuntokun, Bankole O; Patel, Ashish S; Saeed, Shehzad A; Targan, Stephan R; Valentine, John F; Wang, Ming-Hsi; Zonca, Martin; Rioux, John D; Duerr, Richard H; Silverberg, Mark S; Cho, Judy H; Hakonarson, Hakon; Zwick, Michael E; McGovern, Dermot P B; Kugathasan, Subra

    2017-01-01

    The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn's disease (CD) cause significant morbidity and are increasing in prevalence among all populations, including African Americans. More than 200 susceptibility loci have been identified in populations of predominantly European ancestry, but few loci have been associated with IBD in other ethnicities. We performed 2 high-density, genome-wide scans comprising 2345 cases of African Americans with IBD (1646 with CD, 583 with UC, and 116 inflammatory bowel disease unclassified) and 5002 individuals without IBD (controls, identified from the Health Retirement Study and Kaiser Permanente database). Single-nucleotide polymorphisms (SNPs) associated at P < 5.0 × 10 -8 in meta-analysis with a nominal evidence (P < .05) in each scan were considered to have genome-wide significance. We detected SNPs at HLA-DRB1, and African-specific SNPs at ZNF649 and LSAMP, with associations of genome-wide significance for UC. We detected SNPs at USP25 with associations of genome-wide significance for IBD. No associations of genome-wide significance were detected for CD. In addition, 9 genes previously associated with IBD contained SNPs with significant evidence for replication (P < 1.6 × 10 -6 ): ADCY3, CXCR6, HLA-DRB1 to HLA-DQA1 (genome-wide significance on conditioning), IL12B,PTGER4, and TNC for IBD; IL23R, PTGER4, and SNX20 (in strong linkage disequilibrium with NOD2) for CD; and KCNQ2 (near TNFRSF6B) for UC. Several of these genes, such as TNC (near TNFSF15), CXCR6, and genes associated with IBD at the HLA locus, contained SNPs with unique association patterns with African-specific alleles. We performed a genome-wide association study of African Americans with IBD and identified loci associated with UC in only this population; we also replicated IBD, CD, and UC loci identified in European populations. The detection of variants associated with IBD risk in only people of African descent demonstrates the

  18. Next-generation DNA sequencing identifies novel gene variants and pathways involved in specific language impairment.

    PubMed

    Chen, Xiaowei Sylvia; Reader, Rose H; Hoischen, Alexander; Veltman, Joris A; Simpson, Nuala H; Francks, Clyde; Newbury, Dianne F; Fisher, Simon E

    2017-04-25

    A significant proportion of children have unexplained problems acquiring proficient linguistic skills despite adequate intelligence and opportunity. Developmental language disorders are highly heritable with substantial societal impact. Molecular studies have begun to identify candidate loci, but much of the underlying genetic architecture remains undetermined. We performed whole-exome sequencing of 43 unrelated probands affected by severe specific language impairment, followed by independent validations with Sanger sequencing, and analyses of segregation patterns in parents and siblings, to shed new light on aetiology. By first focusing on a pre-defined set of known candidates from the literature, we identified potentially pathogenic variants in genes already implicated in diverse language-related syndromes, including ERC1, GRIN2A, and SRPX2. Complementary analyses suggested novel putative candidates carrying validated variants which were predicted to have functional effects, such as OXR1, SCN9A and KMT2D. We also searched for potential "multiple-hit" cases; one proband carried a rare AUTS2 variant in combination with a rare inherited haplotype affecting STARD9, while another carried a novel nonsynonymous variant in SEMA6D together with a rare stop-gain in SYNPR. On broadening scope to all rare and novel variants throughout the exomes, we identified biological themes that were enriched for such variants, including microtubule transport and cytoskeletal regulation.

  19. Next-generation DNA sequencing identifies novel gene variants and pathways involved in specific language impairment

    PubMed Central

    Chen, Xiaowei Sylvia; Reader, Rose H.; Hoischen, Alexander; Veltman, Joris A.; Simpson, Nuala H.; Francks, Clyde; Newbury, Dianne F.; Fisher, Simon E.

    2017-01-01

    A significant proportion of children have unexplained problems acquiring proficient linguistic skills despite adequate intelligence and opportunity. Developmental language disorders are highly heritable with substantial societal impact. Molecular studies have begun to identify candidate loci, but much of the underlying genetic architecture remains undetermined. We performed whole-exome sequencing of 43 unrelated probands affected by severe specific language impairment, followed by independent validations with Sanger sequencing, and analyses of segregation patterns in parents and siblings, to shed new light on aetiology. By first focusing on a pre-defined set of known candidates from the literature, we identified potentially pathogenic variants in genes already implicated in diverse language-related syndromes, including ERC1, GRIN2A, and SRPX2. Complementary analyses suggested novel putative candidates carrying validated variants which were predicted to have functional effects, such as OXR1, SCN9A and KMT2D. We also searched for potential “multiple-hit” cases; one proband carried a rare AUTS2 variant in combination with a rare inherited haplotype affecting STARD9, while another carried a novel nonsynonymous variant in SEMA6D together with a rare stop-gain in SYNPR. On broadening scope to all rare and novel variants throughout the exomes, we identified biological themes that were enriched for such variants, including microtubule transport and cytoskeletal regulation. PMID:28440294

  20. Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs

    PubMed Central

    Below, Jennifer E.; Parra, Esteban J.; Gamazon, Eric R.; Torres, Jason; Krithika, S.; Candille, Sophie; Lu, Yingchang; Manichakul, Ani; Peralta-Romero, Jesus; Duan, Qing; Li, Yun; Morris, Andrew P.; Gottesman, Omri; Bottinger, Erwin; Wang, Xin-Qun; Taylor, Kent D.; Ida Chen, Y.-D.; Rotter, Jerome I.; Rich, Stephen S.; Loos, Ruth J. F.; Tang, Hua; Cox, Nancy J.; Cruz, Miguel; Hanis, Craig L.; Valladares-Salgado, Adan

    2016-01-01

    We performed genome-wide meta-analysis of lipid traits on three samples of Mexican and Mexican American ancestry comprising 4,383 individuals, and followed up significant and highly suggestive associations in three additional Hispanic samples comprising 7,876 individuals. Genome-wide significant signals were observed in or near CELSR2, ZNF259/APOA5, KANK2/DOCK6 and NCAN/MAU2 for total cholesterol, LPL, ABCA1, ZNF259/APOA5, LIPC and CETP for HDL cholesterol, CELSR2, APOB and NCAN/MAU2 for LDL cholesterol, and GCKR, TRIB1, ZNF259/APOA5 and NCAN/MAU2 for triglycerides. Linkage disequilibrium and conditional analyses indicate that signals observed at ABCA1 and LIPC for HDL cholesterol and NCAN/MAU2 for triglycerides are independent of previously reported lead SNP associations. Analyses of lead SNPs from the European Global Lipids Genetics Consortium (GLGC) dataset in our Hispanic samples show remarkable concordance of direction of effects as well as strong correlation in effect sizes. A meta-analysis of the European GLGC and our Hispanic datasets identified five novel regions reaching genome-wide significance: two for total cholesterol (FN1 and SAMM50), two for HDL cholesterol (LOC100996634 and COPB1) and one for LDL cholesterol (LINC00324/CTC1/PFAS). The top meta-analysis signals were found to be enriched for SNPs associated with gene expression in a tissue-specific fashion, suggesting an enrichment of tissue-specific function in lipid-associated loci. PMID:26780889

  1. [Identifying the specific causes of kidney allograft loss: A population-based study].

    PubMed

    Lohéac, Charlotte; Aubert, Olivier; Loupy, Alexandre; Legendre, Christophe

    2018-04-01

    Results of kidney transplantation have been improving but long-term allograft survival remains disappointing. The objective of the present study was to identify the specific causes of renal allograft loss, to assess their incidence and long-term outcomes. A total of 4783 patients from four French centres, transplanted between January 2004 and January 2014 were prospectively included. A total of 9959 kidney biopsies (protocol and for cause) performed between January 2004 and March 2015 were included. Donor and recipient clinical and biological parameters as well as anti-HLA antibody directed against the donor were included. The main outcome was the long-term kidney allograft survival, including the study of the associated causes of graft loss, the delay of graft loss according to their causes and the determinants of graft loss. There were 732 graft losses during the follow-up period (median time: 4.51 years) with an identified cause in 95.08 %. Kidney allograft survival at 9 years post-transplant was 78 %. The causes of allograft loss were: antibody-mediated rejection (31.69 %), thrombosis (25.55 %), medical intercurrent disease (14.62 %), recurrence of primary renal disease (7.1 %), BK- or CMV-associated nephropathy (n=35, 4.78 %), T cell-mediated rejection (4.78 %), urological disease (2.46 %) and calcineurin inhibitor nephrotoxicity (1.09 %). The main causes of allograft loss were antibody-mediated rejection and thrombosis. These results encourage efforts to prevent and detect these complications earlier in order to improve allograft survival. Copyright © 2018 Association Société de néphrologie. Published by Elsevier Masson SAS. All rights reserved.

  2. Gastric Cancer-Specific Protein Profile Identified Using Endoscopic Biopsy Samples via MALDI Mass Spectrometry

    PubMed Central

    Kim, Hark Kyun; Reyzer, Michelle L.; Choi, Il Ju; Kim, Chan Gyoo; Kim, Hee Sung; Oshima, Akira; Chertov, Oleg; Colantonio, Simona; Fisher, Robert J.; Allen, Jamie L.; Caprioli, Richard M.; Green, Jeffrey E.

    2012-01-01

    To date, proteomic analyses on gastrointestinal cancer tissue samples have been performed using surgical specimens only, which are obtained after a diagnosis is made. To determine if a proteomic signature obtained from endoscopic biopsy samples could be found to assist with diagnosis, frozen endoscopic biopsy samples collected from 63 gastric cancer patients and 43 healthy volunteers were analyzed using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. A statistical classification model was developed to distinguish tumor from normal tissues using half the samples and validated with the other half. A protein profile was discovered consisting of 73 signals that could classify 32 cancer and 22 normal samples in the validation set with high predictive values (positive and negative predictive values for cancer, 96.8% and 91.3%; sensitivity, 93.8%; specificity, 95.5%). Signals overexpressed in tumors were identified as α-defensin-1, α-defensin-2, calgranulin A, and calgranulin B. A protein profile was also found to distinguish pathologic stage Ia (pT1N0M0) samples (n = 10) from more advanced stage (Ib or higher) tumors (n = 48). Thus, protein profiles obtained from endoscopic biopsy samples may be useful in assisting with the diagnosis of gastric cancer and, possibly, in identifying early stage disease. PMID:20557134

  3. Registered Dietitians in School Nutrition Leadership: Motivational Aspects of Job Selection and Job Satisfaction

    ERIC Educational Resources Information Center

    Dodson, Linette J.; Arendt, Susan W.

    2014-01-01

    Purpose/Objectives: This study examined motivational aspects related to selecting school nutrition leadership as a career by registered dietitians (RDs). Motivational aspects were defined as valued characteristics which influence individuals' desires for specific work environments. Aspects of job satisfaction were also explored. Methods: An online…

  4. Sensitivity and specificity of the Chinese version of the Schizotypal Personality Questionnaire-Brief for identifying undergraduate students susceptible to psychosis.

    PubMed

    Ma, Wei-Fen; Wu, Po-Lun; Yang, Shu-Ju; Cheng, Kuang-Fu; Chiu, Hsien-Tsai; Lane, Hsien-Yuan

    2010-12-01

    Early interventions can improve treatment outcomes for individuals with major psychiatric disorders and with nonspecific symptoms but increasingly impaired cognitive perception, emotions, and behaviour. One way used to identify people susceptible to psychosis is through the schizotypal personality trait. Persons with schizotypal characteristics have been identified with the widely used Schizotypal Personality Questionnaire-Brief. However, no suitable instruments are available to screen individuals in the Taiwanese population for evidence of early psychotic symptoms. The purpose of this study was to test the sensitivity and specificity of the Chinese version of the Schizotypal Personality Questionnaire-Brief for identifying undergraduate students' susceptibility to psychosis. Two-stage, cross-sectional survey design. The self-administered scale was tested in a convenience sample of 618 undergraduate students at a medical university in Taiwan. Among these students, 54 completed the scale 2 weeks apart for test-retest reliability, and 80 were tested to identify their susceptibility to psychosis. In Stage I, participants with scores in the top 6.5% were classified as the high-score group (n=40). The control group (n=40) was randomly selected from the remaining participants with scores <15 and matched by gender. These 80 students were asked to participate in psychiatric interviews in Stage II. The instrument was tested for reliability using intraclass correlation coefficients and the Kuder-Richardson formula 20. The instrument was analysed for optimal sensitivity and specificity using odds-ratio analysis and receiver operating characteristic curves. The 22-item Chinese version of the Schizotypal Personality Questionnaire-Brief had a 2-week test-retest reliability of 0.82 and internal consistency of 0.76. The optimal cut-off score was 17, with odds ratios of 24.4 and an area under the receiver operating characteristic curves of 0.83. The instrument had a sensitivity of

  5. Long-Term Memory: A Review and Meta-Analysis of Studies of Declarative and Procedural Memory in Specific Language Impairment

    ERIC Educational Resources Information Center

    Lum, Jarrad A. G.; Conti-Ramsden, Gina

    2013-01-01

    This review examined the status of long-term memory systems in specific language impairment (SLI)--declarative memory and aspects of procedural memory in particular. Studies included in the review were identified following a systematic search of the literature and findings combined using meta-analysis. This review showed that individuals with SLI…

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

    PubMed

    Woda, Marcia; Mathew, Anuja

    2015-01-01

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

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

    PubMed Central

    Woda, Marcia; Mathew, Anuja

    2015-01-01

    Low frequencies of memory B cells in the peripheral blood make it challenging to measure the functional and phenotypic characteristics of this antigen experienced subset of B cells without in vitro culture. To date, reagents are lacking to measure ex vivo frequencies of dengue virus (DENV)-specific memory B cells. We wanted to explore the possibility of using fluorescently labeled DENV as probes to detect antigen-specific memory B cells in the peripheral blood of DENV immune individuals. Alexa Fluor dye-labeled DENV yielded viable virus that could be stored at −80°C for long periods of time. Using a careful gating strategy and methods to decrease non-specific binding, we were able to identify a small frequency of B cells from dengue immune individuals that bound labeled DENV. Sorted DENV+ B cells from immune, but not naïve donors secreted antibodies that bound intact virions after in vitro stimulation. Overall, Alexa Fluor dye labeled -DENV are useful reagents to enable the detection and characterization of memory B cells in DENV immune individuals. PMID:25497702

  8. Specific PCR primers directed to identify cryI and cryIII genes within a Bacillus thuringiensis strain collection.

    PubMed Central

    Cerón, J; Ortíz, A; Quintero, R; Güereca, L; Bravo, A

    1995-01-01

    In this paper we describe a PCR strategy that can be used to rapidly identify Bacillus thuringiensis strains that harbor any of the known cryI or cryIII genes. Four general PCR primers which amplify DNA fragments from the known cryI or cryIII genes were selected from conserved regions. Once a strain was identified as an organism that contains a particular type of cry gene, it could be easily characterized by performing additional PCR with specific cryI and cryIII primers selected from variable regions. The method described in this paper can be used to identify the 10 different cryI genes and the five different cryIII genes. One feature of this screening method is that each cry gene is expected to produce a PCR product having a precise molecular weight. The genes which produce PCR products having different sizes probably represent strains that harbor a potentially novel cry gene. Finally, we present evidence that novel crystal genes can be identified by the method described in this paper. PMID:8526493

  9. Genome-wide Association Study Identifies Peanut Allergy-Specific Loci and Evidence of Epigenetic Mediation in U.S. Children

    PubMed Central

    Hong, Xiumei; Hao, Ke; Ladd-Acosta, Christine; Hansen, Kasper D; Tsai, Hui-Ju; Liu, Xin; Xu, Xin; Thornton, Timothy A.; Caruso, Deanna; Keet, Corinne A; Sun, Yifei; Wang, Guoying; Luo, Wei; Kumar, Rajesh; Fuleihan, Ramsay; Singh, Anne Marie; Kim, Jennifer S; Story, Rachel E; Gupta, Ruchi S; Gao, Peisong; Chen, Zhu; Walker, Sheila O.; Bartell, Tami R; Beaty, Terri H; Fallin, M Daniele; Schleimer, Robert; Holt, Patrick G; Nadeau, Kari Christine; Wood, Robert A; Pongracic, Jacqueline A; Weeks, Daniel E; Wang, Xiaobin

    2015-01-01

    Food allergy (FA) affects 2–10% of U.S. children and is a growing clinical and public health problem. Here we conduct the first genome-wide association study of well-defined FA, including specific subtypes (peanut, milk, and egg) in 2,759 U.S. participants (1,315 children; 1,444 parents) from the Chicago Food Allergy Study; and identify peanut allergy (PA)-specific loci in the HLA-DR and -DQ gene region at 6p21.32, tagged by rs7192 (p=5.5×10−8) and rs9275596 (p=6.8×10−10), in 2,197 participants of European ancestry. We replicate these associations in an independent sample of European ancestry. These associations are further supported by meta-analyses across the discovery and replication samples. Both single-nucleotide polymorphisms (SNPs) are associated with differential DNA methylation levels at multiple CpG sites (p<5×10−8); and differential DNA methylation of the HLA-DQB1 and HLA-DRB1 genes partially mediate the identified SNP-PA associations. This study suggests that the HLA-DR and -DQ gene region likely poses significant genetic risk for PA. PMID:25710614

  10. Application of DNA markers to identify the individual-specific hosts of tsetse feeding on cattle.

    PubMed

    Torr, S J; Wilson, P J; Schofield, S; Mangwiro, T N; Akber, S; White, B N

    2001-03-01

    Primer sets for five different ungulate loci were used to obtain individual microsatellite DNA profiles for 29 Mashona cattle from a herd in Zimbabwe. There were 3-13 alleles for each locus and, using the entire suite of five loci, each animal within the herd, including closely related individuals, could be unequivocally distinguished. Wild-caught Glossina pallidipes Austen (Diptera: Glossinidae) were fed on specific cattle and the bloodmeal was profiled 0.5-72 h after feeding. The individual specific sources of the bloodmeals, including mixe meals produced by allowing tsetse to feed on two different cattle, were reliabl identified up to 24 h after feeding. The technique was used in field studies of hos selection by G. pallidipes and G. morsitans morsitans Westwood (Diptera Glossinidae) attracted to pairs of cattle. When the pair comprised an adult and a calf, 100% of meals were from the adult. For some pairs of adult cattle, tsetse were biased significantly towards feeding on one animal, whereas for other pairs there was no such bias. In general, feeding was greater on the animal known to have lower rate of host defensive behaviour. Results suggest that relatively slight differences in the inherent defensive behaviour of cattle produce large difference in host-specific feeding rates when the hosts are adjacent. For flies attracted to pair of cattle, < 2% contained blood from both hosts. The DNA profiling technique will be useful in studying the epidemiology of vector-borne diseases of livestock.

  11. Identifying Specific Learning Disabilities: Legislation, Regulation, and Court Decisions

    ERIC Educational Resources Information Center

    Zumeta, Rebecca O.; Zirkel, Perry A.; Danielson, Louis

    2014-01-01

    Specific learning disability (SLD) identification and eligibility practices are evolving and sometimes contentious. This article describes the historical context and current status of the SLD definition, legislation, regulation, and case law related to the identification of students eligible for special education services. The first part traces…

  12. Genetic Screening Identifies Cyanogenesis-Deficient Mutants of Lotus japonicus and Reveals Enzymatic Specificity in Hydroxynitrile Glucoside Metabolism[W][OA

    PubMed Central

    Takos, Adam; Lai, Daniela; Mikkelsen, Lisbeth; Abou Hachem, Maher; Shelton, Dale; Motawia, Mohammed Saddik; Olsen, Carl Erik; Wang, Trevor L.; Martin, Cathie; Rook, Fred

    2010-01-01

    Cyanogenesis, the release of hydrogen cyanide from damaged plant tissues, involves the enzymatic degradation of amino acid–derived cyanogenic glucosides (α-hydroxynitrile glucosides) by specific β-glucosidases. Release of cyanide functions as a defense mechanism against generalist herbivores. We developed a high-throughput screening method and used it to identify cyanogenesis deficient (cyd) mutants in the model legume Lotus japonicus. Mutants in both biosynthesis and catabolism of cyanogenic glucosides were isolated and classified following metabolic profiling of cyanogenic glucoside content. L. japonicus produces two cyanogenic glucosides: linamarin (derived from Val) and lotaustralin (derived from Ile). Their biosynthesis may involve the same set of enzymes for both amino acid precursors. However, in one class of mutants, accumulation of lotaustralin and linamarin was uncoupled. Catabolic mutants could be placed in two complementation groups, one of which, cyd2, encoded the β-glucosidase BGD2. Despite the identification of nine independent cyd2 alleles, no mutants involving the gene encoding a closely related β-glucosidase, BGD4, were identified. This indicated that BGD4 plays no role in cyanogenesis in L. japonicus in vivo. Biochemical analysis confirmed that BGD4 cannot hydrolyze linamarin or lotaustralin and in L. japonicus is specific for breakdown of related hydroxynitrile glucosides, such as rhodiocyanoside A. By contrast, BGD2 can hydrolyze both cyanogenic glucosides and rhodiocyanosides. Our genetic analysis demonstrated specificity in the catabolic pathways for hydroxynitrile glucosides and implied specificity in their biosynthetic pathways as well. In addition, it has provided important tools for elucidating and potentially modifying cyanogenesis pathways in plants. PMID:20453117

  13. Identifying sex-specific risk factors for low bone mineral density in adolescent runners.

    PubMed

    Tenforde, Adam Sebastian; Fredericson, Michael; Sayres, Lauren Carter; Cutti, Phil; Sainani, Kristin Lynn

    2015-06-01

    Adolescent runners may be at risk for low bone mineral density (BMD) associated with sports participation. Few prior investigations have evaluated bone health in young runners, particularly males. To characterize sex-specific risk factors for low BMD in adolescent runners. Cross-sectional study; Level of evidence, 3. Training characteristics, fracture history, eating behaviors and attitudes, and menstrual history were measured using online questionnaires. A food frequency questionnaire was used to identify dietary patterns and measure calcium intake. Runners (female: n = 94, male: n = 42) completed dual-energy x-ray absorptiometry (DXA) to measure lumbar spine (LS) and total body less head (TBLH) BMD and body composition values, including android-to-gynoid (A:G) fat mass ratio. The BMD was standardized to Z-scores using age, sex, and race/ethnicity reference values. Questionnaire values were combined with DXA values to determine risk factors associated with differences in BMD Z-scores in LS and TBLH and low bone mass (defined as BMD Z-score ≤-1). In multivariable analyses, risk factors for lower LS BMD Z-scores in girls included lower A:G ratio, being shorter, and the combination of (interaction between) current menstrual irregularity and a history of fracture (all P < .01). Later age of menarche, lower A:G ratio, lower lean mass, and drinking less milk were associated with lower TBLH BMD Z-scores (P < .01). In boys, lower body mass index (BMI) Z-scores and the belief that being thinner improves performance were associated with lower LS and TBLH BMD Z-scores (all P < .05); lower A:G ratio was additionally associated with lower TBLH Z-scores (P < .01). Thirteen girls (14%) and 9 boys (21%) had low bone mass. Girls with a BMI ≤17.5 kg/m(2) or both menstrual irregularity and a history of fracture were significantly more likely to have low bone mass. Boys with a BMI ≤17.5 kg/m(2) and belief that thinness improves performance were significantly more likely to have

  14. Omics of Brucella: Species-Specific sRNA-Mediated Gene Ontology Regulatory Networks Identified by Computational Biology.

    PubMed

    Vishnu, Udayakumar S; Sankarasubramanian, Jagadesan; Gunasekaran, Paramasamy; Sridhar, Jayavel; Rajendhran, Jeyaprakash

    2016-06-01

    Brucella is an intracellular bacterium that causes the zoonotic infectious disease, brucellosis. Brucella species are currently intensively studied with a view to developing novel global health diagnostics and therapeutics. In this context, small RNAs (sRNAs) are one of the emerging topical areas; they play significant roles in regulating gene expression and cellular processes in bacteria. In the present study, we forecast sRNAs in three Brucella species that infect humans, namely Brucella melitensis, Brucella abortus, and Brucella suis, using a computational biology analysis. We combined two bioinformatic algorithms, SIPHT and sRNAscanner. In B. melitensis 16M, 21 sRNA candidates were identified, of which 14 were novel. Similarly, 14 sRNAs were identified in B. abortus, of which four were novel. In B. suis, 16 sRNAs were identified, and five of them were novel. TargetRNA2 software predicted the putative target genes that could be regulated by the identified sRNAs. The identified mRNA targets are involved in carbohydrate, amino acid, lipid, nucleotide, and coenzyme metabolism and transport, energy production and conversion, replication, recombination, repair, and transcription. Additionally, the Gene Ontology (GO) network analysis revealed the species-specific, sRNA-based regulatory networks in B. melitensis, B. abortus, and B. suis. Taken together, although sRNAs are veritable modulators of gene expression in prokaryotes, there are few reports on the significance of sRNAs in Brucella. This report begins to address this literature gap by offering a series of initial observations based on computational biology to pave the way for future experimental analysis of sRNAs and their targets to explain the complex pathogenesis of Brucella.

  15. Temps, aspect et modalisation dans un acte de communication (Tense, Aspect and Mood in an Act of Communication)

    ERIC Educational Resources Information Center

    Bentolila, Alain

    1977-01-01

    Syntactic analysis identifies the "conductor wires" permitting the listener to conceptualize the speaker's image of reality from information furnished by the linguistic message. Syntactic study is thus situated in the economy of the communication process. Mood, aspect and tense are studied in this framework. (Text is in French.) (AMH)

  16. Aspects of science engagement, student background, and school characteristics: Impacts on science achievement of U.S. students

    NASA Astrophysics Data System (ADS)

    Grabau, Larry J.

    Science achievement of U.S. students has lagged significantly behind other nations; educational reformers have suggested science engagement may enhance this critical measure. The 2006 Program for International Student Assessment (PISA) was science-focused and measured science achievement along with nine aspects of science engagement: science self-efficacy, science self-concept, enjoyment of science, general interest in learning science, instrumental motivation for science, future-oriented science motivation, general value of science, personal value of science, and science-related activities. I used multilevel modeling techniques to address both aspects of science engagement and science achievement as outcome variables in the context of student background and school characteristics. Treating aspects of science engagement as outcome variables provided tests for approaches for their enhancement; meanwhile, treating science achievement as the outcome variable provided tests for the influence of the aspects of science engagement on science achievement under appropriate controls. When aspects of science engagement were treated as outcome variables, gender and father's SES had frequent (significant) influences, as did science teaching strategies which focused on applications or models and hands-on activities over-and-above influences of student background and other school characteristics. When science achievement was treated as the outcome variable, each aspect of science engagement was significant, and eight had medium or large effect sizes (future-oriented science motivation was the exception). The science teaching strategy which involved hands-on activities frequently enhanced science achievement over-and-above influences of student background and other school characteristics. Policy recommendations for U.S. science educators included enhancing eight aspects of science engagement and implementing two specific science teaching strategies (focus on applications or models

  17. Genome-wide histone state profiling of fibroblasts from the opossum, Monodelphis domestica, identifies the first marsupial-specific imprinted gene

    PubMed Central

    2014-01-01

    Background Imprinted genes have been extensively documented in eutherian mammals and found to exhibit significant interspecific variation in the suites of genes that are imprinted and in their regulation between tissues and developmental stages. Much less is known about imprinted loci in metatherian (marsupial) mammals, wherein studies have been limited to a small number of genes previously known to be imprinted in eutherians. We describe the first ab initio search for imprinted marsupial genes, in fibroblasts from the opossum, Monodelphis domestica, based on a genome-wide ChIP-seq strategy to identify promoters that are simultaneously marked by mutually exclusive, transcriptionally opposing histone modifications. Results We identified a novel imprinted gene (Meis1) and two additional monoallelically expressed genes, one of which (Cstb) showed allele-specific, but non-imprinted expression. Imprinted vs. allele-specific expression could not be resolved for the third monoallelically expressed gene (Rpl17). Transcriptionally opposing histone modifications H3K4me3, H3K9Ac, and H3K9me3 were found at the promoters of all three genes, but differential DNA methylation was not detected at CpG islands at any of these promoters. Conclusions In generating the first genome-wide histone modification profiles for a marsupial, we identified the first gene that is imprinted in a marsupial but not in eutherian mammals. This outcome demonstrates the practicality of an ab initio discovery strategy and implicates histone modification, but not differential DNA methylation, as a conserved mechanism for marking imprinted genes in all therian mammals. Our findings suggest that marsupials use multiple epigenetic mechanisms for imprinting and support the concept that lineage-specific selective forces can produce sets of imprinted genes that differ between metatherian and eutherian lines. PMID:24484454

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

    PubMed

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

    2011-10-01

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

  19. Identifying and tracing potential energy surfaces of electronic excitations with specific character via their transition origins: application to oxirane.

    PubMed

    Li, Jian-Hao; Zuehlsdorff, T J; Payne, M C; Hine, N D M

    2015-05-14

    We show that the transition origins of electronic excitations identified by quantified natural transition orbital (QNTO) analysis can be employed to connect potential energy surfaces (PESs) according to their character across a wide range of molecular geometries. This is achieved by locating the switching of transition origins of adiabatic potential surfaces as the geometry changes. The transition vectors for analysing transition origins are provided by linear response time-dependent density functional theory (TDDFT) calculations under the Tamm-Dancoff approximation. We study the photochemical CO ring opening of oxirane as an example and show that the results corroborate the traditional Gomer-Noyes mechanism derived experimentally. The knowledge of specific states for the reaction also agrees well with that given by previous theoretical work using TDDFT surface-hopping dynamics that was validated by high-quality quantum Monte Carlo calculations. We also show that QNTO can be useful for considerably larger and more complex systems: by projecting the excitations to those of a reference oxirane molecule, the approach is able to identify and analyse specific excitations of a trans-2,3-diphenyloxirane molecule.

  20. Identifying Specific Reading Disability Subtypes for Effective Educational Remediation

    ERIC Educational Resources Information Center

    Feifer, Steven G.; Nader, Rebecca Gerhardstein; Flanagan, Dawn P.; Fitzer, Kim R.; Hicks, Kelly

    2014-01-01

    The primary purpose of this study was to investigate the various neurocognitive processes concomitant to reading by attempting to identify various subtypes of reading disorders in a referred sample. Participants were 216 elementary school students in grades two through five who were given select subtests of the Woodcock Johnson-III Tests of…

  1. Identifying Specific Combinations of Multimorbidity that Contribute to Health Care Resource Utilization: An Analytic Approach.

    PubMed

    Schiltz, Nicholas K; Warner, David F; Sun, Jiayang; Bakaki, Paul M; Dor, Avi; Given, Charles W; Stange, Kurt C; Koroukian, Siran M

    2017-03-01

    Multimorbidity affects the majority of elderly adults and is associated with higher health costs and utilization, but how specific patterns of morbidity influence resource use is less understood. The objective was to identify specific combinations of chronic conditions, functional limitations, and geriatric syndromes associated with direct medical costs and inpatient utilization. Retrospective cohort study using the Health and Retirement Study (2008-2010) linked to Medicare claims. Analysis used machine-learning techniques: classification and regression trees and random forest. A population-based sample of 5771 Medicare-enrolled adults aged 65 and older in the United States. Main covariates: self-reported chronic conditions (measured as none, mild, or severe), geriatric syndromes, and functional limitations. Secondary covariates: demographic, social, economic, behavioral, and health status measures. Medicare expenditures in the top quartile and inpatient utilization. Median annual expenditures were $4354, and 41% were hospitalized within 2 years. The tree model shows some notable combinations: 64% of those with self-rated poor health plus activities of daily living and instrumental activities of daily living disabilities had expenditures in the top quartile. Inpatient utilization was highest (70%) in those aged 77-83 with mild to severe heart disease plus mild to severe diabetes. Functional limitations were more important than many chronic diseases in explaining resource use. The multimorbid population is heterogeneous and there is considerable variation in how specific combinations of morbidity influence resource use. Modeling the conjoint effects of chronic conditions, functional limitations, and geriatric syndromes can advance understanding of groups at greatest risk and inform targeted tailored interventions aimed at cost containment.

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

    PubMed

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

    2018-04-02

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

  3. Novel aspects of plasma control in ITER

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Humphreys, D.; Jackson, G.; Walker, M.

    2015-02-15

    ITER plasma control design solutions and performance requirements are strongly driven by its nuclear mission, aggressive commissioning constraints, and limited number of operational discharges. In addition, high plasma energy content, heat fluxes, neutron fluxes, and very long pulse operation place novel demands on control performance in many areas ranging from plasma boundary and divertor regulation to plasma kinetics and stability control. Both commissioning and experimental operations schedules provide limited time for tuning of control algorithms relative to operating devices. Although many aspects of the control solutions required by ITER have been well-demonstrated in present devices and even designed satisfactorily formore » ITER application, many elements unique to ITER including various crucial integration issues are presently under development. We describe selected novel aspects of plasma control in ITER, identifying unique parts of the control problem and highlighting some key areas of research remaining. Novel control areas described include control physics understanding (e.g., current profile regulation, tearing mode (TM) suppression), control mathematics (e.g., algorithmic and simulation approaches to high confidence robust performance), and integration solutions (e.g., methods for management of highly subscribed control resources). We identify unique aspects of the ITER TM suppression scheme, which will pulse gyrotrons to drive current within a magnetic island, and turn the drive off following suppression in order to minimize use of auxiliary power and maximize fusion gain. The potential role of active current profile control and approaches to design in ITER are discussed. Issues and approaches to fault handling algorithms are described, along with novel aspects of actuator sharing in ITER.« less

  4. Novel aspects of plasma control in ITER

    DOE PAGES

    Humphreys, David; Ambrosino, G.; de Vries, Peter; ...

    2015-02-12

    ITER plasma control design solutions and performance requirements are strongly driven by its nuclear mission, aggressive commissioning constraints, and limited number of operational discharges. In addition, high plasma energy content, heat fluxes, neutron fluxes, and very long pulse operation place novel demands on control performance in many areas ranging from plasma boundary and divertor regulation to plasma kinetics and stability control. Both commissioning and experimental operations schedules provide limited time for tuning of control algorithms relative to operating devices. Although many aspects of the control solutions required by ITER have been well-demonstrated in present devices and even designed satisfactorily formore » ITER application, many elements unique to ITER including various crucial integration issues are presently under development. We describe selected novel aspects of plasma control in ITER, identifying unique parts of the control problem and highlighting some key areas of research remaining. Novel control areas described include control physics understanding (e.g. current profile regulation, tearing mode suppression (TM)), control mathematics (e.g. algorithmic and simulation approaches to high confidence robust performance), and integration solutions (e.g. methods for management of highly-subscribed control resources). We identify unique aspects of the ITER TM suppression scheme, which will pulse gyrotrons to drive current within a magnetic island, and turn the drive off following suppression in order to minimize use of auxiliary power and maximize fusion gain. The potential role of active current profile control and approaches to design in ITER are discussed. Finally, issues and approaches to fault handling algorithms are described, along with novel aspects of actuator sharing in ITER.« less

  5. The Emotional Exhaustion Aspect of Burnout and Stressors in Resource LD Teachers.

    ERIC Educational Resources Information Center

    Shea, Catherine A.

    This study sought to develop a clearer understanding of the correlates of the emotional exhaustion aspect of burnout among learning disabilities (LD) teachers in resource programs. Specifically, the study examined the relationship between the emotional aspect of burnout as measured by the Maslach Burnout Inventory (MBI) and: (1) background…

  6. The essential aspect in sewerage regulation in Indonesia

    NASA Astrophysics Data System (ADS)

    Siami, L.

    2018-01-01

    Several cities in Indonesia have the sewerage local regulation such as Banjarmasin, Bantul, Surakarta and Denpasar. Meanwhile, The National Government have guideline in composing domestic sewerage regulation. Each city have their own characteristic and issues that need to be carried out by the local regulation. By using SWOT analysis, this study tries to figure out several aspect that need to be included in the local regulation. International references from developed and developing countries like Japan, Phillipines, Malaysia and Thailand were also used as benchmark without neglecting the local conditions of cities in Indonesia. Several crucial aspect of local regulation are institutional authority, composition on-site and off-site system, tariff, evaluation and monitoring, as well as punishment and rewards. Both tariff and evaluation aspects need to be narrowed down into specific regulations.

  7. Quantifying site-specific physical heterogeneity within an estuarine seascape

    USGS Publications Warehouse

    Kennedy, Cristina G.; Mather, Martha E.; Smith, Joseph M.

    2017-01-01

    Quantifying physical heterogeneity is essential for meaningful ecological research and effective resource management. Spatial patterns of multiple, co-occurring physical features are rarely quantified across a seascape because of methodological challenges. Here, we identified approaches that measured total site-specific heterogeneity, an often overlooked aspect of estuarine ecosystems. Specifically, we examined 23 metrics that quantified four types of common physical features: (1) river and creek confluences, (2) bathymetric variation including underwater drop-offs, (3) land features such as islands/sandbars, and (4) major underwater channel networks. Our research at 40 sites throughout Plum Island Estuary (PIE) provided solutions to two problems. The first problem was that individual metrics that measured heterogeneity of a single physical feature showed different regional patterns. We solved this first problem by combining multiple metrics for a single feature using a within-physical feature cluster analysis. With this approach, we identified sites with four different types of confluences and three different types of underwater drop-offs. The second problem was that when multiple physical features co-occurred, new patterns of total site-specific heterogeneity were created across the seascape. This pattern of total heterogeneity has potential ecological relevance to structure-oriented predators. To address this second problem, we identified sites with similar types of total physical heterogeneity using an across-physical feature cluster analysis. Then, we calculated an additive heterogeneity index, which integrated all physical features at a site. Finally, we tested if site-specific additive heterogeneity index values differed for across-physical feature clusters. In PIE, the sites with the highest additive heterogeneity index values were clustered together and corresponded to sites where a fish predator, adult striped bass (Morone saxatilis), aggregated in a

  8. The Extension of the Progressive Aspect in Black South African English

    ERIC Educational Resources Information Center

    van Rooy, Bertus

    2006-01-01

    The extension of the progressive aspect to stative verbs has been identified as a characteristic feature of New Varieties of English across the world, including the English of black South Africans (BSAfE). This paper examines the use of the progressive aspect in BSAfE, by doing a comparative analysis of three corpora of argumentative student…

  9. Meanings and aspects of quality of life for cancer patients: a descriptive exploratory qualitative study.

    PubMed

    Bahrami, Masoud

    2011-08-01

    Given the importance of quality of life (QoL) for cancer patients, it is important to work out what this concept means not only for cancer patients, and for the nurses who care for them, but also the aspects of which it is composed. Therefore, an interpretive research study was conducted to explore in-depth meanings and aspects of QoL as expressed by cancer nurses. Participants were selected from different inpatient and outpatient oncology services and a palliative setting in Adelaide, South Australia. Results showed that many aspects contribute to an individual's QoL. These include the physical, the psychological, the spiritual, and both environmental and social interactions. More importantly, participants stated that spirituality is multifaceted and that there may be aspects in life that may be taken for granted. The meaning of patients' QoL was viewed by nurses as a patient's overall happiness and satisfaction. Also, nurses identified that providing choices to patients made an important contribution to a patient's QoL. Therefore, this exploration into the in-depth meanings and aspects of QoL for cancer patients from nurses' perspectives identified that, in addition to the aspects related to QoL that have been identified previously in the literature, aspects related to spirituality would need to be extensively covered, and providing choices to patients would be important in patients' QoL in an Australian setting.

  10. Gambogic acid identifies an isoform-specific druggable pocket in the middle domain of Hsp90β

    PubMed Central

    Yim, Kendrick H.; Prince, Thomas L.; Qu, Shiwei; Bai, Fang; Jennings, Patricia A.; Onuchic, José N.; Theodorakis, Emmanuel A.; Neckers, Leonard

    2016-01-01

    Because of their importance in maintaining protein homeostasis, molecular chaperones, including heat-shock protein 90 (Hsp90), represent attractive drug targets. Although a number of Hsp90 inhibitors are in preclinical/clinical development, none strongly differentiate between constitutively expressed Hsp90β and stress-induced Hsp90α, the two cytosolic paralogs of this molecular chaperone. Thus, the importance of inhibiting one or the other paralog in different disease states remains unknown. We show that the natural product, gambogic acid (GBA), binds selectively to a site in the middle domain of Hsp90β, identifying GBA as an Hsp90β-specific Hsp90 inhibitor. Furthermore, using computational and medicinal chemistry, we identified a GBA analog, referred to as DAP-19, which binds potently and selectively to Hsp90β. Because of its unprecedented selectivity for Hsp90β among all Hsp90 paralogs, GBA thus provides a new chemical tool to study the unique biological role of this abundantly expressed molecular chaperone in health and disease. PMID:27466407

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

    PubMed

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

    2015-01-01

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

  12. Identifying influential individuals on intensive care units: using cluster analysis to explore culture.

    PubMed

    Fong, Allan; Clark, Lindsey; Cheng, Tianyi; Franklin, Ella; Fernandez, Nicole; Ratwani, Raj; Parker, Sarah Henrickson

    2017-07-01

    The objective of this paper is to identify attribute patterns of influential individuals in intensive care units using unsupervised cluster analysis. Despite the acknowledgement that culture of an organisation is critical to improving patient safety, specific methods to shift culture have not been explicitly identified. A social network analysis survey was conducted and an unsupervised cluster analysis was used. A total of 100 surveys were gathered. Unsupervised cluster analysis was used to group individuals with similar dimensions highlighting three general genres of influencers: well-rounded, knowledge and relational. Culture is created locally by individual influencers. Cluster analysis is an effective way to identify common characteristics among members of an intensive care unit team that are noted as highly influential by their peers. To change culture, identifying and then integrating the influencers in intervention development and dissemination may create more sustainable and effective culture change. Additional studies are ongoing to test the effectiveness of utilising these influencers to disseminate patient safety interventions. This study offers an approach that can be helpful in both identifying and understanding influential team members and may be an important aspect of developing methods to change organisational culture. © 2017 John Wiley & Sons Ltd.

  13. Phylogenetic analysis of rubella viruses identified in Uganda, 2003-2012.

    PubMed

    Namuwulya, Prossy; Abernathy, Emily; Bukenya, Henry; Bwogi, Josephine; Tushabe, Phionah; Birungi, Molly; Seguya, Ronald; Kabaliisa, Theopista; Alibu, Vincent P; Kayondo, Jonathan K; Rivailler, Pierre; Icenogle, Joseph; Bakamutumaho, Barnabas

    2014-12-01

    Molecular data on rubella viruses are limited in Uganda despite the importance of congenital rubella syndrome (CRS). Routine rubella vaccination, while not administered currently in Uganda, is expected to begin by 2015. The World Health Organization recommends that countries without rubella vaccination programs assess the burden of rubella and CRS before starting a routine vaccination program. Uganda is already involved in integrated case-based surveillance, including laboratory testing to confirm measles and rubella, but molecular epidemiologic aspects of rubella circulation have so far not been documented in Uganda. Twenty throat swab or oral fluid samples collected from 12 districts during routine rash and fever surveillance between 2003 and 2012 were identified as rubella virus RNA positive and PCR products encompassing the region used for genotyping were sequenced. Phylogenetic analysis of the 20 sequences identified 19 genotype 1G viruses and 1 genotype 1E virus. Genotype-specific trees showed that the Uganda viruses belonged to specific clusters for both genotypes 1G and 1E and grouped with similar sequences from neighboring countries. Genotype 1G was predominant in Uganda. More epidemiological and molecular epidemiological data are required to determine if genotype 1E is also endemic in Uganda. The information obtained in this study will assist the immunization program in monitoring changes in circulating genotypes. © 2014 Wiley Periodicals, Inc.

  14. PROMISE: a tool to identify genomic features with a specific biologically interesting pattern of associations with multiple endpoint variables.

