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Identifying mechanistic similarities in drug responses

KAUST Repository

Zhao, C.

2012-05-15

Motivation: In early drug development, it would be beneficial to be able to identify those dynamic patterns of gene response that indicate that drugs targeting a particular gene will be likely or not to elicit the desired response. One approach would be to quantitate the degree of similarity between the responses that cells show when exposed to drugs, so that consistencies in the regulation of cellular response processes that produce success or failure can be more readily identified.Results: We track drug response using fluorescent proteins as transcription activity reporters. Our basic assumption is that drugs inducing very similar alteration in transcriptional regulation will produce similar temporal trajectories on many of the reporter proteins and hence be identified as having similarities in their mechanisms of action (MOA). The main body of this work is devoted to characterizing similarity in temporal trajectories/signals. To do so, we must first identify the key points that determine mechanistic similarity between two drug responses. Directly comparing points on the two signals is unrealistic, as it cannot handle delays and speed variations on the time axis. Hence, to capture the similarities between reporter responses, we develop an alignment algorithm that is robust to noise, time delays and is able to find all the contiguous parts of signals centered about a core alignment (reflecting a core mechanism in drug response). Applying the proposed algorithm to a range of real drug experiments shows that the result agrees well with the prior drug MOA knowledge. © The Author 2012. Published by Oxford University Press. All rights reserved.
Identifying mechanistic similarities in drug responses

KAUST Repository

Zhao, C.; Hua, J.; Bittner, M. L.; Ivanov, I.; Dougherty, a. E. R.

2012-01-01

Motivation: In early drug development, it would be beneficial to be able to identify those dynamic patterns of gene response that indicate that drugs targeting a particular gene will be likely or not to elicit the desired response. One approach
Identifying salt stress-responsive transcripts from Roselle ( Hibiscus ...

African Journals Online (AJOL)

Hibiscus sabdariffa L.). Identifying the potentially novel transcripts responsible for salt stress tolerance in roselle will increase knowledge of the molecular mechanism underlying salt stress responses. In this study, differential display reverse ...
Identifying Predictors, Moderators, and Mediators of Antidepressant Response in Major Depressive Disorder: Neuroimaging Approaches

Science.gov (United States)

Phillips, Mary L.; Chase, Henry W.; Sheline, Yvette I.; Etkin, Amit; Almeida, Jorge R.C.; Deckersbach, Thilo; Trivedi, Madhukar H.

2015-01-01

Objective Despite significant advances in neuroscience and treatment development, no widely accepted biomarkers are available to inform diagnostics or identify preferred treatments for individuals with major depressive disorder. Method In this critical review, the authors examine the extent to which multimodal neuroimaging techniques can identify biomarkers reflecting key pathophysiologic processes in depression and whether such biomarkers may act as predictors, moderators, and mediators of treatment response that might facilitate development of personalized treatments based on a better understanding of these processes. Results The authors first highlight the most consistent findings from neuroimaging studies using different techniques in depression, including structural and functional abnormalities in two parallel neural circuits: serotonergically modulated implicit emotion regulation circuitry, centered on the amygdala and different regions in the medial prefrontal cortex; and dopaminergically modulated reward neural circuitry, centered on the ventral striatum and medial prefrontal cortex. They then describe key findings from the relatively small number of studies indicating that specific measures of regional function and, to a lesser extent, structure in these neural circuits predict treatment response in depression. Conclusions Limitations of existing studies include small sample sizes, use of only one neuroimaging modality, and a focus on identifying predictors rather than moderators and mediators of differential treatment response. By addressing these limitations and, most importantly, capitalizing on the benefits of multimodal neuroimaging, future studies can yield moderators and mediators of treatment response in depression to facilitate significant improvements in shorter- and longer-term clinical and functional outcomes. PMID:25640931
Identifying predictors, moderators, and mediators of antidepressant response in major depressive disorder: neuroimaging approaches.

Science.gov (United States)

Phillips, Mary L; Chase, Henry W; Sheline, Yvette I; Etkin, Amit; Almeida, Jorge R C; Deckersbach, Thilo; Trivedi, Madhukar H

2015-02-01

Despite significant advances in neuroscience and treatment development, no widely accepted biomarkers are available to inform diagnostics or identify preferred treatments for individuals with major depressive disorder. In this critical review, the authors examine the extent to which multimodal neuroimaging techniques can identify biomarkers reflecting key pathophysiologic processes in depression and whether such biomarkers may act as predictors, moderators, and mediators of treatment response that might facilitate development of personalized treatments based on a better understanding of these processes. The authors first highlight the most consistent findings from neuroimaging studies using different techniques in depression, including structural and functional abnormalities in two parallel neural circuits: serotonergically modulated implicit emotion regulation circuitry, centered on the amygdala and different regions in the medial prefrontal cortex; and dopaminergically modulated reward neural circuitry, centered on the ventral striatum and medial prefrontal cortex. They then describe key findings from the relatively small number of studies indicating that specific measures of regional function and, to a lesser extent, structure in these neural circuits predict treatment response in depression. Limitations of existing studies include small sample sizes, use of only one neuroimaging modality, and a focus on identifying predictors rather than moderators and mediators of differential treatment response. By addressing these limitations and, most importantly, capitalizing on the benefits of multimodal neuroimaging, future studies can yield moderators and mediators of treatment response in depression to facilitate significant improvements in shorter- and longer-term clinical and functional outcomes.
25 CFR 256.16 - Who is responsible for identifying what work will be done on my dwelling?

Science.gov (United States)

2010-04-01

... on my dwelling? 256.16 Section 256.16 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR... my dwelling? The servicing housing office is responsible for identifying what work is to be done on your dwelling or whether your dwelling will be replaced. This includes responsibility to communicate...
30 CFR 254.23 - What information must I include in the “Emergency response action plan” section?