    PubMed

    Pounds, Stan; Cheng, Cheng; Cao, Xueyuan; Crews, Kristine R; Plunkett, William; Gandhi, Varsha; Rubnitz, Jeffrey; Ribeiro, Raul C; Downing, James R; Lamba, Jatinder

    2009-08-15

    In some applications, prior biological knowledge can be used to define a specific pattern of association of multiple endpoint variables with a genomic variable that is biologically most interesting. However, to our knowledge, there is no statistical procedure designed to detect specific patterns of association with multiple endpoint variables. Projection onto the most interesting statistical evidence (PROMISE) is proposed as a general procedure to identify genomic variables that exhibit a specific biologically interesting pattern of association with multiple endpoint variables. Biological knowledge of the endpoint variables is used to define a vector that represents the biologically most interesting values for statistics that characterize the associations of the endpoint variables with a genomic variable. A test statistic is defined as the dot-product of the vector of the observed association statistics and the vector of the most interesting values of the association statistics. By definition, this test statistic is proportional to the length of the projection of the observed vector of correlations onto the vector of most interesting associations. Statistical significance is determined via permutation. In simulation studies and an example application, PROMISE shows greater statistical power to identify genes with the interesting pattern of associations than classical multivariate procedures, individual endpoint analyses or listing genes that have the pattern of interest and are significant in more than one individual endpoint analysis. Documented R routines are freely available from www.stjuderesearch.org/depts/biostats and will soon be available as a Bioconductor package from www.bioconductor.org.

  15. Property Specification Patterns for intelligence building software

    NASA Astrophysics Data System (ADS)

    Chun, Seungsu

    2018-03-01

    In this paper, through the property specification pattern research for Modal MU(μ) logical aspects present a single framework based on the pattern of intelligence building software. In this study, broken down by state property specification pattern classification of Dwyer (S) and action (A) and was subdivided into it again strong (A) and weaknesses (E). Through these means based on a hierarchical pattern classification of the property specification pattern analysis of logical aspects Mu(μ) was applied to the pattern classification of the examples used in the actual model checker. As a result, not only can a more accurate classification than the existing classification systems were easy to create and understand the attributes specified.

  16. Dream content: Individual and generic aspects.

    PubMed

    Hobson, Allan; Kahn, David

    2007-12-01

    Dream reports were collected from normal subjects in an effort to determine the degree to which dream reports can be used to identify individual dreamers. Judges were asked to group the reports by their authors. The judges scored the reports correctly at chance levels. This finding indicated that dreams may be at least as much like each other as they are the signature of individual dreamers. Our results suggest that dream reports cannot be used to identify the individuals who produced them when identifiers like names and gender of friends and family members are removed from the dream report. In addition to using dreams to learn about an individual, we must look at dreams as telling us about important common or generic aspects of human consciousness.

  17. Following the Social Media: Aspect Evolution of Online Discussion

    NASA Astrophysics Data System (ADS)

    Tang, Xuning; Yang, Christopher C.

    Due to the advance of Internet and Web 2.0 technologies, it is easy to extract thousands of threads about a topic of interest from an online forum but it is nontrivial to capture the blueprint of different aspects (i.e., subtopic, or facet) associated with the topic. To better understand and analyze a forum discussion given topic, it is important to uncover the evolution relationships (temporal dependencies) between different topic aspects (i.e. how the discussion topic is evolving). Traditional Topic Detection and Tracking (TDT) techniques usually organize topics as a flat structure but it does not present the evolution relationships between topic aspects. In addition, the properties of short and sparse messages make the content-based TDT techniques difficult to perform well in identifying evolution relationships. The contributions in this paper are two-folded. We formally define a topic aspect evolution graph modeling framework and propose to utilize social network information, content similarity and temporal proximity to model evolution relationships between topic aspects. The experimental results showed that, by incorporating social network information, our technique significantly outperformed content-based technique in the task of extracting evolution relationships between topic aspects.

  18. GCS plan for software aspects of certification

    NASA Technical Reports Server (NTRS)

    Shagnea, Anita M.; Lowman, Douglas S.; Withers, B. Edward

    1990-01-01

    As part of the Guidance and Control Software (GCS) research project being sponsored by NASA to evaluate the failure processes of software, standard industry software development procedures are being employed. To ensure that these procedures are authentic, the guidelines outlined in the Radio Technical Commission for Aeronautics (RTCA/DO-178A document entitled, software considerations in airborne systems and equipment certification, were adopted. A major aspect of these guidelines is proper documentation. As such, this report, the plan for software aspects of certification, was produced in accordance with DO-178A. An overview is given of the GCS research project, including the goals of the project, project organization, and project schedules. It also specifies the plans for all aspects of the project which relate to the certification of the GCS implementations developed under a NASA contract. These plans include decisions made regarding the software specification, accuracy requirements, configuration management, implementation development and verification, and the development of the GCS simulator.

  19. Role of Aspect in Understanding Tense: An Investigation with Adolescents with SLI

    ERIC Educational Resources Information Center

    Stuart, Nichola J.; van der Lely, Heather

    2015-01-01

    Background: Morphosyntax has been well researched in specific language impairment (SLI) and there is general agreement that children with SLI have particular difficulties with tense-marking. Less well researched is the role that aspect plays in the difficulties found in tense-marking, especially as tense and aspect are often confounded in English.…

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

    NASA Astrophysics Data System (ADS)

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

    2008-12-01

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

  1. CT-guided bipolar and multipolar radiofrequency ablation (RF ablation) of renal cell carcinoma: specific technical aspects and clinical results.

    PubMed

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

    2013-06-01

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

  2. Specificity and Sensitivity of Claims-Based Algorithms for Identifying Members of Medicare+Choice Health Plans That Have Chronic Medical Conditions

    PubMed Central

    Rector, Thomas S; Wickstrom, Steven L; Shah, Mona; Thomas Greeenlee, N; Rheault, Paula; Rogowski, Jeannette; Freedman, Vicki; Adams, John; Escarce, José J

    2004-01-01

    Objective To examine the effects of varying diagnostic and pharmaceutical criteria on the performance of claims-based algorithms for identifying beneficiaries with hypertension, heart failure, chronic lung disease, arthritis, glaucoma, and diabetes. Study Setting Secondary 1999–2000 data from two Medicare+Choice health plans. Study Design Retrospective analysis of algorithm specificity and sensitivity. Data Collection Physician, facility, and pharmacy claims data were extracted from electronic records for a sample of 3,633 continuously enrolled beneficiaries who responded to an independent survey that included questions about chronic diseases. Principal Findings Compared to an algorithm that required a single medical claim in a one-year period that listed the diagnosis, either requiring that the diagnosis be listed on two separate claims or that the diagnosis to be listed on one claim for a face-to-face encounter with a health care provider significantly increased specificity for the conditions studied by 0.03 to 0.11. Specificity of algorithms was significantly improved by 0.03 to 0.17 when both a medical claim with a diagnosis and a pharmacy claim for a medication commonly used to treat the condition were required. Sensitivity improved significantly by 0.01 to 0.20 when the algorithm relied on a medical claim with a diagnosis or a pharmacy claim, and by 0.05 to 0.17 when two years rather than one year of claims data were analyzed. Algorithms that had specificity more than 0.95 were found for all six conditions. Sensitivity above 0.90 was not achieved all conditions. Conclusions Varying claims criteria improved the performance of case-finding algorithms for six chronic conditions. Highly specific, and sometimes sensitive, algorithms for identifying members of health plans with several chronic conditions can be developed using claims data. PMID:15533190

  3. Which aspects of functioning are relevant for patients with ankylosing spondylitis: results of focus group interviews.

    PubMed

    Boonen, Annelies; van Berkel, Monique; Cieza, Alarcos; Stucki, Gerold; van der Heijde, Désirée

    2009-11-01

    To investigate whether concepts important to patients with ankylosing spondylitis (AS) are covered by disease-specific self-report health status instruments. A qualitative focus group study was conducted with AS patients on problems in daily functioning. Group sessions with 4 to 5 patients each were organized up to the point that no new information was brought forward. Group sessions were tape-recorded, transcribed, and divided into meaning units. Concepts contained in the meaning units were extracted. Self-report instruments on health status specific for AS were identified in a literature search. Using the International Classification of Functioning, Disability and Health (ICF) as a common reference, it was determined whether the concepts identified in the focus groups were covered by the instruments. Nineteen patients participated in 4 focus group interviews. In total, 332 unique meaning units were linked to 90 second-level ICF categories, of which 25 referred to body functions, 10 to body structures, 35 to activities and participation and 30 to environmental factors. In addition, several concepts relating to personal factors were identified. Only 47 categories were also covered by one of the self-report instruments in AS. Only a minority of concepts addressed by the AS-specific questionnaires were not revealed as relevant in the interviews. Relevant aspects of the influence of AS are not covered by the classic disease-specific instruments. In particular, the influence of AS on socializing and leisure and the relevance of environmental and personal factors are not adequately assessed by available instruments.

  4. The genetics of alcoholism: identifying specific genes through family studies.

    PubMed

    Edenberg, Howard J; Foroud, Tatiana

    2006-09-01

    Alcoholism is a complex disorder with both genetic and environmental risk factors. Studies in humans have begun to elucidate the genetic underpinnings of the risk for alcoholism. Here we briefly review strategies for identifying individual genes in which variations affect the risk for alcoholism and related phenotypes, in the context of one large study that has successfully identified such genes. The Collaborative Study on the Genetics of Alcoholism (COGA) is a family-based study that has collected detailed phenotypic data on individuals in families with multiple alcoholic members. A genome-wide linkage approach led to the identification of chromosomal regions containing genes that influenced alcoholism risk and related phenotypes. Subsequently, single nucleotide polymorphisms (SNPs) were genotyped in positional candidate genes located within the linked chromosomal regions, and analyzed for association with these phenotypes. Using this sequential approach, COGA has detected association with GABRA2, CHRM2 and ADH4; these associations have all been replicated by other researchers. COGA has detected association to additional genes including GABRG3, TAS2R16, SNCA, OPRK1 and PDYN, results that are awaiting confirmation. These successes demonstrate that genes contributing to the risk for alcoholism can be reliably identified using human subjects.

  5. Trustworthy persistent identifier systems of the future

    NASA Astrophysics Data System (ADS)

    Golodoniuc, Pavel; Klump, Jens; Car, Nicholas

    2016-04-01

    Over the last two decades, persistent identifier (PID) systems have seen some significant changes in their governance policies, system capabilities, and technology. The development of most systems was driven by two main application areas, namely archives and libraries. Guidelines and criteria for trustworthy PID systems have been clearly devised (Bütikofer, 2009) and many PID system implementations for the identification of static digital objects have been built (e.g., PURL). However systems delivering persistent identifiers for dynamic datasets are not yet mature. There has been a rapid proliferation of different PID systems caused by the specific technical or organisational requirements of various communities that could not be met by existing systems such as DOI, ISBN, and EAN. Many of these different systems were limited by their inability to provide native means of persistent identifier resolution. This has prompted a decoupling of PID-associated data from the resolution service and this is where the Handle system has played a significant role. The Handle allowed to build a distributed system of independently managed resolver services. A trustworthy PID system must be designed to outlive the objects it provides persistent identifiers for, which may cease to exist or otherwise be deprecated, and the technology used to implement it, which will certainly need to change with time. We propose that such a system should rest on four pillars of agreements - (i) definitions, (ii) policies, (iii) services, and (iv) data services, to ensure longevity. While we believe all four pillars are equally important, we intentionally leave regulating aspects of issuing of identifiers and their registration out of the scope of this paper and focus on the agreements that have to be established between PID resolver services and the data sources indicated by the persistent identifiers. We propose an approach to development of PID systems that combines the use of (a) the Handle system

  6. Preformed Frequencies of Cytomegalovirus (CMV)–Specific Memory T and B Cells Identify Protected CMV-Sensitized Individuals Among Seronegative Kidney Transplant Recipients

    PubMed Central

    Lúcia, Marc; Crespo, Elena; Melilli, Edoardo; Cruzado, Josep M.; Luque, Sergi; Llaudó, Inés; Niubó, Jordi; Torras, Joan; Fernandez, Núria; Grinyó, Josep M.; Bestard, Oriol

    2014-01-01

    Background. Cytomegalovirus (CMV) infection remains a major complication after kidney transplantation. Baseline CMV risk is typically determined by the serological presence of preformed CMV-specific immunoglobulin (Ig) G antibodies, even though T-cell responses to major viral antigens are crucial when controlling viral replication. Some IgG-seronegative patients who receive an IgG-seropositive allograft do not develop CMV infection despite not receiving prophylaxis. We hypothesized that a more precise evaluation of pretransplant CMV-specific immune-sensitization using the B and T-cell enzyme-linked immunospot assays may identify CMV-sensitized individuals more accurately, regardless of serological evidence of CMV-specific IgG titers. Methods. We compared the presence of preformed CMV-specific memory B and T cells in kidney transplant recipients between 43 CMV IgG–seronegative (sR−) and 86 CMV IgG–seropositive (sR+) patients. Clinical outcome was evaluated in both groups. Results. All sR+ patients showed a wide range of CMV-specific memory T- and B-cell responses. High memory T- and B-cell frequencies were also clearly detected in 30% of sR− patients, and those with high CMV-specific T-cell frequencies had a significantly lower incidence of late CMV infection after prophylactic therapy. Receiver operating characteristic curve analysis for predicting CMV viremia and disease showed a high area under the receiver operating characteristic curve (>0.8), which translated into a high sensitivity and negative predictive value of the test. Conclusions. Assessment of CMV-specific memory T- and B-cell responses before kidney transplantation among sR− recipients may help identify immunized individuals more precisely, being ultimately at lower risk for CMV infection. PMID:25048845

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

    PubMed Central

    Tromp, Gerard; Kuivaniemi, Helena; Gretarsdottir, Solveig; Baas, Annette F.; Giusti, Betti; Strauss, Ewa; van‘t Hof, Femke N.G.; Webb, Thomas R.; Erdman, Robert; Ritchie, Marylyn D.; Elmore, James R.; Verma, Anurag; Pendergrass, Sarah; Kullo, Iftikhar J.; Ye, Zi; Peissig, Peggy L.; Gottesman, Omri; Verma, Shefali S.; Malinowski, Jennifer; Rasmussen-Torvik, Laura J.; Borthwick, Kenneth M.; Smelser, Diane T.; Crosslin, David R.; de Andrade, Mariza; Ryer, Evan J.; McCarty, Catherine A.; Böttinger, Erwin P.; Pacheco, Jennifer A.; Crawford, Dana C.; Carrell, David S.; Gerhard, Glenn S.; Franklin, David P.; Carey, David J.; Phillips, Victoria L.; Williams, Michael J.A.; Wei, Wenhua; Blair, Ross; Hill, Andrew A.; Vasudevan, Thodor M.; Lewis, David R.; Thomson, Ian A.; Krysa, Jo; Hill, Geraldine B.; Roake, Justin; Merriman, Tony R.; Oszkinis, Grzegorz; Galora, Silvia; Saracini, Claudia; Abbate, Rosanna; Pulli, Raffaele; Pratesi, Carlo; Saratzis, Athanasios; Verissimo, Ana R.; Bumpstead, Suzannah; Badger, Stephen A.; Clough, Rachel E.; Cockerill, Gillian; Hafez, Hany; Scott, D. Julian A.; Futers, T. Simon; Romaine, Simon P.R.; Bridge, Katherine; Griffin, Kathryn J.; Bailey, Marc A.; Smith, Alberto; Thompson, Matthew M.; van Bockxmeer, Frank M.; Matthiasson, Stefan E.; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Blankensteijn, Jan D.; Teijink, Joep A.W.; Wijmenga, Cisca; de Graaf, Jacqueline; Kiemeney, Lambertus A.; Lindholt, Jes S.; Hughes, Anne; Bradley, Declan T.; Stirrups, Kathleen; Golledge, Jonathan; Norman, Paul E.; Powell, Janet T.; Humphries, Steve E.; Hamby, Stephen E.; Goodall, Alison H.; Nelson, Christopher P.; Sakalihasan, Natzi; Courtois, Audrey; Ferrell, Robert E.; Eriksson, Per; Folkersen, Lasse; Franco-Cereceda, Anders; Eicher, John D.; Johnson, Andrew D.; Betsholtz, Christer; Ruusalepp, Arno; Franzén, Oscar; Schadt, Eric E.; Björkegren, Johan L.M.; Lipovich, Leonard; Drolet, Anne M.; Verhoeven, Eric L.; Zeebregts, Clark J.; Geelkerken, Robert H.; van Sambeek, Marc R.; van Sterkenburg, Steven M.; de Vries, Jean-Paul; Stefansson, Kari; Thompson, John R.; de Bakker, Paul I.W.; Deloukas, Panos; Sayers, Robert D.; Harrison, Seamus C.; van Rij, Andre M.; Samani, Nilesh J.

    2017-01-01

    Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease. PMID:27899403

  8. Gene-Based Sequencing Identifies Lipid-Influencing Variants with Ethnicity-Specific Effects in African Americans

    PubMed Central

    Bentley, Amy R.; Chen, Guanjie; Shriner, Daniel; Doumatey, Ayo P.; Zhou, Jie; Huang, Hanxia; Mullikin, James C.; Blakesley, Robert W.; Hansen, Nancy F.; Bouffard, Gerard G.; Cherukuri, Praveen F.; Maskeri, Baishali; Young, Alice C.; Adeyemo, Adebowale; Rotimi, Charles N.

    2014-01-01

    Although a considerable proportion of serum lipids loci identified in European ancestry individuals (EA) replicate in African Americans (AA), interethnic differences in the distribution of serum lipids suggest that some genetic determinants differ by ethnicity. We conducted a comprehensive evaluation of five lipid candidate genes to identify variants with ethnicity-specific effects. We sequenced ABCA1, LCAT, LPL, PON1, and SERPINE1 in 48 AA individuals with extreme serum lipid concentrations (high HDLC/low TG or low HDLC/high TG). Identified variants were genotyped in the full population-based sample of AA (n = 1694) and tested for an association with serum lipids. rs328 (LPL) and correlated variants were associated with higher HDLC and lower TG. Interestingly, a stronger effect was observed on a “European” vs. “African” genetic background at this locus. To investigate this effect, we evaluated the region among West Africans (WA). For TG, the effect size among WA was the same in AA with only African local ancestry (2–3% lower TG), while the larger association among AA with local European ancestry matched previous reports in EA (10%). For HDLC, there was no association with rs328 in AA with only African local ancestry or in WA, while the association among AA with European local ancestry was much greater than what has been observed for EA (15 vs. ∼5 mg/dl), suggesting an interaction with an environmental or genetic factor that differs by ethnicity. Beyond this ancestry effect, the importance of African ancestry-focused, sequence-based work was also highlighted by serum lipid associations of variants that were in higher frequency (or present only) among those of African ancestry. By beginning our study with the sequence variation present in AA individuals, investigating local ancestry effects, and seeking replication in WA, we were able to comprehensively evaluate the role of a set of candidate genes in serum lipids in AA. PMID:24603370

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

    PubMed

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

    2013-04-01

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

  10. Aspects of depression associated with borderline personality disorder.

    PubMed

    Rogers, J H; Widiger, T A; Krupp, A

    1995-02-01

    Shared symptoms between borderline personality disorder and depression have resulted in inherent difficulties in evaluating the relationship between these disorders. Some theorists have argued that depression in patients with borderline personality disorder is qualitatively distinct from depression in nonborderline patients. The purpose of this study was to empirically identify aspects of depression most associated with borderline personality disorder. Through interview and self-report measures, the authors studied depression in 50 inpatients, 21 of whom had borderline personality disorder. The aspects of depression most associated with borderline personality disorder were self-condemnation, emptiness, abandonment fears, self-destructiveness, and hopelessness; boredom and somatic complaints exhibited no association. Depression associated with borderline pathology appears to be in some respects unique, as well as distinct from nonborderline depression. The study's implications delineate the importance of considering the phenomenological aspects of depression in borderline personality disorder.

  11. Comparing the effectiveness of using generic and specific search terms in electronic databases to identify health outcomes for a systematic review: a prospective comparative study of literature search methods

    PubMed Central

    MacLean, Alice; Sweeting, Helen; Hunt, Kate

    2012-01-01

    Objective To compare the effectiveness of systematic review literature searches that use either generic or specific terms for health outcomes. Design Prospective comparative study of two electronic literature search strategies. The ‘generic’ search included general terms for health such as ‘adolescent health’, ‘health status’, ‘morbidity’, etc. The ‘specific’ search focused on terms for a range of specific illnesses, such as ‘headache’, ‘epilepsy’, ‘diabetes mellitus’, etc. Data sources The authors searched Medline, Embase, the Cumulative Index to Nursing and Allied Health Literature, PsycINFO and the Education Resources Information Center for studies published in English between 1992 and April 2010. Main outcome measures Number and proportion of studies included in the systematic review that were identified from each search. Results The two searches tended to identify different studies. Of 41 studies included in the final review, only three (7%) were identified by both search strategies, 21 (51%) were identified by the generic search only and 17 (41%) were identified by the specific search only. 5 of the 41 studies were also identified through manual searching methods. Studies identified by the two ELS differed in terms of reported health outcomes, while each ELS uniquely identified some of the review's higher quality studies. Conclusions Electronic literature searches (ELS) are a vital stage in conducting systematic reviews and therefore have an important role in attempts to inform and improve policy and practice with the best available evidence. While the use of both generic and specific health terms is conventional for many reviewers and information scientists, there are also reviews that rely solely on either generic or specific terms. Based on the findings, reliance on only the generic or specific approach could increase the risk of systematic reviews missing important evidence and, consequently, misinforming decision makers

  12. Tularaemia: clinical aspects in Europe.

    PubMed

    Maurin, Max; Gyuranecz, Miklós

    2016-01-01

    Tularaemia is a zoonotic disease caused by Francisella tularensis, a Gram-negative, facultative intracellular bacterium. Typically, human and animal infections are caused by F tularensis subspecies tularensis (type A) strains mainly in Canada and USA, and F tularensis subspecies holarctica (type B) strains throughout the northern hemisphere, including Europe. In the past, the epidemiological, clinical, therapeutic, and prognostic aspects of tularaemia reported in the English medical literature were mainly those that had been reported in the USA, where the disease was first described. Tularaemia has markedly changed in the past decade, and a large number of studies have provided novel data for the disease characteristics in Europe. In this Review we aim to emphasise the specific and variable aspects of tularaemia in different European countries. In particular, two natural lifecycles of F tularensis have been described in this continent, although not fully characterised, which are associated with different modes of transmission, clinical features, and public health burdens of tularaemia. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    PubMed Central

    Wittig-Blaich, Stephanie; Wittig, Rainer; Schmidt, Steffen; Lyer, Stefan; Bewerunge-Hudler, Melanie; Gronert-Sum, Sabine; Strobel-Freidekind, Olga; Müller, Carolin; List, Markus; Jaskot, Aleksandra; Christiansen, Helle; Hafner, Mathias; Schadendorf, Dirk; Block, Ines; Mollenhauer, Jan

    2017-01-01

    Next-generation sequencing has dramatically increased genome-wide profiling options and conceptually initiates the possibility for personalized cancer therapy. State-of-the-art sequencing studies yield large candidate gene sets comprising dozens or hundreds of mutated genes. However, few technologies are available for the systematic downstream evaluation of these results to identify novel starting points of future cancer therapies. We improved and extended a site-specific recombination-based system for systematic analysis of the individual functions of a large number of candidate genes. This was facilitated by a novel system for the construction of isogenic constitutive and inducible gain- and loss-of-function cell lines. Additionally, we demonstrate the construction of isogenic cell lines with combinations of the traits for advanced functional in vitro analyses. In a proof-of-concept experiment, a library of 108 isogenic melanoma cell lines was constructed and 8 genes were identified that significantly reduced viability in a discovery screen and in an independent validation screen. Here, we demonstrate the broad applicability of this recombination-based method and we proved its potential to identify new drug targets via the identification of the tumor suppressor DUSP6 as potential synthetic lethal target in melanoma cell lines with BRAF V600E mutations and high DUSP6 expression. PMID:28423600

  14. Whole genome co-expression analysis of soybean cytochrome P450 genes identifies nodulation-specific P450 monooxygenases

    PubMed Central

    2010-01-01

    Background Cytochrome P450 monooxygenases (P450s) catalyze oxidation of various substrates using oxygen and NAD(P)H. Plant P450s are involved in the biosynthesis of primary and secondary metabolites performing diverse biological functions. The recent availability of the soybean genome sequence allows us to identify and analyze soybean putative P450s at a genome scale. Co-expression analysis using an available soybean microarray and Illumina sequencing data provides clues for functional annotation of these enzymes. This approach is based on the assumption that genes that have similar expression patterns across a set of conditions may have a functional relationship. Results We have identified a total number of 332 full-length P450 genes and 378 pseudogenes from the soybean genome. From the full-length sequences, 195 genes belong to A-type, which could be further divided into 20 families. The remaining 137 genes belong to non-A type P450s and are classified into 28 families. A total of 178 probe sets were found to correspond to P450 genes on the Affymetrix soybean array. Out of these probe sets, 108 represented single genes. Using the 28 publicly available microarray libraries that contain organ-specific information, some tissue-specific P450s were identified. Similarly, stress responsive soybean P450s were retrieved from 99 microarray soybean libraries. We also utilized Illumina transcriptome sequencing technology to analyze the expressions of all 332 soybean P450 genes. This dataset contains total RNAs isolated from nodules, roots, root tips, leaves, flowers, green pods, apical meristem, mock-inoculated and Bradyrhizobium japonicum-infected root hair cells. The tissue-specific expression patterns of these P450 genes were analyzed and the expression of a representative set of genes were confirmed by qRT-PCR. We performed the co-expression analysis on many of the 108 P450 genes on the Affymetrix arrays. First we confirmed that CYP93C5 (an isoflavone synthase gene) is

  15. The impact of disease on family members: a critical aspect of medical care.

    PubMed

    Golics, Catherine Jane; Basra, Mohammad Khurshid Azam; Finlay, Andrew Yule; Salek, Sam

    2013-10-01

    Most existing health-related quality of life research concerns the impact of disease on patients. However, in several medical specialties including dermatology, oncology, and physical and mental disability, studies have been carried out investigating the impact of disease on the lives of families of patients. The aim of this paper is to review the literature which relates to the impact of disease on family members of patients. The OVIDSP Medline was selected as the primary database, Searches were limited to sources published in English. 158 papers were identified for review. The definition of "family" varied across the literature, and a broad definition was accepted in this review. This review shows that a wide variety of aspects of family members' lives can be affected, including emotional, financial, family relationships, education and work, leisure time, and social activities. Many of these themes are linked to one another, with themes including financial impact and social impact being linked to emotional impact. Some positive aspects were also identified from the literature, including family relationships growing stronger. Several instruments exist to measure the impact of illness on the family, and most are disease or specialty- specific. The impact of disease on families of patients is often unrecognised and underestimated. Taking into account the quality of life of families as well as patients can offer the clinician a unique insight into issues such as family relationships and the effect of treatment decisions on the patient's close social group of partner and family.

  16. Human Aspects of High Tech in Special Libraries.

    ERIC Educational Resources Information Center

    Bichteler, Julie

    1986-01-01

    This investigation of library employees who spend significant portion of time in online computer interaction provides information on intellectual, psychological, social, and physical aspects of their work. Long- and short-term effects of special libraries are identified and solutions to "technostress" problems are suggested. (16…

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

    PubMed

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

    2014-12-01

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

  18. ["Gender-specific needs of nursing home residents" : Focus on personal hygiene].

    PubMed

    Heusinger, J; Dummert, S

    2016-12-01

    Residential nursing homes are specialized in dealing with people in need of care and are required to respect their dignity and right to self-determination. This includes the respectful handling of gender-specific needs and wishes of residents. Personal hygiene is one important area to which this applies. This study was carried out to investigate residents' gender-specific perception of life and care in nursing homes. This article focuses on unspecific and gender-specific needs in the area of personal hygiene, seeking to identify where changes are needed. Structured interviews were conducted in four nursing homes with a total of ten male and ten female residents without cognitive impairments. Content analysis and description of findings proceeded in two stages: interviewees' experiences of everyday life and care were first reconstructed before gender-specific aspects were analyzed. Both universal and gender-specific needs were identified in the area of personal hygiene. The gender-unspecific wish for respect for dignity and privacy was in some cases neglected. A need for meaningful communication and respectful relationships was also gender-unspecific. Gender-specific wishes related in particular to the gender of persons assisting with or conducting personal hygiene measures. In addition to improved perception and consideration of gender-specific needs, it is also necessary to adapt nursing in residential institutions more closely to the individual needs of residents. Further research is needed in relation to the perspectives of nursing staff and the development of participatory methods for involving residents in shaping everyday life in residential institutions.

  19. Biomedical and environmental aspects of the thorium fuel cycle: a selected, annotated bibliography

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Faust, R.A.; Fore, C.S.; Cone, M.V.

    1979-07-01

    This bibliography was compiled to assist in the evaluation of the health and environmental consequences of high specific activity thorium and related nuclides which could be released to the environment by activities related to the Thorium Fuel Cycle. The general scope covers studies regarding potential releases, environmental transport, metabolism, dosimetry, dose assessment, and overall risk assessment for radionuclides specific to the NASAP project. This publication of 740 abstracted references highlights the biological and medical aspects of thorium 228 and thorium 232 in man and animals. Similar studies on related nuclides such as radium 224, radium 226, radium 228, and thoriummore » 230 are also emphasized. Additional categories relevant to these radionuclides are included as follows: chemical analysis; ecological aspects; energy; geological aspects; instrumentation; legal and political aspects; monitoring, measurement and analysis; physical aspects; production; radiation safety and control; and waste disposal and management. Environmental assessment and sources categories were used for entries which contain a multiple use of categories. Leading authors appear alphabetically within each category. Indexes are provided for : author(s), geographic location, keywords, title, and publication description. The bibliography contains literature dating from December 1925 to February 1978.« less

  20. MicroRNAs in osteosarcoma: diagnostic and therapeutic aspects.

    PubMed

    Miao, Jinglei; Wu, Song; Peng, Zhi; Tania, Mousumi; Zhang, Chaoyue

    2013-08-01

    MicroRNAs (miRNAs) are small RNA molecules, which can interfere with the expression of several genes and act as gene regulator. miRNAs have been proved as a successful diagnostic and therapeutic tool in several cancers. In this review, the differential expression of miRNAs in osteosarcoma and their possibility to be used as diagnostic and therapeutic tools have been discussed. Osteosarcoma is the most common primary bone tumor that mainly affects children and adolescents. The current treatment of osteosarcoma remains difficult, and osteosarcoma causes many deaths because of its complex pathogenesis and resistance to conventional treatments. Several studies demonstrated that the differential expression patterns of miRNAs are a promising tool for the diagnosis and treatment of osteosarcoma. Although some aspect of the mechanism of action of miRNAs in controlling osteosarcoma has been identified (e.g., targeting the Notch signaling pathway), it is far beyond to the clear understanding of miRNA targets in osteosarcoma. Identification of the specific target of miRNAs may aid molecular targets for drug development and future relief of osteosarcoma.

  1. [SOME ASPECTS OF NON-SPECIFIC PROPHYLAXIS AND THERAPY OF ESPECIALLY DANGEROUS INFECTIONS].

    PubMed

    Filippenko, A V; Omelchenko, N D; Ivanova, I A; Bespalova, I A; Doroshenko, E P; Galicheva, A L

    2015-01-01

    Recently, due to spread of dangerous and especially dangerous infections much attention is given to development of complex approaches to their prophylaxis and therapy. Data on use of immune modulators, cytokines, probiotics, preparations of plant origin for non-specific prophylaxis of especially dangerous infections are analyzed in the review, and expediency of their combined use with specific and emergency prophlaxis of these diseases is evaluated.

  2. m6A-Driver: Identifying Context-Specific mRNA m6A Methylation-Driven Gene Interaction Networks

    PubMed Central

    Zhang, Song-Yao; Zhang, Shao-Wu; Liu, Lian; Huang, Yufei

    2016-01-01

    As the most prevalent mammalian mRNA epigenetic modification, N6-methyladenosine (m6A) has been shown to possess important post-transcriptional regulatory functions. However, the regulatory mechanisms and functional circuits of m6A are still largely elusive. To help unveil the regulatory circuitry mediated by mRNA m6A methylation, we develop here m6A-Driver, an algorithm for predicting m6A-driven genes and associated networks, whose functional interactions are likely to be actively modulated by m6A methylation under a specific condition. Specifically, m6A-Driver integrates the PPI network and the predicted differential m6A methylation sites from methylated RNA immunoprecipitation sequencing (MeRIP-Seq) data using a Random Walk with Restart (RWR) algorithm and then builds a consensus m6A-driven network of m6A-driven genes. To evaluate the performance, we applied m6A-Driver to build the context-specific m6A-driven networks for 4 known m6A (de)methylases, i.e., FTO, METTL3, METTL14 and WTAP. Our results suggest that m6A-Driver can robustly and efficiently identify m6A-driven genes that are functionally more enriched and associated with higher degree of differential expression than differential m6A methylated genes. Pathway analysis of the constructed context-specific m6A-driven gene networks further revealed the regulatory circuitry underlying the dynamic interplays between the methyltransferases and demethylase at the epitranscriptomic layer of gene regulation. PMID:28027310

  3. Psychosocial Aspects of Siblings' Experiences of Pediatric Cancer.

    ERIC Educational Resources Information Center

    Shapiro, Marla; Brack, Gregory

    1994-01-01

    Identified those aspects of experiences of siblings of children with cancer that might have impact on school functioning. Also examined extent to which parents and siblings concurred in their reports of siblings' psychosocial functioning and adjustment. Findings from 15 children and adults attending pediatric oncology camp revealed that most…

  4. Compounds with species and cell type specific toxicity identified in a 2000 compound drug screen of neural stem cells and rat mixed cortical neurons.

    PubMed

    Malik, Nasir; Efthymiou, Anastasia G; Mather, Karly; Chester, Nathaniel; Wang, Xiantao; Nath, Avindra; Rao, Mahendra S; Steiner, Joseph P

    2014-12-01

    Human primary neural tissue is a vital component for the quick and simple determination of chemical compound neurotoxicity in vitro. In particular, such tissue would be ideal for high-throughput screens that can be used to identify novel neurotoxic or neurotherapeutic compounds. We have previously established a high-throughput screening platform using human induced pluripotent stem cell (iPSC)-derived neural stem cells (NSCs) and neurons. In this study, we conducted a 2000 compound screen with human NSCs and rat cortical cells to identify compounds that are selectively toxic to each group. Approximately 100 of the tested compounds showed specific toxicity to human NSCs. A secondary screen of a small subset of compounds from the primary screen on human iPSCs, NSC-derived neurons, and fetal astrocytes validated the results from >80% of these compounds with some showing cell specific toxicity. Amongst those compounds were several cardiac glycosides, all of which were selectively toxic to the human cells. As the screen was able to reliably identify neurotoxicants, many with species and cell-type specificity, this study demonstrates the feasibility of this NSC-driven platform for higher-throughput neurotoxicity screens. Published by Elsevier B.V.

  5. Quality and Safety Aspects of Cereals (Wheat) and Their Products.

    PubMed

    Varzakas, Theo

    2016-11-17

    Cereals and, most specifically, wheat are described in this chapter highlighting on their safety and quality aspects. Moreover, wheat quality aspects are adequately addressed since they are used to characterize dough properties and baking quality. Determination of dough properties is also mentioned and pasta quality is also described in this chapter. Chemometrics-multivariate analysis is one of the analyses carried out. Regarding production weighing/mixing of flours, kneading, extruded wheat flours, and sodium chloride are important processing steps/raw materials used in the manufacturing of pastry products. Staling of cereal-based products is also taken into account. Finally, safety aspects of cereal-based products are well documented with special emphasis on mycotoxins, acrylamide, and near infrared methodology.

  6. A note on ethical aspects of BCI.

    PubMed

    Haselager, Pim; Vlek, Rutger; Hill, Jeremy; Nijboer, Femke

    2009-11-01

    This paper focuses on ethical aspects of BCI, as a research and a clinical tool, that are challenging for practitioners currently working in the field. Specifically, the difficulties involved in acquiring informed consent from locked-in patients are investigated, in combination with an analysis of the shared moral responsibility in BCI teams, and the complications encountered in establishing effective communication with media.

  7. Phylogenetic Analysis of Rubella Viruses Identified in Uganda, 2003–2012

    PubMed Central

    Namuwulya, Prossy; Abernathy, Emily; Bukenya, Henry; Bwogi, Josephine; Tushabe, Phionah; Birungi, Molly; Seguya, Ronald; Kabaliisa, Theopista; Alibu, Vincent P.; Kayondo, Jonathan K.; Rivailler, Pierre; Icenogle, Joseph; Bakamutumaho, Barnabas

    2014-01-01

    Molecular data on rubella viruses are limited in Uganda despite the importance of congenital rubella syndrome (CRS). Routine rubella vaccination, while not administered currently in Uganda, is expected to begin by 2015. The World Health Organization recommends that countries without rubella vaccination programs assess the burden of rubella and CRS before starting a routine vaccination program. Uganda is already involved in integrated case-based surveillance, including laboratory testing to confirm measles and rubella, but molecular epidemiologic aspects of rubella circulation have so far not been documented in Uganda. Twenty throat swab or oral fluid samples collected from 12 districts during routine rash and fever surveillance between 2003 and 2012 were identified as rubella virus RNA positive and PCR products encompassing the region used for genotyping were sequenced. Phylogenetic analysis of the 20 sequences identified 19 genotype 1G viruses and 1 genotype 1E virus. Genotype-specific trees showed that the Uganda viruses belonged to specific clusters for both genotypes 1G and 1E and grouped with similar sequences from neighboring countries. Genotype 1G was predominant in Uganda. More epidemiological and molecular epidemiological data are required to determine if genotype 1E is also endemic in Uganda. The information obtained in this study will assist the immunization program in monitoring changes in circulating genotypes. PMID:24700073

  8. Mass Casualty Decontamination Guidance and Psychosocial Aspects of CBRN Incident Management: A Review and Synthesis

    PubMed Central

    Carter, Holly; Amlôt, Richard

    2016-01-01

    Introduction: Mass casualty decontamination is an intervention employed by first responders at the scene of an incident involving noxious contaminants.  Many countries have sought to address the challenge of decontaminating large numbers of affected casualties through the provision of rapidly deployable temporary showering structures, with accompanying decontamination protocols.  In this paper we review decontamination guidance for emergency responders and associated research evidence, in order to establish to what extent psychosocial aspects of casualty management have been considered within these documents. The review focuses on five psychosocial aspects of incident management: likely public behaviour; responder management style; communication strategy; privacy/ modesty concerns; and vulnerable groups. Methods: Two structured literature reviews were carried out; one to identify decontamination guidance documents for first responders, and another to identify evidence which is relevant to the understanding of the psychosocial aspects of mass decontamination.  The guidance documents and relevant research were reviewed to identify whether the guidance documents contain information relating to psychosocial issues and where it exists, that the guidance is consistent with the existing evidence-base. Results: Psychosocial aspects of incident management receive limited attention in current decontamination guidance.  In addition, our review has identified a number of gaps and inconsistencies between guidance and research evidence.  For each of the five areas we identify: what is currently presented in guidance documents, to what extent this is consistent with the existing research evidence and where it diverges.  We present a series of evidence-based recommendations for updating decontamination guidance to address the psychosocial aspects of mass decontamination. Conclusions: Effective communication and respect for casualties’ needs are critical in ensuring

  9. Variola Virus-Specific Diagnostic Assays: Characterization, Sensitivity, and Specificity

    PubMed Central

    Kondas, Ashley V.; Olson, Victoria A.; Li, Yu; Abel, Jason; Laker, Miriam; Rose, Laura; Wilkins, Kimberly; Turner, Jonathan; Kline, Richard

    2015-01-01

    A public health response relies upon rapid and reliable confirmation of disease by diagnostic assays. Here, we detail the design and validation of two variola virus-specific real-time PCR assays, since previous assays cross-reacted with newly identified cowpox viruses. The assay specificity must continually be reassessed as other closely related viruses are identified. PMID:25673790

  10. Comparative genome-scale modelling of Staphylococcus aureus strains identifies strain-specific metabolic capabilities linked to pathogenicity

    PubMed Central

    Bosi, Emanuele; Monk, Jonathan M.; Aziz, Ramy K.; Fondi, Marco; Nizet, Victor; Palsson, Bernhard Ø.

    2016-01-01

    Staphylococcus aureus is a preeminent bacterial pathogen capable of colonizing diverse ecological niches within its human host. We describe here the pangenome of S. aureus based on analysis of genome sequences from 64 strains of S. aureus spanning a range of ecological niches, host types, and antibiotic resistance profiles. Based on this set, S. aureus is expected to have an open pangenome composed of 7,411 genes and a core genome composed of 1,441 genes. Metabolism was highly conserved in this core genome; however, differences were identified in amino acid and nucleotide biosynthesis pathways between the strains. Genome-scale models (GEMs) of metabolism were constructed for the 64 strains of S. aureus. These GEMs enabled a systems approach to characterizing the core metabolic and panmetabolic capabilities of the S. aureus species. All models were predicted to be auxotrophic for the vitamins niacin (vitamin B3) and thiamin (vitamin B1), whereas strain-specific auxotrophies were predicted for riboflavin (vitamin B2), guanosine, leucine, methionine, and cysteine, among others. GEMs were used to systematically analyze growth capabilities in more than 300 different growth-supporting environments. The results identified metabolic capabilities linked to pathogenic traits and virulence acquisitions. Such traits can be used to differentiate strains responsible for mild vs. severe infections and preference for hosts (e.g., animals vs. humans). Genome-scale analysis of multiple strains of a species can thus be used to identify metabolic determinants of virulence and increase our understanding of why certain strains of this deadly pathogen have spread rapidly throughout the world. PMID:27286824

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  12. Constituent Aspects of Workplace Guidance in Secondary VET

    ERIC Educational Resources Information Center

    Swager, Robert; Klarus, Ruud; van Merriënboer, Jeroen J. G.; Nieuwenhuis, Loek F. M.

    2015-01-01

    Purpose: This paper aims to present an integrated model of workplace guidance to enhance awareness of what constitutes good guidance, to improve workplace guidance practices in vocational education and training. Design/methodology/approach: To identify constituent aspects of workplace guidance, a systematic search of Web of Science was conducted,…

  13. Analysis of the Human Prostate-Specific Proteome Defined by Transcriptomics and Antibody-Based Profiling Identifies TMEM79 and ACOXL as Two Putative, Diagnostic Markers in Prostate Cancer

    PubMed Central

    O'Hurley, Gillian; Busch, Christer; Fagerberg, Linn; Hallström, Björn M.; Stadler, Charlotte; Tolf, Anna; Lundberg, Emma; Schwenk, Jochen M.; Jirström, Karin; Bjartell, Anders; Gallagher, William M.; Uhlén, Mathias; Pontén, Fredrik

    2015-01-01

    To better understand prostate function and disease, it is important to define and explore the molecular constituents that signify the prostate gland. The aim of this study was to define the prostate specific transcriptome and proteome, in comparison to 26 other human tissues. Deep sequencing of mRNA (RNA-seq) and immunohistochemistry-based protein profiling were combined to identify prostate specific gene expression patterns and to explore tissue biomarkers for potential clinical use in prostate cancer diagnostics. We identified 203 genes with elevated expression in the prostate, 22 of which showed more than five-fold higher expression levels compared to all other tissue types. In addition to previously well-known proteins we identified two poorly characterized proteins, TMEM79 and ACOXL, with potential to differentiate between benign and cancerous prostatic glands in tissue biopsies. In conclusion, we have applied a genome-wide analysis to identify the prostate specific proteome using transcriptomics and antibody-based protein profiling to identify genes with elevated expression in the prostate. Our data provides a starting point for further functional studies to explore the molecular repertoire of normal and diseased prostate including potential prostate cancer markers such as TMEM79 and ACOXL. PMID:26237329

  14. PROMISE: a tool to identify genomic features with a specific biologically interesting pattern of associations with multiple endpoint variables

    PubMed Central

    Pounds, Stan; Cheng, Cheng; Cao, Xueyuan; Crews, Kristine R.; Plunkett, William; Gandhi, Varsha; Rubnitz, Jeffrey; Ribeiro, Raul C.; Downing, James R.; Lamba, Jatinder

    2009-01-01

    Motivation: In some applications, prior biological knowledge can be used to define a specific pattern of association of multiple endpoint variables with a genomic variable that is biologically most interesting. However, to our knowledge, there is no statistical procedure designed to detect specific patterns of association with multiple endpoint variables. Results: Projection onto the most interesting statistical evidence (PROMISE) is proposed as a general procedure to identify genomic variables that exhibit a specific biologically interesting pattern of association with multiple endpoint variables. Biological knowledge of the endpoint variables is used to define a vector that represents the biologically most interesting values for statistics that characterize the associations of the endpoint variables with a genomic variable. A test statistic is defined as the dot-product of the vector of the observed association statistics and the vector of the most interesting values of the association statistics. By definition, this test statistic is proportional to the length of the projection of the observed vector of correlations onto the vector of most interesting associations. Statistical significance is determined via permutation. In simulation studies and an example application, PROMISE shows greater statistical power to identify genes with the interesting pattern of associations than classical multivariate procedures, individual endpoint analyses or listing genes that have the pattern of interest and are significant in more than one individual endpoint analysis. Availability: Documented R routines are freely available from www.stjuderesearch.org/depts/biostats and will soon be available as a Bioconductor package from www.bioconductor.org. Contact: stanley.pounds@stjude.org Supplementary information: Supplementary data are available at Bioinformatics online. PMID:19528086

  15. NGST telescope aspects

    NASA Astrophysics Data System (ADS)

    Ghibaudo, J.-B.

    2017-11-01

    This paper is focused on the NGST telescope aspects and presents the main results of the ESA study "NGST Payload Suite and Telescope". The first part summarises the trade-off analyses on optical, mechanical and control telescope concepts, and eventually proposes a baseline design for the telescope. The second part describes the possible European contributions to the NGST telescope : invitations to tender based on the selected telescope design have been sent out to specialised European companies, and the results have been reported as well as the identified critical areas and needed associated developments. Alcatel is well known in the field of cryogenic optics through the realisation of the Infrared Space Observatory, and in the field of high resolution telescopes, notably in the framework of military programmes.

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

    PubMed Central

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

    2013-01-01

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

  17. Patients' priorities in assessing organisational aspects of a general dental practice.

    PubMed

    Sonneveld, Rutger E; Brands, Wolter G; Bronkhorst, Ewald M; Welie, Jos V M; Truin, Gert-Jan

    2013-02-01

    To explore which organisational aspects are considered most important by patients when assessing a general dental practice, and which patients' characteristics influence their views on these aspects by a paper questionnaire. The questionnaire was handed out to a sample of 5,000 patients in the Netherlands. The response rate was 63%. Six organisational aspects out of a list of 41 aspects were valued as most important by at least 50%. In decreasing order of importance, these were: accessibility by telephone; continuing education for general dental practitioners; Dutch-speaking general dental practitioners; in-office waiting times; information about treatments offered; and waiting lists. For four out of these six aspects, respondents' age and education significantly influenced their preferences. Aspects concerning the infrastructure of a general dental practice were chosen more often than aspects such as working to professional standards, working according to protocols and guidelines, quality assessment and guaranteed treatment outcomes. The findings will enable organisations to increase the transparency of health-care delivery systems to focus on those organisational aspects of dental practices that patients themselves consider most important. These findings can also assist general dental practitioners in adapting their organisational services to the preferences of patients or specific patient groups. © 2013 FDI World Dental Federation.

  18. Trans-Ethnic Fine-Mapping of Lipid Loci Identifies Population-Specific Signals and Allelic Heterogeneity That Increases the Trait Variance Explained

    PubMed Central

    Wu, Ying; Waite, Lindsay L.; Jackson, Anne U.; Sheu, Wayne H-H.; Buyske, Steven; Absher, Devin; Arnett, Donna K.; Boerwinkle, Eric; Bonnycastle, Lori L.; Carty, Cara L.; Cheng, Iona; Cochran, Barbara; Croteau-Chonka, Damien C.; Dumitrescu, Logan; Eaton, Charles B.; Franceschini, Nora; Guo, Xiuqing; Henderson, Brian E.; Hindorff, Lucia A.; Kim, Eric; Kinnunen, Leena; Komulainen, Pirjo; Lee, Wen-Jane; Le Marchand, Loic; Lin, Yi; Lindström, Jaana; Lingaas-Holmen, Oddgeir; Mitchell, Sabrina L.; Narisu, Narisu; Robinson, Jennifer G.; Schumacher, Fred; Stančáková, Alena; Sundvall, Jouko; Sung, Yun-Ju; Swift, Amy J.; Wang, Wen-Chang; Wilkens, Lynne; Wilsgaard, Tom; Young, Alicia M.; Adair, Linda S.; Ballantyne, Christie M.; Bůžková, Petra; Chakravarti, Aravinda; Collins, Francis S.; Duggan, David; Feranil, Alan B.; Ho, Low-Tone; Hung, Yi-Jen; Hunt, Steven C.; Hveem, Kristian; Juang, Jyh-Ming J.; Kesäniemi, Antero Y.; Kuusisto, Johanna; Laakso, Markku; Lakka, Timo A.; Lee, I-Te; Leppert, Mark F.; Matise, Tara C.; Moilanen, Leena; Njølstad, Inger; Peters, Ulrike; Quertermous, Thomas; Rauramaa, Rainer; Rotter, Jerome I.; Saramies, Jouko; Tuomilehto, Jaakko; Uusitupa, Matti; Wang, Tzung-Dau; Mohlke, Karen L.

    2013-01-01

    Genome-wide association studies (GWAS) have identified ∼100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, in individuals of African American (n = 6,832), East Asian (n = 9,449), and European (n = 10,829) ancestry. We aimed to identify the variants with strongest association at each locus, identify additional and population-specific signals, refine association signals, and assess the relative significance of previously described functional variants. Among the 58 loci, 33 exhibited evidence of association at P<1×10−4 in at least one ancestry group. Sequential conditional analyses revealed that ten, nine, and four loci in African Americans, Europeans, and East Asians, respectively, exhibited two or more signals. At these loci, accounting for all signals led to a 1.3- to 1.8-fold increase in the explained phenotypic variance compared to the strongest signals. Distinct signals across ancestry groups were identified at PCSK9 and APOA5. Trans-ethnic analyses narrowed the signals to smaller sets of variants at GCKR, PPP1R3B, ABO, LCAT, and ABCA1. Of 27 variants reported previously to have functional effects, 74% exhibited the strongest association at the respective signal. In conclusion, trans-ethnic high-density genotyping and analysis confirm the presence of allelic heterogeneity, allow the identification of population-specific variants, and limit the number of candidate SNPs for functional studies. PMID:23555291

  19. Esophageal motor function: technical aspects of manometry.

    PubMed

    Gyawali, C Prakash; Patel, Amit

    2014-10-01

    High-resolution manometry (HRM) has advanced the understanding of esophageal peristaltic mechanisms and has simplified esophageal motor testing. In this article the technical aspects of HRM are addressed, focusing on test protocols, in addition to concerns and pitfalls in performing esophageal motor studies. Specifically, catheter positioning, equipment-related artifacts, basal data acquisition, adequate swallows, and provocative maneuvers are discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Caveolin1 Identifies a Specific Subpopulation of Cerebral Cortex Callosal Projection Neurons (CPN) Including Dual Projecting Cortical Callosal/Frontal Projection Neurons (CPN/FPN)

    PubMed Central

    2018-01-01

    Abstract The neocortex is composed of many distinct subtypes of neurons that must form precise subtype-specific connections to enable the cortex to perform complex functions. Callosal projection neurons (CPN) are the broad population of commissural neurons that connect the cerebral hemispheres via the corpus callosum (CC). Currently, how the remarkable diversity of CPN subtypes and connectivity is specified, and how they differentiate to form highly precise and specific circuits, are largely unknown. We identify in mouse that the lipid-bound scaffolding domain protein Caveolin 1 (CAV1) is specifically expressed by a unique subpopulation of Layer V CPN that maintain dual ipsilateral frontal projections to premotor cortex. CAV1 is expressed by over 80% of these dual projecting callosal/frontal projection neurons (CPN/FPN), with expression peaking early postnatally as axonal and dendritic targets are being reached and refined. CAV1 is localized to the soma and dendrites of CPN/FPN, a unique population of neurons that shares information both between hemispheres and with premotor cortex, suggesting function during postmitotic development and refinement of these neurons, rather than in their specification. Consistent with this, we find that Cav1 function is not necessary for the early specification of CPN/FPN, or for projecting to their dual axonal targets. CPN subtype-specific expression of Cav1 identifies and characterizes a first molecular component that distinguishes this functionally unique projection neuron population, a population that expands in primates, and is prototypical of additional dual and higher-order projection neuron subtypes. PMID:29379878

  1. Development, dissemination, and applications of a new terminological resource, the Q-Code taxonomy for professional aspects of general practice/family medicine.

    PubMed

    Jamoulle, Marc; Resnick, Melissa; Grosjean, Julien; Ittoo, Ashwin; Cardillo, Elena; Vander Stichele, Robert; Darmoni, Stefan; Vanmeerbeek, Marc

    2018-12-01

    While documentation of clinical aspects of General Practice/Family Medicine (GP/FM) is assured by the International Classification of Primary Care (ICPC), there is no taxonomy for the professional aspects (context and management) of GP/FM. To present the development, dissemination, applications, and resulting face validity of the Q-Codes taxonomy specifically designed to describe contextual features of GP/FM, proposed as an extension to the ICPC. The Q-Codes taxonomy was developed from Lamberts' seminal idea for indexing contextual content (1987) by a multi-disciplinary team of knowledge engineers, linguists and general practitioners, through a qualitative and iterative analysis of 1702 abstracts from six GP/FM conferences using Atlas.ti software. A total of 182 concepts, called Q-Codes, representing professional aspects of GP/FM were identified and organized in a taxonomy. Dissemination: The taxonomy is published as an online terminological resource, using semantic web techniques and web ontology language (OWL) ( http://www.hetop.eu/Q ). Each Q-Code is identified with a unique resource identifier (URI), and provided with preferred terms, and scope notes in ten languages (Portuguese, Spanish, English, French, Dutch, Korean, Vietnamese, Turkish, Georgian, German) and search filters for MEDLINE and web searches. This taxonomy has already been used to support queries in bibliographic databases (e.g., MEDLINE), to facilitate indexing of grey literature in GP/FM as congress abstracts, master theses, websites and as an educational tool in vocational teaching, Conclusions: The rapidly growing list of practical applications provides face-validity for the usefulness of this freely available new terminological resource.

  2. How to identify the key factors that affect driver perception of accident risk. A comparison between Italian and Spanish driver behavior.

    PubMed

    de Oña, Juan; de Oña, Rocio; Eboli, Laura; Forciniti, Carmen; Mazzulla, Gabriella

    2014-12-01

    Road crashes can be caused by different factors, including infrastructure, vehicles, and human variables. Many research studies have focused solely on identifying the key factors that cause road crashes. From these studies, it emerged that human factors have the most relevant impact on accident severity. More specifically, accident severity depends on several factors related directly to the driver, i.e., driving experience, driver's socio-economic characteristics, and driving behavior and attitudes. In this paper, we investigate driver behaviors and attitudes while driving and specifically focus on different methods for identifying the factors that most affect the driver's perception of accident risk. To this end, we designed and conducted a survey in two different European contexts: the city of Cosenza, which is located in the south of Italy, and the city of Granada, which is located in the south of Spain. Samples of drivers were contacted for their opinions on certain aspects of driving rules and attitudes while driving, and different types of questions were addressed to the drivers to assess their judgments of these aspects. Consequently, different methods of data analysis were applied to determine the aspects that heavily influence driver perception of accident risk. An experiment based on the stated preferences (SP) was carried out with the drivers, and the SP data were analyzed using an ordered probit (OP) model. Interesting findings emerged from different analyses of the data and from the comparisons among the data collected in the two different territorial contexts. We found that both Italian and Spanish drivers consider driving in an altered psychophysical state and violating the overtaking rules to be the most risky behaviors. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. A method for identifying color vision deficiency malingering.

    PubMed

    Pouw, Andrew; Karanjia, Rustum; Sadun, Alfredo

    2017-03-01

    To propose a new test to identify color vision deficiency malingering. An online survey was distributed to 130 truly color vision deficient participants and 160 participants willing to simulate color vision deficiency. The survey contained three sets of six color-adjusted versions of the standard Ishihara color plates each, as well as one set of six control plates. The plates that best discriminated both participant groups were selected for a "balanced" test emphasizing both sensitivity and specificity. A "specific" test that prioritized high specificity was also created by selecting from these plates. Statistical measures of the test (sensitivity, specificity, and Youden index) were assessed at each possible cut-off threshold, and a receiver operating characteristic (ROC) function with its area under the curve (AUC) charted. The redshift plate set was identified as having the highest difference of means between groups (-58%, CI: -64 to -52%), as well as the widest gap between group modes. Statistical measures of the "balanced" test show an optimal cut-off of at least two incorrectly identified plates to suggest malingering (Youden index: 0.773, sensitivity: 83.3%, specificity: 94.0%, AUC of ROC 0.918). The "specific" test was able to identify color vision deficiency simulators with a specificity of 100% when using a cut-off of at least two incorrectly identified plates (Youden index 0.599, sensitivity 59.9%, specificity 100%, AUC of ROC 0.881). Our proposed test for identifying color vision deficiency malingering demonstrates a high degree of reliability with AUCs of 0.918 and 0.881 for the "balanced" and "specific" tests, respectively. A cut-off threshold of at least two missed plates on the "specific" test was able to identify color vision deficiency simulators with 100% specificity.

  4. Variola virus-specific diagnostic assays: characterization, sensitivity, and specificity.

    PubMed

    Kondas, Ashley V; Olson, Victoria A; Li, Yu; Abel, Jason; Laker, Miriam; Rose, Laura; Wilkins, Kimberly; Turner, Jonathan; Kline, Richard; Damon, Inger K

    2015-04-01

    A public health response relies upon rapid and reliable confirmation of disease by diagnostic assays. Here, we detail the design and validation of two variola virus-specific real-time PCR assays, since previous assays cross-reacted with newly identified cowpox viruses. The assay specificity must continually be reassessed as other closely related viruses are identified. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  5. Assessing Method to Identifying Water Resilience Against Natural and Climate Change Hazards.

    NASA Astrophysics Data System (ADS)

    Amril, Rofi; Maryono

    2018-02-01

    A geographic region may become vulnerable toward water resources in a variety of ways. Common issues arise when man-made infrastructure such as housing, industrial, agriculture and other spatial land use policy implementation exceeds more than desired level. Vulnerability of a region due to water resources could be interpreted as the inability of the region to sustaining economic and social activity associated to socio-economic water availability. This study assess four aspects of water resilience: water quantity, water distribution, water quality, and water requirements. Literature review then followed by interview with academic expert used as method of study. This study found that four aspect of water vulnerability mostly have been applied to asses water resource vulnerability. Each aspect have a specific characteristic and could be define more specific and detail indicator according to the local content.

  6. Domain and Specification Models for Software Engineering

    NASA Technical Reports Server (NTRS)

    Iscoe, Neil; Liu, Zheng-Yang; Feng, Guohui

    1992-01-01

    This paper discusses our approach to representing application domain knowledge for specific software engineering tasks. Application domain knowledge is embodied in a domain model. Domain models are used to assist in the creation of specification models. Although many different specification models can be created from any particular domain model, each specification model is consistent and correct with respect to the domain model. One aspect of the system-hierarchical organization is described in detail.

  7. Single-cell transcriptomes identify human islet cell signatures and reveal cell-type–specific expression changes in type 2 diabetes

    PubMed Central

    Bolisetty, Mohan; Kursawe, Romy; Sun, Lili; Sivakamasundari, V.; Kycia, Ina

    2017-01-01

    Blood glucose levels are tightly controlled by the coordinated action of at least four cell types constituting pancreatic islets. Changes in the proportion and/or function of these cells are associated with genetic and molecular pathophysiology of monogenic, type 1, and type 2 (T2D) diabetes. Cellular heterogeneity impedes precise understanding of the molecular components of each islet cell type that govern islet (dys)function, particularly the less abundant delta and gamma/pancreatic polypeptide (PP) cells. Here, we report single-cell transcriptomes for 638 cells from nondiabetic (ND) and T2D human islet samples. Analyses of ND single-cell transcriptomes identified distinct alpha, beta, delta, and PP/gamma cell-type signatures. Genes linked to rare and common forms of islet dysfunction and diabetes were expressed in the delta and PP/gamma cell types. Moreover, this study revealed that delta cells specifically express receptors that receive and coordinate systemic cues from the leptin, ghrelin, and dopamine signaling pathways implicating them as integrators of central and peripheral metabolic signals into the pancreatic islet. Finally, single-cell transcriptome profiling revealed genes differentially regulated between T2D and ND alpha, beta, and delta cells that were undetectable in paired whole islet analyses. This study thus identifies fundamental cell-type–specific features of pancreatic islet (dys)function and provides a critical resource for comprehensive understanding of islet biology and diabetes pathogenesis. PMID:27864352

  8. Autism and Overcoming Job Barriers: Comparing Job-Related Barriers and Possible Solutions in and outside of Autism-Specific Employment

    PubMed Central

    Lorenz, Timo; Frischling, Cora; Cuadros, Raphael; Heinitz, Kathrin

    2016-01-01

    The aim of this study was to discover how individuals with autism succeed in entering the job market. We therefore sought to identify expected and occurred barriers, keeping them from taking up and staying in employment as well as to identify the solutions used to overcome these barriers. Sixty-six employed individuals with autism–17 of them with autism-specific employment–participated in an online survey. Results showed a variety of possible barriers. Individuals in autism-specific employment named formality problems–problems with organizational and practical process-related aspects of the job entry–most frequently while individuals in non-autism-specific employment mentioned social problems–obstacles concerning communication and human interaction–most. In terms of solutions, both groups used their own resources as much as external help, but differed in their specific strategies. In addition, correlations of an autism-specific employment with general and occupational self-efficacy as well as life and job satisfaction were examined. Possible implications of the results are discussed with regard to problem solving behavior and the use of strengths. PMID:26766183

  9. Australian primary health care nurses most and least satisfying aspects of work.

    PubMed

    Halcomb, Elizabeth; Ashley, Christine

    2017-02-01

    To identify the aspects of working in Australian primary health care that nurses rate as the most and least satisfying. The nursing workforce in Australian primary health care has grown exponentially to meet the growing demand for health care. To maintain and further growth requires the recruitment and retention of nurses to this setting. Understanding the factors that nurses' rate as the most and least satisfying about their job will inform strategies to enhance nurse retention. A cross-sectional online survey. Nurses employed in primary health care settings across Australia were recruited (n = 1166) to participate in a survey which combined items related to the respondent, their job, type of work, clinical activities, job satisfaction and future intention, with two open-ended items about the most and least satisfying aspects of their work. Patient interactions, respect, teamwork, collegiality and autonomy were identified as the most satisfying professional aspects of their role. Personal considerations such as family friendly work arrangements and a satisfactory work-life balance were also important, overriding negative components of the role. The least satisfying aspects were poor financial support and remuneration, lack of a career path, physical work environment and time constraints. National restructuring of the primary health care environment was seen as a barrier to role stability and ability to work to a full scope of practice. This study has identified a range of positive and negative professional and personal aspects of the primary health care nursing role, which may impact on staff recruitment and retention. Findings from the study should be considered by employers seeking to retain and maximise the skills of their primary health care workforce. Understanding the factors that nurses perceive as being the most and least satisfying aspects of the work is can open up dialogue about how to improve the working experience of nurses in primary health care.

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

    PubMed Central

    Zheng, Yao; Cleveland, H. Harrington

    2013-01-01

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

  11. The impact of disease on family members: a critical aspect of medical care

    PubMed Central

    Golics, Catherine Jane; Basra, Mohammad Khurshid Azam; Finlay, Andrew Yule; Salek, Sam

    2013-01-01

    Most existing health-related quality of life research concerns the impact of disease on patients. However, in several medical specialties including dermatology, oncology, and physical and mental disability, studies have been carried out investigating the impact of disease on the lives of families of patients. The aim of this paper is to review the literature which relates to the impact of disease on family members of patients. The OVIDSP Medline was selected as the primary database, Searches were limited to sources published in English. 158 papers were identified for review. The definition of “family” varied across the literature, and a broad definition was accepted in this review. This review shows that a wide variety of aspects of family members’ lives can be affected, including emotional, financial, family relationships, education and work, leisure time, and social activities. Many of these themes are linked to one another, with themes including financial impact and social impact being linked to emotional impact. Some positive aspects were also identified from the literature, including family relationships growing stronger. Several instruments exist to measure the impact of illness on the family, and most are disease or specialty- specific. The impact of disease on families of patients is often unrecognised and underestimated. Taking into account the quality of life of families as well as patients can offer the clinician a unique insight into issues such as family relationships and the effect of treatment decisions on the patient's close social group of partner and family. PMID:23759884

  12. Positive aspects of being a heterosexual ally to lesbian, gay, bisexual and transgender (LGBT) people.

    PubMed

    Rostosky, Sharon S; Black, Whitney W; Riggle, Ellen D B; Rosenkrantz, Dani

    2015-07-01

    Research on heterosexual allies has focused on heterosexual identity development models and pathways to ally activism. The positive aspects or positive experiences of identifying as an ally to lesbian, gay, bisexual, and transgender (LGBT) identified individuals and communities have received little attention. Using an online survey of participants recruited from LGBT ally related social media, we collected open-ended responses to a question about the positive aspects of self-identifying as a heterosexual ally. A final analytic sample of 292 self-identified male and female heterosexual adults (age 18-71, M = 33.47, SD = 13.32) provided responses that generated 8 themes. Positive aspects of being a heterosexual ally were: (a) increased knowledge and awareness, (b) upholding values of justice, (c) beneficial individual relationships, (d) community belonging, (e) educating others, (f) being a role model, (g) using social privilege, and (h) speaking out and taking a stand. The findings suggest that being a heterosexual ally is rewarding and may enhance individual well-being. These findings provide information that may contribute to effective ally development efforts. (c) 2015 APA, all rights reserved).

  13. Structural aspects of digestion of medium chain triglycerides studied in real time using sSAXS and Cryo-TEM.

    PubMed

    Phan, Stephanie; Hawley, Adrian; Mulet, Xavier; Waddington, Lynne; Prestidge, Clive A; Boyd, Ben J

    2013-12-01

    The purpose of this study was to investigate the colloidal structures formed on digestion of medium chain triglyceride (MCT) with a specific objective of identifying and characterizing a previously reported vesicular phase, which has been linked to supersaturation and anomalous digestion kinetics, and to evaluate the influence of lipid mass and enzyme inhibition on self assembled structure. MCT was digested in vitro and nanostructure was monitored in real time using synchrotron small angle X-ray scattering (sSAXS), and morphology was studied using cryogenic transmission electron microscopy (cryo-TEM). Formation of the putative vesicular phase formed on digestion of MCT was confirmed and its structural attributes were determined. Vesicle formation was dependent on lipid mass and bile salt concentration. The use of enzyme inhibitor for offline analysis of lipolysis samples did influence structural aspects of the digestion medium when compared to real time evaluation. The formation of a vesicular phase was directly linked to the kinetics of lipid digestion. Vesicle formation is linked to lipid mass, or more specifically the ratio of lipid to bile salts present in the digestion mixture. Inhibition of lipase to halt digestion during sampling for offline analysis must be done with caution as structural aspects were shown to differ for the MCT digests with and without inhibitor present.

  14. Analysis of SEER Adenosquamous Carcinoma Data to Identify Cause Specific Survival Predictors and Socioeconomic Disparities.

    PubMed

    Cheung, Rex

    2016-01-01

    This study used receiver operating characteristic curve to analyze Surveillance, Epidemiology and End Results (SEER) adenosquamous carcinoma data to identify predictive models and potential disparities in outcome. This study analyzed socio-economic, staging and treatment factors available in the SEER database for adenosquamous carcinoma. For the risk modeling, each factor was fitted by a generalized linear model to predict the cause specific survival. An area under the receiver operating characteristic curve (ROC) was computed. Similar strata were combined to construct the most parsimonious models. A total of 20,712 patients diagnosed from 1973 to 2009 were included in this study. The mean follow up time (S.D.) was 54.2 (78.4) months. Some 2/3 of the patients were female. The mean (S.D.) age was 63 (13.8) years. SEER stage was the most predictive factor of outcome (ROC area of 0.71). 13.9% of the patients were un-staged and had risk of cause specific death of 61.3% that was higher than the 45.3% risk for the regional disease and lower than the 70.3% for metastatic disease. Sex, site, radiotherapy, and surgery had ROC areas of about 0.55-0.65. Rural residence and race contributed to socioeconomic disparity for treatment outcome. Radiotherapy was underused even with localized and regional stages when the intent was curative. This under use was most pronounced in older patients. Anatomic stage was predictive and useful in treatment selection. Under-staging may have contributed to poor outcome.

  15. Distinct ontogenic and regional expressions of newly identified Cajal-Retzius cell-specific genes during neocorticogenesis.

    PubMed

    Yamazaki, Hiroshi; Sekiguchi, Mariko; Takamatsu, Masako; Tanabe, Yasuto; Nakanishi, Shigetada

    2004-10-05

    Cajal-Retzius (CR) cells are early-generated transient neurons and are important in the regulation of cortical neuronal migration and cortical laminar formation. Molecular entities characterizing the CR cell identity, however, remain largely elusive. We purified mouse cortical CR cells expressing GFP to homogeneity by fluorescence-activated cell sorting and examined a genome-wide expression profile of cortical CR cells at embryonic and postnatal periods. We identified 49 genes that exceeded hybridization signals by >10-fold in CR cells compared with non-CR cells at embryonic day 13.5, postnatal day 2, or both. Among these CR cell-specific genes, 25 genes, including the CR cell marker genes such as the reelin and calretinin genes, are selectively and highly expressed in both embryonic and postnatal CR cells. These genes, which encode generic properties of CR cell specificity, are eminently characterized as modulatory composites of voltage-dependent calcium channels and sets of functionally related cellular components involved in cell migration, adhesion, and neurite extension. Five genes are highly expressed in CR cells at the early embryonic period and are rapidly down-regulated thereafter. Furthermore, some of these genes have been shown to mark two distinctly different focal regions corresponding to the CR cell origins. At the late prenatal and postnatal periods, 19 genes are selectively up-regulated in CR cells. These genes include functional molecules implicated in synaptic transmission and modulation. CR cells thus strikingly change their cellular phenotypes during cortical development and play a pivotal role in both corticogenesis and cortical circuit maturation.

  16. Cell Death Pathways in Mutant Rhodopsin Rat Models Identifies Genotype-Specific Targets Controlling Retinal Degeneration.

    PubMed

    Viringipurampeer, Ishaq A; Gregory-Evans, Cheryl Y; Metcalfe, Andrew L; Bashar, Emran; Moritz, Orson L; Gregory-Evans, Kevin

    2018-06-18

    Retinitis pigmentosa (RP) is a group of inherited neurological disorders characterized by rod photoreceptor cell death, followed by secondary cone cell death leading to progressive blindness. Currently, there are no viable treatment options for RP. Due to incomplete knowledge of the molecular signaling pathways associated with RP pathogenesis, designing therapeutic strategies remains a challenge. In particular, preventing secondary cone photoreceptor cell loss is a key goal in designing potential therapies. In this study, we identified the main drivers of rod cell death and secondary cone loss in the transgenic S334ter rhodopsin rat model, tested the efficacy of specific cell death inhibitors on retinal function, and compared the effect of combining drugs to target multiple pathways in the S334ter and P23H rhodopsin rat models. The primary driver of early rod cell death in the S334ter model was a caspase-dependent process, whereas cone cell death occurred though RIP3-dependent necroptosis. In comparison, rod cell death in the P23H model was via necroptotic signaling, whereas cone cell loss occurred through inflammasome activation. Combination therapy of four drugs worked better than the individual drugs in the P23H model but not in the S334ter model. These differences imply that treatment modalities need to be tailored for each genotype. Taken together, our data demonstrate that rationally designed genotype-specific drug combinations will be an important requisite to effectively target primary rod cell loss and more importantly secondary cone survival.

  17. Fisheries Aspects of Seamounts and Taylor Columns

    DTIC Science & Technology

    1986-09-01

    the armorhead population. Due to a probable combination of overfishing and poor recruitment, the large fishery of the early 1970’s began a rapid...ACCESSION NO T I TLE (include Security Classification) FISHERIES ASPECTS OF SEAMOUNTS AND TAYLOR COLUMNS 2 PERSONAL AUTHOR(S) Brainard, Russell E. 13a...retention Seamount oceanography Taylor column Fisheries Nutrient enrichment 𔄃 3ASTRACT (Continue on reverse of necessary and identify by block number

  18. Training specificity and transfer in time and distance estimation.

    PubMed

    Healy, Alice F; Tack, Lindsay Anderson; Schneider, Vivian I; Barshi, Immanuel

    2015-07-01

    Learning is often specific to the conditions of training, making it important to identify which aspects of the testing environment are crucial to be matched in the training environment. In the present study, we examined training specificity in time and distance estimation tasks that differed only in the focus of processing (FOP). External spatial cues were provided for the distance estimation task and for the time estimation task in one condition, but not in another. The presence of a concurrent alphabet secondary task was manipulated during training and testing in all estimation conditions in Experiment 1. For distance as well as for time estimation in both conditions, training of the primary estimation task was found to be specific to the presence of the secondary task. In Experiments 2 and 3, we examined transfer between one estimation task and another, with no secondary task in either case. When all conditions were equal aside from the FOP instructions, including the presence of external spatial cues, Experiment 2 showed "transfer" between tasks, suggesting that training might not be specific to the FOP. When the external spatial cues were removed from the time estimation task, Experiment 3 showed no transfer between time and distance estimations, suggesting that external task cues influenced the procedures used in the estimation tasks.

  19. Aspects of Theories, Frameworks and Paradigms in Mathematics Education Research

    ERIC Educational Resources Information Center

    Stoilescu, Dorian

    2016-01-01

    This article discusses major theoretical debates and paradigms from the last decades in general education and their specific influences in mathematics education contexts. Behaviourism, cognitive science, constructivism, situated cognition, critical theory, place-based learning, postmodernism and poststructuralism and their significant aspects in…

  20. Identifying N6-methyladenosine sites using multi-interval nucleotide pair position specificity and support vector machine

    NASA Astrophysics Data System (ADS)

    Xing, Pengwei; Su, Ran; Guo, Fei; Wei, Leyi

    2017-04-01

    N6-methyladenosine (m6A) refers to methylation of the adenosine nucleotide acid at the nitrogen-6 position. It plays an important role in a series of biological processes, such as splicing events, mRNA exporting, nascent mRNA synthesis, nuclear translocation and translation process. Numerous experiments have been done to successfully characterize m6A sites within sequences since high-resolution mapping of m6A sites was established. However, as the explosive growth of genomic sequences, using experimental methods to identify m6A sites are time-consuming and expensive. Thus, it is highly desirable to develop fast and accurate computational identification methods. In this study, we propose a sequence-based predictor called RAM-NPPS for identifying m6A sites within RNA sequences, in which we present a novel feature representation algorithm based on multi-interval nucleotide pair position specificity, and use support vector machine classifier to construct the prediction model. Comparison results show that our proposed method outperforms the state-of-the-art predictors on three benchmark datasets across the three species, indicating the effectiveness and robustness of our method. Moreover, an online webserver implementing the proposed predictor has been established at http://server.malab.cn/RAM-NPPS/. It is anticipated to be a useful prediction tool to assist biologists to reveal the mechanisms of m6A site functions.

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

    NASA Astrophysics Data System (ADS)

    Mesic, Vanes

    2012-11-01

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

  2. A rapid method to identify Salmonella enterica serovar Gallinarum biovar Pullorum using a specific target gene ipaJ.

    PubMed

    Xu, Lijuan; Liu, Zijian; Li, Yang; Yin, Chao; Hu, Yachen; Xie, Xiaolei; Li, Qiuchun; Jiao, Xinan

    2018-06-01

    Salmonella enterica serovar Gallinarum biovar Pullorum (S. Pullorum) is the pathogen of pullorum disease, which leads to severe economic losses in many developing countries. Traditional methods to identify S. enterica have relied on biochemical reactions and serotyping, which are time-consuming with accurate identification if properly carried out. In this study, we developed a rapid polymerase chain reaction (PCR) method targeting the specific gene ipaJ to detect S. Pullorum. Among the 650 S. Pullorum strains isolated from 1962 to 2016 all over China, 644 strains were identified to harbour ipaJ gene in the plasmid pSPI12, accounting for a detection rate of 99.08%. Six strains were ipaJ negative because pSPI12 was not found in these strains according to whole genome sequencing results. There was no cross-reaction with other Salmonella serotypes, including Salmonella enterica serovar Gallinarum biovar Gallinarum (S. Gallinarum), which show a close genetic relationship with S. Pullorum. This shows that the PCR method could distinguish S. Gallinarum from S. Pullorum in one-step PCR without complicated biochemical identification. The limit of detection of this PCR method was as low as 90 fg/μl or 10 2 CFU, which shows a high sensitivity. Moreover, this method was applied to identify Salmonella isolated from the chicken farm and the results were consistent with what we obtained from biochemical reactions and serotyping. Together, all the results demonstrated that this one-step PCR method is simple and feasible to efficiently identify S. Pullorum.

  3. The valuation of nursing begins with identifying value drivers.

    PubMed

    Rutherford, Marcella M

    2010-03-01

    Adequate investment in a profession links to its ability to define and document its value. This requires identifying those elements or value drivers that demonstrate its worth. To completely identify nursing's value drivers requires meshing the economic, technical, and caring aspects of its profession. Nursing's valuation includes assessing nursing's tangible and intangible assets and documenting these assets. This information communicates nursing's worth and ensures adequate economic investment in its services.

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

    PubMed

    Rollins, Derrick K; Teh, Ailing

    2010-12-17

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

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

    PubMed

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

    2017-07-01

    Genome-wide association study (GWAS)-identified variants are enriched for functional elements. However, we have limited knowledge of how functional enrichment may differ by disease/trait and tissue type. We tested a broad set of eight functional elements for enrichment among GWAS-identified SNPs (p < 5×10 -8 ) from the NHGRI-EBI Catalog across seven disease/trait categories: cancer, cardiovascular disease, diabetes, autoimmune disease, psychiatric disease, neurological disease, and anthropometric traits. SNPs were annotated using HaploReg for the eight functional elements across any tissue: DNase sites, expression quantitative trait loci (eQTL), sequence conservation, enhancers, promoters, missense variants, sequence motifs, and protein binding sites. In addition, tissue-specific annotations were considered for brain vs. blood. Disease/trait SNPs were compared to a control set of 4809 SNPs matched to the GWAS SNPs (N = 1639) on allele frequency, gene density, distance to nearest gene, and linkage disequilibrium at ~3:1 ratio. Enrichment analyses were conducted using logistic regression, with Bonferroni correction. Overall, a significant enrichment was observed for all functional elements, except sequence motifs. Missense SNPs showed the strongest magnitude of enrichment. eQTLs were the only functional element significantly enriched across all diseases/traits. Magnitudes of enrichment were generally similar across diseases/traits, where enrichment was statistically significant. Blood vs. brain tissue effects on enrichment were dependent on disease/trait and functional element (e.g., cardiovascular disease: eQTLs P TissueDifference  = 1.28 × 10 -6 vs. enhancers P TissueDifference  = 0.94). Identifying disease/trait-relevant functional elements and tissue types could provide new insight into the underlying biology, by guiding a priori GWAS analyses (e.g., brain enhancer elements for psychiatric disease) or facilitating post hoc interpretation.

  6. Ethical aspects of human biobanks: a systematic review

    PubMed Central

    Budimir, Danijela; Polašek, Ozren; Marušić, Ana; Kolčić, Ivana; Zemunik, Tatijana; Boraska, Vesna; Jerončić, Ana; Boban, Mladen; Campbell, Harry; Rudan, Igor

    2011-01-01

    Aim To systematically assess the existing literature on ethical aspects of human biobanks. Method We searched the Web of Science and PubMed databases to find studies addressing ethical problems in biobanks with no limits set (study design, study population, time period, or language of publication). All identified articles published until November 2010 were included. We analyzed the type of published articles, journals publishing them, involvement of countries/institutions, year of publication, and citations received, and qualitatively assessed every article in order to identify ethical issues addressed by the majority of published research on human biobanking. Results Hundred and fifty four studies satisfied our review criteria. The studies mainly came from highly developed countries and were all published in the last two decades, with over half of them published in 2009 or 2010. They most commonly discussed the informed consent, privacy and identifiability, return of results to participants, importance of public trust, involvement of children, commercialization, the role of ethics boards, international data exchange, ownership of samples, and benefit sharing. Conclusions The focus on ethical aspects is strongly present through the whole biobanking research field. Although there is a consensus on the old and most typical ethical issues, with further development of the field and increasingly complex structure of human biobanks, these issues will likely continue to arise and accumulate, hence requiring constant re-appraisal and continuing discussion. PMID:21674823

  7. Respiratory complaints in Chinese: cultural and diagnostic specificities.

    PubMed

    Han, Jiangna; Zhu, Yuanjue; Li, Shunwei; Chen, Xiansheng; Put, Claudia; Van de Woestijne, Karel P; Van den Bergh, Omer

    2005-06-01

    We investigated the qualitative components of a wide range of Chinese descriptors of dyspnea and associated symptoms, and their relevance for clinical diagnosis. Sixty-one spontaneously reported descriptors were elicited in Chinese patients to make a symptom checklist, which was administered to new groups of patients with different cardiopulmonary diseases, to patients with medically unexplained dyspnea and to healthy subjects. Test-retest reliability was satisfactory for most of the descriptors. A principal component analysis on 61 descriptors yielded the following eight factors: dyspnea-effort of breathing; dyspnea-affective aspect; wheezing; anxiety; tingling; palpitation; coughing and sputum; and dying experience. Although the descriptors of dyspnea-effort of breathing resembled Western wordings and were shared by patients with a variety of diseases, the descriptors of dyspnea-affective aspect appeared to be more culturally specific and were primarily linked to the diagnosis of medically unexplained dyspnea, whereas wheezing was specifically linked to asthma. Three factors of breathlessness were found in Chinese. The descriptors of dyspnea-effort of breathing and wheezing appear to be similar to Western descriptors, whereas the dyspnea-affective aspect seems to bear cultural specificity.

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

    PubMed Central

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

    2017-01-01

    Bacterial signaling systems such as protein kinases and quorum sensing have become increasingly attractive targets for the development of novel antimicrobial agents in a time of rising antibiotic resistance. The family of bacterial Penicillin-binding-protein And Serine/Threonine kinase-Associated (PASTA) kinases is of particular interest due to the role of these kinases in regulating resistance to β-lactam antibiotics. As such, small-molecule kinase inhibitors that target PASTA kinases may prove beneficial as treatments adjunctive to β-lactam therapy. Despite this interest, only limited progress has been made in identifying functional inhibitors of the PASTA kinases that have both activity against the intact microbe and high kinase specificity. Here, we report the results of a small-molecule screen that identified GSK690693, an imidazopyridine aminofurazan-type kinase inhibitor that increases the sensitivity of the intracellular pathogen Listeria monocytogenes to various β-lactams by inhibiting the PASTA kinase PrkA. GSK690693 potently inhibited PrkA kinase activity biochemically and exhibited significant selectivity for PrkA relative to the Staphylococcus aureus PASTA kinase Stk1. Furthermore, other imidazopyridine aminofurazans could effectively inhibit PrkA and potentiate β-lactam antibiotic activity to varying degrees. The presence of the 2-methyl-3-butyn-2-ol (alkynol) moiety was important for both biochemical and antimicrobial activity. Finally, mutagenesis studies demonstrated residues in the back pocket of the active site are important for GSK690693 selectivity. These data suggest that targeted screens can successfully identify PASTA kinase inhibitors with both biochemical and antimicrobial specificity. Moreover, the imidazopyridine aminofurazans represent a family of PASTA kinase inhibitors that have the potential to be optimized for selective PASTA kinase inhibition. PMID:28821610

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

    PubMed

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

    2017-10-13

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

  10. Charles Darwin and Evolution: Illustrating Human Aspects of Science

    ERIC Educational Resources Information Center

    Kampourakis, Kostas; McComas, William F.

    2010-01-01

    Recently, the nature of science (NOS) has become recognized as an important element within the K-12 science curriculum. Despite differences in the ultimate lists of recommended aspects, a consensus is emerging on what specific NOS elements should be the focus of science instruction and inform textbook writers and curriculum developers. In this…

  11. Instructional Aides: Employment, Payroll Procedures, Supervision, Performance Appraisal, Legal Aspects.

    ERIC Educational Resources Information Center

    Nielsen, Earl T.

    Designed to assist school administrators in their efforts to secure, train, and retain the most qualified instructional aides available, the monograph discusses procedures for employment, payroll processing, aide supervision, performance appraisal, and legal aspects involved in the hiring of instructional aides. Specific topics include…

  12. Investigation of evolution-related aspects of bacterial rhodopsins

    NASA Technical Reports Server (NTRS)

    1994-01-01

    We have investigated evolution-related aspects of bacterial rhodopsins, the unique retinal-based energy transducing systems of halophilic archae. The approach was to describe both structural and functional aspects: the structure by sequencing genes to explore which regions are conserved, and the function by comparing proton and chloride transport in the closely related systems, bacteriorhodopsin and halorhodopsin, respectively. In the latter, we have made a good start toward the ultimate goal of separating the attributes of the general principles of retinal-based ionic pumps from those of the specific ion specificities, by determining the thermodynamics of the internal steps of the protein-mediated active transport process, as well as some of the intraprotein ion-transfer steps. Our present emphasis is on continuing to acquire the tools for studying what distinguishes proton transport from chloride transport. We consider it important, therefore, that we have been able to provide firm mathematical grounds for the kinetics analyses which underlies these studies. Our molecular biological studies have received a great boost from the expression vector for the bop gene based on a halobacterial plasmid, that we recently developed.