Science.gov (United States)

2010-07-01

... response operations on your behalf. You must describe the team's organizational structure as well as the... include the number and types of personnel available from each identified labor source. (d) A planned... primary and secondary radio frequencies that will be used. (e) A listing of the types and characteristics...
Integrating Genetic and Gene Co-expression Analysis Identifies Gene Networks Involved in Alcohol and Stress Responses.

Science.gov (United States)

Luo, Jie; Xu, Pei; Cao, Peijian; Wan, Hongjian; Lv, Xiaonan; Xu, Shengchun; Wang, Gangjun; Cook, Melloni N; Jones, Byron C; Lu, Lu; Wang, Xusheng

2018-01-01

Although the link between stress and alcohol is well recognized, the underlying mechanisms of how they interplay at the molecular level remain unclear. The purpose of this study is to identify molecular networks underlying the effects of alcohol and stress responses, as well as their interaction on anxiety behaviors in the hippocampus of mice using a systems genetics approach. Here, we applied a gene co-expression network approach to transcriptomes of 41 BXD mouse strains under four conditions: stress, alcohol, stress-induced alcohol and control. The co-expression analysis identified 14 modules and characterized four expression patterns across the four conditions. The four expression patterns include up-regulation in no restraint stress and given an ethanol injection (NOE) but restoration in restraint stress followed by an ethanol injection (RSE; pattern 1), down-regulation in NOE but rescue in RSE (pattern 2), up-regulation in both restraint stress followed by a saline injection (RSS) and NOE, and further amplification in RSE (pattern 3), and up-regulation in RSS but reduction in both NOE and RSE (pattern 4). We further identified four functional subnetworks by superimposing protein-protein interactions (PPIs) to the 14 co-expression modules, including γ-aminobutyric acid receptor (GABA) signaling, glutamate signaling, neuropeptide signaling, cAMP-dependent signaling. We further performed module specificity analysis to identify modules that are specific to stress, alcohol, or stress-induced alcohol responses. Finally, we conducted causality analysis to link genetic variation to these identified modules, and anxiety behaviors after stress and alcohol treatments. This study underscores the importance of integrative analysis and offers new insights into the molecular networks underlying stress and alcohol responses.
Integrating Genetic and Gene Co-expression Analysis Identifies Gene Networks Involved in Alcohol and Stress Responses

Directory of Open Access Journals (Sweden)

Jie Luo

2018-04-01

Full Text Available Although the link between stress and alcohol is well recognized, the underlying mechanisms of how they interplay at the molecular level remain unclear. The purpose of this study is to identify molecular networks underlying the effects of alcohol and stress responses, as well as their interaction on anxiety behaviors in the hippocampus of mice using a systems genetics approach. Here, we applied a gene co-expression network approach to transcriptomes of 41 BXD mouse strains under four conditions: stress, alcohol, stress-induced alcohol and control. The co-expression analysis identified 14 modules and characterized four expression patterns across the four conditions. The four expression patterns include up-regulation in no restraint stress and given an ethanol injection (NOE but restoration in restraint stress followed by an ethanol injection (RSE; pattern 1, down-regulation in NOE but rescue in RSE (pattern 2, up-regulation in both restraint stress followed by a saline injection (RSS and NOE, and further amplification in RSE (pattern 3, and up-regulation in RSS but reduction in both NOE and RSE (pattern 4. We further identified four functional subnetworks by superimposing protein-protein interactions (PPIs to the 14 co-expression modules, including γ-aminobutyric acid receptor (GABA signaling, glutamate signaling, neuropeptide signaling, cAMP-dependent signaling. We further performed module specificity analysis to identify modules that are specific to stress, alcohol, or stress-induced alcohol responses. Finally, we conducted causality analysis to link genetic variation to these identified modules, and anxiety behaviors after stress and alcohol treatments. This study underscores the importance of integrative analysis and offers new insights into the molecular networks underlying stress and alcohol responses.
A consistent response spectrum analysis including the resonance range

International Nuclear Information System (INIS)

Schmitz, D.; Simmchen, A.

1983-01-01

The report provides a complete consistent Response Spectrum Analysis for any component. The effect of supports with different excitation is taken into consideration, at is the description of the resonance ranges. It includes information explaining how the contributions of the eigenforms with higher eigenfrequencies are to be considered. Stocking of floor response spectra is also possible using the method described here. However, modified floor response spectra must now be calculated for each building mode. Once these have been prepared, the calculation of the dynamic component values is practically no more complicated than with the conventional, non-consistent methods. The consistent Response Spectrum Analysis can supply smaller and larger values than the conventional theory, a fact which can be demonstrated using simple examples. The report contains a consistent Response Spectrum Analysis (RSA), which, as far as we know, has been formulated in this way for the first time. A consistent RSA is so important because today this method is preferentially applied as an important tool for the earthquake proof of components in nuclear power plants. (orig./HP)
A target based approach identifies genomic predictors of breast cancer patient response to chemotherapy

Directory of Open Access Journals (Sweden)

Hallett Robin M

2012-05-01

Full Text Available Abstract Background The efficacy of chemotherapy regimens in breast cancer patients is variable and unpredictable. Whether individual patients either achieve long-term remission or suffer recurrence after therapy may be dictated by intrinsic properties of their breast tumors including genetic lesions and consequent aberrant transcriptional programs. Global gene expression profiling provides a powerful tool to identify such tumor-intrinsic transcriptional programs, whose analyses provide insight into the underlying biology of individual patient tumors. For example, multi-gene expression signatures have been identified that can predict the likelihood of disease reccurrence, and thus guide patient prognosis. Whereas such prognostic signatures are being introduced in the clinical setting, similar signatures that predict sensitivity or resistance to chemotherapy are not currently clinically available. Methods We used gene expression profiling to identify genes that were co-expressed with genes whose transcripts encode the protein targets of commonly used chemotherapeutic agents. Results Here, we present target based expression indices that predict breast tumor response to anthracycline and taxane based chemotherapy. Indeed, these signatures were independently predictive of chemotherapy response after adjusting for standard clinic-pathological variables such as age, grade, and estrogen receptor status in a cohort of 488 breast cancer patients treated with adriamycin and taxotere/taxol. Conclusions Importantly, our findings suggest the practicality of developing target based indices that predict response to therapeutics, as well as highlight the possibility of using gene signatures to guide the use of chemotherapy during treatment of breast cancer patients.
On-line structural response analysis: using the extended Kalman estimator/identifier

International Nuclear Information System (INIS)

Candy, J.V.