  13. Literacy Course Priorities and Signature Aspects of Nine Elementary Initial Licensure Programs

    ERIC Educational Resources Information Center

    Lenski, Susan; Ganske, Kathy; Chambers, Sandy; Wold, Linda; Dobler, Elizabeth; Grisham, Dana L.; Scales, Roya; Smetana, Linda; Wolsey, Thomas Devere; Yoder, Karen K.; Young, Janet

    2013-01-01

    The purpose of this article is to describe the first part of a three-phase study to learn what makes an effective elementary literacy initial licensure program. The first step was to identify how nine programs prioritized research-based literacy practices and to identify each program's unique features, which we called "signature aspects." Findings…

  14. Tip cell-specific requirement for an atypical Gpr124- and Reck-dependent Wnt/β-catenin pathway during brain angiogenesis

    PubMed Central

    Vanhollebeke, Benoit; Stone, Oliver A; Bostaille, Naguissa; Cho, Chris; Zhou, Yulian; Maquet, Emilie; Gauquier, Anne; Cabochette, Pauline; Fukuhara, Shigetomo; Mochizuki, Naoki; Nathans, Jeremy; Stainier, Didier YR

    2015-01-01

    Despite the critical role of endothelial Wnt/β-catenin signaling during central nervous system (CNS) vascularization, how endothelial cells sense and respond to specific Wnt ligands and what aspects of the multistep process of intra-cerebral blood vessel morphogenesis are controlled by these angiogenic signals remain poorly understood. We addressed these questions at single-cell resolution in zebrafish embryos. We identify the GPI-anchored MMP inhibitor Reck and the adhesion GPCR Gpr124 as integral components of a Wnt7a/Wnt7b-specific signaling complex required for brain angiogenesis and dorsal root ganglia neurogenesis. We further show that this atypical Wnt/β-catenin signaling pathway selectively controls endothelial tip cell function and hence, that mosaic restoration of single wild-type tip cells in Wnt/β-catenin-deficient perineural vessels is sufficient to initiate the formation of CNS vessels. Our results identify molecular determinants of ligand specificity of Wnt/β-catenin signaling and provide evidence for organ-specific control of vascular invasion through tight modulation of tip cell function. DOI: http://dx.doi.org/10.7554/eLife.06489.001 PMID:26051822

  15. A chemical proteomic atlas of brain serine hydrolases identifies cell type-specific pathways regulating neuroinflammation

    PubMed Central

    Viader, Andreu; Ogasawara, Daisuke; Joslyn, Christopher M; Sanchez-Alavez, Manuel; Mori, Simone; Nguyen, William; Conti, Bruno; Cravatt, Benjamin F

    2016-01-01

    Metabolic specialization among major brain cell types is central to nervous system function and determined in large part by the cellular distribution of enzymes. Serine hydrolases are a diverse enzyme class that plays fundamental roles in CNS metabolism and signaling. Here, we perform an activity-based proteomic analysis of primary mouse neurons, astrocytes, and microglia to furnish a global portrait of the cellular anatomy of serine hydrolases in the brain. We uncover compelling evidence for the cellular compartmentalization of key chemical transmission pathways, including the functional segregation of endocannabinoid (eCB) biosynthetic enzymes diacylglycerol lipase-alpha (DAGLα) and –beta (DAGLβ) to neurons and microglia, respectively. Disruption of DAGLβ perturbed eCB-eicosanoid crosstalk specifically in microglia and suppressed neuroinflammatory events in vivo independently of broader effects on eCB content. Mapping the cellular distribution of metabolic enzymes thus identifies pathways for regulating specialized inflammatory responses in the brain while avoiding global alterations in CNS function. DOI: http://dx.doi.org/10.7554/eLife.12345.001 PMID:26779719

  16. General Aspects of Two-Component Regulatory Circuits in Bacteria: Domains, Signals and Roles.

    PubMed

    Padilla-Vaca, Felipe; Mondragón-Jaimes, Verónica; Franco, Bernardo

    2017-01-01

    All living organisms are subject to changing environments, which must be sensed in order to respond swiftly and efficiently. Two-component systems (TCS) are signal transduction regulatory circuits based typically on a membrane bound sensor kinase and a cytoplasmic response regulator, that is activated through a histidine to aspartate phosphorelay reactions. Activated response regulator acts usually as a transcription factor. The best known examples were identified in bacteria, but they are also found in fungi, algae and plants. Thus far, they are not found in mammals. Regulatory circuits coupled to two-component systems exhibit a myriad of responses to environmental stimuli such as: redox potential, pH, specific metabolites, pressure, light and more recently to specific antimicrobial peptides that activate a sensor kinase responsible for expressing virulence factors through the active response regulator. In this review we explore general aspects on two-component systems that ultimately can play a role on virulence regulation, also the intriguing domain properties of the sensor kinases that can be a potential target for antimicrobial compounds. Only a handful of sensor kinases are extensively characterized, the vast majority belong to what we call 'the dark matter of bacterial signal transduction' since no known signal, structure and biochemical properties are available. Regulatory circuits from vertebrate pathogenic organisms can explain virulence in terms of either response to environmental factors or specific niche occupancy. Hopefully, knowledge on these signal transduction systems can lead to identify novel molecules that target two-component systems, since the increase of drug resistant microorganisms is worrisome. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    PubMed Central

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

    1998-01-01

    Mesodermal development is a multistep process in which cells become increasingly specialized to form specific tissue types. In Drosophila and mammals, proper segregation and patterning of the mesoderm involves the bHLH factor Twist. We investigated the activity of a Twist-related factor, CeTwist, during Caenorhabditis elegans mesoderm development. Embryonic mesoderm in C. elegans derives from a number of distinct founder cells that are specified during the early lineages; in contrast, a single blast cell (M) is responsible for all nongonadal mesoderm formation during postembryonic development. Using immunofluorescence and reporter fusions, we determined the activity pattern of the gene encoding CeTwist. No activity was observed during specification of mesodermal lineages in the early embryo; instead, the gene was active within the M lineage and in a number of mesodermal cells with nonstriated muscle fates. A role for CeTwist in postembryonic mesodermal cell fate specification was indicated by ectopic expression and genetic interference assays. These experiments showed that CeTwist was responsible for activating two target genes normally expressed in specific subsets of nonstriated muscles derived from the M lineage. In vitro and in vivo assays suggested that CeTwist cooperates with the C. elegans E/Daughterless homolog in directly activating these targets. The two target genes that we have studied, ceh-24 and egl-15, encode an NK-2 class homeodomain and an FGF receptor (FGFR) homolog, respectively. Twist activates FGFR and NK-homeodomain target genes during mesodermal patterning of Drosophila and similar target interactions have been proposed to modulate mesenchymal growth during closure of the vertebrate skull. These results suggest the possibility that a conserved pathway may be used for diverse functions in mesodermal specification. PMID:9716413

  18. Toxicological aspects of fire.

    PubMed

    Stefanidou, M; Athanaselis, S

    2004-08-01

    Most fatalities from fires are not due to burns, but are a result of inhalation of toxic gases produced during combustion. Fire produces a complex toxic environment, involving flame, heat, oxygen depletion, smoke and toxic gases. As a wide variety of synthetic materials is used in buildings (insulation, furniture, carpeting, electric wiring covering, decorative items), the potential for poisoning from inhalation of products of combustion is continuously increasing. In the present review, the problems that are present in a fire event, the toxicology of the toxic substances and the specific chemical hazards to firefighters are described. Regulatory toxicology aspects are presented concerning the use of non-flammable building and furnishing materials to prevent fires and decrease of poisonings and deaths resulting from fires.

  19. Functional genomics identifies regulators of the phototransduction machinery in the Drosophila larval eye and adult ocelli.

    PubMed

    Mishra, Abhishek Kumar; Bargmann, Bastiaan O R; Tsachaki, Maria; Fritsch, Cornelia; Sprecher, Simon G

    2016-02-15

    Sensory perception of light is mediated by specialized Photoreceptor neurons (PRs) in the eye. During development all PRs are genetically determined to express a specific Rhodopsin (Rh) gene and genes mediating a functional phototransduction pathway. While the genetic and molecular mechanisms of PR development is well described in the adult compound eye, it remains unclear how the expression of Rhodopsins and the phototransduction cascade is regulated in other visual organs in Drosophila, such as the larval eye and adult ocelli. Using transcriptome analysis of larval PR-subtypes and ocellar PRs we identify and study new regulators required during PR differentiation or necessary for the expression of specific signaling molecules of the functional phototransduction pathway. We found that the transcription factor Krüppel (Kr) is enriched in the larval eye and controls PR differentiation by promoting Rh5 and Rh6 expression. We also identified Camta, Lola, Dve and Hazy as key genes acting during ocellar PR differentiation. Further we show that these transcriptional regulators control gene expression of the phototransduction cascade in both larval eye and adult ocelli. Our results show that PR cell type-specific transcriptome profiling is a powerful tool to identify key transcriptional regulators involved during several aspects of PR development and differentiation. Our findings greatly contribute to the understanding of how combinatorial action of key transcriptional regulators control PR development and the regulation of a functional phototransduction pathway in both larval eye and adult ocelli. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Neurologic aspects of microcephalic osteodysplastic primordial dwarfism type II.

    PubMed

    Galasso, Cinzia; Lo-Castro, Adriana; Lalli, Cristina; Cerminara, Caterina; Curatolo, Paolo

    2008-06-01

    Microcephalic osteodysplastic primordial dwarfism type II is a specific disorder characterized by severe intrauterine and postnatal growth retardation, acquired microcephaly, cerebrovascular abnormalities, progressive bone dysplasia, and a characteristic face. Whereas the diagnostic features of this syndrome are well-recognized, the neurologic aspects have not been clearly defined. We report on a detailed neurodevelopmental follow-up study of a new case of microcephalic osteodysplastic primordial dwarfism type II, followed from the first years of life to adolescence, and we discuss the neurocognitive features of our patient. We also review the neurologic aspects of this disorder compared with syndromes with overlapping phenotypes, such as microcephalic osteodysplastic primordial dwarfism types I and III and Seckel syndrome.

  1. Biomphalaria glabrata transcriptome: cDNA microarray profiling identifies resistant- and susceptible-specific gene expression in haemocytes from snail strains exposed to Schistosoma mansoni

    PubMed Central

    Lockyer, Anne E; Spinks, Jenny; Kane, Richard A; Hoffmann, Karl F; Fitzpatrick, Jennifer M; Rollinson, David; Noble, Leslie R; Jones, Catherine S

    2008-01-01

    Background Biomphalaria glabrata is an intermediate snail host for Schistosoma mansoni, one of the important schistosomes infecting man. B. glabrata/S. mansoni provides a useful model system for investigating the intimate interactions between host and parasite. Examining differential gene expression between S. mansoni-exposed schistosome-resistant and susceptible snail lines will identify genes and pathways that may be involved in snail defences. Results We have developed a 2053 element cDNA microarray for B. glabrata containing clones from ORESTES (Open Reading frame ESTs) libraries, suppression subtractive hybridization (SSH) libraries and clones identified in previous expression studies. Snail haemocyte RNA, extracted from parasite-challenged resistant and susceptible snails, 2 to 24 h post-exposure to S. mansoni, was hybridized to the custom made cDNA microarray and 98 differentially expressed genes or gene clusters were identified, 94 resistant-associated and 4 susceptible-associated. Quantitative PCR analysis verified the cDNA microarray results for representative transcripts. Differentially expressed genes were annotated and clustered using gene ontology (GO) terminology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis. 61% of the identified differentially expressed genes have no known function including the 4 susceptible strain-specific transcripts. Resistant strain-specific expression of genes implicated in innate immunity of invertebrates was identified, including hydrolytic enzymes such as cathepsin L, a cysteine proteinase involved in lysis of phagocytosed particles; metabolic enzymes such as ornithine decarboxylase, the rate-limiting enzyme in the production of polyamines, important in inflammation and infection processes, as well as scavenging damaging free radicals produced during production of reactive oxygen species; stress response genes such as HSP70; proteins involved in signalling, such as importin 7 and copine 1

  2. Biomphalaria glabrata transcriptome: cDNA microarray profiling identifies resistant- and susceptible-specific gene expression in haemocytes from snail strains exposed to Schistosoma mansoni.

    PubMed

    Lockyer, Anne E; Spinks, Jenny; Kane, Richard A; Hoffmann, Karl F; Fitzpatrick, Jennifer M; Rollinson, David; Noble, Leslie R; Jones, Catherine S

    2008-12-29

    Biomphalaria glabrata is an intermediate snail host for Schistosoma mansoni, one of the important schistosomes infecting man. B. glabrata/S. mansoni provides a useful model system for investigating the intimate interactions between host and parasite. Examining differential gene expression between S. mansoni-exposed schistosome-resistant and susceptible snail lines will identify genes and pathways that may be involved in snail defences. We have developed a 2053 element cDNA microarray for B. glabrata containing clones from ORESTES (Open Reading frame ESTs) libraries, suppression subtractive hybridization (SSH) libraries and clones identified in previous expression studies. Snail haemocyte RNA, extracted from parasite-challenged resistant and susceptible snails, 2 to 24 h post-exposure to S. mansoni, was hybridized to the custom made cDNA microarray and 98 differentially expressed genes or gene clusters were identified, 94 resistant-associated and 4 susceptible-associated. Quantitative PCR analysis verified the cDNA microarray results for representative transcripts. Differentially expressed genes were annotated and clustered using gene ontology (GO) terminology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis. 61% of the identified differentially expressed genes have no known function including the 4 susceptible strain-specific transcripts. Resistant strain-specific expression of genes implicated in innate immunity of invertebrates was identified, including hydrolytic enzymes such as cathepsin L, a cysteine proteinase involved in lysis of phagocytosed particles; metabolic enzymes such as ornithine decarboxylase, the rate-limiting enzyme in the production of polyamines, important in inflammation and infection processes, as well as scavenging damaging free radicals produced during production of reactive oxygen species; stress response genes such as HSP70; proteins involved in signalling, such as importin 7 and copine 1, cytoplasmic intermediate

  3. Folded concave penalized learning in identifying multimodal MRI marker for Parkinson’s disease

    PubMed Central

    Liu, Hongcheng; Du, Guangwei; Zhang, Lijun; Lewis, Mechelle M.; Wang, Xue; Yao, Tao; Li, Runze; Huang, Xuemei

    2016-01-01

    Background Brain MRI holds promise to gauge different aspects of Parkinson’s disease (PD)-related pathological changes. Its analysis, however, is hindered by the high-dimensional nature of the data. New method This study introduces folded concave penalized (FCP) sparse logistic regression to identify biomarkers for PD from a large number of potential factors. The proposed statistical procedures target the challenges of high-dimensionality with limited data samples acquired. The maximization problem associated with the sparse logistic regression model is solved by local linear approximation. The proposed procedures then are applied to the empirical analysis of multimodal MRI data. Results From 45 features, the proposed approach identified 15 MRI markers and the UPSIT, which are known to be clinically relevant to PD. By combining the MRI and clinical markers, we can enhance substantially the specificity and sensitivity of the model, as indicated by the ROC curves. Comparison to existing methods We compare the folded concave penalized learning scheme with both the Lasso penalized scheme and the principle component analysis-based feature selection (PCA) in the Parkinson’s biomarker identification problem that takes into account both the clinical features and MRI markers. The folded concave penalty method demonstrates a substantially better clinical potential than both the Lasso and PCA in terms of specificity and sensitivity. Conclusions For the first time, we applied the FCP learning method to MRI biomarker discovery in PD. The proposed approach successfully identified MRI markers that are clinically relevant. Combining these biomarkers with clinical features can substantially enhance performance. PMID:27102045

  4. The Multidimensional Aspects of Sleep Spindles and Their Relationship to Word-Pair Memory Consolidation

    PubMed Central

    Lustenberger, Caroline; Wehrle, Flavia; Tüshaus, Laura; Achermann, Peter; Huber, Reto

    2015-01-01

    Study Objectives: Several studies proposed a link between sleep spindles and sleep dependent memory consolidation in declarative learning tasks. In addition to these state-like aspects of sleep spindles, they have also trait-like characteristics, i.e., were related to general cognitive performance, an important distinction that has often been neglected in correlative studies. Furthermore, from the multitude of different sleep spindle measures, often just one specific aspect was analyzed. Thus, we aimed at taking multidimensional aspects of sleep spindles into account when exploring their relationship to word-pair memory consolidation. Design: Each subject underwent 2 study nights with all-night high-density electroencephalographic (EEG) recordings. Sleep spindles were automatically detected in all EEG channels. Subjects were trained and tested on a word-pair learning task in the evening, and retested in the morning to assess sleep related memory consolidation (overnight retention). Trait-like aspects refer to the mean of both nights and state-like aspects were calculated as the difference between night 1 and night 2. Setting: Sleep laboratory. Participants: Twenty healthy male subjects (age: 23.3 ± 2.1 y) Measurements and Results: Overnight retention was negatively correlated with trait-like aspects of fast sleep spindle density and positively with slow spindle density on a global level. In contrast, state-like aspects were observed for integrated slow spindle activity, which was positively related to the differences in overnight retention in specific regions. Conclusion: Our results demonstrate the importance of a multidimensional approach when investigating the relationship between sleep spindles and memory consolidation and thereby provide a more complete picture explaining divergent findings in the literature. Citation: Lustenberger C, Wehrle F, Tüshaus L, Achermann P, Huber R. The multidimensional aspects of sleep spindles and their relationship to word

  5. Alternative Effector-Function Profiling Identifies Broad HIV-Specific T-Cell Responses in Highly HIV-Exposed Individuals Who Remain Uninfected

    PubMed Central

    Ruiz-Riol, Marta; Llano, Anuska; Ibarrondo, Javier; Zamarreño, Jennifer; Yusim, Karina; Bach, Vanessa; Mothe, Beatriz; Perez-Alvarez, Susana; Fernandez, Marco A.; Requena, Gerard; Meulbroek, Michael; Pujol, Ferran; Leon, Agathe; Cobarsi, Patricia; Korber, Bette T.; Clotet, Bonaventura; Ganoza, Carmela; Sanchez, Jorge; Coll, Josep; Brander, Christian

    2015-01-01

    The characterization of host immune responses to human immunodeficiency virus (HIV) in HIV controllers and individuals with high exposure but seronegativity to HIV (HESN) is needed to guide the development of effective preventive and therapeutic vaccine candidates. However, several technical hurdles severely limit the definition of an effective virus-specific T-cell response. By using a toggle-peptide approach, which takes HIV sequence diversity into account, and a novel, boosted cytokine staining/flow cytometry strategy, we here describe new patterns of T-cell responses to HIV that would be missed by standard assays. Importantly, this approach also allows detection of broad and strong virus-specific T-cell responses in HESN individuals that are characterized by a T-helper type 1 cytokine–like effector profile and produce cytokines that have been associated with potential control of HIV infection, including interleukin 10, interleukin 13, and interleukin 22. These results establish a novel approach to improve the current understanding of HIV-specific T-cell immunity and identify cellular immune responses and individual cytokines as potential markers of relative HIV resistance. As such, the findings also help develop similar strategies for more-comprehensive assessments of host immune responses to other human infections and immune-mediated disorders. PMID:25249264

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

    PubMed

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

    2013-01-11

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

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

    PubMed Central

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

    2013-01-01

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

  8. A review on non-linear aeroelasticity of high aspect-ratio wings

    NASA Astrophysics Data System (ADS)

    Afonso, Frederico; Vale, José; Oliveira, Éder; Lau, Fernando; Suleman, Afzal

    2017-02-01

    Current economic constraints and environmental regulations call for design of more efficient aircraft configurations. An observed trend in aircraft design to reduce the lift induced drag and improve fuel consumption and emissions is to increase the wing aspect-ratio. However, a slender wing is more flexible and subject to higher deflections under the same operating conditions. This effect may lead to changes in dynamic behaviour and in aeroelastic response, potentially resulting in instabilities. Therefore, it is important to take into account geometric non-linearities in the design of high aspect-ratio wings, as well as having accurate computational codes that couple the aerodynamic and structural models in the presence of non-linearities. Here, a review on the state-of-the-art on non-linear aeroelasticity of high aspect-ratio wings is presented. The methodologies employed to analyse high aspect-ratio wings are presented and their applications discussed. Important observations from the state-of-the-art studies are drawn and the current challenges in the field are identified.

  9. groHMM: a computational tool for identifying unannotated and cell type-specific transcription units from global run-on sequencing data.

    PubMed

    Chae, Minho; Danko, Charles G; Kraus, W Lee

    2015-07-16

    Global run-on coupled with deep sequencing (GRO-seq) provides extensive information on the location and function of coding and non-coding transcripts, including primary microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and enhancer RNAs (eRNAs), as well as yet undiscovered classes of transcripts. However, few computational tools tailored toward this new type of sequencing data are available, limiting the applicability of GRO-seq data for identifying novel transcription units. Here, we present groHMM, a computational tool in R, which defines the boundaries of transcription units de novo using a two state hidden-Markov model (HMM). A systematic comparison of the performance between groHMM and two existing peak-calling methods tuned to identify broad regions (SICER and HOMER) favorably supports our approach on existing GRO-seq data from MCF-7 breast cancer cells. To demonstrate the broader utility of our approach, we have used groHMM to annotate a diverse array of transcription units (i.e., primary transcripts) from four GRO-seq data sets derived from cells representing a variety of different human tissue types, including non-transformed cells (cardiomyocytes and lung fibroblasts) and transformed cells (LNCaP and MCF-7 cancer cells), as well as non-mammalian cells (from flies and worms). As an example of the utility of groHMM and its application to questions about the transcriptome, we show how groHMM can be used to analyze cell type-specific enhancers as defined by newly annotated enhancer transcripts. Our results show that groHMM can reveal new insights into cell type-specific transcription by identifying novel transcription units, and serve as a complete and useful tool for evaluating functional genomic elements in cells.

  10. Vascular Targeting of Nanocarriers: Perplexing Aspects of the Seemingly Straightforward Paradigm

    PubMed Central

    2015-01-01

    Targeted nanomedicine holds promise to find clinical use in many medical areas. Endothelial cells that line the luminal surface of blood vessels represent a key target for treatment of inflammation, ischemia, thrombosis, stroke, and other neurological, cardiovascular, pulmonary, and oncological conditions. In other cases, the endothelium is a barrier for tissue penetration or a victim of adverse effects. Several endothelial surface markers including peptidases (e.g., ACE, APP, and APN) and adhesion molecules (e.g., ICAM-1 and PECAM) have been identified as key targets. Binding of nanocarriers to these molecules enables drug targeting and subsequent penetration into or across the endothelium, offering therapeutic effects that are unattainable by their nontargeted counterparts. We analyze diverse aspects of endothelial nanomedicine including (i) circulation and targeting of carriers with diverse geometries, (ii) multivalent interactions of carrier with endothelium, (iii) anchoring to multiple determinants, (iv) accessibility of binding sites and cellular response to their engagement, (v) role of cell phenotype and microenvironment in targeting, (vi) optimization of targeting by lowering carrier avidity, (vii) endocytosis of multivalent carriers via molecules not implicated in internalization of their ligands, and (viii) modulation of cellular uptake and trafficking by selection of specific epitopes on the target determinant, carrier geometry, and hydrodynamic factors. Refinement of these aspects and improving our understanding of vascular biology and pathology is likely to enable the clinical translation of vascular endothelial targeting of nanocarriers. PMID:24787360

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

    PubMed Central

    Boldt, Karsten; van Reeuwijk, Jeroen; Lu, Qianhao; Koutroumpas, Konstantinos; Nguyen, Thanh-Minh T.; Texier, Yves; van Beersum, Sylvia E. C.; Horn, Nicola; Willer, Jason R.; Mans, Dorus A.; Dougherty, Gerard; Lamers, Ideke J. C.; Coene, Karlien L. M.; Arts, Heleen H.; Betts, Matthew J.; Beyer, Tina; Bolat, Emine; Gloeckner, Christian Johannes; Haidari, Khatera; Hetterschijt, Lisette; Iaconis, Daniela; Jenkins, Dagan; Klose, Franziska; Knapp, Barbara; Latour, Brooke; Letteboer, Stef J. F.; Marcelis, Carlo L.; Mitic, Dragana; Morleo, Manuela; Oud, Machteld M.; Riemersma, Moniek; Rix, Susan; Terhal, Paulien A.; Toedt, Grischa; van Dam, Teunis J. P.; de Vrieze, Erik; Wissinger, Yasmin; Wu, Ka Man; Apic, Gordana; Beales, Philip L.; Blacque, Oliver E.; Gibson, Toby J.; Huynen, Martijn A.; Katsanis, Nicholas; Kremer, Hannie; Omran, Heymut; van Wijk, Erwin; Wolfrum, Uwe; Kepes, François; Davis, Erica E.; Franco, Brunella; Giles, Rachel H.; Ueffing, Marius; Russell, Robert B.; Roepman, Ronald; Al-Turki, Saeed; Anderson, Carl; Antony, Dinu; Barroso, Inês; Bentham, Jamie; Bhattacharya, Shoumo; Carss, Keren; Chatterjee, Krishna; Cirak, Sebahattin; Cosgrove, Catherine; Danecek, Petr; Durbin, Richard; Fitzpatrick, David; Floyd, Jamie; Reghan Foley, A.; Franklin, Chris; Futema, Marta; Humphries, Steve E.; Hurles, Matt; Joyce, Chris; McCarthy, Shane; Mitchison, Hannah M.; Muddyman, Dawn; Muntoni, Francesco; O'Rahilly, Stephen; Onoufriadis, Alexandros; Payne, Felicity; Plagnol, Vincent; Raymond, Lucy; Savage, David B.; Scambler, Peter; Schmidts, Miriam; Schoenmakers, Nadia; Semple, Robert; Serra, Eva; Stalker, Jim; van Kogelenberg, Margriet; Vijayarangakannan, Parthiban; Walter, Klaudia; Whittall, Ros; Williamson, Kathy

    2016-01-01

    Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub-complexes in exocyst and intraflagellar transport complexes, which we validate biochemically, and by probing structurally predicted, disruptive, genetic variants from ciliary disease patients. The landscape suggests other genetic diseases could be ciliary including 3M syndrome. We show that 3M genes are involved in ciliogenesis, and that patient fibroblasts lack cilia. Overall, this organelle-specific targeting strategy shows considerable promise for Systems Medicine. PMID:27173435

  12. Acetobixan, an Inhibitor of Cellulose Synthesis Identified by Microbial Bioprospecting

    PubMed Central

    Xia, Ye; Lei, Lei; Brabham, Chad; Stork, Jozsef; Strickland, James; Ladak, Adam; Gu, Ying; Wallace, Ian; DeBolt, Seth

    2014-01-01

    In plants, cellulose biosynthesis is an essential process for anisotropic growth and therefore is an ideal target for inhibition. Based on the documented utility of small-molecule inhibitors to dissect complex cellular processes we identified a cellulose biosynthesis inhibitor (CBI), named acetobixan, by bio-prospecting among compounds secreted by endophytic microorganisms. Acetobixan was identified using a drug-gene interaction screen to sift through hundreds of endophytic microbial secretions for one that caused synergistic reduction in root expansion of the leaky AtcesA6prc1-1 mutant. We then mined this microbial secretion for compounds that were differentially abundant compared with Bacilli that failed to mimic CBI action to isolate a lead pharmacophore. Analogs of this lead compound were screened for CBI activity, and the most potent analog was named acetobixan. In living Arabidopsis cells visualized by confocal microscopy, acetobixan treatment caused CESA particles localized at the plasma membrane (PM) to rapidly re-localize to cytoplasmic vesicles. Acetobixan inhibited 14C-Glc uptake into crystalline cellulose. Moreover, cortical microtubule dynamics were not disrupted by acetobixan, suggesting specific activity towards cellulose synthesis. Previous CBI resistant mutants such as ixr1-2, ixr2-1 or aegeus were not cross resistant to acetobixan indicating that acetobixan targets a different aspect of cellulose biosynthesis. PMID:24748166

  13. A Solar Aspect System for the HEROES Mission

    NASA Technical Reports Server (NTRS)

    Christe, Steven; Shih, Albert; Rodriguez, Marcello; Gregory, Kyle; Cramer, Alexander; Edgerton, Melissa; Gaskin, Jessica; O'Connor, Brian; Sobey, Alexander

    2014-01-01

    A new Solar Aspect System (SAS) has been developed to provide the ability to observe the Sun on an existing balloon payload HERO (short for High Energy Replicated Optics). Developed under the HEROES program (High Energy Replicated Optics to Explore the Sun), the SAS aspect system provides solar pointing knowledge in pitch, yaw, and roll. The required precision of these measurements must be better than the HEROES X-ray resolution of approximately 20 arcsec Full Width at Half Maximum (FWHM) so as to not degrade the image resolution. The SAS consists of two separate systems: the Pitch-Yaw Aspect System (PYAS) and the Roll Aspect System (RAS). The PYAS functions by projecting an image of the Sun onto a screen with precision fiducials. A CCD camera takes an image of these fiducials, and an automated algorithm determines the location of the Sun as well as the location of the fiducials. The spacing between fiducials is unique and allows each to be identified so that the location of the Sun on the screen can be precisely determined. The RAS functions by imaging the Earth's horizon in opposite directions using a silvered prism imaged by a CCD camera. The design and first results of the performance of these systems during the HEROES flight which occurred in September 2013 are presented here.

  14. The Multidimensional Aspects of Sleep Spindles and Their Relationship to Word-Pair Memory Consolidation.

    PubMed

    Lustenberger, Caroline; Wehrle, Flavia; Tüshaus, Laura; Achermann, Peter; Huber, Reto

    2015-07-01

    Several studies proposed a link between sleep spindles and sleep dependent memory consolidation in declarative learning tasks. In addition to these state-like aspects of sleep spindles, they have also trait-like characteristics, i.e., were related to general cognitive performance, an important distinction that has often been neglected in correlative studies. Furthermore, from the multitude of different sleep spindle measures, often just one specific aspect was analyzed. Thus, we aimed at taking multidimensional aspects of sleep spindles into account when exploring their relationship to word-pair memory consolidation. Each subject underwent 2 study nights with all-night high-density electroencephalographic (EEG) recordings. Sleep spindles were automatically detected in all EEG channels. Subjects were trained and tested on a word-pair learning task in the evening, and retested in the morning to assess sleep related memory consolidation (overnight retention). Trait-like aspects refer to the mean of both nights and state-like aspects were calculated as the difference between night 1 and night 2. Sleep laboratory. Twenty healthy male subjects (age: 23.3 ± 2.1 y). Overnight retention was negatively correlated with trait-like aspects of fast sleep spindle density and positively with slow spindle density on a global level. In contrast, state-like aspects were observed for integrated slow spindle activity, which was positively related to the differences in overnight retention in specific regions. Our results demonstrate the importance of a multidimensional approach when investigating the relationship between sleep spindles and memory consolidation and thereby provide a more complete picture explaining divergent findings in the literature. © 2015 Associated Professional Sleep Societies, LLC.

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

    ERIC Educational Resources Information Center

    Goldsmith, Ronald E.

    2001-01-01

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

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

    ERIC Educational Resources Information Center

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

    2016-01-01

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

  17. Structural analyses to identify selective inhibitors of glyceraldehyde 3-phosphate dehydrogenase-S, a sperm-specific glycolytic enzyme

    PubMed Central

    Danshina, Polina V.; Qu, Weidong; Temple, Brenda R.; Rojas, Rafael J.; Miley, Michael J.; Machius, Mischa; Betts, Laurie; O'Brien, Deborah A.

    2016-01-01

    STUDY HYPOTHESIS Detailed structural comparisons of sperm-specific glyceraldehyde 3-phosphate dehydrogenase, spermatogenic (GAPDHS) and the somatic glyceraldehyde 3-phosphate dehydrogenase (GAPDH) isozyme should facilitate the identification of selective GAPDHS inhibitors for contraceptive development. STUDY FINDING This study identified a small-molecule GAPDHS inhibitor with micromolar potency and >10-fold selectivity that exerts the expected inhibitory effects on sperm glycolysis and motility. WHAT IS KNOWN ALREADY Glycolytic ATP production is required for sperm motility and male fertility in many mammalian species. Selective inhibition of GAPDHS, one of the glycolytic isozymes with restricted expression during spermatogenesis, is a potential strategy for the development of a non-hormonal contraceptive that directly blocks sperm function. STUDY DESIGN, SAMPLES/MATERIALS, METHODS Homology modeling and x-ray crystallography were used to identify structural features that are conserved in GAPDHS orthologs in mouse and human sperm, but distinct from the GAPDH orthologs present in somatic tissues. We identified three binding pockets surrounding the substrate and cofactor in these isozymes and conducted a virtual screen to identify small-molecule compounds predicted to bind more tightly to GAPDHS than to GAPDH. Following the production of recombinant human and mouse GAPDHS, candidate compounds were tested in dose–response enzyme assays to identify inhibitors that blocked the activity of GAPDHS more effectively than GAPDH. The effects of a selective inhibitor on the motility of mouse and human sperm were monitored by computer-assisted sperm analysis, and sperm lactate production was measured to assess inhibition of glycolysis in the target cell. MAIN RESULTS AND THE ROLE OF CHANCE Our studies produced the first apoenzyme crystal structures for human and mouse GAPDHS and a 1.73 Å crystal structure for NAD+-bound human GAPDHS, facilitating the identification of unique

  18. Organisational aspects of dental practices: do dental students think like patients or like general dental practitioners?

    PubMed

    Sonneveld, R E; Brands, W G; Bronkhorst, E M; Welie, J V M; Truin, G J

    2013-02-01

    In view of transparency in health care, the widespread desire for more patient-centred care, and in an attempt to facilitate educational programmes that effectively respond to these changes, two research questions are formulated: (i) How do dental students rate the importance of various organisational aspects of dental practices compared with dental patients and general dental practitioners (GDPs), and what prescripts, defined as specific operational responsibilities of GDPs in these matters, do dental students propose? and (ii) In doing so, do students resemble patients or GDPs? In two survey studies, dental students (n = 198), patients (n = 3127) and GDPs (n = 303) were asked to rate by questionnaire the importance of 41 organisational aspects of a general dental practice and proposed specific operational responsibilities ('prescripts'). Seven of 41 aspects were rated as important by the majority of the students. Although in a different rank order, three aspects were predominantly selected by all three groups: continuing education, accessibility by telephone and Dutch-speaking GDP. For most aspects, significant differences were found between the prescripts proposed by students and those proposed by patients, and few differences were found between students and GDPs. The findings do not permit the general conclusion that the views of dental students resemble those of patients or GPDs. Looking at the overall rank order, the three respondent groups showed a great resemblance although significant differences were found for specific aspects. With regard to the proposed prescripts, students showed realistic views and the majority wants to participate in continuing education and work with protocols and guidelines. In this, they tend to resemble GDPs more than they resemble patients. © 2012 John Wiley & Sons A/S.

  19. Triple-aspect monism: physiological, mental unconscious and conscious aspects of brain activity.

    PubMed

    Pereira, Alfredo

    2014-06-01

    Brain activity contains three fundamental aspects: (a) The physiological aspect, covering all kinds of processes that involve matter and/or energy; (b) the mental unconscious aspect, consisting of dynamical patterns (i.e., frequency, amplitude and phase-modulated waves) embodied in neural activity. These patterns are variously operated (transmitted, stored, combined, matched, amplified, erased, etc), forming cognitive and emotional unconscious processes and (c) the mental conscious aspect, consisting of feelings experienced in the first-person perspective and cognitive functions grounded in feelings, as memory formation, selection of the focus of attention, voluntary behavior, aesthetical appraisal and ethical judgment. Triple-aspect monism (TAM) is a philosophical theory that provides a model of the relation of the three aspects. Spatially distributed neuronal dendritic potentials generate amplitude-modulated waveforms transmitted to the extracellular medium and adjacent astrocytes, prompting the formation of large waves in the astrocyte network, which are claimed to both integrate distributed information and instantiate feelings. According to the valence of the feeling, the large wave feeds back on neuronal synapses, modulating (reinforcing or depressing) cognitive and behavioral functions.

  20. Interactive Book Reading to Accelerate Word Learning by Kindergarten Children with Specific Language Impairment: Identifying an Adequate Intensity and Variation in Treatment Response

    ERIC Educational Resources Information Center

    Storkel, Holly L.; Voelmle, Krista; Fierro, Veronica; Flake, Kelsey; Fleming, Kandace K.; Romine, Rebecca Swinburne

    2017-01-01

    Purpose: This study sought to identify an adequate intensity of interactive book reading for new word learning by children with specific language impairment (SLI) and to examine variability in treatment response. Method: An escalation design adapted from nontoxic drug trials (Hunsberger, Rubinstein, Dancey, & Korn, 2005) was used in this Phase…

  1. Medical and psychological aspects of irritable bowel syndrome.

    PubMed

    Kim, E C; Dundon, M

    1998-01-01

    Irritable bowel syndrome is a disease process commonly encountered by primary care providers. Although the cause of this illness is unknown, much is known about the pathophysiology and strong psychosocial influences. Medical practitioners often are aware of the medical aspects of managing irritable bowel syndrome but are not familiar with specific psychologic options. Long-term care of these patients may be aided by collaboration with mental health professionals.

  2. Non-coding cancer driver candidates identified with a sample- and position-specific model of the somatic mutation rate

    PubMed Central

    Juul, Malene; Bertl, Johanna; Guo, Qianyun; Nielsen, Morten Muhlig; Świtnicki, Michał; Hornshøj, Henrik; Madsen, Tobias; Hobolth, Asger; Pedersen, Jakob Skou

    2017-01-01

    Non-coding mutations may drive cancer development. Statistical detection of non-coding driver regions is challenged by a varying mutation rate and uncertainty of functional impact. Here, we develop a statistically founded non-coding driver-detection method, ncdDetect, which includes sample-specific mutational signatures, long-range mutation rate variation, and position-specific impact measures. Using ncdDetect, we screened non-coding regulatory regions of protein-coding genes across a pan-cancer set of whole-genomes (n = 505), which top-ranked known drivers and identified new candidates. For individual candidates, presence of non-coding mutations associates with altered expression or decreased patient survival across an independent pan-cancer sample set (n = 5454). This includes an antigen-presenting gene (CD1A), where 5’UTR mutations correlate significantly with decreased survival in melanoma. Additionally, mutations in a base-excision-repair gene (SMUG1) correlate with a C-to-T mutational-signature. Overall, we find that a rich model of mutational heterogeneity facilitates non-coding driver identification and integrative analysis points to candidates of potential clinical relevance. DOI: http://dx.doi.org/10.7554/eLife.21778.001 PMID:28362259

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

    PubMed

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

    2000-01-01

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

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

    ERIC Educational Resources Information Center

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

    2016-01-01

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

  5. Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci

    PubMed Central

    Zubair, Niha; Luis Ambite, Jose; Bush, William S.; Kichaev, Gleb; Lu, Yingchang; Manichaikul, Ani; Sheu, Wayne H-H.; Absher, Devin; Assimes, Themistocles L.; Bielinski, Suzette J.; Bottinger, Erwin P.; Buzkova, Petra; Chuang, Lee-Ming; Chung, Ren-Hua; Cochran, Barbara; Dumitrescu, Logan; Gottesman, Omri; Haessler, Jeffrey W.; Haiman, Christopher; Heiss, Gerardo; Hsiung, Chao A.; Hung, Yi-Jen; Hwu, Chii-Min; Juang, Jyh-Ming J.; Le Marchand, Loic; Lee, I-Te; Lee, Wen-Jane; Lin, Li-An; Lin, Danyu; Lin, Shih-Yi; Mackey, Rachel H.; Martin, Lisa W.; Pasaniuc, Bogdan; Peters, Ulrike; Predazzi, Irene; Quertermous, Thomas; Reiner, Alex P.; Robinson, Jennifer; Rotter, Jerome I.; Ryckman, Kelli K.; Schreiner, Pamela J.; Stahl, Eli; Tao, Ran; Tsai, Michael Y.; Waite, Lindsay L.; Wang, Tzung-Dau; Buyske, Steven; Ida Chen, Yii-Der; Cheng, Iona; Crawford, Dana C.; Loos, Ruth J.F.; Rich, Stephen S.; Fornage, Myriam; North, Kari E.; Kooperberg, Charles; Carty, Cara L.

    2016-01-01

    Abstract Genome-wide association studies have identified over 150 loci associated with lipid traits, however, no large-scale studies exist for Hispanics and other minority populations. Additionally, the genetic architecture of lipid-influencing loci remains largely unknown. We performed one of the most racially/ethnically diverse fine-mapping genetic studies of HDL-C, LDL-C, and triglycerides to-date using SNPs on the MetaboChip array on 54,119 individuals: 21,304 African Americans, 19,829 Hispanic Americans, 12,456 Asians, and 530 American Indians. The majority of signals found in these groups generalize to European Americans. While we uncovered signals unique to racial/ethnic populations, we also observed systematically consistent lipid associations across these groups. In African Americans, we identified three novel signals associated with HDL-C (LPL, APOA5, LCAT) and two associated with LDL-C (ABCG8, DHODH). In addition, using this population, we refined the location for 16 out of the 58 known MetaboChip lipid loci. These results can guide tailored screening efforts, reveal population-specific responses to lipid-lowering medications, and aid in the development of new targeted drug therapies. PMID:28426890

  6. Formal Specification of Information Systems Requirements.

    ERIC Educational Resources Information Center

    Kampfner, Roberto R.

    1985-01-01

    Presents a formal model for specification of logical requirements of computer-based information systems that incorporates structural and dynamic aspects based on two separate models: the Logical Information Processing Structure and the Logical Information Processing Network. The model's role in systems development is discussed. (MBR)

  7. Initial Performance of the Aspect System on the Chandra Observatory: Post-Facto Aspect Reconstruction

    NASA Technical Reports Server (NTRS)

    Aldcroft, T.; Karovska, M.; Cresitello-Dittmar, M.; Cameron, R.

    2000-01-01

    The aspect system of the Chandra Observatory plays a key role in realizing the full potential of Chandra's x-ray optics and detectors. To achieve the highest spatial and spectral resolution (for grating observations), an accurate post-facto time history of the spacecraft attitude and internal alignment is needed. The CXC has developed a suite of tools which process sensor data from the aspect camera assembly and gyroscopes, and produce the spacecraft aspect solution. In this poster, the design of the aspect pipeline software is briefly described, followed by details of aspect system performance during the first eight months of flight. The two key metrics of aspect performance are: image reconstruction accuracy, which measures the x-ray image blurring introduced by aspect; and celestial location, which is the accuracy of detected source positions in absolute sky coordinates.

  8. Identifying specific cues and contexts related to smoking craving for the development of effective virtual environments.

    PubMed

    García-Rodríguez, Olaya; Ferrer-García, Marta; Pericot-Valverde, Irene; Gutiérrez-Maldonado, José; Secades-Villa, Roberto; Carballo, José L

    2011-03-01

    Craving is considered the main variable associated with relapse after smoking cessation. Cue Exposure Therapy (CET) consists of controlled and repeated exposure to drug-related cues with the aim of extinguishing craving responses. Some virtual reality (VR) environments, such as virtual bars or parties, have previously shown their efficacy as tools for eliciting smoking craving. However, in order to adapt this technology to smoking cessation interventions, there is a need for more diverse environments that enhance the probability of generalization of extinction in real life. The main objective of this study was to identify frequent situations that produce smoking craving, as well as detecting specific craving cues in those contexts. Participants were 154 smokers who responded to an ad hoc self-administered inventory for assessing craving level in 12 different situations. Results showed that having a drink in a bar/pub at night, after having lunch/dinner in a restaurant and having a coffee in a cafe or after lunch/dinner at home were reported as the most craving-inducing scenarios. Some differences were found with regard to participants' gender, age, and number of cigarettes smoked per day. Females, younger people, and heavier smokers reported higher levels of craving in most situations. In general, the most widely cited specific cues across the contexts were people smoking, having a coffee, being with friends, and having finished eating. These results are discussed with a view to their consideration in the design of valid and reliable VR environments that could be used in the treatment of nicotine addicts who wish to give up smoking.

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

    PubMed

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

    2014-01-01

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

  10. Grammatical verb aspect and event roles in sentence processing.

    PubMed

    Madden-Lombardi, Carol; Dominey, Peter Ford; Ventre-Dominey, Jocelyne

    2017-01-01

    , showing how verb aspect drives not only the temporal structure of event representation, but also the focus on specific roles of the event. More generally, the findings of visual match during online sentence-picture processing are consistent with theories of perceptual simulation.

  11. Grammatical verb aspect and event roles in sentence processing

    PubMed Central

    Madden-Lombardi, Carol; Dominey, Peter Ford; Ventre-Dominey, Jocelyne

    2017-01-01

    , showing how verb aspect drives not only the temporal structure of event representation, but also the focus on specific roles of the event. More generally, the findings of visual match during online sentence-picture processing are consistent with theories of perceptual simulation. PMID:29287091

  12. What Aspects of Face Processing Are Impaired in Developmental Prosopagnosia?

    ERIC Educational Resources Information Center

    Le Grand, Richard; Cooper, Philip A.; Mondloch, Catherine J.; Lewis, Terri L.; Sagiv, Noam; de Gelder, Beatrice; Maurer, Daphne

    2006-01-01

    Developmental prosopagnosia (DP) is a severe impairment in identifying faces that is present from early in life and that occurs despite no apparent brain damage and intact visual and intellectual function. Here, we investigated what aspects of face processing are impaired/spared in developmental prosopagnosia by examining a relatively large group…

  13. Intrauterine Growth Restriction: Antenatal and Postnatal Aspects

    PubMed Central

    Sharma, Deepak; Shastri, Sweta; Sharma, Pradeep

    2016-01-01

    Intrauterine growth restriction (IUGR), a condition that occurs due to various reasons, is an important cause of fetal and neonatal morbidity and mortality. It has been defined as a rate of fetal growth that is less than normal in light of the growth potential of that specific infant. Usually, IUGR and small for gestational age (SGA) are used interchangeably in literature, even though there exist minute differences between them. SGA has been defined as having birth weight less than two standard deviations below the mean or less than the 10th percentile of a population-specific birth weight for specific gestational age. These infants have many acute neonatal problems that include perinatal asphyxia, hypothermia, hypoglycemia, and polycythemia. The likely long-term complications that are prone to develop when IUGR infants grow up includes growth retardation, major and subtle neurodevelopmental handicaps, and developmental origin of health and disease. In this review, we have covered various antenatal and postnatal aspects of IUGR. PMID:27441006

  14. Modeling and Composing Scenario-Based Requirements with Aspects

    NASA Technical Reports Server (NTRS)

    Araujo, Joao; Whittle, Jon; Ki, Dae-Kyoo

    2004-01-01

    There has been significant recent interest, within the Aspect-Oriented Software Development (AOSD) community, in representing crosscutting concerns at various stages of the software lifecycle. However, most of these efforts have concentrated on the design and implementation phases. We focus in this paper on representing aspects during use case modeling. In particular, we focus on scenario-based requirements and show how to compose aspectual and non-aspectual scenarios so that they can be simulated as a whole. Non-aspectual scenarios are modeled as UML sequence diagram. Aspectual scenarios are modeled as Interaction Pattern Specifications (IPS). In order to simulate them, the scenarios are transformed into a set of executable state machines using an existing state machine synthesis algorithm. Previous work composed aspectual and non-aspectual scenarios at the sequence diagram level. In this paper, the composition is done at the state machine level.