1979-01-01

This report disucsses the development of on-line state and parameter estimators used to analyze the structural response of buildings. The estimator/identifier is an extended Kalman filter (EKF), which has been applied with great success in other technological areas. It is shown that the EKF can perform quite well on simulated noisy structural response data
Reactive inspection response of NRC Region III to potential technical deficiencies identified in recent Nuclear Air Cleaning Conference papers

International Nuclear Information System (INIS)

Gill, C.F.

1987-01-01

In order to effectively meet its responsibility to protect the public health and safety, the Nuclear Regulatory Commission (NRC) nuclear power plant licensing and inspection programs respond to potential technical deficiencies identified by conference and professional society meeting papers when deemed appropriate. The NRC staff's response mechanisms for such technical deficiencies include: generic letters, Bulletins, Information Notices, Standard Review Plan (NUREG-0800) revisions, docketed Final Safety Analysis Report (FSAR) questions, special studies, special (reactive) inspection, and inspection program revisions. This paper describes reactive inspection efforts by Region III in response to potential technical deficiencies identified in recent air cleaning conference papers, including: post-accident effluent sample line deposition losses; failure to implement good engineering practices in the design, construction, and testing of Nuclear Air Treatment Systems (NATS); filter bypass via filter housing drain lines; spinster carbon degradation; use of silicone sealants and other temporary patching material in NATS; filter housing fire protection deluge system problems; lack of charcoal batch traceability; Quality Assurance records problems involving equipment, vendor, filter, and personnel qualifications; inadequate ANSI/ASME N510 acceptance criteria and tests; and failure to adequately demonstrate control room habitability per 10 CFR 50, Appendix A, General Design Criterion-19. Region III inspections indicate that many of these deficiencies appear to be prevalent. Inspection findings and utility responses to the findings are discussed. NRC Region III and Headquarters programmatic reactions to the identified generic problem areas are also discussed
Highly identified power-holders feel responsible: The interplay between social identification and social power within groups.

Science.gov (United States)

Scholl, Annika; Sassenberg, Kai; Ellemers, Naomi; Scheepers, Daan; de Wit, Frank

2018-01-01

Power relations affect dynamics within groups. Power-holders' decisions not only determine their personal outcomes, but also the outcomes of others in the group that they control. Yet, power-holders often tend to overlook this responsibility to take care of collective interests. The present research investigated how social identification - with the group to which both the powerful and the powerless belong - alters perceived responsibility among power-holders (and the powerless). Combining research on social power and social identity, we argue that power-holders perceive more responsibility than the powerless when strongly (rather than when weakly) identifying with the group. A study among leaders and an experiment supported this, highlighting that although power-holders are often primarily concerned about personal outcomes, they do feel responsible for considering others' interests when these others are included in the (social) self. © 2017 The British Psychological Society.
Identifying predictive features in drug response using machine learning: opportunities and challenges.

Science.gov (United States)

Vidyasagar, Mathukumalli

2015-01-01

This article reviews several techniques from machine learning that can be used to study the problem of identifying a small number of features, from among tens of thousands of measured features, that can accurately predict a drug response. Prediction problems are divided into two categories: sparse classification and sparse regression. In classification, the clinical parameter to be predicted is binary, whereas in regression, the parameter is a real number. Well-known methods for both classes of problems are briefly discussed. These include the SVM (support vector machine) for classification and various algorithms such as ridge regression, LASSO (least absolute shrinkage and selection operator), and EN (elastic net) for regression. In addition, several well-established methods that do not directly fall into machine learning theory are also reviewed, including neural networks, PAM (pattern analysis for microarrays), SAM (significance analysis for microarrays), GSEA (gene set enrichment analysis), and k-means clustering. Several references indicative of the application of these methods to cancer biology are discussed.
Identifying functional groups for response to disturbance in an abandoned pasture

Science.gov (United States)

Lavorel, Sandra; Touzard, Blaise; Lebreton, Jean-Dominique; Clément, Bernard

1998-06-01

In an abandoned pasture in Brittany, we compared artificial small-scale disturbances to natural disturbances by wild boar and undisturbed vegetation. We developed a multivariate statistical approach which analyses how species biological attributes explain the response of community composition to disturbances. This technique, which reconciles the inductive and deductive approaches for functional classifications, identifies groups of species with similar responses to disturbance and characterizes their biological profiles. After 5 months of recolonization, artificial disturbances had a greater species richness than undisturbed vegetation as a result of recruitment of new species without the exclusion of pre-existing matrix species. Species morphology, described by canopy structure, canopy height and lateral spread, explained a large part (16 %) of community response to disturbance. Regeneration strategies, described by life history, seed mass, dispersal agent, dormancy and the existence of vegetative multiplication, explained a smaller part of community response to disturbance (8 %). Artificial disturbances were characterized by therophyte and compact rosettes with moderately dormant seeds, including a number of Asteraceae and other early successional species. Natural disturbances were colonized by leafy guerrilla species without seed dormancy. Few species were tightly related to undisturbed vegetation and were essentially grasses with a phalanx rosette morphology. The functional classification obtained is consistent with the classification of the community into fugitives, regenerators and persistors. These groups are structured according to Grubb's model for temperate grasslands, with regenerators and persistors in the matrix and fugitives taking advantage of gaps open by small-scale disturbances. The conjunction of functional diversity and species diversity within functional groups is the key to resilience to disturbance, an important ecosystem function.
Smart Farming: Including Rights Holders for Responsible Agricultural Innovation

OpenAIRE

Kelly Bronson

2018-01-01

This article draws on the literature of responsible innovation to suggest concrete processes for including rights holders in the “smart” agricultural revolution. It first draws upon historical agricultural research in Canada to highlight how productivist values drove seed innovations with particular consequences for the distribution of power in the food system. Next, the article uses document analysis to suggest that a similar value framework is motivating public investment in smart farming i...
Pathogenic mutations in TULP1 responsible for retinitis pigmentosa identified in consanguineous familial cases

Science.gov (United States)

Ullah, Inayat; Kabir, Firoz; Iqbal, Muhammad; Gottsch, Clare Brooks S.; Naeem, Muhammad Asif; Assir, Muhammad Zaman; Khan, Shaheen N.; Akram, Javed; Riazuddin, Sheikh; Ayyagari, Radha; Hejtmancik, J. Fielding

2016-01-01

Purpose To identify pathogenic mutations responsible for autosomal recessive retinitis pigmentosa (arRP) in consanguineous familial cases. Methods Seven large familial cases with multiple individuals diagnosed with retinitis pigmentosa were included in the study. Affected individuals in these families underwent ophthalmic examinations to document the symptoms and confirm the initial diagnosis. Blood samples were collected from all participating members, and genomic DNA was extracted. An exclusion analysis with microsatellite markers spanning the TULP1 locus on chromosome 6p was performed, and two-point logarithm of odds (LOD) scores were calculated. All coding exons along with the exon–intron boundaries of TULP1 were sequenced bidirectionally. We constructed a single nucleotide polymorphism (SNP) haplotype for the four familial cases harboring the K489R allele and estimated the likelihood of a founder effect. Results The ophthalmic examinations of the affected individuals in these familial cases were suggestive of RP. Exclusion analyses confirmed linkage to chromosome 6p harboring TULP1 with positive two-point LOD scores. Subsequent Sanger sequencing identified the single base pair substitution in exon14, c.1466A>G (p.K489R), in four families. Additionally, we identified a two-base deletion in exon 4, c.286_287delGA (p.E96Gfs77*); a homozygous splice site variant in intron 14, c.1495+4A>C; and a novel missense variation in exon 15, c.1561C>T (p.P521S). All mutations segregated with the disease phenotype in the respective families and were absent in ethnically matched control chromosomes. Haplotype analysis suggested (p<10−6) that affected individuals inherited the causal mutation from a common ancestor. Conclusions Pathogenic mutations in TULP1 are responsible for the RP phenotype in seven familial cases with a common ancestral mutation responsible for the disease phenotype in four of the seven families. PMID:27440997
Transient Response Dynamic Module Modifications to Include Static and Kinetic Friction Effects

Science.gov (United States)

Misel, J. E.; Nenno, S. B.; Takahashi, D.

1984-01-01

A methodology that supports forced transient response dynamic solutions when both static and kinetic friction effects are included in a structural system model is described. Modifications that support this type of nonlinear transient response solution are summarized for the transient response dynamics (TRD) NASTRAN module. An overview of specific modifications for the NASTRAN processing subroutines, INITL, TRD1C, and TRD1D, are described with further details regarding inspection of nonlinear input definitions to define the type of nonlinear solution required, along with additional initialization requirements and specific calculation subroutines to successfully solve the transient response problem. The extension of the basic NASTRAN nonlinear methodology is presented through several stages of development to the point where constraint equations and residual flexibility effects are introduced into the finite difference Newmark-Beta recurrsion formulas. Particular emphasis is placed on cost effective solutions for large finite element models such as the Space Shuttle with friction degrees of freedom between the orbiter and payloads mounted in the cargo bay. An alteration to the dynamic finite difference equations of motion is discussed, which allows one to include friction effects at reasonable cost for large structural systems such as the Space Shuttle. Data are presented to indicate the possible impact of transient friction loads to the payload designer for the Space Shuttle. Transient response solution data are also included, which compare solutions without friction forces and those with friction forces for payloads mounted in the Space Shuttle cargo bay. These data indicate that payload components can be sensitive to friction induced loads.
Objective Model Selection for Identifying the Human Feedforward Response in Manual Control.

Science.gov (United States)

Drop, Frank M; Pool, Daan M; van Paassen, Marinus Rene M; Mulder, Max; Bulthoff, Heinrich H

2018-01-01

Realistic manual control tasks typically involve predictable target signals and random disturbances. The human controller (HC) is hypothesized to use a feedforward control strategy for target-following, in addition to feedback control for disturbance-rejection. Little is known about human feedforward control, partly because common system identification methods have difficulty in identifying whether, and (if so) how, the HC applies a feedforward strategy. In this paper, an identification procedure is presented that aims at an objective model selection for identifying the human feedforward response, using linear time-invariant autoregressive with exogenous input models. A new model selection criterion is proposed to decide on the model order (number of parameters) and the presence of feedforward in addition to feedback. For a range of typical control tasks, it is shown by means of Monte Carlo computer simulations that the classical Bayesian information criterion (BIC) leads to selecting models that contain a feedforward path from data generated by a pure feedback model: "false-positive" feedforward detection. To eliminate these false-positives, the modified BIC includes an additional penalty on model complexity. The appropriate weighting is found through computer simulations with a hypothesized HC model prior to performing a tracking experiment. Experimental human-in-the-loop data will be considered in future work. With appropriate weighting, the method correctly identifies the HC dynamics in a wide range of control tasks, without false-positive results.

Identifying and training non-technical skills of nuclear emergency response teams

International Nuclear Information System (INIS)

Crichton, M.T.; Flin, R.