  15. Examples of testing global identifiability of biological and biomedical models with the DAISY software.

    PubMed

    Saccomani, Maria Pia; Audoly, Stefania; Bellu, Giuseppina; D'Angiò, Leontina

    2010-04-01

    DAISY (Differential Algebra for Identifiability of SYstems) is a recently developed computer algebra software tool which can be used to automatically check global identifiability of (linear and) nonlinear dynamic models described by differential equations involving polynomial or rational functions. Global identifiability is a fundamental prerequisite for model identification which is important not only for biological or medical systems but also for many physical and engineering systems derived from first principles. Lack of identifiability implies that the parameter estimation techniques may not fail but any obtained numerical estimates will be meaningless. The software does not require understanding of the underlying mathematical principles and can be used by researchers in applied fields with a minimum of mathematical background. We illustrate the DAISY software by checking the a priori global identifiability of two benchmark nonlinear models taken from the literature. The analysis of these two examples includes comparison with other methods and demonstrates how identifiability analysis is simplified by this tool. Thus we illustrate the identifiability analysis of other two examples, by including discussion of some specific aspects related to the role of observability and knowledge of initial conditions in testing identifiability and to the computational complexity of the software. The main focus of this paper is not on the description of the mathematical background of the algorithm, which has been presented elsewhere, but on illustrating its use and on some of its more interesting features. DAISY is available on the web site http://www.dei.unipd.it/ approximately pia/. 2010 Elsevier Ltd. All rights reserved.

  16. Global Aspects of Charged Particle Motion in Axially Symmetric Multipole Magnetic Fields

    NASA Technical Reports Server (NTRS)

    Shebalin, John V.

    2003-01-01

    The motion of a single charged particle in the space outside of a compact region of steady currents is investigated. The charged particle is assumed to produce negligible electromagnetic radiation, so that its energy is conserved. The source of the magnetic field is represented as a point multipole. After a general description, attention is focused on magnetic fields with axial symmetry. Lagrangian dynamical theory is utilized to identify constants of the motion as well as the equations of motion themselves. The qualitative method of Stonner is used to examine charged particle motion in axisymmetric multipole fields of all orders. Although the equations of motion generally have no analytical solutions and must be integrated numerically to produce a specific orbit, a topological examination of dynamics is possible, and can be used, d la Stonner, to completely describe the global aspects of the motion of a single charged particle in a space with an axisymmetric multipole magnetic field.

  17. Mechanical and Assembly Units of Viral Capsids Identified via Quasi-Rigid Domain Decomposition

    PubMed Central

    Polles, Guido; Indelicato, Giuliana; Potestio, Raffaello; Cermelli, Paolo; Twarock, Reidun; Micheletti, Cristian

    2013-01-01

    Key steps in a viral life-cycle, such as self-assembly of a protective protein container or in some cases also subsequent maturation events, are governed by the interplay of physico-chemical mechanisms involving various spatial and temporal scales. These salient aspects of a viral life cycle are hence well described and rationalised from a mesoscopic perspective. Accordingly, various experimental and computational efforts have been directed towards identifying the fundamental building blocks that are instrumental for the mechanical response, or constitute the assembly units, of a few specific viral shells. Motivated by these earlier studies we introduce and apply a general and efficient computational scheme for identifying the stable domains of a given viral capsid. The method is based on elastic network models and quasi-rigid domain decomposition. It is first applied to a heterogeneous set of well-characterized viruses (CCMV, MS2, STNV, STMV) for which the known mechanical or assembly domains are correctly identified. The validated method is next applied to other viral particles such as L-A, Pariacoto and polyoma viruses, whose fundamental functional domains are still unknown or debated and for which we formulate verifiable predictions. The numerical code implementing the domain decomposition strategy is made freely available. PMID:24244139

  18. Allele specific expression analysis identifies regulatory variation associated with stress-related genes in the Mexican highland maize landrace Palomero Toluqueño

    PubMed Central

    González-Segovia, Eric; Ross-Ibarra, Jeffrey; Simpson, June K.

    2017-01-01

    Background Gene regulatory variation has been proposed to play an important role in the adaptation of plants to environmental stress. In the central highlands of Mexico, farmer selection has generated a unique group of maize landraces adapted to the challenges of the highland niche. In this study, gene expression in Mexican highland maize and a reference maize breeding line were compared to identify evidence of regulatory variation in stress-related genes. It was hypothesised that local adaptation in Mexican highland maize would be associated with a transcriptional signature observable even under benign conditions. Methods Allele specific expression analysis was performed using the seedling-leaf transcriptome of an F1 individual generated from the cross between the highland adapted Mexican landrace Palomero Toluqueño and the reference line B73, grown under benign conditions. Results were compared with a published dataset describing the transcriptional response of B73 seedlings to cold, heat, salt and UV treatments. Results A total of 2,386 genes were identified to show allele specific expression. Of these, 277 showed an expression difference between Palomero Toluqueño and B73 alleles under benign conditions that anticipated the response of B73 cold, heat, salt and/or UV treatments, and, as such, were considered to display a prior stress response. Prior stress response candidates included genes associated with plant hormone signaling and a number of transcription factors. Construction of a gene co-expression network revealed further signaling and stress-related genes to be among the potential targets of the transcription factors candidates. Discussion Prior activation of responses may represent the best strategy when stresses are severe but predictable. Expression differences observed here between Palomero Toluqueño and B73 alleles indicate the presence of cis-acting regulatory variation linked to stress-related genes in Palomero Toluqueño. Considered alongside

  19. Identifying Aspects of Parental Involvement that Affect the Academic Achievement of High School Students

    ERIC Educational Resources Information Center

    Roulette-McIntyre, Ovella; Bagaka's, Joshua G.; Drake, Daniel D.

    2005-01-01

    This study identified parental practices that relate positively to high school students' academic performance. Parents of 643 high school students participated in the study. Data analysis, using a multiple linear regression model, shows parent-school connection, student gender, and race are significant predictors of student academic performance.…

  20. Introspection of subjective feelings is sensitive and specific.

    PubMed

    Questienne, Laurence; van Dijck, Jean-Philippe; Gevers, Wim

    2018-02-01

    Conversely to behaviorist ideas, recent studies suggest that introspection can be accurate and reliable. However, an unresolved question is whether people are able to report specific aspects of their phenomenal experience, or whether they report more general nonspecific experiences. To address this question, we investigated the sensitivity and validity of our introspection for different types of conflict. Taking advantage of the congruency sequence effect, we dissociated response conflict while keeping visual conflict unchanged in a Stroop and in a priming task. Participants were subsequently asked to report on either their experience of urge to err or on their feeling of visual conflict. Depending on the focus of the introspection, subjective reports specifically followed either the response conflict or the visual conflict. These results demonstrate that our introspective reports can be sensitive and that we are able to dissociate specific aspects of our phenomenal experiences in a valid manner. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  1. Whole transcriptome profiling of patient-derived xenograft models as a tool to identify both tumor and stromal specific biomarkers.

    PubMed

    Bradford, James R; Wappett, Mark; Beran, Garry; Logie, Armelle; Delpuech, Oona; Brown, Henry; Boros, Joanna; Camp, Nicola J; McEwen, Robert; Mazzola, Anne Marie; D'Cruz, Celina; Barry, Simon T

    2016-04-12

    The tumor microenvironment is emerging as a key regulator of cancer growth and progression, however the exact mechanisms of interaction with the tumor are poorly understood. Whilst the majority of genomic profiling efforts thus far have focused on the tumor, here we investigate RNA-Seq as a hypothesis-free tool to generate independent tumor and stromal biomarkers, and explore tumor-stroma interactions by exploiting the human-murine compartment specificity of patient-derived xenografts (PDX).Across a pan-cancer cohort of 79 PDX models, we determine that mouse stroma can be separated into distinct clusters, each corresponding to a specific stromal cell type. This implies heterogeneous recruitment of mouse stroma to the xenograft independent of tumor type. We then generate cross-species expression networks to recapitulate a known association between tumor epithelial cells and fibroblast activation, and propose a potentially novel relationship between two hypoxia-associated genes, human MIF and mouse Ddx6. Assessment of disease subtype also reveals MMP12 as a putative stromal marker of triple-negative breast cancer. Finally, we establish that our ability to dissect recruited stroma from trans-differentiated tumor cells is crucial to identifying stem-like poor-prognosis signatures in the tumor compartment.In conclusion, RNA-Seq is a powerful, cost-effective solution to global analysis of human tumor and mouse stroma simultaneously, providing new insights into mouse stromal heterogeneity and compartment-specific disease markers that are otherwise overlooked by alternative technologies. The study represents the first comprehensive analysis of its kind across multiple PDX models, and supports adoption of the approach in pre-clinical drug efficacy studies, and compartment-specific biomarker discovery.

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

    PubMed

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

    2014-07-01

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

  3. Microarray Detection Call Methodology as a Means to Identify and Compare Transcripts Expressed within Syncytial Cells from Soybean (Glycine max) Roots Undergoing Resistant and Susceptible Reactions to the Soybean Cyst Nematode (Heterodera glycines)

    PubMed Central

    Klink, Vincent P.; Overall, Christopher C.; Alkharouf, Nadim W.; MacDonald, Margaret H.; Matthews, Benjamin F.

    2010-01-01

    Background. A comparative microarray investigation was done using detection call methodology (DCM) and differential expression analyses. The goal was to identify genes found in specific cell populations that were eliminated by differential expression analysis due to the nature of differential expression methods. Laser capture microdissection (LCM) was used to isolate nearly homogeneous populations of plant root cells. Results. The analyses identified the presence of 13,291 transcripts between the 4 different sample types. The transcripts filtered down into a total of 6,267 that were detected as being present in one or more sample types. A comparative analysis of DCM and differential expression methods showed a group of genes that were not differentially expressed, but were expressed at detectable amounts within specific cell types. Conclusion. The DCM has identified patterns of gene expression not shown by differential expression analyses. DCM has identified genes that are possibly cell-type specific and/or involved in important aspects of plant nematode interactions during the resistance response, revealing the uniqueness of a particular cell population at a particular point during its differentiation process. PMID:20508855

  4. Allele-specific gene expression in a wild nonhuman primate population

    PubMed Central

    Tung, J.; Akinyi, M. Y.; Mutura, S.; Altmann, J.; Wray, G. A.; Alberts, S. C.

    2015-01-01

    Natural populations hold enormous potential for evolutionary genetic studies, especially when phenotypic, genetic and environmental data are all available on the same individuals. However, untangling the genotype-phenotype relationship in natural populations remains a major challenge. Here, we describe results of an investigation of one class of phenotype, allele-specific gene expression (ASGE), in the well-studied natural population of baboons of the Amboseli basin, Kenya. ASGE measurements identify cases in which one allele of a gene is overexpressed relative to the alternative allele of the same gene, within individuals, thus providing a control for background genetic and environmental effects. Here, we characterize the incidence of ASGE in the Amboseli baboon population, focusing on the genetic and environmental contributions to ASGE in a set of eleven genes involved in immunity and defence. Within this set, we identify evidence for common ASGE in four genes. We also present examples of two relationships between cis-regulatory genetic variants and the ASGE phenotype. Finally, we identify one case in which this relationship is influenced by a novel gene-environment interaction. Specifically, the dominance rank of an individual’s mother during its early life (an aspect of that individual’s social environment) influences the expression of the gene CCL5 via an interaction with cis-regulatory genetic variation. These results illustrate how environmental and ecological data can be integrated into evolutionary genetic studies of functional variation in natural populations. They also highlight the potential importance of early life environmental variation in shaping the genetic architecture of complex traits in wild mammals. PMID:21226779

  5. ICT and the future of health care: aspects of health promotion.

    PubMed

    Haluza, Daniela; Jungwirth, David

    2015-01-01

    Increasingly, Information and Communication Technology (ICT) applications enter the daily lives of consumers. Availability of various multimedia interfaces offers the opportunity to develop and adjust ICT solutions to all aspects of society including health care. To address the challenges of the ongoing adaptive progress of ICT, decision makers profit from estimates of expectable merits and risks of future technological developments. The aim of the present study was to assess the prevailing opinions and expectations among Austrian stakeholders regarding ICT-assisted health promotion. In total, 73 experts (74% males) engaged in the Austrian health care sector participated in a biphasic online Delphi survey. Panellists were assigned to three groups representing medical professionals, patient advocates, and administrative personnel. In a scenario-based questionnaire, experts evaluated potential advantages and barriers as well as degree of innovation, desirability, and estimated date of implementation of six future ICT scenarios. Scenario-specific and consolidated overall opinions were ranked. Inter-group differences were assessed using ANOVA. Panellists expected the future ICT-supported health promotion strategies to especially improve the factors living standard (56%), quality of health care (53%), and patient's knowledge (44%). Nevertheless, monetary aspects (57%), acceptance by patient advocates (45%), and data security and privacy (27%) were considered as the three most substantial hampering factors for ICT applications. Although overall mean desirability of the scenarios was quite high (80%) amongst panellists, it was considerably lower in medical professionals compared to patient advocates and administrative personnel (p=0.006). This observation suggests a more precautious attitude of this specific interest group regarding technological innovations. The present Delphi survey identified issues relevant for successful implementation of ICT-based health care

  6. A hypothetical model for predicting the toxicity of high aspect ratio nanoparticles (HARN)

    NASA Astrophysics Data System (ADS)

    Tran, C. L.; Tantra, R.; Donaldson, K.; Stone, V.; Hankin, S. M.; Ross, B.; Aitken, R. J.; Jones, A. D.

    2011-12-01

    The ability to predict nanoparticle (dimensional structures which are less than 100 nm in size) toxicity through the use of a suitable model is an important goal if nanoparticles are to be regulated in terms of exposures and toxicological effects. Recently, a model to predict toxicity of nanoparticles with high aspect ratio has been put forward by a consortium of scientists. The High aspect ratio nanoparticles (HARN) model is a platform that relates the physical dimensions of HARN (specifically length and diameter ratio) and biopersistence to their toxicity in biological environments. Potentially, this model is of great public health and economic importance, as it can be used as a tool to not only predict toxicological activity but can be used to classify the toxicity of various fibrous nanoparticles, without the need to carry out time-consuming and expensive toxicology studies. However, this model of toxicity is currently hypothetical in nature and is based solely on drawing similarities in its dimensional geometry with that of asbestos and synthetic vitreous fibres. The aim of this review is two-fold: (a) to present findings from past literature, on the physicochemical property and pathogenicity bioassay testing of HARN (b) to identify some of the challenges and future research steps crucial before the HARN model can be accepted as a predictive model. By presenting what has been done, we are able to identify scientific challenges and research directions that are needed for the HARN model to gain public acceptance. Our recommendations for future research includes the need to: (a) accurately link physicochemical data with corresponding pathogenicity assay data, through the use of suitable reference standards and standardised protocols, (b) develop better tools/techniques for physicochemical characterisation, (c) to develop better ways of monitoring HARN in the workplace, (d) to reliably measure dose exposure levels, in order to support future epidemiological

  7. Caregiver burden in Alzheimer's disease: Moderation effects of social support and mediation effects of positive aspects of caregiving.

    PubMed

    Wang, Zhixin; Ma, Caiyun; Han, Hongjuan; He, Runlian; Zhou, Liye; Liang, Ruifeng; Yu, Hongmei

    2018-06-01

    Although there are many studies on the relationship between patient-related factors and negative caregiver outcomes, the specifics of this relationship are poorly understood. We aimed to examine whether caregiver social support moderated the relationship between patient factors and negative outcomes for caregivers of community-dwelling older adults with Alzheimer's disease (AD), and whether positive aspects of caregiving mediated this relationship. We conducted a cross-sectional study of patients diagnosed with AD from 2 hospitals and 3 communities in Taiyuan, China, and their caregivers. Latent moderated structural equations and the bias-corrected percentile bootstrap method were used to estimate the parameters of moderating and mediating effects, respectively. Social support significantly moderated the effects of AD patient cognitive function (P < 0.001) and depression (P = 0.001) on caregiver burden. Positive aspects of caregiving completely mediated the association between patient depression and caregiver burden (P = 0.006), caregiver anxiety (P = 0.007), and caregiver depression (P = 0.034). The findings identify social support as a moderator and positive aspects of caregiving as a mediator of the relationship between patient-related factors and negative caregiver outcomes. The results suggest that health care providers must offer more effective social support for caregivers. In addition, prompt identification of patient and caregiver emotional states could help to improve quality of life. Copyright © 2018 John Wiley & Sons, Ltd.

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

    PubMed

    Johnston, Iain G; Williams, Ben P

    2016-02-24

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

  9. Cloning of a newly identified heart-specific troponin I isoform, which lacks the troponin T binding portion, using the yeast hybrid system.

    PubMed

    Suzuki, Hideaki; Arakawa, Yasuhiro; Ito, Masaki; Yamada, Hisashi; Horiguchi-Yamada, Junko

    2006-01-01

    To elucidate the molecular pathogenesis behind increased levels of laminin in cardiac muscle cells in cardiomyopathy by using a yeast hybrid screen. The present study reports the cloning of a newly identified heart-specific troponin I isoform, which is putatively linked to laminin. Future studies will explore the functional significance of this connection. Yeast two-hybrid screen analysis was performed using MLF1-interacting protein (amino acids 1 to 318) as bait. The human heart complementary DNA library was screened by using the yeast-mating method for overnight culture. Two final positive clones from the heart library were isolated. These two clones encoded the same protein, a short isoform of human cardiac troponin I (TnI) that lacked TnI exons 5 and 6. The TnI isoform has a heart-specific expression pattern and it shares several sequence features with human cardiac TnI; however, it lacks the troponin T binding portion. The heart-specific segment of the human cardiac TnI isoform shares several sequence features with human cardiac TnI, but it lacks the troponin T binding portion. These results suggest that the heart-specific TnI isoform may be involved in cardiac development and disease.

  10. Improved E-ELT subsystem and component specifications, thanks to M1 test facility

    NASA Astrophysics Data System (ADS)

    Dimmler, M.; Marrero, J.; Leveque, S.; Barriga, Pablo; Sedghi, B.; Kornweibel, N.

    2014-07-01

    During the last 2 years ESO has operated the "M1 Test Facility", a test stand consisting of a representative section of the E-ELT primary mirror equipped with 4 complete prototype segment subunits including sensors, actuators and control system. The purpose of the test facility is twofold: it serves to study and get familiar with component and system aspects like calibration, alignment and handling procedures and suitable control strategies on real hardware long before the primary mirror (hereafter M1) components are commissioned. Secondly, and of major benefit to the project, it offered the possibility to evaluate component and subsystem performance and interface issues in a system context in such detail, that issues could be identified early enough to feed back into the subsystem and component specifications. This considerably reduces risk and cost of the production units and allows refocusing the project team on important issues for the follow-up of the production contracts. Experiences are presented in which areas the results of the M1 Test Facility particularly helped to improve subsystem specifications and areas, where additional tests were adopted independent of the main test facility. Presented are the key experiences of the M1 Test Facility which lead to improved specifications or identified the need for additional testing outside of the M1 Test Facility.

  11. Operationalising the health aspects of sustainable diets: a review.

    PubMed

    Mertens, Elly; Van't Veer, Pieter; Hiddink, Gerrit J; Steijns, Jan Mjm; Kuijsten, Anneleen

    2017-03-01

    Shifting towards a more sustainable food consumption pattern is an important strategy to mitigate climate change. In the past decade, various studies have optimised environmentally sustainable diets using different methodological approaches. The aim of the present review was to categorise and summarise the different approaches to operationalise the health aspects of environmentally sustainable diets. Conventional keyword and reference searches were conducted in PubMed, Scopus, Web of Knowledge and CAB Abstracts. Inclusion criteria were: (i) English-language publication; (ii) published between 2005 and October 2015; (iii) dietary data collected for the diet as a whole at the national, household or individual level; (iv) comparison of the current diet with dietary scenarios; and (v) for results to consider the health aspect in some way. Consumer diets. Adult population. We reviewed forty-nine studies that combined the health and environmental aspects of consumer diets. Hereby, five approaches to operationalise the health aspect of the diet were identified: (i) food item replacements; (ii) dietary guidelines; (iii) dietary quality scores; (iv) diet modelling techniques; and (v) diet-related health impact analysis. Although the sustainability concept is increasingly popular and widely advocated by nutritional and environmental scientists, the journey towards designing sustainable diets for consumers has only just begun. In the context of operationalising the health aspects, diet modelling might be considered the preferred approach since it captures the complexity of the diet as a whole. For the future, we propose SHARP diets: environmentally Sustainable (S), Healthy (H), Affordable (A), Reliable (R) and Preferred from the consumer's perspective (P).

  12. Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci.

    PubMed

    Zubair, Niha; Graff, Mariaelisa; Luis Ambite, Jose; Bush, William S; Kichaev, Gleb; Lu, Yingchang; Manichaikul, Ani; Sheu, Wayne H-H; Absher, Devin; Assimes, Themistocles L; Bielinski, Suzette J; Bottinger, Erwin P; Buzkova, Petra; Chuang, Lee-Ming; Chung, Ren-Hua; Cochran, Barbara; Dumitrescu, Logan; Gottesman, Omri; Haessler, Jeffrey W; Haiman, Christopher; Heiss, Gerardo; Hsiung, Chao A; Hung, Yi-Jen; Hwu, Chii-Min; Juang, Jyh-Ming J; Le Marchand, Loic; Lee, I-Te; Lee, Wen-Jane; Lin, Li-An; Lin, Danyu; Lin, Shih-Yi; Mackey, Rachel H; Martin, Lisa W; Pasaniuc, Bogdan; Peters, Ulrike; Predazzi, Irene; Quertermous, Thomas; Reiner, Alex P; Robinson, Jennifer; Rotter, Jerome I; Ryckman, Kelli K; Schreiner, Pamela J; Stahl, Eli; Tao, Ran; Tsai, Michael Y; Waite, Lindsay L; Wang, Tzung-Dau; Buyske, Steven; Ida Chen, Yii-Der; Cheng, Iona; Crawford, Dana C; Loos, Ruth J F; Rich, Stephen S; Fornage, Myriam; North, Kari E; Kooperberg, Charles; Carty, Cara L

    2016-12-15

    Genome-wide association studies have identified over 150 loci associated with lipid traits, however, no large-scale studies exist for Hispanics and other minority populations. Additionally, the genetic architecture of lipid-influencing loci remains largely unknown. We performed one of the most racially/ethnically diverse fine-mapping genetic studies of HDL-C, LDL-C, and triglycerides to-date using SNPs on the MetaboChip array on 54,119 individuals: 21,304 African Americans, 19,829 Hispanic Americans, 12,456 Asians, and 530 American Indians. The majority of signals found in these groups generalize to European Americans. While we uncovered signals unique to racial/ethnic populations, we also observed systematically consistent lipid associations across these groups. In African Americans, we identified three novel signals associated with HDL-C (LPL, APOA5, LCAT) and two associated with LDL-C (ABCG8, DHODH). In addition, using this population, we refined the location for 16 out of the 58 known MetaboChip lipid loci. These results can guide tailored screening efforts, reveal population-specific responses to lipid-lowering medications, and aid in the development of new targeted drug therapies. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Methodological Aspects of Focus Groups in Health Research

    PubMed Central

    Tausch, Anja P.; Menold, Natalja

    2016-01-01

    Although focus groups are commonly used in health research to explore the perspectives of patients or health care professionals, few studies consider methodological aspects in this specific context. For this reason, we interviewed nine researchers who had conducted focus groups in the context of a project devoted to the development of an electronic personal health record. We performed qualitative content analysis on the interview data relating to recruitment, communication between the focus group participants, and appraisal of the focus group method. The interview data revealed aspects of the focus group method that are particularly relevant for health research and that should be considered in that context. They include, for example, the preferability of face-to-face recruitment, the necessity to allow participants in patient groups sufficient time to introduce themselves, and the use of methods such as participant-generated cards and prioritization. PMID:28462326

  14. ASPECT

    EPA Pesticide Factsheets

    Able to deploy within one hour of notification, EPA's Airborne Spectral Photometric Environmental Collection Technology (ASPECT) is the nation’s only airborne real-time chemical and radiological detection, infrared and photographic imagery platform.

  15. [Euthanasia/assisted suicide. Ethical and socio-religious aspects].

    PubMed

    Chiriţă, V; Chiriţă, Roxana; Duică, Lavinia; Talau, Gh

    2009-01-01

    Euthanasia/Assisted Suicide are viewed differently by moral and religious references. In a religious way, cardinal confessions (Christianity, Judaism, Islamism, Buddhism) condemn euthanasia/assisted suicide and, in the same time have a more relaxed attitude regarding passive euthanasia. Other aspects of euthanasia regard financial/economic and ethical-medical considerations. All these contradictory standpoints are expressed in some legal acts that make specifications on the concept of "euthanasia"--Oregon's Death with Dignity Act (1994) and Netherlands's Euthanasia Law (2001).

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

    PubMed

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

    2017-11-13

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

  17. Lifelong-RL: Lifelong Relaxation Labeling for Separating Entities and Aspects in Opinion Targets.

    PubMed

    Shu, Lei; Liu, Bing; Xu, Hu; Kim, Annice

    2016-11-01

    It is well-known that opinions have targets. Extracting such targets is an important problem of opinion mining because without knowing the target of an opinion, the opinion is of limited use. So far many algorithms have been proposed to extract opinion targets. However, an opinion target can be an entity or an aspect (part or attribute) of an entity. An opinion about an entity is an opinion about the entity as a whole, while an opinion about an aspect is just an opinion about that specific attribute or aspect of an entity. Thus, opinion targets should be separated into entities and aspects before use because they represent very different things about opinions. This paper proposes a novel algorithm, called Lifelong-RL , to solve the problem based on lifelong machine learning and relaxation labeling . Extensive experiments show that the proposed algorithm Lifelong-RL outperforms baseline methods markedly.

  18. From Universal Laws of Cognition to Specific Cognitive Models

    ERIC Educational Resources Information Center

    Chater, Nick; Brown, Gordon D. A.

    2008-01-01

    The remarkable successes of the physical sciences have been built on highly general quantitative laws, which serve as the basis for understanding an enormous variety of specific physical systems. How far is it possible to construct universal principles in the cognitive sciences, in terms of which specific aspects of perception, memory, or decision…

  19. Functional specificity in the human brain: A window into the functional architecture of the mind

    PubMed Central

    Kanwisher, Nancy

    2010-01-01

    Is the human mind/brain composed of a set of highly specialized components, each carrying out a specific aspect of human cognition, or is it more of a general-purpose device, in which each component participates in a wide variety of cognitive processes? For nearly two centuries, proponents of specialized organs or modules of the mind and brain—from the phrenologists to Broca to Chomsky and Fodor—have jousted with the proponents of distributed cognitive and neural processing—from Flourens to Lashley to McClelland and Rumelhart. I argue here that research using functional MRI is beginning to answer this long-standing question with new clarity and precision by indicating that at least a few specific aspects of cognition are implemented in brain regions that are highly specialized for that process alone. Cortical regions have been identified that are specialized not only for basic sensory and motor processes but also for the high-level perceptual analysis of faces, places, bodies, visually presented words, and even for the very abstract cognitive function of thinking about another person’s thoughts. I further consider the as-yet unanswered questions of how much of the mind and brain are made up of these functionally specialized components and how they arise developmentally. PMID:20484679

  20. Association-heterogeneity mapping identifies an Asian-specific association of the GTF2I locus with rheumatoid arthritis

    PubMed Central

    Kim, Kwangwoo; Bang, So-Young; Ikari, Katsunori; Yoo, Dae Hyun; Cho, Soo-Kyung; Choi, Chan-Bum; Sung, Yoon-Kyoung; Kim, Tae-Hwan; Jun, Jae-Bum; Kang, Young Mo; Suh, Chang-Hee; Shim, Seung-Cheol; Lee, Shin-Seok; Lee, Jisoo; Chung, Won Tae; Kim, Seong-Kyu; Choe, Jung-Yoon; Momohara, Shigeki; Taniguchi, Atsuo; Yamanaka, Hisashi; Nath, Swapan K.; Lee, Hye-Soon; Bae, Sang-Cheol

    2016-01-01

    Considerable sharing of disease alleles among populations is well-characterized in autoimmune disorders (e.g., rheumatoid arthritis), but there are some exceptional loci showing heterogenic association among populations. Here we investigated genetic variants with distinct effects on the development of rheumatoid arthritis in Asian and European populations. Ancestry-related association heterogeneity was examined using Cochran’s homogeneity tests for the disease association data from large Asian (n = 14,465; 9,299 discovery subjects and 5,166 validation subjects; 4 collections) and European (n = 45,790; 11 collections) rheumatoid arthritis case-control cohorts with Immunochip and genome-wide SNP array data. We identified significant heterogeneity between the two ancestries for the common variants in the GTF2I locus (PHeterogeneity = 9.6 × 10−9 at rs73366469) and showed that this heterogeneity was due to an Asian-specific association effect (ORMeta = 1.37 and PMeta = 4.2 × 10−13 in Asians; ORMeta = 1.00 and PMeta = 1.00 in Europeans). Trans-ancestral comparison and bioinfomatics analysis revealed a plausibly causal or disease-variant-tagging SNP (rs117026326; in linkage disequilibrium with rs73366469), whose minor allele is common in Asians but rare in Europeans. In conclusion, we identified largest-ever effect on Asian rheumatoid arthritis across human non-HLA regions at GTF2I by heterogeneity mapping followed by replication studies, and pinpointed a possible causal variant. PMID:27272985

  1. Developing and testing an instrument for identifying performance incentives in the Greek health care sector.

    PubMed

    Paleologou, Victoria; Kontodimopoulos, Nick; Stamouli, Aggeliki; Aletras, Vassilis; Niakas, Dimitris

    2006-09-13

    In the era of cost containment, managers are constantly pursuing increased organizational performance and productivity by aiming at the obvious target, i.e. the workforce. The health care sector, in which production processes are more complicated compared to other industries, is not an exception. In light of recent legislation in Greece in which efficiency improvement and achievement of specific performance targets are identified as undisputable health system goals, the purpose of this study was to develop a reliable and valid instrument for investigating the attitudes of Greek physicians, nurses and administrative personnel towards job-related aspects, and the extent to which these motivate them to improve performance and increase productivity. A methodological exploratory design was employed in three phases: a) content development and assessment, which resulted in a 28-item instrument, b) pilot testing (N = 74) and c) field testing (N = 353). Internal consistency reliability was tested via Cronbach's alpha coefficient and factor analysis was used to identify the underlying constructs. Tests of scaling assumptions, according to the Multitrait-Multimethod Matrix, were used to confirm the hypothesized component structure. Four components, referring to intrinsic individual needs and external job-related aspects, were revealed and explain 59.61% of the variability. They were subsequently labeled: job attributes, remuneration, co-workers and achievement. Nine items not meeting item-scale criteria were removed, resulting in a 19-item instrument. Scale reliability ranged from 0.782 to 0.901 and internal item consistency and discriminant validity criteria were satisfied. Overall, the instrument appears to be a promising tool for hospital administrations in their attempt to identify job-related factors, which motivate their employees. The psychometric properties were good and warrant administration to a larger sample of employees in the Greek healthcare system.

  2. Developing and testing an instrument for identifying performance incentives in the Greek health care sector

    PubMed Central

    Paleologou, Victoria; Kontodimopoulos, Nick; Stamouli, Aggeliki; Aletras, Vassilis; Niakas, Dimitris

    2006-01-01

    Background In the era of cost containment, managers are constantly pursuing increased organizational performance and productivity by aiming at the obvious target, i.e. the workforce. The health care sector, in which production processes are more complicated compared to other industries, is not an exception. In light of recent legislation in Greece in which efficiency improvement and achievement of specific performance targets are identified as undisputable health system goals, the purpose of this study was to develop a reliable and valid instrument for investigating the attitudes of Greek physicians, nurses and administrative personnel towards job-related aspects, and the extent to which these motivate them to improve performance and increase productivity. Methods A methodological exploratory design was employed in three phases: a) content development and assessment, which resulted in a 28-item instrument, b) pilot testing (N = 74) and c) field testing (N = 353). Internal consistency reliability was tested via Cronbach's alpha coefficient and factor analysis was used to identify the underlying constructs. Tests of scaling assumptions, according to the Multitrait-Multimethod Matrix, were used to confirm the hypothesized component structure. Results Four components, referring to intrinsic individual needs and external job-related aspects, were revealed and explain 59.61% of the variability. They were subsequently labeled: job attributes, remuneration, co-workers and achievement. Nine items not meeting item-scale criteria were removed, resulting in a 19-item instrument. Scale reliability ranged from 0.782 to 0.901 and internal item consistency and discriminant validity criteria were satisfied. Conclusion Overall, the instrument appears to be a promising tool for hospital administrations in their attempt to identify job-related factors, which motivate their employees. The psychometric properties were good and warrant administration to a larger sample of employees in

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sharpe, Richard A.; Cocq, Kate Le; Nikolaou, Vasilis

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

  4. 48 CFR 936.202-70 - Specifications charges.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... payments, the invitations for bids should so state, and the architect-engineer or construction management... CATEGORIES OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Special Aspects of Contracting for Construction 936.202-70 Specifications charges. (a) To support all invitations for bids, plans and...

  5. 48 CFR 936.202-70 - Specifications charges.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... payments, the invitations for bids should so state, and the architect-engineer or construction management... CATEGORIES OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Special Aspects of Contracting for Construction 936.202-70 Specifications charges. (a) To support all invitations for bids, plans and...

  6. 48 CFR 936.202-70 - Specifications charges.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... payments, the invitations for bids should so state, and the architect-engineer or construction management... CATEGORIES OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Special Aspects of Contracting for Construction 936.202-70 Specifications charges. (a) To support all invitations for bids, plans and...

  7. 48 CFR 936.202-70 - Specifications charges.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... payments, the invitations for bids should so state, and the architect-engineer or construction management... CATEGORIES OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Special Aspects of Contracting for Construction 936.202-70 Specifications charges. (a) To support all invitations for bids, plans and...

  8. 48 CFR 936.202-70 - Specifications charges.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... payments, the invitations for bids should so state, and the architect-engineer or construction management... CATEGORIES OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Special Aspects of Contracting for Construction 936.202-70 Specifications charges. (a) To support all invitations for bids, plans and...

  9. Encoding specificity manipulations do affect retrieval from memory.

    PubMed

    Zeelenberg, René

    2005-05-01

    In a recent article, P.A. Higham (2002) [Strong cues are not necessarily weak: Thomson and Tulving (1970) and the encoding specificity principle revisited. Memory &Cognition, 30, 67-80] proposed a new way to analyze cued recall performance in terms of three separable aspects of memory (retrieval, monitoring, and report bias) by comparing performance under both free-report and forced-report instructions. He used this method to derive estimates of these aspects of memory in an encoding specificity experiment similar to that reported by D.M. Thomson and E. Tulving (1970) [Associative encoding and retrieval: weak and strong cues. Journal of Experimental Psychology, 86, 255-262]. Under forced-report instructions, the encoding specificity manipulation did not affect performance. Higham concluded that the manipulation affected monitoring and report bias, but not retrieval. I argue that this interpretation of the results is problematic because the Thomson and Tulving paradigm is confounded, and show in three experiments using a more appropriate design that encoding specificity manipulations do affect performance in forced-report cued recall. Because in Higham's framework forced-report performance provides a measure of retrieval that is uncontaminated by monitoring and report bias it is concluded that encoding specificity manipulations do affect retrieval from memory.

  10. A Novel Highly Divergent Protein Family Identified from a Viviparous Insect by RNA-seq Analysis: A Potential Target for Tsetse Fly-Specific Abortifacients

    PubMed Central

    Benoit, Joshua B.; Attardo, Geoffrey M.; Michalkova, Veronika; Krause, Tyler B.; Bohova, Jana; Zhang, Qirui; Baumann, Aaron A.; Mireji, Paul O.; Takáč, Peter; Denlinger, David L.; Ribeiro, Jose M.; Aksoy, Serap

    2014-01-01

    In tsetse flies, nutrients for intrauterine larval development are synthesized by the modified accessory gland (milk gland) and provided in mother's milk during lactation. Interference with at least two milk proteins has been shown to extend larval development and reduce fecundity. The goal of this study was to perform a comprehensive characterization of tsetse milk proteins using lactation-specific transcriptome/milk proteome analyses and to define functional role(s) for the milk proteins during lactation. Differential analysis of RNA-seq data from lactating and dry (non-lactating) females revealed enrichment of transcripts coding for protein synthesis machinery, lipid metabolism and secretory proteins during lactation. Among the genes induced during lactation were those encoding the previously identified milk proteins (milk gland proteins 1–3, transferrin and acid sphingomyelinase 1) and seven new genes (mgp4–10). The genes encoding mgp2–10 are organized on a 40 kb syntenic block in the tsetse genome, have similar exon-intron arrangements, and share regions of amino acid sequence similarity. Expression of mgp2–10 is female-specific and high during milk secretion. While knockdown of a single mgp failed to reduce fecundity, simultaneous knockdown of multiple variants reduced milk protein levels and lowered fecundity. The genomic localization, gene structure similarities, and functional redundancy of MGP2–10 suggest that they constitute a novel highly divergent protein family. Our data indicates that MGP2–10 function both as the primary amino acid resource for the developing larva and in the maintenance of milk homeostasis, similar to the function of the mammalian casein family of milk proteins. This study underscores the dynamic nature of the lactation cycle and identifies a novel family of lactation-specific proteins, unique to Glossina sp., that are essential to larval development. The specificity of MGP2–10 to tsetse and their critical role during

  11. A novel highly divergent protein family identified from a viviparous insect by RNA-seq analysis: a potential target for tsetse fly-specific abortifacients.

    PubMed

    Benoit, Joshua B; Attardo, Geoffrey M; Michalkova, Veronika; Krause, Tyler B; Bohova, Jana; Zhang, Qirui; Baumann, Aaron A; Mireji, Paul O; Takáč, Peter; Denlinger, David L; Ribeiro, Jose M; Aksoy, Serap

    2014-04-01

    In tsetse flies, nutrients for intrauterine larval development are synthesized by the modified accessory gland (milk gland) and provided in mother's milk during lactation. Interference with at least two milk proteins has been shown to extend larval development and reduce fecundity. The goal of this study was to perform a comprehensive characterization of tsetse milk proteins using lactation-specific transcriptome/milk proteome analyses and to define functional role(s) for the milk proteins during lactation. Differential analysis of RNA-seq data from lactating and dry (non-lactating) females revealed enrichment of transcripts coding for protein synthesis machinery, lipid metabolism and secretory proteins during lactation. Among the genes induced during lactation were those encoding the previously identified milk proteins (milk gland proteins 1-3, transferrin and acid sphingomyelinase 1) and seven new genes (mgp4-10). The genes encoding mgp2-10 are organized on a 40 kb syntenic block in the tsetse genome, have similar exon-intron arrangements, and share regions of amino acid sequence similarity. Expression of mgp2-10 is female-specific and high during milk secretion. While knockdown of a single mgp failed to reduce fecundity, simultaneous knockdown of multiple variants reduced milk protein levels and lowered fecundity. The genomic localization, gene structure similarities, and functional redundancy of MGP2-10 suggest that they constitute a novel highly divergent protein family. Our data indicates that MGP2-10 function both as the primary amino acid resource for the developing larva and in the maintenance of milk homeostasis, similar to the function of the mammalian casein family of milk proteins. This study underscores the dynamic nature of the lactation cycle and identifies a novel family of lactation-specific proteins, unique to Glossina sp., that are essential to larval development. The specificity of MGP2-10 to tsetse and their critical role during lactation

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

    PubMed Central

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

    2017-01-01

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

  13. Neurological aspects of human parvovirus B19 infection: a systematic review

    PubMed Central

    Barah, Faraj; Whiteside, Sigrid; Batista, Sonia; Morris, Julie

    2014-01-01

    Parvovirus B19 has been linked with various clinical syndromes including neurological manifestations. However, its role in the latter remains not completely understood. Although the last 10 years witnessed a surge of case reports on B19-associated neurological aspects, the literature data remains scattered and heterogeneous, and epidemiological information on the incidence of B19-associated neurological aspects cannot be accurately extrapolated. The aim of this review is to identify the characteristics of cases of B19-associated neurological manifestations. A computerized systematic review of existing literature concerning cases of B19-related neurological aspects revealed 89 articles describing 129 patients; 79 (61.2%) were associated with CNS manifestations, 41 (31.8%) were associated with peripheral nervous system manifestations, and 9 (7.0%) were linked with myalgic encephalomyelitis. The majority of the cases (50/129) had encephalitis. Clinical characteristic features of these cases were analyzed, and possible pathological mechanisms were also described. In conclusion, B19 should be included in differential diagnosis of encephalitic syndromes of unknown etiology in all age groups. Diagnosis should rely on investigation of anti-B19 IgM antibodies and detection of B19 DNA in serum or CSF. Treatment of severe cases might benefit from a combined regime of intravenous immunoglobulins and steroids. To confirm these outcomes, goal-targeted studies are recommended to exactly identify epidemiological scenarios and explore potential pathogenic mechanisms of these complications. Performing retrospective and prospective and multicenter studies concerning B19 and neurological aspects in general, and B19 and encephalitic syndromes in particular, are required. © 2014 The Authors. Reviews in Medical Virology published by John Wiley & Sons, Ltd. PMID:24459081

  14. [Psychological specificities of living donor kidney transplantation].

    PubMed

    Papeloux-Heitzmann, Élodie

    2016-12-01

    For people with end-stage kidney disease, a transplant is the promise of a future without dialysis. Living donor kidney transplantation comprises many specificities and is distinct from cadaveric donor transplantation. Some psychological aspects explain these specificities. They may be subconscious and difficult to access, but it is essential to decipher them in order to adapt the support provided to these people. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  15. Collapse of elongated voids in porous energetic materials: Effects of void orientation and aspect ratio on initiation

    NASA Astrophysics Data System (ADS)

    Rai, Nirmal Kumar; Schmidt, Martin J.; Udaykumar, H. S.

    2017-04-01

    The sensitivity of porous energetic materials depends on mesostructural heterogeneities such as voids, defects, cracks, and grain boundaries. The mesostructure of pressed explosives contains voids of arbitrary shapes including elongated voids of various orientations and aspect ratios. Mesoscale simulations to date have analyzed the effect of void morphology on the sensitivity of energetic materials for idealized shapes such as cylindrical, conical, and elliptical. This work analyzes the sensitivity behavior of elongated voids in an HMX matrix subject to shock loading. Simulations show that sensitivity of elongated voids depends strongly on orientation as well as aspect ratio. Ranges of orientations and aspects ratios are identified that enhance or inhibit initiation. Insights obtained from single elongated void analyses are used to identify sensitive locations in an imaged mesostructure of a pressed explosive sample.

  16. Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function.

    PubMed

    Floyd, Brendan J; Wilkerson, Emily M; Veling, Mike T; Minogue, Catie E; Xia, Chuanwu; Beebe, Emily T; Wrobel, Russell L; Cho, Holly; Kremer, Laura S; Alston, Charlotte L; Gromek, Katarzyna A; Dolan, Brendan K; Ulbrich, Arne; Stefely, Jonathan A; Bohl, Sarah L; Werner, Kelly M; Jochem, Adam; Westphall, Michael S; Rensvold, Jarred W; Taylor, Robert W; Prokisch, Holger; Kim, Jung-Ja P; Coon, Joshua J; Pagliarini, David J

    2016-08-18

    Mitochondria are essential for numerous cellular processes, yet hundreds of their proteins lack robust functional annotation. To reveal functions for these proteins (termed MXPs), we assessed condition-specific protein-protein interactions for 50 select MXPs using affinity enrichment mass spectrometry. Our data connect MXPs to diverse mitochondrial processes, including multiple aspects of respiratory chain function. Building upon these observations, we validated C17orf89 as a complex I (CI) assembly factor. Disruption of C17orf89 markedly reduced CI activity, and its depletion is found in an unresolved case of CI deficiency. We likewise discovered that LYRM5 interacts with and deflavinates the electron-transferring flavoprotein that shuttles electrons to coenzyme Q (CoQ). Finally, we identified a dynamic human CoQ biosynthetic complex involving multiple MXPs whose topology we map using purified components. Collectively, our data lend mechanistic insight into respiratory chain-related activities and prioritize hundreds of additional interactions for further exploration of mitochondrial protein function. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2014-04-01

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

  18. [Types of medical registries - definitions, methodological aspects and quality of the scientific work with registries].

    PubMed

    Mathis-Edenhofer, Stefan; Piso, Brigitte

    2011-12-01

    This work presents a comprehensive list of registry definitions including broader and narrower definitions. Compared to each other different methodological issues can be identified. Some of these issues are common for all registry types; some can be assigned more easily to a specific registry type. Instruments for evaluating the quality of registers reflect many of the mentioned aspects. Generally, and especially at registers with a descriptive or exploratory research dimension it is important to consider their intended purpose and in about it was achieved. This includes, for instance, whether the purpose and the methodology are coordinated. From the start of registration an initiator should be - based on the purpose - aware of the methodological dimension of the registry. This helps to apply the correct type of the registry, the appropriate guidance and, ultimately, the arguments for the effort (cost-benefit ratio).

  19. A comprehensive representation of the birth-experience: identification and prioritization of birth-specific domains based on a mixed-method design

    PubMed Central

    2014-01-01

    Background In obstetrics, effectiveness and cost-effectiveness studies often present several specific outcomes with likely contradicting results and may not reflect what is important for women. A birth-specific outcome measure that combines the core domains into one utility score would solve this problem. The aim of this study was to investigate which domains are most relevant for women’s overall experience of labor and birth and should be included in such a measure. Methods A sequential mixed-method design with three steps was applied. First, the domains were identified by literature review and online focus groups consisting of pregnant women, women who recently gave birth, and their partners. Second, in a prioritizing task, women who recently gave birth and professionals (midwives, gynecologists, and researchers) selected and ranked their top seven domains. Third, the domains that were most frequently selected and had the highest ranking scores determined the basis for a consensus discussion with experts, whereby the definitive list of domains was formed. Results In the first step, 34 birth-specific domains were identified, which cover domains regarding the caregivers, intrapersonal aspects of the mother, partner support, and contextual and medical aspects of birth. Based on the prioritizing task results (step 2) of 96 women and 89 professionals, this list was reduced to 14 most relevant domains. In a consensus discussion, the final seven domains were selected by combining several of the 14 remaining domains and giving priority to the domains indicated to be relevant by mothers. The seven definite domains were: 1) availability of competent health professionals; 2) health professionals’ support; 3) provision of information; 4) health professionals’ response to needs and requests; 5) feelings of safety; 6) worries about the child’s health; and 7) experienced duration until the first contact with the child. Conclusions The experienced availability and

  20. Interrogator system for identifying electrical circuits

    DOEpatents

    Jatko, W.B.; McNeilly, D.R.

    1988-04-12

    A system for interrogating electrical leads to correctly ascertain the identity of equipment attached to remote ends of the leads is disclosed. The system includes a source of a carrier signal generated in a controller/receiver to be sent over the leads and an identifier unit at the equipment. The identifier is activated by command of the carrier and uses a portion of the carrier to produce a supply voltage. Each identifier is uniquely programmed for a specific piece of equipment, and causes the impedance of the circuit to be modified whereby the carrier signal is modulated according to that program. The modulation can be amplitude, frequency or phase modulation. A demodulator in the controller/receiver analyzes the modulated carrier signal, and if a verified signal is recognized displays and/or records the information. This information can be utilized in a computer system to prepare a wiring diagram of the electrical equipment attached to specific leads. Specific circuit values are given for amplitude modulation, and the system is particularly described for use with thermocouples. 6 figs.

  1. Interrogator system for identifying electrical circuits

    DOEpatents

    Jatko, William B.; McNeilly, David R.

    1988-01-01

    A system for interrogating electrical leads to correctly ascertain the identity of equipment attached to remote ends of the leads. The system includes a source of a carrier signal generated in a controller/receiver to be sent over the leads and an identifier unit at the equipment. The identifier is activated by command of the carrier and uses a portion of the carrier to produce a supply voltage. Each identifier is uniquely programmed for a specific piece of equipment, and causes the impedance of the circuit to be modified whereby the carrier signal is modulated according to that program. The modulation can be amplitude, frequency or phase modulation. A demodulator in the controller/receiver analyzes the modulated carrier signal, and if a verified signal is recognized displays and/or records the information. This information can be utilized in a computer system to prepare a wiring diagram of the electrical equipment attached to specific leads. Specific circuit values are given for amplitude modulation, and the system is particularly described for use with thermocouples.

  2. Sleep quality and communication aspects in children.

    PubMed

    de Castro Corrêa, Camila; José, Maria Renata; Andrade, Eduardo Carvalho; Feniman, Mariza Ribeiro; Fukushiro, Ana Paula; Berretin-Felix, Giédre; Maximino, Luciana Paula

    2017-09-01

    To correlate quality of life of children in terms of sleep, with their oral language skills, auditory processing and orofacial myofunctional aspects. Nineteen children (12 males and seven females, in the mean age 9.26) undergoing otorhinolaryngological and speech evaluations participated in this study. The OSA-18 questionnaire was applied, followed by verbal and nonverbal sequential memory tests, dichotic digit test, nonverbal dichotic test and Sustained Auditory Attention Ability Test, related to auditory processing. The Phonological Awareness Profile test, Rapid Automatized Naming and Phonological Working Memory were used for assessment of the phonological processing. Language was assessed by the ABFW Child Language Test, analyzing the phonological and lexical levels. Orofacial myofunctional aspects were evaluated through the MBGR Protocol. Statistical tests used: the Mann-Whitney Test, Fisher's exact test and Spearman Correlation. Relating the performance of children in all evaluations to the results obtained in the OSA-18, there was a statistically significant correlation in the phonological working memory for backward digits (p = 0.04); as well as in the breathing item (p = 0.03), posture of the mandible (p = 0.03) and mobility of lips (p = 0.04). A correlation was seen between the sleep quality of life and the skills related to the phonological processing, specifically in the phonological working memory in backward digits, and related to orofacial myofunctional aspects. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Success in School for Justice-Involved Girls: Do Specific Aspects of Developmental Immaturity Matter?

    PubMed Central

    Haney-Caron, Emily; Goldstein, Naomi E. S.; Giallella, Christy L.; Kemp, Kathleen; Romaine, Christina Riggs

    2016-01-01

    Developmental immaturity (DI) may help explain some of the variability in aspects of academic achievement among girls in the juvenile justice system, a population with high rates of truancy, dropout, and school failure. This study examined the relationships among the decision making and independent functioning components of DI, verbal intelligence, and academic achievement within this population. Using data from 60 girls in residential juvenile justice facilities, multiple regression analyses indicated that verbal IQ moderated the relationship between the DI construct of decision making and academic achievement. Self-reported school attendance and number of previous arrests did not significantly mediate the relationship between DI and academic achievement. These results may indicate that the decision-making factor of DI may be particularly important, and, if results are replicated, future intervention efforts could focus more on improving this skill within this juvenile justice population. Additionally, the overall importance of the full DI construct is an important area of future study. PMID:28082833

  4. Cloning of a newly identified heart-specific troponin I isoform, which lacks the troponin T binding portion, using the yeast hybrid system

    PubMed Central

    Suzuki, Hideaki; Arakawa, Yasuhiro; Ito, Masaki; Yamada, Hisashi; Horiguchi-Yamada, Junko

    2006-01-01

    OBJECTIVE To elucidate the molecular pathogenesis behind increased levels of laminin in cardiac muscle cells in cardiomyopathy by using a yeast hybrid screen. The present study reports the cloning of a newly identified heart-specific troponin I isoform, which is putatively linked to laminin. Future studies will explore the functional significance of this connection. METHODS Yeast two-hybrid screen analysis was performed using MLF1-interacting protein (amino acids 1 to 318) as bait. The human heart complementary DNA library was screened by using the yeast-mating method for overnight culture. RESULTS Two final positive clones from the heart library were isolated. These two clones encoded the same protein, a short isoform of human cardiac troponin I (TnI) that lacked TnI exons 5 and 6. The TnI isoform has a heart-specific expression pattern and it shares several sequence features with human cardiac TnI; however, it lacks the troponin T binding portion. CONCLUSION The heart-specific segment of the human cardiac TnI isoform shares several sequence features with human cardiac TnI, but it lacks the troponin T binding portion. These results suggest that the heart-specific TnI isoform may be involved in cardiac development and disease. PMID:18651010

  5. Identifying Country-Specific Cultures of Physics Education: A Differential Item Functioning Approach

    ERIC Educational Resources Information Center

    Mesic, Vanes

    2012-01-01

    In international large-scale assessments of educational outcomes, student achievement is often represented by unidimensional constructs. This approach allows for drawing general conclusions about country rankings with respect to the given achievement measure, but it typically does not provide specific diagnostic information which is necessary for…

  6. Are Parents Identifying Positive Aspects to Parenting Their Child with an Intellectual Disability or Are They Just Coping? A Qualitative Exploration

    ERIC Educational Resources Information Center

    Beighton, Carole; Wills, Jane

    2017-01-01

    Although acknowledging the stress of raising their child with intellectual disabilities, parents also report that their child has brought about many positive changes in themselves and family. This study reports what parents perceive to be a positive aspect of parenting their child, as currently what constitutes a "positive" is unclear.…

  7. Which Aspects of the English Language Do Distance Learners Find Difficult?

    ERIC Educational Resources Information Center

    Teoh, George Boon Sai; Lin, Agnes Liau Wei; Belaja, Kathy

    2016-01-01

    This study reports the findings of a research carried out on distance learners at the School of Distance Education (SDE), University Sains Malaysia (USM). The study was explorative in nature with the purpose identifying the aspects of the English language which distance learners found difficult to learn. A quantitative survey questionnaire design…

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

    PubMed

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

    2008-01-01

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

  9. Identifying potential dropouts from college physics classes

    NASA Astrophysics Data System (ADS)

    Wollman, Warren; Lawrenz, Frances

    Hudson and Rottman (1981) established that mathematics ability is probably a secondary factor influencing dropout from college physics courses. Other factors remain to be found for predicting who will drop out or at least have difficulty with the course. When mathematics ability is coupled with general indicators of performance (total GPA and ACT natural science), prediction of performance for those who complete the course is substantially improved. Moreover, discriminant analyses reveal who will have at least some difficulty, but not who will drop out. The problem of isolating specific weaknesses of students who have difficulty persists. Physics achievement appears to depend on mathematics ability only to the extent that students possess the ability to utilize mathematics knowledge for solving physics problems. Identification of the specific aspects of this ability as well as the specific deficiencies leading to dropout should be the object of future research. For the present, interviews might be more revealing than group testing methods.

  10. Experimental analysis for fabrication of high-aspect-ratio piezoelectric ceramic structure by micro-powder injection molding process

    NASA Astrophysics Data System (ADS)

    Han, Jun Sae; Gal, Chang Woo; Park, Jae Man; Kim, Jong Hyun; Park, Seong Jin

    2018-04-01

    Aspect ratio effects in the micro-powder injection molding process were experimentally analyzed for fabrication of high-aspect-ratio piezoelectric ceramic structure. The mechanisms of critical defects have been studied according to individual manufacturing steps. In the molding process, incomplete filling phenomenon determines the critical aspect ratios of a micro pattern. According to mold temperature, an incomplete filling phenomenon has been analyzed with respect to different pattern sizes and aspect ratio. In demolding and drying process, the capillary behavior of sacrificial polymeric mold insert determines the critical aspect ratio of a micro pattern. With respect to pattern dimensions, slumping behavior has been analyzed. Based on our current systems, micro PZT feature has stability when it has lower aspect ratio than 5. Under optimized processing conditions, 20 μm and 40 μm ceramic rod array feature which has 5 of aspect ratio were successfully fabricated by the developed process. Further modification points to fabricate the smaller and higher feature were specifically addressed.

  11. Identifying Immune Drivers of Gulf War Illness Using a Novel Daily Sampling Approach

    DTIC Science & Technology

    2017-10-01

    AWARD NUMBER: W81XWH-12-1-0557 TITLE: Identifying Immune Drivers of Gulf War Illness Using a Novel Daily Sampling Approach PRINCIPAL...TITLE AND SUBTITLE Identifying Immune Drivers of Gulf War Illness Using A Novel 5a. CONTRACT NUMBER Daily Sampling Approach 5b. GRANT NUMBER...INTRODUCTION: The major aim of this research project is to identify aspects of the immune system that are dysregulated in veterans with Gulf War Illness

  12. Design aspects of harmonic drive gear and performance improvement of its by problems identification: A review

    NASA Astrophysics Data System (ADS)

    Routh, Bikash

    2018-04-01

    The present paper aims at review on different aspects of harmonic drive gear to identify literature gap for future research. The present article is started first making the comparative study of harmonic drive gear over conventional gear, highlighting its historical background, its application, limitation etc. and then describing working principle of each and every components of it with detail dimensioning and modelling. The present article is further extended to study the different design aspects i.e. synthesis of tooth profiles, lubrication, stress, strain, torque, load sharing, kinematics error and vibration in details etc., identifying problems and then suggesting future perspective for the performance improvement of harmonic drive gear.

  13. Development of DNA markers for newly identified high-oleate peanut mutants

    USDA-ARS?s Scientific Manuscript database

    Development of high-oleate cultivars is one of the important objectives of peanut breeding because consuming products containing high oleate can benefit human health in many aspects. By screening the entire USDA cultivated peanut collection, we have identified two new high-oleate mutants (PI 342664...

  14. ATE accomplishes receiver specification testing with increased speed and throughput

    NASA Astrophysics Data System (ADS)

    Moser, S. A.

    1982-12-01

    The use of automatic test equipment (ATE) for receiver specifications testing can result in a 90-95% reduction of test time, with a corresponding reduction of labor costs due both to the reduction of personnel numbers and a simplification of tasks that permits less skilled personnel to be employed. These benefits free high-level technicians for more challenging system management assignments. Accuracy and repeatability also improve with the adoption of ATE, since no possibility of human error can be introduced into the readings that are taken by the system. A massive and expensive software design and development effort is identified as the most difficult aspect of ATE implementation, since programming is both time-consuming and labor intensive. An attempt is therefore made by system manufacturers to conduct an integrated development program for both ATE system hardware and software.

  15. Identifying the Effects of Specific CHC Factors on College Students' Reading Comprehension

    ERIC Educational Resources Information Center

    Taub, Gordon E.; Benson, Nicholas

    2013-01-01

    Reading comprehension is an important skill for college academic success. Much of the research pertaining to reading in general, and reading comprehension specifically, focuses on the success of primary and secondary school-age students. The present study goes beyond previous research by extending such investigation to the reading comprehension of…

  16. Isl1 Is required for multiple aspects of motor neuron development

    PubMed Central

    Liang, Xingqun; Song, Mi-Ryoung; Xu, ZengGuang; Lanuza, Guillermo M.; Liu, Yali; Zhuang, Tao; Chen, Yihan; Pfaff, Samuel L.; Evans, Sylvia M.; Sun, Yunfu

    2011-01-01

    The LIM homeodomain transcription factor Islet1 (Isl1) is expressed in multiple organs and plays essential roles during embryogenesis. Isl1 is required for the survival and specification of spinal cord motor neurons. Due to early embryonic lethality and loss of motor neurons, the role of Isl1 in other aspects of motor neuron development remains unclear. In this study, we generated Isl1 mutant mouse lines expressing graded doses of Isl1. Our study has revealed essential roles of Isl1 in multiple aspects of motor neuron development, including motor neuron cell body localization, motor column formation and axon growth. In addition, Isl1 is required for survival of cranial ganglia neurons. PMID:21569850

  17. Synoptic and climatological aspects of extra-tropical cyclones

    NASA Astrophysics Data System (ADS)

    Leckebusch, G. C.

    2010-09-01

    Mid-latitude cyclones are highly complex dynamical features embedded in the general atmospheric circulation of the extra-tropics. Although the basic mechanisms leading to the formation of cyclones are commonly understood, the specific conditions and physical reasons triggering extreme, partly explosive development, are still under investigation. This includes also the identification of processes which might modulate the frequency and intensity of cyclone systems on time scales from days to centennials. This overview presentation will thus focus on three main topics: Firstly, the dynamic-synoptic structures of cyclones, the possibility to objectively identify cyclones and wind storms, and actual statistical properties of cyclone occurrence under recent climate conditions are addressed. In a second part, aspects of the interannual variability and its causing mechanisms are related to the seasonal predictability of extreme cyclones producing severe storm events. Extending the time frame will mean to deduce information on decadal or even centennial time periods. Thus, actual work to decadal as well as climatological variability and changes will be presented. In the last part of the talk focus will be laid on potential socio-economical impacts of changed cyclone occurrence. By means of global and regional climate modeling, future damages in terms of insured losses will be investigated and measures of uncertainty estimated from a multi-model ensemble analysis will be presented.

  18. New Method for Simultaneous Species-Specific Identification of Equine Strongyles (Nematoda, Strongylida) by Reverse Line Blot Hybridization▿

    PubMed Central

    Traversa, Donato; Iorio, Raffaella; Klei, Thomas R.; Kharchenko, Vitaliy A.; Gawor, Jakub; Otranto, Domenico; Sparagano, Olivier A. E.

    2007-01-01

    The ability of a reverse line blot (RLB) assay to identify 13 common species of equine small strongyles (cyathostomins) and to discriminate them from three Strongylus spp. (large strongyles) was demonstrated. The assay relied on the specific hybridization of PCR-amplified intergenic spacer DNA fragments of the nuclear ribosomal DNA to membrane-bound species-specific probes. All cyathostomins examined were unequivocally identified and simultaneously discriminated from each other and from three large strongyles (Strongylus edentatus, Strongylus equinus, and Strongylus vulgaris). This assay will enable the accurate and rapid identification of equine cyathostomins irrespective of their life cycle stage, opening important avenues for a better understanding of their biology and epidemiology and of the pathogenesis of cyathostomin-associated disease. In particular, this RLB method promises to be a powerful diagnostic tool to determine the roles of individual species in the pathogenesis of mixed infections and to elucidate some aspects of cyathostominosis. Also, it could represent a basic step toward the development of a rapid and simple molecular test for the early detection of drug-resistant genotypes of horse strongyle species. PMID:17626168

  19. Is Judgement of Biotechnological Ethical Aspects Related to High School Students' Knowledge?

    ERIC Educational Resources Information Center

    Crne-Hladnik, Helena; Hladnik, Ales; Javornik, Branka; Kosmelj, Katarina; Peklaj, Cirila

    2012-01-01

    Quantitative and qualitative studies of various aspects of the perception of biotechnology were conducted among 469 Slovenian high school students of average age 17 years. Our research aimed to explore relationships among students' pre-knowledge of molecular and human genetics, and their attitudes to four specific biotechnological applications.…

  20. Functional requirements for the man-vehicle systems research facility. [identifying and correcting human errors during flight simulation

    NASA Technical Reports Server (NTRS)

    Clement, W. F.; Allen, R. W.; Heffley, R. K.; Jewell, W. F.; Jex, H. R.; Mcruer, D. T.; Schulman, T. M.; Stapleford, R. L.

    1980-01-01

    The NASA Ames Research Center proposed a man-vehicle systems research facility to support flight simulation studies which are needed for identifying and correcting the sources of human error associated with current and future air carrier operations. The organization of research facility is reviewed and functional requirements and related priorities for the facility are recommended based on a review of potentially critical operational scenarios. Requirements are included for the experimenter's simulation control and data acquisition functions, as well as for the visual field, motion, sound, computation, crew station, and intercommunications subsystems. The related issues of functional fidelity and level of simulation are addressed, and specific criteria for quantitative assessment of various aspects of fidelity are offered. Recommendations for facility integration, checkout, and staffing are included.

  1. Geologic, geophysical, and geochemical aspects of site-specific studies of the geopressured-geothermal energy resource of southern Louisiana. Final report

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pilger, R.H. Jr.

    1985-01-01

    The report consists of four sections dealing with progress in evaluating geologic, geochemical, and geophysical aspects of geopressured-geothermal energy resources in Louisiana. Separate abstracts have been prepared for the individual sections. (ACR)

  2. Is Judgement of Biotechnological Ethical Aspects Related to High School Students' Knowledge?

    NASA Astrophysics Data System (ADS)

    Črne-Hladnik, Helena; Hladnik, Aleš; Javornik, Branka; Košmelj, Katarina; Peklaj, Cirila

    2012-05-01

    Quantitative and qualitative studies of various aspects of the perception of biotechnology were conducted among 469 Slovenian high school students of average age 17 years. Our research aimed to explore relationships among students' pre-knowledge of molecular and human genetics, and their attitudes to four specific biotechnological applications. These applications-Bt corn, genetically modified (GM) salmon, somatic and germ line gene therapy (GT)-were investigated from the viewpoints of usefulness, moral acceptance and risk perception. In addition, patterns and quality of moral reasoning related to the biotechnological applications from the aspect of moral acceptability were examined. Clear gender differences were found regarding the relationship between our students' pre-knowledge of genetics and their attitudes to biotechnological applications. While females with a better genetics background expressed a higher risk perception in the case of GM salmon, their similarly well-educated male colleagues emphasized the risk associated with the use of germ line GT. With all four biotechnological applications, patterns of both rationalistic-deontological and teleological-and intuitive moral reasoning were identified. Students with poorer genetics pre-knowledge applied an intuitive pattern of moral reasoning more frequently than their peers with better pre-knowledge. A pattern of emotive reasoning was detected only in the case of GM salmon. A relatively low quality of students' moral reasoning, as demonstrated by their brief and small number of supporting justifications (explanations), show that there is a strong need for practising skills of argumentation about socio-scientific issues in Slovenian high schools on a much larger scale. The implications for future research and classroom applications are discussed.

  3. Early Changes in Costameric and Mitochondrial Protein Expression with Unloading Are Muscle Specific

    PubMed Central

    Li, Ruowei; Linnehan, Richard M.; Castells, Josiane; Tesch, Per; Gustafsson, Thomas

    2014-01-01

    We hypothesised that load-sensitive expression of costameric proteins, which hold the sarcomere in place and position the mitochondria, contributes to the early adaptations of antigravity muscle to unloading and would depend on muscle fibre composition and chymotrypsin activity of the proteasome. Biopsies were obtained from vastus lateralis (VL) and soleus (SOL) muscles of eight men before and after 3 days of unilateral lower limb suspension (ULLS) and subjected to fibre typing and measures for costameric (FAK and FRNK), mitochondrial (NDUFA9, SDHA, UQCRC1, UCP3, and ATP5A1), and MHCI protein and RNA content. Mean cross-sectional area (MCSA) of types I and II muscle fibres in VL and type I fibres in SOL demonstrated a trend for a reduction after ULLS (0.05 ≤ P < 0.10). FAK phosphorylation at tyrosine 397 showed a 20% reduction in VL muscle (P = 0.029). SOL muscle demonstrated a specific reduction in UCP3 content (−23%; P = 0.012). Muscle-specific effects of ULLS were identified for linear relationships between measured proteins, chymotrypsin activity and fibre MCSA. The molecular modifications in costamere turnover and energy homoeostasis identify that aspects of atrophy and fibre transformation are detectable at the protein level in weight-bearing muscles within 3 days of unloading. PMID:25313365

  4. Playing MMORPGs: connections between addiction and identifying with a character.

    PubMed

    Smahel, David; Blinka, Lukas; Ledabyl, Ondrej

    2008-12-01

    Addiction to online role-playing games is one of the most discussed aspects of recent cyberpsychology, mainly for its potentially negative impact on the social lives of young people. In our study, we focus on some aspects of youth and adolescent addiction to MMORPGs. We investigated connections between players and their game characters and examined if, and in what ways, player relationship to their character affected potential addiction. Players attitude to their characters seems to play a specific role, since players who tend to be addicted view their characters as being superior and more often wish to be like their characters in their real lives. Our research also confirmed that younger players are generally more prone to addiction.

  5. The Return of Lombroso? Ethical Aspects of (Visions of) Preventive Forensic Screening.

    PubMed

    Munthe, Christian; Radovic, Susanna

    2015-11-01

    The vision of legendary criminologist Cesare Lombroso to use scientific theories of individual causes of crime as a basis for screening and prevention programmes targeting individuals at risk for future criminal behaviour has resurfaced, following advances in genetics, neuroscience and psychiatric epidemiology. This article analyses this idea and maps its ethical implications from a public health ethical standpoint. Twenty-seven variants of the new Lombrosian vision of forensic screening and prevention are distinguished, and some scientific and technical limitations are noted. Some lures, biases and structural factors, making the application of the Lombrosian idea likely in spite of weak evidence are pointed out and noted as a specific type of ethical aspect. Many classic and complex ethical challenges for health screening programmes are shown to apply to the identified variants and the choice between them, albeit with peculiar and often provoking variations. These variations are shown to actualize an underlying theoretical conundrum in need of further study, pertaining to the relationship between public health ethics and the ethics and values of criminal law policy.

  6. The Return of Lombroso? Ethical Aspects of (Visions of) Preventive Forensic Screening

    PubMed Central

    Munthe, Christian; Radovic, Susanna

    2015-01-01

    The vision of legendary criminologist Cesare Lombroso to use scientific theories of individual causes of crime as a basis for screening and prevention programmes targeting individuals at risk for future criminal behaviour has resurfaced, following advances in genetics, neuroscience and psychiatric epidemiology. This article analyses this idea and maps its ethical implications from a public health ethical standpoint. Twenty-seven variants of the new Lombrosian vision of forensic screening and prevention are distinguished, and some scientific and technical limitations are noted. Some lures, biases and structural factors, making the application of the Lombrosian idea likely in spite of weak evidence are pointed out and noted as a specific type of ethical aspect. Many classic and complex ethical challenges for health screening programmes are shown to apply to the identified variants and the choice between them, albeit with peculiar and often provoking variations. These variations are shown to actualize an underlying theoretical conundrum in need of further study, pertaining to the relationship between public health ethics and the ethics and values of criminal law policy. PMID:26566397

  7. Recommendations on basic requirements for intensive care units: structural and organizational aspects.

    PubMed

    Valentin, Andreas; Ferdinande, Patrick

    2011-10-01

    To provide guidance and recommendations for the planning or renovation of intensive care units (ICUs) with respect to the specific characteristics relevant to organizational and structural aspects of intensive care medicine. The Working Group on Quality Improvement (WGQI) of the European Society of Intensive Care Medicine (ESICM) identified the basic requirements for ICUs by a comprehensive literature search and an iterative process with several rounds of consensus finding with the participation of 47 intensive care physicians from 23 countries. The starting point of this process was an ESICM recommendation published in 1997 with the need for an updated version. The document consists of operational guidelines and design recommendations for ICUs. In the first part it covers the definition and objectives of an ICU, functional criteria, activity criteria, and the management of equipment. The second part deals with recommendations with respect to the planning process, floorplan and connections, accommodation, fire safety, central services, and the necessary communication systems. This document provides a detailed framework for the planning or renovation of ICUs based on a multinational consensus within the ESICM.

  8. Cross-Species Transcriptome Profiling Identifies New Alveolar Epithelial Type I Cell–Specific Genes

    PubMed Central

    Sunohara, Mitsuhiro; Pouldar, Tiffany M.; Wang, Hongjun; Liu, Yixin; Rieger, Megan E.; Tran, Evelyn; Flodby, Per; Siegmund, Kimberly D.; Crandall, Edward D.; Laird-Offringa, Ite A.

    2017-01-01

    Diseases involving the distal lung alveolar epithelium include chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and lung adenocarcinoma. Accurate labeling of specific cell types is critical for determining the contribution of each to the pathogenesis of these diseases. The distal lung alveolar epithelium is composed of two cell types, alveolar epithelial type 1 (AT1) and type 2 (AT2) cells. Although cell type–specific markers, most prominently surfactant protein C, have allowed detailed lineage tracing studies of AT2 cell differentiation and the cells’ roles in disease, studies of AT1 cells have been hampered by a lack of genes with expression unique to AT1 cells. In this study, we performed genome-wide expression profiling of multiple rat organs together with purified rat AT2, AT1, and in vitro differentiated AT1-like cells, resulting in the identification of 54 candidate AT1 cell markers. Cross-referencing with genes up-regulated in human in vitro differentiated AT1-like cells narrowed the potential list to 18 candidate genes. Testing the top four candidate genes at RNA and protein levels revealed GRAM domain 2 (GRAMD2), a protein of unknown function, as highly specific to AT1 cells. RNA sequencing (RNAseq) confirmed that GRAMD2 is transcriptionally silent in human AT2 cells. Immunofluorescence verified that GRAMD2 expression is restricted to the plasma membrane of AT1 cells and is not expressed in bronchial epithelial cells, whereas reverse transcription–polymerase chain reaction confirmed that it is not expressed in endothelial cells. Using GRAMD2 as a new AT1 cell–specific gene will enhance AT1 cell isolation, the investigation of alveolar epithelial cell differentiation potential, and the contribution of AT1 cells to distal lung diseases. PMID:27749084

  9. Institutional and environmental aspects of geothermal energy development

    NASA Technical Reports Server (NTRS)

    Citron, O. R.

    1977-01-01

    Until recently, the majority of work in geothermal energy development has been devoted to technical considerations of resource identification and extraction technologies. The increasing interest in exploiting the variety of geothermal resources has prompted an examination of the institutional barriers to their introduction for commercial use. A significant effort was undertaken by the Jet Propulsion Laboratory as a part of a national study to identify existing constraints to geothermal development and possible remedial actions. These aspects included legislative and legal parameters plus environmental, social, and economic considerations.

  10. Learning to Identify and Actualize Affordances in a New Tool

    ERIC Educational Resources Information Center

    Haines, Karen J.

    2015-01-01

    Keeping abreast of new technologies and the opportunities they offer is a challenge for inservice teachers (Blake, 2008; Egbert, Akasha, Huff, & Lee, 2011; Hanson-Smith, 2006; Hubbard, 2007; Robb, 2006). An important aspect of teacher learning about the use of technology is the ability to identify the affordances of new tools and how they can…

  11. Development and refinement of the WAItE: a new obesity-specific quality of life measure for adolescents.

    PubMed

    Oluboyede, Yemi; Hulme, Claire; Hill, Andrew

    2017-08-01

    Few weight-specific outcome measures, developed specifically for obese and overweight adolescents, exist and none are suitable for the elicitation of utility values used in the assessment of cost effectiveness. The development of a descriptive system for a new weight-specific measure. Qualitative interviews were conducted with 31 treatment-seeking (above normal weight status) and non-treatment-seeking (school sample) adolescents aged 11-18 years, to identify a draft item pool and associated response options. 315 eligible consenting adolescents, aged 11-18 years, enrolled in weight management services and recruited via an online panel, completed two version of a long-list 29-item descriptive system (consisting of frequency and severity response scales). Psychometric assessments and Rasch analysis were applied to the draft 29-item instrument to identify a brief tool containing the best performing items and associated response options. Seven items were selected, for the final item set; all displayed internal consistency, moderate floor effects and the ability to discriminate between weight categories. The assessment of unidimensionality was supported (t test statistic of 0.024, less than the 0.05 threshold value). The Weight-specific Adolescent Instrument for Economic-evaluation focuses on aspects of life affected by weight that are important to adolescents. It has the potential for adding key information to the assessment of weight management interventions aimed at the younger population.

  12. Immunogenetic mechanisms leading to thyroid autoimmunity: recent advances in identifying susceptibility genes and regions.

    PubMed

    Brand, Oliver J; Gough, Stephen C L

    2011-12-01

    The autoimmune thyroid diseases (AITD) include Graves' disease (GD) and Hashimoto's thyroiditis (HT), which are characterised by a breakdown in immune tolerance to thyroid antigens. Unravelling the genetic architecture of AITD is vital to better understanding of AITD pathogenesis, required to advance therapeutic options in both disease management and prevention. The early whole-genome linkage and candidate gene association studies provided the first evidence that the HLA region and CTLA-4 represented AITD risk loci. Recent improvements in; high throughput genotyping technologies, collection of larger disease cohorts and cataloguing of genome-scale variation have facilitated genome-wide association studies and more thorough screening of candidate gene regions. This has allowed identification of many novel AITD risk genes and more detailed association mapping. The growing number of confirmed AITD susceptibility loci, implicates a number of putative disease mechanisms most of which are tightly linked with aspects of immune system function. The unprecedented advances in genetic study will allow future studies to identify further novel disease risk genes and to identify aetiological variants within specific gene regions, which will undoubtedly lead to a better understanding of AITD patho-physiology.

  13. Immunogenetic Mechanisms Leading to Thyroid Autoimmunity: Recent Advances in Identifying Susceptibility Genes and Regions

    PubMed Central

    Brand, Oliver J; Gough, Stephen C.L

    2011-01-01

    The autoimmune thyroid diseases (AITD) include Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), which are characterised by a breakdown in immune tolerance to thyroid antigens. Unravelling the genetic architecture of AITD is vital to better understanding of AITD pathogenesis, required to advance therapeutic options in both disease management and prevention. The early whole-genome linkage and candidate gene association studies provided the first evidence that the HLA region and CTLA-4 represented AITD risk loci. Recent improvements in; high throughput genotyping technologies, collection of larger disease cohorts and cataloguing of genome-scale variation have facilitated genome-wide association studies and more thorough screening of candidate gene regions. This has allowed identification of many novel AITD risk genes and more detailed association mapping. The growing number of confirmed AITD susceptibility loci, implicates a number of putative disease mechanisms most of which are tightly linked with aspects of immune system function. The unprecedented advances in genetic study will allow future studies to identify further novel disease risk genes and to identify aetiological variants within specific gene regions, which will undoubtedly lead to a better understanding of AITD patho-physiology. PMID:22654554

  14. An agent-based model identifies MRI regions of probable tumor invasion in a patient with glioblastoma

    NASA Astrophysics Data System (ADS)

    Chen, L. Leon; Ulmer, Stephan; Deisboeck, Thomas S.

    2010-01-01

    We present an application of a previously developed agent-based glioma model (Chen et al 2009 Biosystems 95 234-42) for predicting spatio-temporal tumor progression using a patient-specific MRI lattice derived from apparent diffusion coefficient (ADC) data. Agents representing collections of migrating glioma cells are initialized based upon voxels at the outer border of the tumor identified on T1-weighted (Gd+) MRI at an initial time point. These simulated migratory cells exhibit a specific biologically inspired spatial search paradigm, representing a weighting of the differential contribution from haptotactic permission and biomechanical resistance on the migration decision process. ADC data from 9 months after the initial tumor resection were used to select the best search paradigm for the simulation, which was initiated using data from 6 months after the initial operation. Using this search paradigm, 100 simulations were performed to derive a probabilistic map of tumor invasion locations. The simulation was able to successfully predict a recurrence in the dorsal/posterior aspect long before it was depicted on T1-weighted MRI, 18 months after the initial operation.

  15. An agent-based model identifies MRI regions of probable tumor invasion in a patient with glioblastoma.

    PubMed

    Chen, L Leon; Ulmer, Stephan; Deisboeck, Thomas S

    2010-01-21

    We present an application of a previously developed agent-based glioma model (Chen et al 2009 Biosystems 95 234-42) for predicting spatio-temporal tumor progression using a patient-specific MRI lattice derived from apparent diffusion coefficient (ADC) data. Agents representing collections of migrating glioma cells are initialized based upon voxels at the outer border of the tumor identified on T1-weighted (Gd+) MRI at an initial time point. These simulated migratory cells exhibit a specific biologically inspired spatial search paradigm, representing a weighting of the differential contribution from haptotactic permission and biomechanical resistance on the migration decision process. ADC data from 9 months after the initial tumor resection were used to select the best search paradigm for the simulation, which was initiated using data from 6 months after the initial operation. Using this search paradigm, 100 simulations were performed to derive a probabilistic map of tumor invasion locations. The simulation was able to successfully predict a recurrence in the dorsal/posterior aspect long before it was depicted on T1-weighted MRI, 18 months after the initial operation.

  16. Aspect ratio has no effect on genotoxicity of multi-wall carbon nanotubes.

    PubMed

    Kim, Jin Sik; Lee, Kyu; Lee, Young Hee; Cho, Hyun Sun; Kim, Ki Heon; Choi, Kyung Hee; Lee, Sang Hee; Song, Kyung Seuk; Kang, Chang Soo; Yu, Il Je

    2011-07-01

    Carbon nanotubes (CNTs) have specific physico-chemical and electrical properties that are useful for telecommunications, medicine, materials, manufacturing processes and the environmental and energy sectors. Yet, despite their many advantages, it is also important to determine whether CNTs may represent a hazard to the environment and human health. Like asbestos, the aspect ratio (length:diameter) and metal components of CNTs are known to have an effect on the toxicity of carbon nanotubes. Thus, to evaluate the toxic potential of CNTs in relation to their aspect ratio and metal contamination, in vivo and in vitro genotoxicity tests were conducted using high-aspect-ratio (diameter: 10-15 nm, length: ~10 μm) and low-aspect-ratio multi-wall carbon nanotubes (MWCNTs, diameter: 10-15 nm, length: ~150 nm) according to OECD test guidelines 471 (bacterial reverse mutation test), 473 (in vitro chromosome aberration test), and 474 (in vivo micronuclei test) with a good laboratory practice system. To determine the treatment concentration for all the tests, a solubility and dispersive test was performed, and a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) solution found to be more suitable than distilled water. Neither the high- nor the low-aspect-ratio MWCNTs induced any genotoxicity in a bacterial reverse mutation test (~1,000 μg/plate), in vitro chromosome aberration test (without S9: ~6.25 μg/ml, with S9: ~50 μg/ml), or in vivo micronuclei test (~50 mg/kg). However, the high-aspect-ratio MWCNTs were found to be more toxic than the low-aspect-ratio MWCNTs. Thus, while high-aspect-ratio MWCNTs do not induce direct genotoxicity or metabolic activation-mediated genotoxicity, genotoxicity could still be induced indirectly through oxidative stress or inflammation.

  17. Genetically identified spinal interneurons integrating tactile afferents for motor control

    PubMed Central

    Panek, Izabela; Farah, Carl

    2015-01-01

    Our movements are shaped by our perception of the world as communicated by our senses. Perception of sensory information has been largely attributed to cortical activity. However, a prior level of sensory processing occurs in the spinal cord. Indeed, sensory inputs directly project to many spinal circuits, some of which communicate with motor circuits within the spinal cord. Therefore, the processing of sensory information for the purpose of ensuring proper movements is distributed between spinal and supraspinal circuits. The mechanisms underlying the integration of sensory information for motor control at the level of the spinal cord have yet to be fully described. Recent research has led to the characterization of spinal neuron populations that share common molecular identities. Identification of molecular markers that define specific populations of spinal neurons is a prerequisite to the application of genetic techniques devised to both delineate the function of these spinal neurons and their connectivity. This strategy has been used in the study of spinal neurons that receive tactile inputs from sensory neurons innervating the skin. As a result, the circuits that include these spinal neurons have been revealed to play important roles in specific aspects of motor function. We describe these genetically identified spinal neurons that integrate tactile information and the contribution of these studies to our understanding of how tactile information shapes motor output. Furthermore, we describe future opportunities that these circuits present for shedding light on the neural mechanisms of tactile processing. PMID:26445867

  18. Grammatical aspect, lexical aspect, and event duration constrain the availability of events in narratives.

    PubMed

    Becker, Raymond B; Ferretti, Todd R; Madden-Lombardi, Carol J

    2013-11-01

    The present study investigates how readers' representations of narratives are constrained by three sources of temporal information; grammatical aspect, lexical aspect, and the duration of intervening events. Participants read short stories in which a target event with an intrinsic endpoint or not (lexical aspect: accomplishments/activities) was described as ongoing or completed (grammatical aspect: imperfective/perfective). An intervening sentence described either a long or short duration event before the target situation was reintroduced later in the story. The electroencephalogram time-locked to the reintroduction of the target event elicited a larger N400 for perfective versus imperfective accomplishments, and this effect occurred only after short intervening events. Alternatively, the N400 to targets in the activity condition did not vary as a function of grammatical aspect or duration of intervening events. These results provide novel insight into how the temporal properties of events interact to constrain the availability of concepts in situation models. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Charles Darwin and Evolution: Illustrating Human Aspects of Science

    NASA Astrophysics Data System (ADS)

    Kampourakis, Kostas; McComas, William F.

    2010-06-01

    Recently, the nature of science (NOS) has become recognized as an important element within the K-12 science curriculum. Despite differences in the ultimate lists of recommended aspects, a consensus is emerging on what specific NOS elements should be the focus of science instruction and inform textbook writers and curriculum developers. In this article, we suggest a contextualized, explicit approach addressing one core NOS aspect: the human aspects of science that include the domains of creativity, social influences and subjectivity. To illustrate these ideas, we have focused on Charles Darwin, a scientist whose life, work and thought processes were particularly well recorded at the time and analyzed by scholars in the succeeding years. Historical facts are discussed and linked to core NOS ideas. Creativity is illustrated through the analogies between the struggle for existence in human societies and in nature, between artificial and natural selection, and between the division of labor in human societies and in nature. Social influences are represented by Darwin’s aversion of criticism of various kinds and by his response to the methodological requirements of the science of that time. Finally, subjectivity is discussed through Darwin’s development of a unique but incorrect source for the origin of variations within species.

  20. Laser micro-dissection and qPCR for identifying specific HPV types responsible for malignancy in penile lesions.

    PubMed

    Lebelo, Ramokone L; Thys, Sofie; Benoy, Ina; Depuydt, Christophe E; Bogers, John-Paul; Bida, Meshack N; Mphahlele, M Jeffrey

    2015-10-01

    The aim of the study was to identify specific human papillomavirus (HPV) type responsible for malignancy in penile tissue samples using laser micro-dissection and TaqMan quantitative real-time PCR (qPCR). The study was based on two pre-malignant and seven malignant penile tissue samples and laser micro-dissection was performed on all. Genotyping was performed on whole tissue sections and laser micro-dissection samples using qPCR. Two whole tissue section samples were HPV negative while seven were HPV positive. In four samples that were single HPV infections with whole tissue section PCR, identical HPV types were confirmed with laser micro-dissection PCR. Clearly confirming that the single HPV type detected is responsible for malignancy. In two samples that had multiple HPV infections with whole tissue section PCR, only one HPV type with the highest viral load was detected with laser micro-dissection PCR, suggesting that the HPV type with the highest viral load is most likely the cause of that particular lesion. HPV 11 and/or HPV 16 were the only types detected with laser micro-dissection PCR in these cases, compared to multiple HPV types (HPV 11, HPV 16, HPV 18, HPV 31, HPV 33, HPV 35, and HPV 39) initially detected with whole tissue section PCR. HPV 11 was associated with verrucous lesions while HPV 16 was associated with squamous cell carcinoma and PIN 3 lesions. This study confirms that laser micro-dissection and qPCR are essential tools in identifying the HPV types responsible for malignancy in penile lesions, particularly in samples with multiple infections. © 2015 Wiley Periodicals, Inc.