2004-01-01

Training of the non-technical (social and cognitive) skills that are crucial to safe and effective management by teams in emergency situations is an issue that is receiving increasing emphasis in many organisations, particularly in the nuclear power industry. As teams play a major role in emergency response organisations (ERO), effective functioning and interactions within, between and across teams is crucial, particularly as the management of an emergency situation often requires that teams are extended by members from various other sections and strategic groups throughout the company, as well as members of external agencies. A series of interviews was recently conducted with members of a UK nuclear emergency response organisation to identify the non-technical skills required by team members that would be required for managing an emergency. Critical skills have been identified as decision making and situation assessment, as well as communication, teamwork, and stress management. A number of training strategies are discussed which can be tailored to the roles and responsibilities of the team members and the team leader, based on the roles within the team being defined as either Decision Maker, Evaluator, or Implementor, according to Nuclear Energy Institute (NEI) classifications. It is anticipated that enhanced learning of the necessary non-technical skills, through experience and directed practice, will improve the skills of members of emergency response teams
Identifying and training non-technical skills of nuclear emergency response teams

Energy Technology Data Exchange (ETDEWEB)

Crichton, M.T. E-mail: m.crichton@abdn.ac.uk; Flin, R

2004-08-01

Training of the non-technical (social and cognitive) skills that are crucial to safe and effective management by teams in emergency situations is an issue that is receiving increasing emphasis in many organisations, particularly in the nuclear power industry. As teams play a major role in emergency response organisations (ERO), effective functioning and interactions within, between and across teams is crucial, particularly as the management of an emergency situation often requires that teams are extended by members from various other sections and strategic groups throughout the company, as well as members of external agencies. A series of interviews was recently conducted with members of a UK nuclear emergency response organisation to identify the non-technical skills required by team members that would be required for managing an emergency. Critical skills have been identified as decision making and situation assessment, as well as communication, teamwork, and stress management. A number of training strategies are discussed which can be tailored to the roles and responsibilities of the team members and the team leader, based on the roles within the team being defined as either Decision Maker, Evaluator, or Implementor, according to Nuclear Energy Institute (NEI) classifications. It is anticipated that enhanced learning of the necessary non-technical skills, through experience and directed practice, will improve the skills of members of emergency response teams.
Identifying a compound modifying a cellular response, comprises attaching cells having a reporter system onto solid supports, releasing a library member, screening and identifying target cells

DEFF Research Database (Denmark)

2011-01-01

The present invention relates to methods for identifying compounds capable of modulating a cellular response. The methods involve attaching living cells to solid supports comprising a library of test compounds. Test compounds modulating a cellular response, for example via a cell surface molecule...... may be identified by selecting solid supports comprising cells, wherein the cellular response of interest has been modulated. The cellular response may for example be changes in signal transduction pathways modulated by a cell surface molecule....
TAMING TROJAN HORSES: IDENTIFYING AND MITIGATING CORPORATE SOCIAL RESPONSIBILITY RISKS

OpenAIRE

P. P. M. A. R. HEUGENS; N. A. DENTCHEV

2007-01-01

textabstractOrganizations are exposed to increasing pressures from their constituents to integrate corporate social responsibility (CSR) principles into their ongoing business practices. But accepting new and potentially open-ended commitments is not a harmless exercise, and companies may well expose themselves to serious risks when embracing such principles. To identify these risks, we conducted two naturalistic studies: one exploratory, the other corroborative. The results show that CSR ado...
Aggregated Demand Modelling Including Distributed Generation, Storage and Demand Response

OpenAIRE

Marzooghi, Hesamoddin; Hill, David J.; Verbic, Gregor

2014-01-01

It is anticipated that penetration of renewable energy sources (RESs) in power systems will increase further in the next decades mainly due to environmental issues. In the long term of several decades, which we refer to in terms of the future grid (FG), balancing between supply and demand will become dependent on demand actions including demand response (DR) and energy storage. So far, FG feasibility studies have not considered these new demand-side developments for modelling future demand. I...
Identifying Industry-Specific Components of Product Liability Response System Using Delphi-AHP Method

Directory of Open Access Journals (Sweden)

Seo JunHyeok

2016-12-01

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

Directory of Open Access Journals (Sweden)

Kelly Bronson

2018-02-01

Full Text Available This article draws on the literature of responsible innovation to suggest concrete processes for including rights holders in the “smart” agricultural revolution. It first draws upon historical agricultural research in Canada to highlight how productivist values drove seed innovations with particular consequences for the distribution of power in the food system. Next, the article uses document analysis to suggest that a similar value framework is motivating public investment in smart farming innovations. The article is of interest to smart farming’s decision makers (from farmers to governance actors and a broader audience – anyone interested in engendering equity through innovation-led societal transitions.
Metabolomic screening using ESI-FT MS identifies potential radiation-responsive molecules in mouse urine

International Nuclear Information System (INIS)

Iizuka, Daisuke; Yoshioka, Susumu; Kawai, Hidehiko; Izumi, Shunsuke; Suzuki, Fumio; Kamiya, Kenji

2017-01-01

The demand for establishment of high-throughput biodosimetric methods is increasing. Our aim in this study was to identify low-molecular-weight urinary radiation-responsive molecules using electrospray ionization Fourier transform mass spectrometry (ESI-FT MS), and our final goal was to develop a sensitive biodosimetry technique that can be applied in the early triage of a radiation emergency medical system. We identified nine metabolites by statistical comparison of mouse urine before and 8 h after irradiation. Time-course analysis showed that, of these metabolites, thymidine and either thymine or imidazoleacetic acid were significantly increased dose-dependently 8 h after radiation exposure; these molecules have already been reported as potential radiation biomarkers. Phenyl glucuronide was significantly decreased 8 h after radiation exposure, irrespective of the dose. Histamine and 1-methylhistamine were newly identified by MS/MS and showed significant, dose-dependent increases 72 h after irradiation. Quantification of 1-methylhistamine by enzyme-linked immunosorbent assay (ELISA) analysis also showed a significant increase 72 h after 4 Gy irradiation. These results suggest that urinary metabolomics screening using ESI-FT MS can be a powerful tool for identifying promising radiation-responsive molecules, and that urinary 1-methylhistamine is a potential radiation-responsive molecule for acute, high-dose exposure.
GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes

NARCIS (Netherlands)

Nakayama, A.; Nakaoka, H.; Yamamoto, K.; Sakiyama, M.; Shaukat, A.; Toyoda, Y.; Okada, Y.; Kamatani, Y.; Nakamura, T.; Takada, T.; Inoue, K.; Yasujima, T.; Yuasa, H.; Shirahama, Y.; Nakashima, H.; Shimizu, S.; Higashino, T.; Kawamura, Y.; Ogata, H.; Kawaguchi, M.; Ohkawa, Y.; Danjoh, I.; Tokumasu, A.; Ooyama, K.; Ito, T.; Kondo, T.; Wakai, K.; Stiburkova, B.; Pavelka, K.; Stamp, L.K.; Dalbeth, N.; Sakurai, Y.; Suzuki, H; Hosoyamada, M.; Fujimori, S.; Yokoo, T.; Hosoya, T.; Inoue, I.; Takahashi, A.; Kubo, M.; Ooyama, H.; Shimizu, T.; Ichida, K.; Shinomiya, N.; Merriman, T.R.; Matsuo, H.; Andres, M; Joosten, L.A.; Janssen, M.C.H.; Jansen, T.L.; Liote, F.; Radstake, T.R.; Riches, P.L.; So, A.; Tauches, A.K.

2017-01-01

OBJECTIVE: A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. METHODS: Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were
41 CFR 102-80.50 - Are Federal agencies responsible for identifying/estimating risks and for appropriate risk...

Science.gov (United States)

2010-07-01

... Environmental Management Risks and Risk Reduction Strategies § 102-80.50 Are Federal agencies responsible for... identify and estimate safety and environmental management risks and appropriate risk reduction strategies... responsible for identifying/estimating risks and for appropriate risk reduction strategies? 102-80.50 Section...
Metabolite analysis of endophytic fungi from cultivars of Zingiber officinale Rosc. identifies myriad of bioactive compounds including tyrosol.

Science.gov (United States)

Anisha, C; Radhakrishnan, E K

2017-06-01

Endophytic fungi associated with rhizomes of four cultivars of Zingiber officinale were identified by molecular and morphological methods and evaluated for their activity against soft rot pathogen Pythium myriotylum and clinical pathogens. The volatile bioactive metabolites produced by these isolates were identified by GC-MS analysis of the fungal crude extracts. Understanding of the metabolites produced by endophytes is also important in the context of raw consumption of ginger as medicine and spice. A total of fifteen isolates were identified from the four varieties studied. The various genera identified were Acremonium sp., Gliocladiopsis sp., Fusarium sp., Colletotrichum sp., Aspergillus sp., Phlebia sp., Earliella sp., and Pseudolagarobasidium sp. The endophytic community was unique to each variety, which could be due to the varying host genotype. Fungi from phylum Basidiomycota were identified for the first time from ginger. Seven isolates showed activity against Pythium, while only two showed antibacterial activity. The bioactive metabolites identified in the fungal crude extracts include tyrosol, benzene acetic acid, ergone, dehydromevalonic lactone, N-aminopyrrolidine, and many bioactive fatty acids and their derivatives which included linoleic acid, oleic acid, myristic acid, n-hexadecanoic acid, palmitic acid methyl ester, and methyl linoleate. The presence of these varying bioactive endophytic fungi may be one of the reasons for the differences in the performance of the different ginger varieties.
Use of an activated beta-catenin to identify Wnt pathway target genes in caenorhabditis elegans, including a subset of collagen genes expressed in late larval development.

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Jackson, Belinda M; Abete-Luzi, Patricia; Krause, Michael W; Eisenmann, David M

2014-04-16

The Wnt signaling pathway plays a fundamental role during metazoan development, where it regulates diverse processes, including cell fate specification, cell migration, and stem cell renewal. Activation of the beta-catenin-dependent/canonical Wnt pathway up-regulates expression of Wnt target genes to mediate a cellular response. In the nematode Caenorhabditis elegans, a canonical Wnt signaling pathway regulates several processes during larval development; however, few target genes of this pathway have been identified. To address this deficit, we used a novel approach of conditionally activated Wnt signaling during a defined stage of larval life by overexpressing an activated beta-catenin protein, then used microarray analysis to identify genes showing altered expression compared with control animals. We identified 166 differentially expressed genes, of which 104 were up-regulated. A subset of the up-regulated genes was shown to have altered expression in mutants with decreased or increased Wnt signaling; we consider these genes to be bona fide C. elegans Wnt pathway targets. Among these was a group of six genes, including the cuticular collagen genes, bli-1 col-38, col-49, and col-71. These genes show a peak of expression in the mid L4 stage during normal development, suggesting a role in adult cuticle formation. Consistent with this finding, reduction of function for several of the genes causes phenotypes suggestive of defects in cuticle function or integrity. Therefore, this work has identified a large number of putative Wnt pathway target genes during larval life, including a small subset of Wnt-regulated collagen genes that may function in synthesis of the adult cuticle.
Human immune responses to H. pylori HLA Class II epitopes identified by immunoinformatic methods.