  1. Hypochondriasis Differs From Panic Disorder and Social Phobia: Specific Processes Identified Within Patient Groups.

    PubMed

    Höfling, Volkmar; Weck, Florian

    2017-03-01

    Studies of the comorbidity of hypochondriasis have indicated high rates of cooccurrence with other anxiety disorders. In this study, the contrast among hypochondriasis, panic disorder, and social phobia was investigated using specific processes drawing on cognitive-perceptual models of hypochondriasis. Affective, behavioral, cognitive, and perceptual processes specific to hypochondriasis were assessed with 130 diagnosed participants based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria (66 with hypochondriasis, 32 with panic disorder, and 32 with social phobia). All processes specific to hypochondriasis were more intense for patients with hypochondriasis in contrast to those with panic disorder or social phobia (0.61 < d < 2.67). No differences were found between those with hypochondriasis with comorbid disorders and those without comorbid disorders. Perceptual processes were shown to best discriminate between patients with hypochondriasis and those with panic disorder.

  2. Aspects on Transfer of Aided - Design Files

    NASA Astrophysics Data System (ADS)

    Goanta, A. M.; Anghelache, D. G.

    2016-08-01

    At this stage of development of hardware and software, each company that makes design software packages has a certain type of file created and customized in time to distinguish that company from its competitors. Thus today are widely known the DWG files belonging AutoCAD, IPT / IAM belonging to Inventor, PAR / ASM of Solid Edge's, PRT from the NX and so on. Behind every type of file there is a mathematical model which is common to more types of files. A specific aspect of the computer -aided design is that all softwares are working with both individual parts and assemblies, but their approach is different in that some use the same type of file both for each part and for the whole (PRT ), while others use different types of files (IPT / IAM, PAR / ASM, etc.). Another aspect of the computer -aided design is to transfer files between different companies which use different software packages or even the same software package but in different versions. Each of these situations generates distinct issues. Thus, to solve the partial reading by a project different from the native one, transfer files of STEP and IGES type are used

  3. High-Throughput Screening To Identify Potent and Specific Inhibitors of Microbial Sulfate Reduction.

    PubMed

    Carlson, Hans K; Mullan, Mark R; Mosqueda, Lorraine A; Chen, Steven; Arkin, Michelle R; Coates, John D

    2017-06-20

    The selective perturbation of complex microbial ecosystems to predictably influence outcomes in engineered and industrial environments remains a grand challenge for geomicrobiology. In some industrial ecosystems, such as oil reservoirs, sulfate reducing microorganisms (SRM) produce hydrogen sulfide which is toxic, explosive, and corrosive. Despite the economic cost of sulfidogenesis, there has been minimal exploration of the chemical space of possible inhibitory compounds, and very little work has quantitatively assessed the selectivity of putative souring treatments. We have developed a high-throughput screening strategy to identify potent and selective inhibitors of SRM, quantitatively ranked the selectivity and potency of hundreds of compounds and identified previously unrecognized SRM selective inhibitors and synergistic interactions between inhibitors. Zinc pyrithione is the most potent inhibitor of sulfidogenesis that we identified, and is several orders of magnitude more potent than commonly used industrial biocides. Both zinc and copper pyrithione are also moderately selective against SRM. The high-throughput (HT) approach we present can be readily adapted to target SRM in diverse environments and similar strategies could be used to quantify the potency and selectivity of inhibitors of a variety of microbial metabolisms. Our findings and approach are relevant to efforts to engineer environmental ecosystems and also to understand the role of natural gradients in shaping microbial niche space.

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

    PubMed

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

    2016-05-15

    Biological sequence databases are integral to efforts to characterize and understand biological molecules and share biological data. However, when analyzing these data, scientists are often left holding disparate biological currency-molecular identifiers from different databases. For downstream applications that require converting the identifiers themselves, there are many resources available, but analyzing associated loci and variants can be cumbersome if data is not given in a form amenable to particular analyses. Here we present BISQUE, a web server and customizable command-line tool for converting molecular identifiers and their contained loci and variants between different database conventions. BISQUE uses a graph traversal algorithm to generalize the conversion process for residues in the human genome, genes, transcripts and proteins, allowing for conversion across classes of molecules and in all directions through an intuitive web interface and a URL-based web service. BISQUE is freely available via the web using any major web browser (http://bisque.yulab.org/). Source code is available in a public GitHub repository (https://github.com/hyulab/BISQUE). haiyuan.yu@cornell.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Isl1 is required for multiple aspects of motor neuron development.

    PubMed

    Liang, Xingqun; Song, Mi-Ryoung; Xu, ZengGuang; Lanuza, Guillermo M; Liu, Yali; Zhuang, Tao; Chen, Yihan; Pfaff, Samuel L; Evans, Sylvia M; Sun, Yunfu

    2011-07-01

    The LIM homeodomain transcription factor Islet1 (Isl1) is expressed in multiple organs and plays essential roles during embryogenesis. Isl1 is required for the survival and specification of spinal cord motor neurons. Due to early embryonic lethality and loss of motor neurons, the role of Isl1 in other aspects of motor neuron development remains unclear. In this study, we generated Isl1 mutant mouse lines expressing graded doses of Isl1. Our study has revealed essential roles of Isl1 in multiple aspects of motor neuron development, including motor neuron cell body localization, motor column formation and axon growth. In addition, Isl1 is required for survival of cranial ganglia neurons. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Nuclear Structure Aspects in Nuclear Astrophysics

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Smith, Michael Scott

    2006-12-01

    Nuclear Astrophysics as a broad and diverse field of study can be viewed as a magnifier of the impact of microscopic processes on the evolution of macroscopic events. One of the primary goals in Nuclear Astrophysics is the understanding of the nucleosynthesis processes that take place in the cosmos and the simulation of the correlated stellar and explosive burning scenarios. These simulations are strongly dependent on the input from Nuclear Physics which sets the time scale for all stellar dynamic processes--from giga-years of stellar evolution to milliseconds of stellar explosions--and provides the basis for most of the signatures that wemore » have for the interpretation of these events--from stellar luminosities, elemental and isotopic abundances to neutrino flux from distant supernovae. The Nuclear Physics input comes through nuclear structure, low energy reaction rates, nuclear masses, and decay rates. There is a common perception that low energy reaction rates are the most important component of the required nuclear physics input; however, in this article we take a broader approach and present an overview of the close correlation between various nuclear structure aspects and their impact on nuclear astrophysics. We discuss the interplay between the weak and the strong forces on stellar time scales due to the limitations they provide for the evolution of slow and rapid burning processes. The effects of shell structure in nuclei on stellar burning processes as well as the impact of clustering in nuclei is outlined. Furthermore we illustrate the effects of the various nuclear structure aspects on the major nucleosynthesis processes that have been identified in the last few decades. We summarize and provide a coherent overview of the impact of all aspects of nuclear structure on nuclear astrophysics.« less

  7. Nanomedicinal products: a survey on specific toxicity and side effects

    PubMed Central

    Giannakou, Christina; De Jong, Wim H; Kooi, Myrna W; Park, Margriet VDZ; Vandebriel, Rob J; Bosselaers, Irene EM; Scholl, Joep HG; Geertsma, Robert E

    2017-01-01

    Due to their specific properties and pharmacokinetics, nanomedicinal products (NMPs) may present different toxicity and side effects compared to non-nanoformulated, conventional medicines. To facilitate the safety assessment of NMPs, we aimed to gain insight into toxic effects specific for NMPs by systematically analyzing the available toxicity data on approved NMPs in the European Union. In addition, by comparing five sets of products with the same active pharmaceutical ingredient (API) in a conventional formulation versus a nanoformulation, we aimed to identify any side effects specific for the nano aspect of NMPs. The objective was to investigate whether specific toxicity could be related to certain structural types of NMPs and whether a nanoformulation of an API altered the nature of side effects of the product in humans compared to a conventional formulation. The survey of toxicity data did not reveal nanospecific toxicity that could be related to certain types of structures of NMPs, other than those reported previously in relation to accumulation of iron nanoparticles (NPs). However, given the limited data for some of the product groups or toxicological end points in the analysis, conclusions with regard to (a lack of) potential nanomedicine-specific effects need to be considered carefully. Results from the comparison of side effects of five sets of drugs (mainly liposomes and/or cytostatics) confirmed the induction of pseudo-allergic responses associated with specific NMPs in the literature, in addition to the side effects common to both nanoformulations and regular formulations, eg, with liposomal doxorubicin, and possibly liposomal daunorubicin. Based on the available data, immunotoxicological effects of certain NMPs cannot be excluded, and we conclude that this end point requires further attention. PMID:28883724

  8. Religious and spiritual aspects of family assessment.

    PubMed

    Moncher, Frank J; Josephson, Allan M

    2004-01-01

    Childhood emotional and behavioral problems have increased over the past several decades, and the consequences of these behaviors have an impact on the entire family. The role of the family in these problems is clearly an important consideration for the child psychiatrist. A specific understanding of how the family's spiritual worldview or religious convictions impact clinical problems has been underappreciated. The religious orientation or spirituality of parents influences various aspects of family life, from ideals about marriage and family to specifics regarding child rearing. This article reviews the goals of assessment of family religious or spiritual worldview, which include empathically engaging the family of a child in treatment, developing a formulation of how these spiritual factors impact general family functioning, and determining whether the family's religion and spirituality are a resource for treatment or a contributor to disorder. The spiritual and religious assessment of the family facilitates the development of a treatment plan.

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

    PubMed

    Vilela, W; Lolas, F; Wolpert, E

    1978-01-01

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

  10. Identifying Immune Drivers of Gulf War Illness Using Novel Daily Sampling Approach

    DTIC Science & Technology

    2013-10-01

    of Gulf War Illness (GWI). We are targeting an enrollment of 60 men (40 veterans with GWI, 10 veterans with no GWI, and 10 with fibromyalgia ) over... treatment of the disorder. In order to make gains in curing GWI, it is essential that we develop objective, physiologic-based tests for the disorder...and identify physiological targets for treatments . The major aim of this research project is to identify aspects of the immune system that are

  11. Certifying Domain-Specific Policies

    NASA Technical Reports Server (NTRS)

    Lowry, Michael; Pressburger, Thomas; Rosu, Grigore; Koga, Dennis (Technical Monitor)

    2001-01-01

    Proof-checking code for compliance to safety policies potentially enables a product-oriented approach to certain aspects of software certification. To date, previous research has focused on generic, low-level programming-language properties such as memory type safety. In this paper we consider proof-checking higher-level domain -specific properties for compliance to safety policies. The paper first describes a framework related to abstract interpretation in which compliance to a class of certification policies can be efficiently calculated Membership equational logic is shown to provide a rich logic for carrying out such calculations, including partiality, for certification. The architecture for a domain-specific certifier is described, followed by an implemented case study. The case study considers consistency of abstract variable attributes in code that performs geometric calculations in Aerospace systems.

  12. Cognitive aspects of hypochondriasis and the somatization syndrome.

    PubMed

    Rief, W; Hiller, W; Margraf, J

    1998-11-01

    The aim of this study was to evaluate whether specific cognitive aspects are present in patients suffering from somatoform disorders. With a sample of 493 patients from a center for behavioral medicine, the authors evaluated a questionnaire assessing typical cognitions concerning body perception, illness behavior, and health. The authors further examined 225 participants, including patients with a somatization syndrome, patients with somatization syndrome and additional hypochondriasis, patients with hypochondriasis, patients with other mental disorders (clinical control group), and nonclinical controls. The results showed that not only patients with hypochondriasis but also patients with somatization syndrome had cognitive concerns and assumptions that were specific for the disorder. These patients had a self-concept of being weak and unable to tolerate stress. A catastrophizing interpretation of minor bodily complaints found in hypochondriacal patients in earlier studies was also found for patients with multiple somatization symptoms.

  13. Reading the mind in the touch: Neurophysiological specificity in the communication of emotions by touch.

    PubMed

    Kirsch, Louise P; Krahé, Charlotte; Blom, Nadia; Crucianelli, Laura; Moro, Valentina; Jenkinson, Paul M; Fotopoulou, Aikaterini

    2017-05-29

    Touch is central to interpersonal interactions. Touch conveys specific emotions about the touch provider, but it is not clear whether this is a purely socially learned function or whether it has neurophysiological specificity. In two experiments with healthy participants (N = 76 and 61) and one neuropsychological single case study, we investigated whether a type of touch characterised by peripheral and central neurophysiological specificity, namely the C tactile (CT) system, can communicate specific emotions and mental states. We examined the specificity of emotions elicited by touch delivered at CT-optimal (3cm/s) and CT-suboptimal (18cm/s) velocities (Experiment 1) at different body sites which contain (forearm) vs. do not contain (palm of the hand) CT fibres (Experiment 2). Blindfolded participants were touched without any contextual cues, and were asked to identify the touch provider's emotion and intention. Overall, CT-optimal touch (slow, gentle touch on the forearm) was significantly more likely than other types of touch to convey arousal, lust or desire. Affiliative emotions such as love and related intentions such as social support were instead reliably elicited by gentle touch, irrespective of CT-optimality, suggesting that other top-down factors contribute to these aspects of tactile social communication. To explore the neural basis of this communication, we also tested this paradigm in a stroke patient with right perisylvian damage, including the posterior insular cortex, which is considered as the primary cortical target of CT afferents, but excluding temporal cortex involvement that has been linked to more affiliative aspects of CT-optimal touch. His performance suggested an impairment in 'reading' emotions based on CT-optimal touch. Taken together, our results suggest that the CT system can add specificity to emotional and social communication, particularly with regards to feelings of desire and arousal. On the basis of these findings, we speculate

  14. Bioenvironmental aspects of europium and rhodium: a selected bibliography

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fore, C.S.; Carrier, R.F.; Talmage, S.S.

    This bibliography of 428 abstracted references represents a summary of the domestic and foreign literature relevant to the biological and environmental aspects of europium and rhodium. The collected data are organized by current NAEG interests - research highlighting inventory and distribution of the radionulcides, ecological studies covering terrestrial and aquatic systems, and biological studies in both man and animals. Studies that focus directly on research conducted at specific sites (e.g., the Nevada Test Site) are emphasized throughout the bibliography. (ACR)

  15. Ethnic specificity of lupus-associated loci identified in a genome-wide association study in Korean women.

    PubMed

    Lee, Hye-Soon; Kim, Taehyeung; Bang, So Young; Na, Young Ji; Kim, Il; Kim, Kwangwoo; Kim, Jae-Hoon; Chung, Yeun-Jun; Shin, Hyoung Doo; Kang, Young Mo; Shim, Seung-Cheol; Suh, Chang-Hee; Park, Yong-Beom; Kim, Jong-Sung; Kang, Changwon; Bae, Sang-Cheol

    2014-06-01

    To identify novel genetic candidates for systemic lupus erythematosus (SLE) in the Korean population, and to validate the risk loci for SLE identified in previous genome-wide association studies (GWAS). We performed a GWAS in 400 Korean female SLE patients and 445 controls. Selected single-nucleotide polymorphisms (SNP) were then replicated in an independent cohort of 385 SLE patients and 583 controls (replication cohort 1), and in a further 811 SLE patients and 1502 controls (replication cohort 2). In the GWAS phase, rs9275428 located near HLA-DQB1 showed the strongest association with SLE (OR 0.50, false discovery rate (FDR) p=3.07×10(-6)). Although no loci reached genome-wide significance outside major histocompatibility complex (MHC), C8orf13-BLK, STAT4, CSMD1, DIAPH3, GLDC and TNFSF4 showed FDR p < 0.05. Our results suggest that STAT4, BLK, IRF5, PTTG1-miR-146a, UBE2L3 and TNFAIP3 are shared susceptibility loci among Caucasians and Asians, while ETS1, IKZF1, SLC15A4 are likely to be Asian-specific loci. In a combined analysis of 1596 SLE patients and 2540 controls for selected 22 candidate SNP, STAT4 and BLK as positive controls showed a strong association with SLE (FDR p=9.85×10(-13) and 2.28×10(-8), respectively). Of these, 16 candidates (PEX5L, TRAJ50, MYO18B, SOS1, ARHGAP26, SMURF1, CADPS, HAND1, FAM78B, DIAPH3, TBL1XR1, CSMD1, ZBTB20, C3orf21, HIPK1 and AP001042.1) showed only nominal significance (7.05×10(-4)≤FDR p≤4.38×10(-2)). There are similarities and differences in genetic susceptibility for SLE between Caucasian and Asian ethnic groups. Although 16 putative novel loci for SLE have been suggested in the Korean population, further research on a larger sample is required to discriminate truth from error.

  16. Consensus on surgical aspects of managing osteomyelitis in the diabetic foot

    PubMed Central

    Allahabadi, Sachin; Haroun, Kareem B.; Musher, Daniel M.; Lipsky, Benjamin A.; Barshes, Neal R.

    2016-01-01

    Background The aim of this study was to develop consensus statements that may help share or even establish ‘best practices’ in the surgical aspects of managing diabetic foot osteomyelitis (DFO) that can be applied in appropriate clinical situations pending the publication of more high-quality data. Methods We asked 14 panelists with expertise in DFO management to participate. Delphi methodology was used to develop consensus statements. First, a questionnaire elicited practices and beliefs concerning various aspects of the surgical management of DFO. Thereafter, we constructed 63 statements for analysis and, using a nine-point Likert scale, asked the panelists to indicate the extent to which they agreed or disagreed with the statements. We defined consensus as a mean score of greater than 7.0. Results The panelists reached consensus on 38 items after three rounds. Among these, seven provide guidance on initial diagnosis of DFO and selection of patients for surgical management. Another 15 statements provide guidance on specific aspects of operative management, including the timing of operations and the type of specimens to be obtained. Ten statements provide guidance on postoperative management, including wound closure and offloading, and six statements summarize the panelists’ agreement on general principles for surgical management of DFO. Conclusions Consensus statement on the perioperative management of DFO were formed with an expert panel comprised of a variety of surgical specialties. We believe these statements may serve as ‘best practice’ guidelines until properly performed studies provide more robust evidence to support or refute specific surgical management steps in DFO. PMID:27414481

  17. Environmental aspects and renewable energy sources in the production of construction aggregate

    NASA Astrophysics Data System (ADS)

    Skrzypczak, Izabela; Kokoszka, Wanda; Buda-Ożóg, Lidia; Kogut, Janusz; Słowik, Marta

    2017-11-01

    The main activity of open pit mining of aggregates are aggregates' exploitation of natural mineral deposits and its modification in order to obtain high-quality aggregates. The development of aggregate production is conditioned by a number of factors. The most important are: documented material resources, mining and manufacturing capabilities, the need of environmental protection (environmental aspects), the subordination of the plan of spatial development, formal and legal issues, as well as economic and financial aspects. While identifying and assessing the environmental impacts of manufacturing aggregates one may distinguish those environmental aspects that have or may have the greatest magnitude of the impact on the environment as a result of industrial activities. Manufacturers producing aggregates located in the areas covered by the special environmental protection require extra diligence in the conduct of mining activities for preservation of natural resources. The article discusses some main environmental aspects of the production of construction aggregates on the example of one of the largest producers of this material in Subcarpathian province of Poland. Environmental protection in production of aggregates may refer to four aspects: the use of natural resources, having excluded land from agriculture and forestry, land reclamation after exploitation, and use of energy from renewable energy sources. The economic and environmental impact of production volume of aggregates is evaluated by the index information capacity method and the method of graphs.

  18. Mind over matter? I: philosophical aspects of the mind-brain problem.

    PubMed

    Schimmel, P

    2001-08-01

    To conceptualize the essence of the mind-body or mind-brain problem as one of metaphysics rather than science, and to propose a formulation of the problem in the context of current scientific knowledge and its limitations. The background and conceptual parameters of the mind-body problem are delineated, and the limitations of brain research in formulating a solution identified. The problem is reformulated and stated in terms of two propositions. These constitute a 'double aspect theory'. The problem appears to arise as a consequence of the conceptual limitations of the human mind, and hence remains essentially a metaphysical one. A 'double aspect theory' recognizes the essential unity of mind and brain, while remaining consistent with the dualism inherent in human experience.

  19. Sustaining Open Source Communities through Hackathons - An Example from the ASPECT Community

    NASA Astrophysics Data System (ADS)

    Heister, T.; Hwang, L.; Bangerth, W.; Kellogg, L. H.

    2016-12-01

    The ecosystem surrounding a successful scientific open source software package combines both social and technical aspects. Much thought has been given to the technology side of writing sustainable software for large infrastructure projects and software libraries, but less about building the human capacity to perpetuate scientific software used in computational modeling. One effective format for building capacity is regular multi-day hackathons. Scientific hackathons bring together a group of science domain users and scientific software contributors to make progress on a specific software package. Innovation comes through the chance to work with established and new collaborations. Especially in the domain sciences with small communities, hackathons give geographically distributed scientists an opportunity to connect face-to-face. They foster lively discussions amongst scientists with different expertise, promote new collaborations, and increase transparency in both the technical and scientific aspects of code development. ASPECT is an open source, parallel, extensible finite element code to simulate thermal convection, that began development in 2011 under the Computational Infrastructure for Geodynamics. ASPECT hackathons for the past 3 years have grown the number of authors to >50, training new code maintainers in the process. Hackathons begin with leaders establishing project-specific conventions for development, demonstrating the workflow for code contributions, and reviewing relevant technical skills. Each hackathon expands the developer community. Over 20 scientists add >6,000 lines of code during the >1 week event. Participants grow comfortable contributing to the repository and over half continue to contribute afterwards. A high return rate of participants ensures continuity and stability of the group as well as mentoring for novice members. We hope to build other software communities on this model, but anticipate each to bring their own unique challenges.

  20. Acute effects of moderate aerobic exercise on specific aspects of executive function in different age and fitness groups: A meta-analysis.

    PubMed

    Ludyga, Sebastian; Gerber, Markus; Brand, Serge; Holsboer-Trachsler, Edith; Pühse, Uwe

    2016-11-01

    Whereas a wealth of studies have investigated acute effects of moderate aerobic exercise on executive function, the roles of age, fitness, and the component of executive function in this relationship still remain unclear. Therefore, the present meta-analysis investigates exercise-induced benefits on specific aspects of executive function in different age and aerobic fitness subgroups. Based on data from 40 experimental studies, a small effect of aerobic exercise on time-dependent measures (g = .35) and accuracy (g = .22) in executive function tasks was confirmed. The results further suggest that preadolescent children (g = .54) and older adults (g = .67) compared to other age groups benefit more from aerobic exercise when reaction time is considered as dependent variable. In contrast to age, aerobic fitness and the executive function component had no influence on the obtained effect sizes. Consequently, high aerobic fitness is no prerequisite for temporary improvements of the executive control system, and low- as well as high-fit individuals seem to benefit from exercise in a similar way. However, a higher sensitivity of executive function to acute aerobic exercise was found in individuals undergoing developmental changes. Therefore, preadolescent children and older adults in particular might strategically use a single aerobic exercise session to prepare for a situation demanding high executive control. © 2016 Society for Psychophysiological Research.

  1. Aspects That Arise in the Transition from the Montessori Method to a Traditional Method: A Fourth Grade Mathematics View

    ERIC Educational Resources Information Center

    Hurdle, Zachariah B.

    2017-01-01

    The purpose of the dissertation is to investigate three particular aspects that may affect the transition between a third grade Montessori system and a fourth grade non-Montessori system, specifically within the context of teaching and learning mathematics. These aspects are 1) the change in pacing and structure of the classroom, 2) the removal of…

  2. Integrating mean and variance heterogeneities to identify differentially expressed genes.

    PubMed

    Ouyang, Weiwei; An, Qiang; Zhao, Jinying; Qin, Huaizhen

    2016-12-06

    In functional genomics studies, tests on mean heterogeneity have been widely employed to identify differentially expressed genes with distinct mean expression levels under different experimental conditions. Variance heterogeneity (aka, the difference between condition-specific variances) of gene expression levels is simply neglected or calibrated for as an impediment. The mean heterogeneity in the expression level of a gene reflects one aspect of its distribution alteration; and variance heterogeneity induced by condition change may reflect another aspect. Change in condition may alter both mean and some higher-order characteristics of the distributions of expression levels of susceptible genes. In this report, we put forth a conception of mean-variance differentially expressed (MVDE) genes, whose expression means and variances are sensitive to the change in experimental condition. We mathematically proved the null independence of existent mean heterogeneity tests and variance heterogeneity tests. Based on the independence, we proposed an integrative mean-variance test (IMVT) to combine gene-wise mean heterogeneity and variance heterogeneity induced by condition change. The IMVT outperformed its competitors under comprehensive simulations of normality and Laplace settings. For moderate samples, the IMVT well controlled type I error rates, and so did existent mean heterogeneity test (i.e., the Welch t test (WT), the moderated Welch t test (MWT)) and the procedure of separate tests on mean and variance heterogeneities (SMVT), but the likelihood ratio test (LRT) severely inflated type I error rates. In presence of variance heterogeneity, the IMVT appeared noticeably more powerful than all the valid mean heterogeneity tests. Application to the gene profiles of peripheral circulating B raised solid evidence of informative variance heterogeneity. After adjusting for background data structure, the IMVT replicated previous discoveries and identified novel experiment

  3. The effects of treatment adherence and treatment-specific therapeutic competencies on outcome and goal attainment in telephone-based therapy with caregivers of people with dementia.

    PubMed

    Schinköthe, Denise; Altmann, Uwe; Wilz, Gabriele

    2015-01-01

    Contradictory results have been found for the impact of therapist's adherence and competence on intervention outcomes. Most studies focus on generic aspects of competence and adherence, rather than taking into account treatment-specific aspects or specific challenges of the clientele. Appropriate analyses are lacking for cognitive behavioral therapy (CBT) with caregivers of people with dementia. In a sample of 43 caregivers, we examined adherence and different competence ratings of 80 complete sessions, as predictors of symptom change and goal attainment. Therapist's competence was evaluated by four raters, using an adapted version of the cognitive therapy scale (CTS) on three subscales of competence: General therapeutic (GT), session-structuring (SS), and treatment-specific CBT technique (CT). Therapist's adherence to the manual was also assessed. The results show that GT competencies were associated with lower post-test depression scores and that CT competencies predicted a decrease in caregiver burden and higher goal attainment, while SS competencies predicted higher post-test burden. Therapist's adherence had no relationship to outcome, but the higher application of modifying dysfunctional thoughts was associated with higher goal attainment. The results suggest the importance of treatment-specific competencies for outcome. Future research should identify empirically what kind of therapeutic behavior is appropriate to the challenges of a specific clientele such as caregivers of people with dementia.

  4. Functional Profiling Identifies Genes Involved in Organ-Specific Branches of the PIF3 Regulatory Network in Arabidopsis[C][W

    PubMed Central

    Sentandreu, Maria; Martín, Guiomar; González-Schain, Nahuel; Leivar, Pablo; Soy, Judit; Tepperman, James M.; Quail, Peter H.; Monte, Elena

    2011-01-01

    The phytochrome (phy)-interacting basic helix-loop-helix transcription factors (PIFs) constitutively sustain the etiolated state of dark-germinated seedlings by actively repressing deetiolation in darkness. This action is rapidly reversed upon light exposure by phy-induced proteolytic degradation of the PIFs. Here, we combined a microarray-based approach with a functional profiling strategy and identified four PIF3-regulated genes misexpressed in the dark (MIDAs) that are novel regulators of seedling deetiolation. We provide evidence that each one of these four MIDA genes regulates a specific facet of etiolation (hook maintenance, cotyledon appression, or hypocotyl elongation), indicating that there is branching in the signaling that PIF3 relays. Furthermore, combining inferred MIDA gene function from mutant analyses with their expression profiles in response to light-induced degradation of PIF3 provides evidence consistent with a model where the action of the PIF3/MIDA regulatory network enables an initial fast response to the light and subsequently prevents an overresponse to the initial light trigger, thus optimizing the seedling deetiolation process. Collectively, the data suggest that at least part of the phy/PIF system acts through these four MIDAs to initiate and optimize seedling deetiolation, and that this mechanism might allow the implementation of spatial (i.e., organ-specific) and temporal responses during the photomorphogenic program. PMID:22108407

  5. On a categorial aspect of knowledge representation

    NASA Astrophysics Data System (ADS)

    Tataj, Emanuel; Mulawka, Jan; Nieznański, Edward

    Adequate representation of data is crucial for modeling any type of data. To faithfully present and describe the relevant section of the world it is necessary to select the method that can easily be implemented on a computer system which will help in further description allowing reasoning. The main objective of this contribution is to present methods of knowledge representation using categorial approach. Next to identify the main advantages for computer implementation. Categorical aspect of knowledge representation is considered in semantic networks realisation. Such method borrows already known metaphysics properties for data modeling process. The potential topics of further development of categorical semantic networks implementations are also underlined.

  6. Streamlining Software Aspects of Certification: Report on the SSAC Survey

    NASA Technical Reports Server (NTRS)

    Hayhurst, Kelly J.; Dorsey, Cheryl A.; Knight, John C.; Leveson, Nancy G.; McCormick, G. Frank

    1999-01-01

    The aviation system now depends on information technology more than ever before to ensure safety and efficiency. To address concerns about the efficacy of software aspects of the certification process, the Federal Aviation Administration (FAA) began the Streamlining Software Aspects of Certification (SSAC) program. The SSAC technical team was commissioned to gather data, analyze results, and propose recommendations to maximize efficiency and minimize cost and delay, without compromising safety. The technical team conducted two public workshops to identify and prioritize software approval issues, and conducted a survey to validate the most urgent of those issues. The SSAC survey, containing over two hundred questions about the FAA's software approval process, reached over four hundred industry software developers, aircraft manufacturers, and FAA designated engineering representatives. Three hundred people responded. This report presents the SSAC program rationale, survey process, preliminary findings, and recommendations.

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

    PubMed

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

    2016-01-01

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

  8. Personality affects aspects of health-related quality of life in Parkinson's disease via psychological coping strategies.

    PubMed

    Whitworth, Stephanie R; Loftus, Andrea M; Skinner, Timothy C; Gasson, Natalie; Barker, Roger A; Bucks, Romola S; Thomas, Meghan G

    2013-01-01

    Personality traits influence health-related quality of life (HRQoL) in Parkinson's disease (PD). Further, an individual's personality traits can influence the strategies they use to cope with a particular stressful situation. However, in PD, the interplay between personality traits, choice of coping strategy, and their subsequent effect on HRQoL remains unclear. The objective of this study was to examine whether personality (neuroticism and extraversion) indirectly affects HRQoL through the use of specific psychological coping strategies. One hundred and forty-six patients with PD completed questionnaires on personality (Big Five Aspects Scale; BFAS), coping (Ways of Coping Questionnaire; WCQ), and mood-specific (Depression, Anxiety and Stress Scale; DASS-21) and disease-specific HRQoL (Parkinson's Disease Questionnaire; PDQ-39). After controlling for gender, age at diagnosis, and age at testing, the emotion-focused coping strategy of escape-avoidance was significantly correlated with neuroticism and certain aspects of HRQoL (cognitive impairment and social support). This suggests that neurotic personality traits may negatively impact on some aspects of HRQoL due to an increased use of escape-avoidance coping strategies. By contrast, planned problem-solving and escape-avoidance coping strategies were both significantly linked to extraversion and interpersonal and mood-related domains of HRQoL. This suggests that extraversion may positively impact on some aspects of HRQoL due to patients adopting greater planned, problem-solving coping strategies, and using fewer escape-avoidance coping mechanisms. Psychological interventions aimed at targeting maladaptive coping strategies, such as the use of escape-avoidance coping, may be effective in minimising the negative impact of neuroticism on HRQoL in PD.

  9. [Mothers of visually impaired children: difficult and easy aspects faced in care].

    PubMed

    Pintanel, Aline Campelo; Gomes, Giovana Calcagno; Xavier, Daiani Modernel

    2013-06-01

    This study aimed to identify the difficult and easy aspects faced by mothers of visually impaired (VI) children in their care. It is a descriptive qualitative study, developed in the second semester of 2011, with ten mothers of children with visual impairment from an Educational Center for the Visually Impaired located in southern Brazil. Data were collected by means of semistructured interviews and submitted to thematic content analysis. The identified difficulties were the lack of knowledge regarding the disease and how to take care of the child, the lack of access to health services, overload generated by the dependence of the child and lack of support and prejudice within their own family. The easy aspects involved the desire for the child's healthy development the chance of being in touch with qualified professionals for their education, and the contact with other VI children. Therefore, it is important to qualify the family for the care of VI children so as to ensure the development of skills and competencies enabling them to live with quality.

  10. Specification Theory, Patterns, and Models in Information Systems Domains: An Exploratory Investigation

    ERIC Educational Resources Information Center

    Woolridge, Richard William

    2010-01-01

    Application and project domain specifications are an important aspect of Information Systems (IS) development. Observations of over thirty IS projects suggest dimly perceived structural patterns in specifications that are unaccounted for in research and practice. This investigation utilizes a theory building with case studies methodology to…

  11. ESPEN guideline on ethical aspects of artificial nutrition and hydration.

    PubMed

    Druml, Christiane; Ballmer, Peter E; Druml, Wilfred; Oehmichen, Frank; Shenkin, Alan; Singer, Pierre; Soeters, Peter; Weimann, Arved; Bischoff, Stephan C

    2016-06-01

    The worldwide debate over the use of artificial nutrition and hydration remains controversial although the scientific and medical facts are unequivocal. Artificial nutrition and hydration are a medical intervention, requiring an indication, a therapeutic goal and the will (consent) of the competent patient. The guideline was developed by an international multidisciplinary working group based on the main aspects of the Guideline on "Ethical and Legal Aspects of Artificial Nutrition" published 2013 by the German Society for Nutritional Medicine (DGEM) after conducting a review of specific current literature. The text was extended and introduced a broader view in particular on the impact of culture and religion. The results were discussed at the ESPEN Congress in Lisbon 2015 and accepted in an online survey among ESPEN members. The ESPEN Guideline on Ethical Aspects of Artificial Nutrition and Hydration is focused on the adult patient and provides a critical summary for physicians and caregivers. Special consideration is given to end of life issues and palliative medicine; to dementia and to specific situations like nursing care or the intensive care unit. The respect for autonomy is an important focus of the guideline as well as the careful wording to be used in the communication with patients and families. The other principles of Bioethics like beneficence, non-maleficence and justice are presented in the context of artificial nutrition and hydration. In this respect the withholding and withdrawing of artificial nutrition and/or hydration is discussed. Due to increasingly multicultural societies and the need for awareness of different values and beliefs an elaborated chapter is dedicated to cultural and religious issues and nutrition. Last but not least topics like voluntary refusal of nutrition and fluids, and forced feeding of competent persons (persons on hunger strike) is included in the guideline. Copyright © 2016 Elsevier Ltd and European Society for Clinical

  12. Rapid PCR Assays That Specifically Identify Anthrax and Anthrax Surrogate Chromosomal Signatures

    DTIC Science & Technology

    2002-08-30

    The genetic variation among a set of 175 full-length sspE DNA sequences obtained from representative members of the B. anthracis clade have been...examined. Thirty-six sspE genotypes and seventeen protein phylotypes were identified among the B. cereus, B. thuringiensis, B. anthracis and B. mycoides...the sspE DNA sequence data sets suggests that the B. anthracis dade is more phylogenetically complex than has been inferred by traditional taxonomic methods.

  13. Differential proteomic and tissue expression analyses identify valuable diagnostic biomarkers of hepatocellular differentiation and hepatoid adenocarcinomas.

    PubMed

    Reis, Henning; Padden, Juliet; Ahrens, Maike; Pütter, Carolin; Bertram, Stefanie; Pott, Leona L; Reis, Anna-Carinna; Weber, Frank; Juntermanns, Benjamin; Hoffmann, Andreas-C; Eisenacher, Martin; Schlaak, Joörg F; Canbay, Ali; Meyer, Helmut E; Sitek, Barbara; Baba, Hideo A

    2015-10-01

    The exact discrimination of lesions with true hepatocellular differentiation from secondary tumours and neoplasms with hepatocellular histomorphology like hepatoid adenocarcinomas (HAC) is crucial. Therefore, we aimed to identify ancillary protein biomarkers by using complementary proteomic techniques (2D-DIGE, label-free MS). The identified candidates were immunohistochemically validated in 14 paired samples of hepatocellular carcinoma (HCC) and non-tumourous liver tissue (NT). The candidates and HepPar1/Arginase1 were afterwards tested for consistency in a large cohort of hepatocellular lesions and NT (n = 290), non-hepatocellular malignancies (n = 383) and HAC (n = 13). Eight non-redundant, differentially expressed proteins were suitable for further immunohistochemical validation and four (ABAT, BHMT, FABP1, HAOX1) for further evaluation. Sensitivity and specificity rates for HCC/HAC were as follows: HepPar1 80.2%, 94.3% / 80.2%, 46.2%; Arginase1 82%, 99.4% / 82%, 69.2%; BHMT 61.4%, 93.8% / 61.4%, 100%; ABAT 84.4%, 33.7% / 84.4%, 30.8%; FABP1 87.2%, 95% / 87.2%, 69.2%; HAOX1 95.5%, 36.3% / 95.5%, 46.2%. The best 2×/3× biomarker panels for the diagnosis of HCC consisted of Arginase1/HAOX1 and BHMT/Arginase1/HAOX1 and for HAC consisted of Arginase1/FABP1 and BHMT/Arginase1/FABP1. In summary, we successfully identified, validated and benchmarked protein biomarker candidates of hepatocellular differentiation. BHMT in particular exhibited superior diagnostic characteristics in hepatocellular lesions and specifically in HAC. BHMT is therefore a promising (panel based) biomarker candidate in the differential diagnostic process of lesions with hepatocellular aspect.

  14. Cognitive aspects of color

    NASA Astrophysics Data System (ADS)

    Derefeldt, Gunilla A. M.; Menu, Jean-Pierre; Swartling, Tiina

    1995-04-01

    This report surveys cognitive aspects of color in terms of behavioral, neuropsychological, and neurophysiological data. Color is usually defined as psychophysical color or as perceived color. Behavioral data on categorical color perception, absolute judgement of colors, color coding, visual search, and visual awareness refer to the more cognitive aspects of color. These are of major importance in visual synthesis and spatial organization, as already shown by the Gestalt psychologists. Neuropsychological and neurophysiological findings provide evidence for an interrelation between cognitive color and spatial organization. Color also enhances planning strategies, as has been shown by studies on color and eye movements. Memory colors and the color- language connections in the brain also belong among the cognitive aspects of color.

  15. Sex and tissue specific gene expression patterns identified following de novo transcriptomic analysis of the Norway lobster, Nephrops norvegicus.

    PubMed

    Rotllant, Guiomar; Nguyen, Tuan Viet; Sbragaglia, Valerio; Rahi, Lifat; Dudley, Kevin J; Hurwood, David; Ventura, Tomer; Company, Joan B; Chand, Vincent; Aguzzi, Jacopo; Mather, Peter B

    2017-08-16

    The Norway lobster, Nephrops norvegicus, is economically important in European fisheries and is a key organism in local marine ecosystems. Despite multi-faceted scientific interest in this species, our current knowledge of genetic resources in this species remains very limited. Here, we generated a reference de novo transcriptome for N. norvegicus from multiple tissues in both sexes. Bioinformatic analyses were conducted to detect transcripts that were expressed exclusively in either males or females. Patterns were validated via RT-PCR. Sixteen N. norvegicus libraries were sequenced from immature and mature ovary, testis and vas deferens (including the masculinizing androgenic gland). In addition, eyestalk, brain, thoracic ganglia and hepatopancreas tissues were screened in males and both immature and mature females. RNA-Sequencing resulted in >600 million reads. De novo assembly that combined the current dataset with two previously published libraries from eyestalk tissue, yielded a reference transcriptome of 333,225 transcripts with an average size of 708 base pairs (bp), with an N50 of 1272 bp. Sex-specific transcripts were detected primarily in gonads followed by hepatopancreas, brain, thoracic ganglia, and eyestalk, respectively. Candidate transcripts that were expressed exclusively either in males or females were highlighted and the 10 most abundant ones were validated via RT-PCR. Among the most highly expressed genes were Serine threonine protein kinase in testis and Vitellogenin in female hepatopancreas. These results align closely with gene annotation results. Moreover, a differential expression heatmap showed that the majority of differentially expressed transcripts were identified in gonad and eyestalk tissues. Results indicate that sex-specific gene expression patterns in Norway lobster are controlled by differences in gene regulation pattern between males and females in somatic tissues. The current study presents the first multi-tissue reference

  16. Reciprocal Modulation of Cognitive and Emotional Aspects in Pianistic Performances

    PubMed Central

    Higuchi, Marcia K. Kodama; Fornari, José; Del Ben, Cristina M.; Graeff, Frederico G.; Leite, João Pereira

    2011-01-01

    Background High level piano performance requires complex integration of perceptual, motor, cognitive and emotive skills. Observations in psychology and neuroscience studies have suggested reciprocal inhibitory modulation of the cognition by emotion and emotion by cognition. However, it is still unclear how cognitive states may influence the pianistic performance. The aim of the present study is to verify the influence of cognitive and affective attention in the piano performances. Methods and Findings Nine pianists were instructed to play the same piece of music, firstly focusing only on cognitive aspects of musical structure (cognitive performances), and secondly, paying attention solely on affective aspects (affective performances). Audio files from pianistic performances were examined using a computational model that retrieves nine specific musical features (descriptors) – loudness, articulation, brightness, harmonic complexity, event detection, key clarity, mode detection, pulse clarity and repetition. In addition, the number of volunteers' errors in the recording sessions was counted. Comments from pianists about their thoughts during performances were also evaluated. The analyses of audio files throughout musical descriptors indicated that the affective performances have more: agogics, legatos, pianos phrasing, and less perception of event density when compared to the cognitive ones. Error analysis demonstrated that volunteers misplayed more left hand notes in the cognitive performances than in the affective ones. Volunteers also played more wrong notes in affective than in cognitive performances. These results correspond to the volunteers' comments that in the affective performances, the cognitive aspects of piano execution are inhibited, whereas in the cognitive performances, the expressiveness is inhibited. Conclusions Therefore, the present results indicate that attention to the emotional aspects of performance enhances expressiveness, but constrains

  17. Subject-Specific Characteristics of Instructional Quality in Mathematics Education

    ERIC Educational Resources Information Center

    Schlesinger, Lena; Jentsch, Armin; Kaiser, Gabriele; König, Johannes; Blömeke, Sigrid

    2018-01-01

    Instructional research in German-speaking countries has conceptualized teaching quality recently according to three generic dimensions, namely, classroom management, student support and cognitive activation. However, as these dimensions are mainly regarded as generic, subject-specific aspects of mathematics instruction, e.g., the mathematical…

  18. Distinguishing transient versus stable aspects of depression in New Zealand Pacific Island children using Generalizability Theory.

    PubMed

    Paterson, Janis; Medvedev, Oleg N; Sumich, Alexander; Tautolo, El-Shadan; Krägeloh, Christian U; Sisk, Rose; McNamara, Robert K; Berk, Michael; Narayanan, Ajit; Siegert, Richard J

    2018-02-01

    The distinction between temporary versus enduring or state/trait aspects of depression is important. More precise distinction would improve understanding of the aetiology of depression and those aspects most amenable to intervention thus identifying more homogeneous, dynamic targets for clinical trials. Generalizability Theory has been proposed as useful for disentangling state and trait components of psychopathology. We applied Generalizability Theory to determine the relative contributions of temporary and enduring aspects of depression in a widely used screening measure of depression the - 10-item Children's Depression Inventory (CDI-10; Kovacs, 1985). Participants were children of Pacific Island descent living in New Zealand (n = 668). Data were collected at ages - 9, 11, and 14 years. The CDI-10 demonstrated acceptable generalizability across occasions (G = 0.79) with about one third of variance in total scores attributed to temporary and two thirds to more enduring aspects of depression. There were no other significant sources of error variance. Two items were identified as more sensitive than the remaining eight to more dynamic symptoms. Studies with briefer test-retest intervals are warranted. Use of this Pacific Island cohort limits generalizability of findings to other cultures and ethnicities. No data were collected on whether participants had received intervention for depression. While the CDI-10 reliably measures both stable and transient aspects of depression in children, the scale does not permit clear distinction between them. We advocate application of Generalizability Theory for developing state/trait depression measures and determining which existing measures are most suitable for capturing modifiable features of depression. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Chemical screening identifies filastatin, a small molecule inhibitor of Candida albicans adhesion, morphogenesis, and pathogenesis.