Directory of Open Access Journals (Sweden)

Songhua Zhang

Full Text Available H. pylori persists in the human stomach over decades and promotes several adverse clinical sequelae including gastritis, peptic ulcers and gastric cancer that are linked to the induction and subsequent evasion of chronic gastric inflammation. Emerging evidence indicates that H. pylori infection may also protect against asthma and some other immune-mediated conditions through regulatory T cell effects outside the stomach. To characterize the complexity of the CD4+ T cell response generated during H. pylori infection, computational methods were previously used to generate a panel of 90 predicted epitopes conserved among H. pylori genomes that broadly cover HLA Class II diversity for maximum population coverage. Here, these sequences were tested individually for their ability to induce in vitro responses in peripheral blood mononuclear cells by interferon-γ ELISpot assay. The average number of spot-forming cells/million PBMCs was significantly elevated in H. pylori-infected subjects over uninfected persons. Ten of the 90 peptides stimulated IFN-γ secretion in the H. pylori-infected group only, whereas two out of the 90 peptides elicited a detectable IFN-γ response in the H. pylori-uninfected subjects but no response in the H. pylori-infected group. Cytokine ELISA measurements performed using in vitro PBMC culture supernatants demonstrated significantly higher levels of TNF-α, IL-2, IL-4, IL-6, IL-10, and TGF-β1 in the H. pylori-infected subjects, whereas IL-17A expression was not related to the subjects H. pylori-infection status. Our results indicate that the human T cell responses to these 90 peptides are generally increased in actively H. pylori-infected, compared with H. pylori-naïve, subjects. This information will improve understanding of the complex immune response to H. pylori, aiding rational epitope-driven vaccine design as well as helping identify other H. pylori epitopes with potentially immunoregulatory effects.
Seven Steps in Identifying Local Climate Change Responses for Agriculture in Vietnam

NARCIS (Netherlands)

Bosma, R.H.; Ngo, An T.; Huynh, Chuong V.; Le, Huong T.; Dang, Nhan K.; Van, Tri P.D.; Halsema, van G.E.

2016-01-01

This study presents a seven-step approach to identify and support local climate change (CC) responses in agriculture. The following seven steps comprise this approach: 1. Analyse past trends on the climatic factors and model the future trends. 2. Simulate the possible impacts of CC on the selected
Identifying Demand Responses to Illegal Drug Supply Interdictions.

Science.gov (United States)

Cunningham, Scott; Finlay, Keith

2016-10-01

Successful supply-side interdictions into illegal drug markets are predicated on the responsiveness of drug prices to enforcement and the price elasticity of demand for addictive drugs. We present causal estimates that targeted interventions aimed at methamphetamine input markets ('precursor control') can temporarily increase retail street prices, but methamphetamine consumption is weakly responsive to higher drug prices. After the supply interventions, purity-adjusted prices increased then quickly returned to pre-treatment levels within 6-12 months, demonstrating the short-term effects of precursor control. The price elasticity of methamphetamine demand is -0.13 to -0.21 for self-admitted drug treatment admissions and between -0.24 and -0.28 for hospital inpatient admissions. We find some evidence of a positive cross-price effect for cocaine, but we do not find robust evidence that increases in methamphetamine prices increased heroin, alcohol, or marijuana drug use. This study can inform policy discussions regarding other synthesized drugs, including illicit use of pharmaceuticals. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
Methylation profiling identified novel differentially methylated markers including OPCML and FLRT2 in prostate cancer.

Science.gov (United States)

Wu, Yu; Davison, Jerry; Qu, Xiaoyu; Morrissey, Colm; Storer, Barry; Brown, Lisha; Vessella, Robert; Nelson, Peter; Fang, Min

2016-04-02

To develop new methods to distinguish indolent from aggressive prostate cancers (PCa), we utilized comprehensive high-throughput array-based relative methylation (CHARM) assay to identify differentially methylated regions (DMRs) throughout the genome, including both CpG island (CGI) and non-CGI regions in PCa patients based on Gleason grade. Initially, 26 samples, including 8 each of low [Gleason score (GS) 6] and high (GS ≥7) grade PCa samples and 10 matched normal prostate tissues, were analyzed as a discovery cohort. We identified 3,567 DMRs between normal and cancer tissues, and 913 DMRs distinguishing low from high-grade cancers. Most of these DMRs were located at CGI shores. The top 5 candidate DMRs from the low vs. high Gleason comparison, including OPCML, ELAVL2, EXT1, IRX5, and FLRT2, were validated by pyrosequencing using the discovery cohort. OPCML and FLRT2 were further validated in an independent cohort consisting of 20 low-Gleason and 33 high-Gleason tissues. We then compared patients with biochemical recurrence (n=70) vs. those without (n=86) in a third cohort, and they showed no difference in methylation at these DMR loci. When GS 3+4 cases and GS 4+3 cases were compared, OPCML-DMR methylation showed a trend of lower methylation in the recurrence group (n=30) than in the no-recurrence (n=52) group. We conclude that whole-genome methylation profiling with CHARM revealed distinct patterns of differential DNA methylation between normal prostate and PCa tissues, as well as between different risk groups of PCa as defined by Gleason scores. A panel of selected DMRs may serve as novel surrogate biomarkers for Gleason score in PCa.
Radio Transmitters and Tower Locations, Layer includes all towers identified visually and include cellular and other communication towers., Published in 2008, 1:1200 (1in=100ft) scale, Noble County Government.

Data.gov (United States)

NSGIC Local Govt | GIS Inventory — Radio Transmitters and Tower Locations dataset current as of 2008. Layer includes all towers identified visually and include cellular and other communication towers..
Transcriptomic analysis of rice aleurone cells identified a novel abscisic acid response element.

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Watanabe, Kenneth A; Homayouni, Arielle; Gu, Lingkun; Huang, Kuan-Ying; Ho, Tuan-Hua David; Shen, Qingxi J

2017-09-01

Seeds serve as a great model to study plant responses to drought stress, which is largely mediated by abscisic acid (ABA). The ABA responsive element (ABRE) is a key cis-regulatory element in ABA signalling. However, its consensus sequence (ACGTG(G/T)C) is present in the promoters of only about 40% of ABA-induced genes in rice aleurone cells, suggesting other ABREs may exist. To identify novel ABREs, RNA sequencing was performed on aleurone cells of rice seeds treated with 20 μM ABA. Gibbs sampling was used to identify enriched elements, and particle bombardment-mediated transient expression studies were performed to verify the function. Gene ontology analysis was performed to predict the roles of genes containing the novel ABREs. This study revealed 2443 ABA-inducible genes and a novel ABRE, designated as ABREN, which was experimentally verified to mediate ABA signalling in rice aleurone cells. Many of the ABREN-containing genes are predicted to be involved in stress responses and transcription. Analysis of other species suggests that the ABREN may be monocot specific. This study also revealed interesting expression patterns of genes involved in ABA metabolism and signalling. Collectively, this study advanced our understanding of diverse cis-regulatory sequences and the transcriptomes underlying ABA responses in rice aleurone cells. © 2017 John Wiley & Sons Ltd.
Characterization of Genotoxic Response to 15 Multiwalled Carbon Nanotubes with Variable Physicochemical Properties Including Surface Functionalizations in the FE1-Muta(TM) Mouse Lung Epithelial Cell Line