    PubMed

    Fazly, Ahmed; Jain, Charu; Dehner, Amie C; Issi, Luca; Lilly, Elizabeth A; Ali, Akbar; Cao, Hong; Fidel, Paul L; Rao, Reeta P; Kaufman, Paul D

    2013-08-13

    Infection by pathogenic fungi, such as Candida albicans, begins with adhesion to host cells or implanted medical devices followed by biofilm formation. By high-throughput phenotypic screening of small molecules, we identified compounds that inhibit adhesion of C. albicans to polystyrene. Our lead candidate compound also inhibits binding of C. albicans to cultured human epithelial cells, the yeast-to-hyphal morphological transition, induction of the hyphal-specific HWP1 promoter, biofilm formation on silicone elastomers, and pathogenesis in a nematode infection model as well as alters fungal morphology in a mouse mucosal infection assay. We term this compound filastatin based on its strong inhibition of filamentation, and we use chemical genetic experiments to show that it acts downstream of multiple signaling pathways. These studies show that high-throughput functional assays targeting fungal adhesion can provide chemical probes for study of multiple aspects of fungal pathogenesis.

  20. Chemical screening identifies filastatin, a small molecule inhibitor of Candida albicans adhesion, morphogenesis, and pathogenesis

    PubMed Central

    Fazly, Ahmed; Jain, Charu; Dehner, Amie C.; Issi, Luca; Lilly, Elizabeth A.; Ali, Akbar; Cao, Hong; Fidel, Paul L.; P. Rao, Reeta; Kaufman, Paul D.

    2013-01-01

    Infection by pathogenic fungi, such as Candida albicans, begins with adhesion to host cells or implanted medical devices followed by biofilm formation. By high-throughput phenotypic screening of small molecules, we identified compounds that inhibit adhesion of C. albicans to polystyrene. Our lead candidate compound also inhibits binding of C. albicans to cultured human epithelial cells, the yeast-to-hyphal morphological transition, induction of the hyphal-specific HWP1 promoter, biofilm formation on silicone elastomers, and pathogenesis in a nematode infection model as well as alters fungal morphology in a mouse mucosal infection assay. We term this compound filastatin based on its strong inhibition of filamentation, and we use chemical genetic experiments to show that it acts downstream of multiple signaling pathways. These studies show that high-throughput functional assays targeting fungal adhesion can provide chemical probes for study of multiple aspects of fungal pathogenesis. PMID:23904484

  1. Identified Serotonin-Releasing Neurons Induce Behavioral Quiescence and Suppress Mating in Drosophila.

    PubMed

    Pooryasin, Atefeh; Fiala, André

    2015-09-16

    Animals show different levels of activity that are reflected in sensory responsiveness and endogenously generated behaviors. Biogenic amines have been determined to be causal factors for these states of arousal. It is well established that, in Drosophila, dopamine and octopamine promote increased arousal. However, little is known about factors that regulate arousal negatively and induce states of quiescence. Moreover, it remains unclear whether global, diffuse modulatory systems comprehensively affecting brain activity determine general states of arousal. Alternatively, individual aminergic neurons might selectively modulate the animals' activity in a distinct behavioral context. Here, we show that artificially activating large populations of serotonin-releasing neurons induces behavioral quiescence and inhibits feeding and mating. We systematically narrowed down a role of serotonin in inhibiting endogenously generated locomotor activity to neurons located in the posterior medial protocerebrum. We identified neurons of this cell cluster that suppress mating, but not feeding behavior. These results suggest that serotonin does not uniformly act as global, negative modulator of general arousal. Rather, distinct serotoninergic neurons can act as inhibitory modulators of specific behaviors. An animal's responsiveness to external stimuli and its various types of endogenously generated, motivated behavior are highly dynamic and change between states of high activity and states of low activity. It remains unclear whether these states are mediated by unitary modulatory systems globally affecting brain activity, or whether distinct neurons modulate specific neuronal circuits underlying particular types of behavior. Using the model organism Drosophila melanogaster, we find that activating large proportions of serotonin-releasing neurons induces behavioral quiescence. Moreover, distinct serotonin-releasing neurons that we genetically isolated and identified negatively affect

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

    ERIC Educational Resources Information Center

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

    2015-01-01

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

  3. Performance of e-ASPECTS software in comparison to that of stroke physicians on assessing CT scans of acute ischemic stroke patients.

    PubMed

    Herweh, Christian; Ringleb, Peter A; Rauch, Geraldine; Gerry, Steven; Behrens, Lars; Möhlenbruch, Markus; Gottorf, Rebecca; Richter, Daniel; Schieber, Simon; Nagel, Simon

    2016-06-01

    The Alberta Stroke Program Early CT score (ASPECTS) is an established 10-point quantitative topographic computed tomography scan score to assess early ischemic changes. We compared the performance of the e-ASPECTS software with those of stroke physicians at different professional levels. The baseline computed tomography scans of acute stroke patients, in whom computed tomography and diffusion-weighted imaging scans were obtained less than two hours apart, were retrospectively scored by e-ASPECTS as well as by three stroke experts and three neurology trainees blinded to any clinical information. The ground truth was defined as the ASPECTS on diffusion-weighted imaging scored by another two non-blinded independent experts on consensus basis. Sensitivity and specificity in an ASPECTS region-based and an ASPECTS score-based analysis as well as receiver-operating characteristic curves, Bland-Altman plots with mean score error, and Matthews correlation coefficients were calculated. Comparisons were made between the human scorers and e-ASPECTS with diffusion-weighted imaging being the ground truth. Two methods for clustered data were used to estimate sensitivity and specificity in the region-based analysis. In total, 34 patients were included and 680 (34 × 20) ASPECTS regions were scored. Mean time from onset to computed tomography was 172 ± 135 min and mean time difference between computed tomographyand magnetic resonance imaging was 41 ± 31 min. The region-based sensitivity (46.46% [CI: 30.8;62.1]) of e-ASPECTS was better than three trainees and one expert (p ≤ 0.01) and not statistically different from another two experts. Specificity (94.15% [CI: 91.7;96.6]) was lower than one expert and one trainee (p < 0.01) and not statistically different to the other four physicians. e-ASPECTS had the best Matthews correlation coefficient of 0.44 (experts: 0.38 ± 0.08 and trainees: 0.19 ± 0.05) and the lowest mean score error of 0.56 (experts

  4. Gain-of-function mutations identify amino acids within transmembrane domains of the yeast vacuolar transporter Zrc1 that determine metal specificity

    PubMed Central

    Lin, Huilan; Burton, Damali; Li, Liangtao; Warner, David E.; Phillips, John D.; Ward, Diane McVEY; Kaplan, Jerry

    2015-01-01

    Cation diffusion facilitator transporters are found in all three Kingdoms of life and are involved in transporting transition metals out of the cytosol. The metals they transport include Zn2+, Co2+, Fe2+, Cd2+, Ni2+ and Mn2+; however, no single transporter transports all metals. Previously we showed that a single amino acid mutation in the yeast vacuolar zinc transporter Zrc1 changed its substrate specificity from Zn2+ to Fe2+ and Mn2+ [Lin, Kumanovics, Nelson, Warner, Ward and Kaplan (2008) J. Biol. Chem. 283, 33865–33873]. Mutant Zrc1 that gained iron transport activity could protect cells with a deletion in the vacuolar iron transporter (CCC1) from high iron toxicity. Utilizing suppression of high iron toxicity and PCR mutagenesis of ZRC1, we identified other amino acid substitutions within ZRC1 that changed its metal specificity. All Zrc1 mutants that transported Fe2+ could also transport Mn2+. Some Zrc1 mutants lost the ability to transport Zn2+, but others retained the ability to transport Zn2+. All of the amino acid substitutions that resulted in a gain in Fe2+ transport activity were found in transmembrane domains. In addition to alteration of residues adjacent to the putative metal-binding site in two transmembrane domains, alteration of residues distant from the binding site affected substrate specificity. These results suggest that substrate selection involves co-operativity between transmembrane domains. PMID:19538181

  5. Mathematical aspects of finite element methods for incompressible viscous flows

    NASA Technical Reports Server (NTRS)

    Gunzburger, M. D.

    1986-01-01

    Mathematical aspects of finite element methods are surveyed for incompressible viscous flows, concentrating on the steady primitive variable formulation. The discretization of a weak formulation of the Navier-Stokes equations are addressed, then the stability condition is considered, the satisfaction of which insures the stability of the approximation. Specific choices of finite element spaces for the velocity and pressure are then discussed. Finally, the connection between different weak formulations and a variety of boundary conditions is explored.

  6. Functional gait assessment and balance evaluation system test: reliability, validity, sensitivity, and specificity for identifying individuals with Parkinson disease who fall.

    PubMed

    Leddy, Abigail L; Crowner, Beth E; Earhart, Gammon M

    2011-01-01

    Gait impairments, balance impairments, and falls are prevalent in individuals with Parkinson disease (PD). Although the Berg Balance Scale (BBS) can be considered the reference standard for the determination of fall risk, it has a noted ceiling effect. Development of ceiling-free measures that can assess balance and are good at discriminating "fallers" from "nonfallers" is needed. The purpose of this study was to compare the Functional Gait Assessment (FGA) and the Balance Evaluation Systems Test (BESTest) with the BBS among individuals with PD and evaluate the tests' reliability, validity, and discriminatory sensitivity and specificity for fallers versus nonfallers. This was an observational study of community-dwelling individuals with idiopathic PD. The BBS, FGA, and BESTest were administered to 80 individuals with PD. Interrater reliability (n=15) was assessed by 3 raters. Test-retest reliability was based on 2 tests of participants (n=24), 2 weeks apart. Intraclass correlation coefficients (2,1) were used to calculate reliability, and Spearman correlation coefficients were used to assess validity. Cutoff points, sensitivity, and specificity were based on receiver operating characteristic plots. Test-retest reliability was .80 for the BBS, .91 for the FGA, and .88 for the BESTest. Interrater reliability was greater than .93 for all 3 tests. The FGA and BESTest were correlated with the BBS (r=.78 and r=.87, respectively). Cutoff scores to identify fallers were 47/56 for the BBS, 15/30 for the FGA, and 69% for the BESTest. The overall accuracy (area under the curve) for the BBS, FGA, and BESTest was .79, .80, and .85, respectively. Fall reports were retrospective. Both the FGA and the BESTest have reliability and validity for assessing balance in individuals with PD. The BESTest is most sensitive for identifying fallers.

  7. Chromosome specific repetitive DNA sequences

    DOEpatents

    Moyzis, Robert K.; Meyne, Julianne

    1991-01-01

    A method is provided for determining specific nucleotide sequences useful in forming a probe which can identify specific chromosomes, preferably through in situ hybridization within the cell itself. In one embodiment, chromosome preferential nucleotide sequences are first determined from a library of recombinant DNA clones having families of repetitive sequences. Library clones are identified with a low homology with a sequence of repetitive DNA families to which the first clones respectively belong and variant sequences are then identified by selecting clones having a pattern of hybridization with genomic DNA dissimilar to the hybridization pattern shown by the respective families. In another embodiment, variant sequences are selected from a sequence of a known repetitive DNA family. The selected variant sequence is classified as chromosome specific, chromosome preferential, or chromosome nonspecific. Sequences which are classified as chromosome preferential are further sequenced and regions are identified having a low homology with other regions of the chromosome preferential sequence or with known sequences of other family me This invention is the result of a contract with the Department of Energy (Contract No. W-7405-ENG-36).

  8. Biological preservation of plant derived animal feed with antifungal microorganisms: safety and formulation aspects.

    PubMed

    Melin, Petter; Sundh, Ingvar; Håkansson, Sebastian; Schnürer, Johan

    2007-08-01

    During storage of moist animal feed, growth of detrimental fungi causing spoilage, or being mycotoxigenic or pathogenic, is a severe problem. Addition of biopreservative yeasts or lactic acid bacteria can significantly reduce this problem. However, their use requires several careful considerations. One is the safety to the animal, humans and the environment, tightly connected to legal aspects and the need for pre-market authorisation when supplementing feed with microorganisms. Although both yeasts and lactic acid bacteria are considered comparatively safe organisms due to low production of toxic metabolites, it is of great importance to understand the mechanisms behind the biopreservative abilities. Another important issue concerns practical aspects, such as the economic production of large amounts of the organisms and the development of a suitable formulation giving the organisms a long shelf life. These aspects are discussed and a recommendation of this review is that both safety and formulation aspects of a specific microbe should be considered at an early stage in the selection of new organisms with biopreservation potential.

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

    NASA Astrophysics Data System (ADS)

    Finlinson, Scott Michael

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

  10. Cocoa agronomy, quality, nutritional, and health aspects.

    PubMed

    Badrie, Neela; Bekele, Frances; Sikora, Elzbieta; Sikora, Marek

    2015-01-01

    The history of cocoa and chocolate including the birth and the expansion of the chocolate industry was described. Recent developments in the industry and cocoa economy were briefly depicted. An overview of the classification of cacao as well as studies on phenotypic and genetic diversity was presented. Cocoa agronomic practices including traditional and modern propagation techniques were reviewed. Nutrition-related health benefits derived from cocoa consumption were listed and widely reviewed. The specific action of cocoa antioxidants was compared to those of teas and wines. Effects of adding milk to chocolate and chocolate drinks versus bioavailability of cocoa polyphenols were discussed. Finally, flavor, sensory, microbiological, and toxicological aspects of cocoa consumption were presented.

  11. Culture, Threat, and Mental Illness Stigma: Identifying Culture-Specific Threat among Chinese-American Groups

    PubMed Central

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

    2014-01-01

    We incorporate anthropological insights into a stigma framework to elucidate the role of culture in threat perception and stigma among Chinese groups. Prior work suggests that genetic contamination that jeopardizes the extension of one’s family lineage may comprise a culture-specific threat among Chinese groups. In Study 1, a national survey conducted from 2002–2003 assessed cultural differences in mental illness stigma and perceptions of threat in 56 Chinese-Americans and 589 European-Americans. Study 2 sought to empirically test this culture-specific threat of genetic contamination to lineage via a memory paradigm. Conducted from June to August 2010, 48 Chinese-American and 37 European-American university students in New York City read vignettes containing content referring to lineage or non-lineage concerns. Half the participants in each ethnic group were assigned to a condition in which the illness was likely to be inherited (genetic condition) and the rest read that the illness was unlikely to be inherited (non-genetic condition). Findings from Study 1 and 2 were convergent. In Study 1, culture-specific threat to lineage predicted cultural variation in stigma independently and after accounting for other forms of threat. In Study 2, Chinese-Americans in the genetic condition were more likely to accurately recall and recognize lineage content than the Chinese-Americans in the non-genetic condition, but that memorial pattern was not found for non-lineage content. The identification of this culture-specific threat among Chinese groups has direct implications for culturally-tailored anti-stigma interventions. Further, this framework might be implemented across other conditions and cultural groups to reduce stigma across cultures. PMID:23702210

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

    PubMed

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

    2013-07-01

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

  13. Glycoprotein Biochemistry (Biosynthesis)--A Vehicle for Teaching Many Aspects of Biochemistry and Molecular Biology.

    ERIC Educational Resources Information Center

    Cole, Clair R.; Smith, Christopher A.

    1990-01-01

    Information about the biosynthesis of the carbohydrate portions or glycans of glycoproteins is presented. The teaching of glycosylation can be used to develop and emphasize many general aspects of biosynthesis, in addition to explaining specific biochemical and molecular biological features associated with producing the oligosaccharide portions of…

  14. The assessment of aesthetic and perceptual aspects within environmental impact assessment of renewable energy projects in Italy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tolli, Michela, E-mail: michela.tolli@uniroma1.it; Recanatesi, Fabio, E-mail: fabio.rec@unitus.it; Piccinno, Matteo

    The main aim of this paper is to explore how perceptual and aesthetic impact analyses are considered in Environmental Impact Assessment (EIA), with specific reference to Italian renewable energy projects. To investigate this topic, the paper starts by establishing which factors are linked with perceptual and aesthetic impacts and why it is important to analyze these aspects, which are also related to legislative provisions and procedures in Europe and in Italy. In particular the paper refers to renewable energy projects because environmental policies are encouraging more and more investment in this kind of primary resource. The growing interest in thismore » type of energy is leading to the realization of projects which change the governance of territories, with inevitable effects on the landscape from the aesthetic and perceptual points of view. Legislative references to EIA, including the latest directive regarding this topic show the importance of integrating the assessment of environmental and perceptual impacts, thus there is a need to improve EIA methodological approaches to this purpose. This paper proposes a profile of aesthetic and perceptual impact analysis in EIA for renewable energy projects in Italy, and concludes with recommendations as to how this kind of analysis could be improved. - Highlights: • We analyze 29 EIA Reports of Italian renewable energy projects. • We examine esthetic and perceptual aspects present in Italian EIA reports. • We identified inconsistency in use of methods for esthetic and perceptual aspects. • Local populations are rarely included as stakeholders in EIAs. • A shared understanding of perceptual and esthetic issues in EIA proceedings is required.« less

  15. Scaling laws and size effects for amorphous crystallization kinetics: Constraints imposed by nucleation and growth specificities.

    PubMed

    Descamps, Marc; Willart, Jean-François

    2018-05-05

    In the present paper we review different aspects of the crystallization of amorphous compounds in relation to specificities of the nucleation and growth rates. Its main purpose is: i) to underline the interest of a scaling analysis of recrystallization kinetics to identify similarities or disparities of experimental kinetic regimes. ii) to highlight the intrinsic link between the nucleation rate and growth rate with a temperature dependent characteristic transformation time τ(T), and a characteristic size ξ(T). The consequences on the influence of the sample size on kinetics of crystallization is considered. The significance of size effect and confinement for amorphous stabilization in the pharmaceutical sciences is discussed. Copyright © 2018. Published by Elsevier B.V.

  16. Pathological jealousy: romantic relationship characteristics, emotional and personality aspects, and social adjustment.

    PubMed

    Costa, Andrea Lorenada; Sophia, Eglacy C; Sanches, Cíntia; Tavares, Hermano; Zilberman, Monica L

    2015-03-15

    The aim of this study was to identify romantic relationship characteristics, emotional and personality aspects and social adjustment in subjects with pathological jealousy (PJ) and to compare them to control group. The participants, 32 individuals with PJ and 31 healthy volunteers completed measures of jealousy intensity, attachment type, love and relationship styles, personality, impulsivity, aggressiveness and social adjustment. Socio-demographic profiles were also obtained. Participants with PJ were significantly older than the control group, but no other important socio-demographic differences were observed. Participants with PJ were significantly more jealous and were predominately categorized with anxious-ambivalent attachment type, and Mania love style. They presented with elevated novelty seeking and harm avoidance, low self-directedness and cooperativeness, high levels of impulsivity and trait anxiety, and poor social adjustment. Multivariate analysis showed that jealousy intensity and trait anxiety were the variables that best distinguished participants with PJ from the control group. This study was limited by the cross-sectional design and relatively small sample size. PJ presents a particular pattern of attachment, love style, and personality structure, and deserves further attention as a specific potential disorder of the romantic bonding. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Recent trends in the study of specific phobias.

    PubMed

    Pull, Charles B

    2008-01-01

    Specific phobias are prevalent and often disabling anxiety disorders. The present review examines relevant investigations that have been published during the last 2 years on major aspects of this group of disorders. Recent studies have come mainly from epidemiology, brain imagery and cognitive-behavioral therapy, including virtual reality exposure therapy. Studies published in the last 2 years confirm the high prevalence of specific phobias in the general population and provide new insights into the mechanisms underlying the fear reaction after exposure to a phobic stimulus.

  18. Socio-Cultural Aspects of Chagas Disease: A Systematic Review of Qualitative Research

    PubMed Central

    Ventura-Garcia, Laia; Roura, Maria; Pell, Christopher; Posada, Elisabeth; Gascón, Joaquim; Aldasoro, Edelweis; Muñoz, Jose; Pool, Robert

    2013-01-01

    Background Globally, more than 10 million people are infected with Trypanosoma cruzi, which causes about 20 000 annual deaths. Although Chagas disease is endemic to certain regions of Latin America, migratory flows have enabled its expansion into areas where it was previously unknown. Economic, social and cultural factors play a significant role in its presence and perpetuation. This systematic review aims to provide a comprehensive overview of qualitative research on Chagas disease, both in endemic and non-endemic countries. Methodology/Principal Findings Searches were carried out in ten databases, and the bibliographies of retrieved studies were examined. Data from thirty-three identified studies were extracted, and findings were analyzed and synthesized along key themes. Themes identified for endemic countries included: socio-structural determinants of Chagas disease; health practices; biomedical conceptions of Chagas disease; patient's experience; and institutional strategies adopted. Concerning non-endemic countries, identified issues related to access to health services and health seeking. Conclusions The emergence and perpetuation of Chagas disease depends largely on socio-cultural aspects influencing health. As most interventions do not address the clinical, environmental, social and cultural aspects jointly, an explicitly multidimensional approach, incorporating the experiences of those affected is a potential tool for the development of long-term successful programs. Further research is needed to evaluate this approach. PMID:24069473

  19. Evaluation of the mtDNA-COII Region Based Species Specific Assay for Identifying Members of the Anopheles culicifacies Species Complex

    PubMed Central

    Manonmani, Arulsamy Mary; Mathivanan, Ashok Kumar; Sadanandane, Candassamy; Jambulingam, Purushothaman

    2013-01-01

    Background: Anopheles culicifacies, a major malarial vector has been recognized as a complex of five sibling species, A, B, C, D and E. These sibling species exhibit varied vectorial capacity, host specificity and susceptibility to malarial parasites/ insecticides. In this study, a PCR assay developed earlier for distinguishing the five individual species was validated on samples of An. culicifacies collected from various parts of India. Methods: The samples were initially screened using the rDNA-ITS2 region based primers which categorised the samples into either A/D group or B/C/E group. A proportion of samples belonging to each group were subjected to the mtDNA-COII PCR assay for identifying individual species. Results: Among the 615 samples analysed by rDNA-ITS2 PCR assay, 303 were found to belong to A/D group and 299 to B/C/E group while 13 turned negative. Among 163 samples belonging to A/D group, only one sample displayed the profile characteristic of species A and among the 176 samples falling in the B/C/E group, 51 were identified as species B, 14 as species C and 41 as species E respectively by the mtDNA-COII PCR assay. Samples exhibiting products diagnostic of B/C/E, when subjected to PCR-RFLP assay identified 15 samples as species E. Conclusion: Validation of the mtDNA-COII PCR assay on large number of samples showed that this technique cannot be used universally to distinguish the 5 members of this species complex, as it has been designed based on minor/single base differences observed in the COII region. PMID:24409441

  20. Integrating the epistemic and ontological aspects of content knowledge in science teaching and learning

    NASA Astrophysics Data System (ADS)

    Papadouris, Nicos; Constantinou, Constantinos P.

    2017-04-01

    Promoting facility with content knowledge is one of the most important objectives of science teaching. Conventionally, the focus for this objective is placed on the substantive side of content knowledge (e.g. science concepts/laws), whereas its epistemic or ontological aspects (e.g. why do we construct concepts?) rarely receive explicit attention. In this article, we develop a theoretical argument for the value of elevating the attention paid to the epistemic/ontological aspects of content knowledge and integrating them with its substantive side. Our argument is structured in two parts. The first unpacks the epistemic/ontological aspects of content knowledge and their role in science. For this, we focus on two specific aspects (i.e. ontological status and epistemic value of science concepts), which we elaborate in the context of two particular content domains, namely magnetism and energy. The second part of the argument highlights the potential of discourse on epistemic/ontological aspects to facilitate learning in science. We delineate how such discourse could (a) promote coherent conceptual understanding, (b) foster a productive epistemological stance towards science learning, and (c) enhance students' appreciation of ideas associated with the nature of science. The article concludes with a discussion of ensuing implications for science education.

  1. Is the Use of Information and Communication Technology Associated With Aspects of Women's Primary Health Care in Brazil?

    PubMed

    Matta-Machado, Antônio Thomaz Gonzaga; de Lima, Ângela Maria L Dayrell; de Abreu, Daisy Maria Xavier; Araújo, Lucas Lobato; Sobrinho, Délcio Fonseca; Silva Lopes, Érica Araújo; Teixeira, Gabriel Henrique Silva; Dos Santos, Alaneir de Fátima

    The use of information and communication technology (ICT) is on the increase in the health systems, representing a means of improving the quality of health care. This study analyzed the ICT incorporation in primary care in Brazil and identified the different aspects that may be associated with better quality in the care provided, in relation to certain aspects of women's care. We noted an unevenness regarding ICT incorporation in Brazil. However, the findings indicate an association between ICT and certain aspects of the quality provided in women's health care, which reinforces the need for further studies on this type of evaluation.

  2. Accuracy of Gradient Reconstruction on Grids with High Aspect Ratio

    NASA Technical Reports Server (NTRS)

    Thomas, James

    2008-01-01

    Gradient approximation methods commonly used in unstructured-grid finite-volume schemes intended for solutions of high Reynolds number flow equations are studied comprehensively. The accuracy of gradients within cells and within faces is evaluated systematically for both node-centered and cell-centered formulations. Computational and analytical evaluations are made on a series of high-aspect-ratio grids with different primal elements, including quadrilateral, triangular, and mixed element grids, with and without random perturbations to the mesh. Both rectangular and cylindrical geometries are considered; the latter serves to study the effects of geometric curvature. The study shows that the accuracy of gradient reconstruction on high-aspect-ratio grids is determined by a combination of the grid and the solution. The contributors to the error are identified and approaches to reduce errors are given, including the addition of higher-order terms in the direction of larger mesh spacing. A parameter GAMMA characterizing accuracy on curved high-aspect-ratio grids is discussed and an approximate-mapped-least-square method using a commonly-available distance function is presented; the method provides accurate gradient reconstruction on general grids. The study is intended to be a reference guide accompanying the construction of accurate and efficient methods for high Reynolds number applications

  3. AspectAssay: A Technique for Expanding the Pool of Available Aspect Mining Test Data Using Concern Seeding

    ERIC Educational Resources Information Center

    Moore, David G., Jr.

    2013-01-01

    Aspect-oriented software design (AOSD) enables better and more complete separation of concerns in software-intensive systems. By extracting aspect code and relegating crosscutting functionality to aspects, software engineers can improve the maintainability of their code by reducing code tangling and coupling of code concerns. Further, the number…

  4. Teachers’ perceptions of aspects affecting seminar learning: a qualitative study

    PubMed Central

    2013-01-01

    Background Many medical schools have embraced small group learning methods in their undergraduate curricula. Given increasing financial constraints on universities, active learning groups like seminars (with 25 students a group) are gaining popularity. To enhance the understanding of seminar learning and to determine how seminar learning can be optimised it is important to investigate stakeholders’ views. In this study, we qualitatively explored the views of teachers on aspects affecting seminar learning. Methods Twenty-four teachers with experience in facilitating seminars in a three-year bachelor curriculum participated in semi-structured focus group interviews. Three focus groups met twice with an interval of two weeks led by one moderator. Sessions were audio taped, transcribed verbatim and independently coded by two researchers using thematic analysis. An iterative process of data reduction resulted in emerging aspects that influence seminar learning. Results Teachers identified seven key aspects affecting seminar learning: the seminar teacher, students, preparation, group functioning, seminar goals and content, course coherence and schedule and facilities. Important components of these aspects were: the teachers’ role in developing seminars (‘ownership’), the amount and quality of preparation materials, a non-threatening learning climate, continuity of group composition, suitability of subjects for seminar teaching, the number and quality of seminar questions, and alignment of different course activities. Conclusions The results of this study contribute to the unravelling of the ‘the black box’ of seminar learning. Suggestions for ways to optimise active learning in seminars are made regarding curriculum development, seminar content, quality assurance and faculty development. PMID:23399475

  5. The Development of the Foundations of Modern Pedagogy: Paradigmal and Methodological Aspects of Research

    ERIC Educational Resources Information Center

    Dmitrenko, ?amara ?.; Lavryk, Tatjana V.; Yaresko, Ekaterina V.

    2015-01-01

    Changes in the various fields of knowledge influenced the pedagogical science. The article explains the structure of the foundations of modern pedagogy through paradigmal and methodological aspects. Bases of modern pedagogy include complex of paradigms, object and subject of science, general and specific principles, methods and technologies.…

  6. Genome-wide maps of m6A circRNAs identify widespread and cell-type-specific methylation patterns that are distinct from mRNAs

    PubMed Central

    Zhou, Chan; Molinie, Benoit; Daneshvar, Kaveh; Pondick, Joshua V.; Wang, Jinkai; Van Wittenberghe, Nicholas O.; Xing, Yi; Giallourakis, Cosmas C.; Mullen, Alan C.

    2017-01-01

    Summary N6-methyladenosine (m6A) is the most abundant internal modification of mRNAs and is implicated in all aspects of post-transcriptional RNA metabolism. However, little is known about m6A modifications to circular (circ) RNAs. We developed a computational pipeline (AutoCirc) that together with depletion of ribosomal RNA and m6A immunoprecipitation defined thousands of m6A-circRNAs, with cell-type-specific expression. The presence of m6A-circRNAs is corroborated by interaction between circRNAs and YTHDF1/YTHDF2, proteins that read m6A sites in mRNAs, and by reduced m6A levels upon depletion of METTL3, the m6A writer. Despite sharing m6A readers and writers, m6A-circRNAs are frequently derived from exons that are not methylated in mRNAs, while mRNAs that are methylated on the same exons that compose m6A-circRNAs exhibit less stability, in a process regulated by YTHDF2. These results expand our understanding of the breadth of m6A modifications and uncover regulation of circRNAs through m6A modification. PMID:28854373

  7. Comparison of Gait Aspects According to FES Stimulation Position Applied to Stroke Patients

    PubMed Central

    Mun, Byeong-mu; Kim, Tae-ho; Lee, Jin-hwan; Lim, Jin-youg; Seo, Dong-kwon; Lee, Dong-jin

    2014-01-01

    [Purpose] This study sought to identify the gait aspects according to the FES stimulation position in stroke patients during gait training. [Subjects and Methods] To perform gait analysis, ten stroke patients were grouped based on 4 types of gait conditions: gait without FES stimulation (non-FES), gait with FES stimulation on the tibialis anterior (Ta), gait with FES stimulation on the tibialis anterior and quadriceps (TaQ), and gait with FES stimulation on the tibialis anterior and gluteus medius (TaGm). [Results] Based on repeated measures analysis of variance of measurements of gait aspects comprised of gait speed, gait cycle, and step length according to the FES stimulation position, the FES stimulation significantly affected gait aspects. [Conclusion] In conclusion, stimulating the tibialis anterior and quadriceps and stimulating the tibialis anterior and gluteus medius are much more effective than stimulating only the tibialis anterior during gait training in stroke patients using FES. PMID:24764634

  8. 'Right Now, Sophie (∗)Swims in the Pool?!': Brain Potentials of Grammatical Aspect Processing.

    PubMed

    Flecken, Monique; Walbert, Kelly; Dijkstra, Ton

    2015-01-01

    We investigated whether brain potentials of grammatical aspect processing resemble semantic or morpho-syntactic processing, or whether they instead are characterized by an entirely distinct pattern in the same individuals. We studied aspect from the perspective of agreement between the temporal information in the context (temporal adverbials, e.g., Right now) and a morpho-syntactic marker of grammatical aspect (e.g., progressive is swimming). Participants read questions providing a temporal context that was progressive (What is Sophie doing in the pool right now?) or habitual (What does Sophie do in the pool every Monday?). Following a lead-in sentence context such as Right now, Sophie…, we measured event-related brain potentials (ERPs) time-locked to verb phrases in four different conditions, e.g., (a) is swimming (control); (b) (∗)is cooking (semantic violation); (c) (∗)are swimming (morpho-syntactic violation); or (d)?swims (aspect mismatch); …in the pool." The collected ERPs show typical N400 and P600 effects for semantics and morpho-syntax, while aspect processing elicited an Early Negativity (250-350 ms). The aspect-related Negativity was short-lived and had a central scalp distribution with an anterior onset. This differentiates it not only from the semantic N400 effect, but also from the typical LAN (Left Anterior Negativity), that is frequently reported for various types of agreement processing. Moreover, aspect processing did not show a clear P600 modulation. We argue that the specific context for each item in this experiment provided a trigger for agreement checking with temporal information encoded on the verb, i.e., morphological aspect marking. The aspect-related Negativity obtained for aspect agreement mismatches reflects a violated expectation concerning verbal inflection (in the example above, the expected verb phrase was Sophie is X-ing rather than Sophie X-s in condition d). The absence of an additional P600 for aspect processing suggests

  9. Requirements Specification Document

    DOT National Transportation Integrated Search

    1996-04-26

    The System Definition Document identifies the top level processes, data flows, : and system controls for the Gary-Chicago-Milwaukee (GCM) Corridor Transportation Information Center (C-TIC). This Requirements Specification establishes the requirements...

  10. Fundamental aspects of and failure modes in high-temperature composites

    NASA Technical Reports Server (NTRS)

    Chamis, Christos C.; Ginty, Carol A.

    1990-01-01

    Fundamental aspects of and attendant failure mechanisms for high temperature composites are summarized. These include: (1) in-situ matrix behavior; (2) load transfer; (3) limits on matrix ductility to survive a given number of cyclic loadings; (4) fundamental parameters which govern thermal stresses; (5) vibration stresses; and (6) impact resistance. The resulting guidelines are presented in terms of simple equations which are suitable for the preliminary assessment of the merits of a particular high temperature composite in a specific application.

  11. Identifying, studying and making good use of macromolecular crystals

    PubMed Central

    Calero, Guillermo; Cohen, Aina E.; Luft, Joseph R.; Newman, Janet; Snell, Edward H.

    2014-01-01

    Structural biology has contributed tremendous knowledge to the understanding of life on the molecular scale. The Protein Data Bank, a depository of this structural knowledge, currently contains over 100 000 protein structures, with the majority stemming from X-ray crystallography. As the name might suggest, crystallography requires crystals. As detectors become more sensitive and X-ray sources more intense, the notion of a crystal is gradually changing from one large enough to embellish expensive jewellery to objects that have external dimensions of the order of the wavelength of visible light. Identifying these crystals is a prerequisite to their study. This paper discusses developments in identifying these crystals during crystallization screening and distinguishing them from other potential outcomes. The practical aspects of ensuring that once a crystal is identified it can then be positioned in the X-ray beam for data collection are also addressed. PMID:25084371

  12. A Group of Indonesian Adult EFL Students' Mastery of Tenses and Aspects: Investigating the Internal and External Factors of Learning

    ERIC Educational Resources Information Center

    Muhlisin; Salikin, Hairus

    2015-01-01

    The study aimed, firstly, to assess a group of Indonesian adult EFL students' mastery of tenses and aspects as part of their mastery of English grammar and, secondly, to identify if their experience of going through the instructional processes, their perceptions of and habits in studying English grammar shaped their mastery of tenses and aspects.…

  13. What Aspects of Personal Care Are Most Important to Patients Undergoing Radiation Therapy for Prostate Cancer?

    PubMed

    Foley, Kimberley A; Feldman-Stewart, Deb; Groome, Patti A; Brundage, Michael D; McArdle, Siobhan; Wallace, David; Peng, Yingwei; Mackillop, William J

    2016-02-01

    The overall quality of patient care is a function of the quality of both its technical and its nontechnical components. The purpose of this study was to identify the elements of nontechnical (personal) care that are most important to patients undergoing radiation therapy for prostate cancer. We reviewed the literature and interviewed patients and health professionals to identify elements of personal care pertinent to patients undergoing radiation therapy for prostate cancer. We identified 143 individual elements relating to 10 aspects of personal care. Patients undergoing radical radiation therapy for prostate cancer completed a self-administered questionnaire in which they rated the importance of each element. The overall importance of each element was measured by the percentage of respondents who rated it as "very important." The importance of each aspect of personal care was measured by the mean importance of its elements. One hundred eight patients completed the questionnaire. The percentage of patients who rated each element "very important" ranged from 7% to 95% (mean 61%). The mean importance rating of the elements of each aspect of care varied significantly: "perceived competence of caregivers," 80%; "empathy and respectfulness of caregivers," 67%; "adequacy of information sharing," 67%; "patient centeredness," 59%; "accessibility of caregivers," 57%; "continuity of care," 51%; "privacy," 51%; "convenience," 45%; "comprehensiveness of services," 44%; and "treatment environment," 30% (P<.0001). Neither age nor education was associated with importance ratings, but the patient's health status was associated with the rating of some elements of care. Many different elements of personal care are important to patients undergoing radiation therapy for prostate cancer, but the 3 aspects of care that most believe are most important are these: the perceived competence of their caregivers, the empathy and respectfulness of their caregivers, and the adequacy of

  14. Aspect ratio effects on limited scrape-off layer plasma turbulence

    NASA Astrophysics Data System (ADS)

    Jolliet, Sébastien; Halpern, Federico D.; Loizu, Joaquim; Mosetto, Annamaria; Ricci, Paolo

    2014-02-01

    The drift-reduced Braginskii model describing turbulence in the tokamak scrape-off layer is written for a general magnetic configuration with a limiter. The equilibrium is then specified for a circular concentric magnetic geometry retaining aspect ratio effects. Simulations are then carried out with the help of the global, flux-driven fluid three-dimensional code GBS [Ricci et al., Plasma Phys. Controlled Fusion 54, 124047 (2012)]. Linearly, both simulations and simplified analytical models reveal a stabilization of ballooning modes. Nonlinearly, flux-driven nonlinear simulations give a pressure characteristic length whose trends are correctly captured by the gradient removal theory [Ricci and Rogers, Phys. Plasmas 20, 010702 (2013)], that assumes the profile flattening from the linear modes as the saturation mechanism. More specifically, the linear stabilization of ballooning modes is reflected by a 15% increase in the steady-state pressure gradient obtained from GBS nonlinear simulations when going from an infinite to a realistic aspect ratio.

  15. Human Factors Engineering Aspects of Modifications in Control Room Modernization

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hugo, Jacques; Clefton, Gordon; Joe, Jeffrey

    This report describes the basic aspects of control room modernization projects in the U.S. nuclear industry and the need for supplementary guidance on the integration of human factors considerations into the licensing and regulatory aspects of digital upgrades. The report pays specific attention to the integration of principles described in NUREG-0711 (Human Factors Engineering Program Review Model) and how supplementary guidance can help to raise general awareness in the industry regarding the complexities of control room modernization projects created by many interdependent regulations, standards and guidelines. The report also describes how human factors engineering principles and methods provided by variousmore » resources and international standards can help in navigating through the process of licensing digital upgrades. In particular, the integration of human factors engineering guidance and requirements into the process of licensing digital upgrades can help reduce uncertainty related to development of technical bases for digital upgrades that will avoid the introduction of new failure modes.« less

  16. Neuronal cell fate specification in Drosophila.

    PubMed

    Jan, Y N; Jan, L Y

    1994-02-01

    Recent work indicates that the Drosophila nervous system develops in a progressive process of cell fate specification. Expression of specific proneural genes in clusters of cells (the proneural clusters) in the cellular blastoderm endows these cells with the potential to form certain types of neural precursors. Intercellular interactions that involve both proneural genes and neurogenic genes then allow the neural precursors to be singled out from the proneural clusters. Expression of neural precursor genes in all neural precursors is likely to account for the universal aspects of neuronal differentiation, such as axonal outgrowth. Selective expression of certain neuronal-type selector genes further specifies the type of neuron(s) that a neural precursor will produce.

  17. Aspect-Oriented Subprogram Synthesizes UML Sequence Diagrams

    NASA Technical Reports Server (NTRS)

    Barry, Matthew R.; Osborne, Richard N.

    2006-01-01

    The Rational Sequence computer program described elsewhere includes a subprogram that utilizes the capability for aspect-oriented programming when that capability is present. This subprogram is denoted the Rational Sequence (AspectJ) component because it uses AspectJ, which is an extension of the Java programming language that introduces aspect-oriented programming techniques into the language

  18. Understanding How Grammatical Aspect Influences Legal Judgment

    PubMed Central

    Sherrill, Andrew M.; Eerland, Anita; Zwaan, Rolf A.; Magliano, Joseph P.

    2015-01-01

    Recent evidence suggests that grammatical aspect can bias how individuals perceive criminal intentionality during discourse comprehension. Given that criminal intentionality is a common criterion for legal definitions (e.g., first-degree murder), the present study explored whether grammatical aspect may also impact legal judgments. In a series of four experiments participants were provided with a legal definition and a description of a crime in which the grammatical aspect of provocation and murder events were manipulated. Participants were asked to make a decision (first- vs. second-degree murder) and then indicate factors that impacted their decision. Findings suggest that legal judgments can be affected by grammatical aspect but the most robust effects were limited to temporal dynamics (i.e., imperfective aspect results in more murder actions than perfective aspect), which may in turn influence other representational systems (i.e., number of murder actions positively predicts perceived intentionality). In addition, findings demonstrate that the influence of grammatical aspect on situation model construction and evaluation is dependent upon the larger linguistic and semantic context. Together, the results suggest grammatical aspect has indirect influences on legal judgments to the extent that variability in aspect changes the features of the situation model that align with criteria for making legal judgments. PMID:26496364

  19. Are vision-specific quality of life questionnaires important in assessing rehabilitation for patients with hemianopia post stroke?

    PubMed

    George, Stacey; Hayes, Allison; Chen, Celia; Crotty, Maria

    2011-01-01

    To explore the relationship between disability and functional measures with vision-specific quality of life (QoL) measures for people with hemianopia and stroke. The Behavioral Inattention Test (BIT) and the Mayo-Portland Adaptability Inventory (MPAI) were compared with scores on 2 vision-specific QoL measures, the National Eye Institute Visual Function Questionnaire (NEI VFQ-25) and Veteran Low Vision Visual Function Questionnaire (VA LV VFQ-48). Rehabilitation hospitals in Adelaide, South Australia. Stroke patients (n = 24) with homonymous hemianopia. Most of the BIT and MPAI scores were significantly associated with the NEI VFQ-25 and VA LV VFQ-48 scores. Behavioral test scores of the BIT and the MPAI total score correlated with more aspects of the QoL measures than the other components of the BIT and the MPAI. BIT and MPAI measure constructs associated with QoL for people with hemianopia following stroke. Vision-specific QoL questionnaires can complement the functional instruments by identifying the domains of difficulty, based on the instrument's subscale, that can guide rehabilitation therapists to address the person's deficit.

  20. Serum proteomic analysis identifies sex-specific differences in lipid metabolism and inflammation profiles in adults diagnosed with Asperger syndrome

    PubMed Central

    2014-01-01

    Background The higher prevalence of Asperger Syndrome (AS) and other autism spectrum conditions in males has been known for many years. However, recent multiplex immunoassay profiling studies have shown that males and females with AS have distinct proteomic changes in serum. Methods Here, we analysed sera from adults diagnosed with AS (males = 14, females = 16) and controls (males = 13, females = 16) not on medication at the time of sample collection, using a combination of multiplex immunoassay and shotgun label-free liquid chromatography mass spectrometry (LC-MSE). The main objective was to identify sex-specific serum protein changes associated with AS. Results Multiplex immunoassay profiling led to identification of 16 proteins that were significantly altered in AS individuals in a sex-specific manner. Three of these proteins were altered in females (ADIPO, IgA, APOA1), seven were changed in males (BMP6, CTGF, ICAM1, IL-12p70, IL-16, TF, TNF-alpha) and six were changed in both sexes but in opposite directions (CHGA, EPO, IL-3, TENA, PAP, SHBG). Shotgun LC-MSE profiling led to identification of 13 serum proteins which had significant sex-specific changes in the AS group and, of these, 12 were altered in females (APOC2, APOE, ARMC3, CLC4K, FETUB, GLCE, MRRP1, PTPA, RN149, TLE1, TRIPB, ZC3HE) and one protein was altered in males (RGPD4). The free androgen index in females with AS showed an increased ratio of 1.63 compared to controls. Conclusion Taken together, the serum multiplex immunoassay and shotgun LC-MSE profiling results indicate that adult females with AS had alterations in proteins involved mostly in lipid transport and metabolism pathways, while adult males with AS showed changes predominantly in inflammation signalling. These results provide further evidence that the search for biomarkers or novel drug targets in AS may require stratification into male and female subgroups, and could lead to the development of novel targeted treatment