DEFF Research Database (Denmark)

Jackson, Petra; Kling, Kirsten; Jensen, Keld Alstrup

2015-01-01

Carbon nanotubes vary greatly in physicochemical properties. We compared cytotoxic and genotoxic response to 15 multiwalled carbon nanotubes (MWCNT) with varying physicochemical properties to identify drivers of toxic responses. The studied MWCNT included OECD Working Party on Manufactured...... Nanomaterials (WPMN) (NM-401, NM-402, and NM-403), materials (NRCWE-026 and MWCNT-XNRI-7), and three sets of surface-modified MWCNT grouped by physical characteristics (thin, thick, and short I-III, respectively). Each Groups I-III included pristine, hydroxylated and carboxylated MWCNT. Group III also included...... an amino-functionalized MWCNT. The level of surface functionalization of the MWCNT was low. The level and type of elemental impurities of the MWCNT varied by...
Global phosphotyrosine proteomics identifies PKCδ as a marker of responsiveness to Src inhibition in colorectal cancer.

Directory of Open Access Journals (Sweden)

Eliot T McKinley

Full Text Available Sensitive and specific biomarkers of protein kinase inhibition can be leveraged to accelerate drug development studies in oncology by associating early molecular responses with target inhibition. In this study, we utilized unbiased shotgun phosphotyrosine (pY proteomics to discover novel biomarkers of response to dasatinib, a small molecule Src-selective inhibitor, in preclinical models of colorectal cancer (CRC. We performed unbiased mass spectrometry shotgun pY proteomics to reveal the pY proteome of cultured HCT-116 colonic carcinoma cells, and then extended this analysis to HCT-116 xenograft tumors to identify pY biomarkers of dasatinib-responsiveness in vivo. Major dasatinib-responsive pY sites in xenograft tumors included sites on delta-type protein kinase C (PKCδ, CUB-domain-containing protein 1 (CDCP1, Type-II SH2-domain-containing inositol 5-phosphatase (SHIP2, and receptor protein-tyrosine phosphatase alpha (RPTPα. The pY313 site PKCδ was further supported as a relevant biomarker of dasatinib-mediated Src inhibition in HCT-116 xenografts by immunohistochemistry and immunoblotting with a phosphospecific antibody. Reduction of PKCδ pY313 was further correlated with dasatinib-mediated inhibition of Src and diminished growth as spheroids of a panel of human CRC cell lines. These studies reveal PKCδ pY313 as a promising readout of Src inhibition in CRC and potentially other solid tumors and may reflect responsiveness to dasatinib in a subset of colorectal cancers.

The Fukushima radiological emergency and challenges identified for future public health responses.

Science.gov (United States)

Miller, Charles W

2012-05-01

On 11 March 2011, northern Japan was rocked by first a magnitude 9.0 earthquake off the eastern coast and then an ensuing tsunami. The Fukushima Daiichi Nuclear Power Plant complex was hit by these twin disasters, and a cascade of events was initiated that led to radionuclide releases causing widespread radioactive contamination of residential areas, agricultural land, and coastal waters. Radioactive material from Japan was subsequently transmitted to locations around the globe, including the U.S. The levels of radioactive material that arrived in the U.S. were never large enough to be a concern for health effects, but the presence of this material in the environment was enough to create a public health emergency in the U.S. The radiation safety and public health communities in the U.S. are identifying challenges they faced in responding to this incident. This paper discusses three of those challenges: (1) The growing shortage of trained radiation subject matter experts in the field of environmental transport and dosimetry of radionuclides; (2) the need to begin expressing all radiation-related quantities in terms of the International System of Units; and (3) the need to define when a radiation dose is or is not one of "public health concern." This list represents only a small subset of the list of challenges being identified by public health agencies that responded to the Fukushima incident. However, these three challenges are fundamental to any radiological emergency response. Addressing them will have a significant positive impact on how the U.S. responds to the next radiological emergency.
GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes.

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Nakayama, Akiyoshi; Nakaoka, Hirofumi; Yamamoto, Ken; Sakiyama, Masayuki; Shaukat, Amara; Toyoda, Yu; Okada, Yukinori; Kamatani, Yoichiro; Nakamura, Takahiro; Takada, Tappei; Inoue, Katsuhisa; Yasujima, Tomoya; Yuasa, Hiroaki; Shirahama, Yuko; Nakashima, Hiroshi; Shimizu, Seiko; Higashino, Toshihide; Kawamura, Yusuke; Ogata, Hiraku; Kawaguchi, Makoto; Ohkawa, Yasuyuki; Danjoh, Inaho; Tokumasu, Atsumi; Ooyama, Keiko; Ito, Toshimitsu; Kondo, Takaaki; Wakai, Kenji; Stiburkova, Blanka; Pavelka, Karel; Stamp, Lisa K; Dalbeth, Nicola; Sakurai, Yutaka; Suzuki, Hiroshi; Hosoyamada, Makoto; Fujimori, Shin; Yokoo, Takashi; Hosoya, Tatsuo; Inoue, Ituro; Takahashi, Atsushi; Kubo, Michiaki; Ooyama, Hiroshi; Shimizu, Toru; Ichida, Kimiyoshi; Shinomiya, Nariyoshi; Merriman, Tony R; Matsuo, Hirotaka

2017-05-01

A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zealand Polynesian samples was done to further validate the loci identified in this study. In addition to the five loci we reported previously, further susceptibility loci were identified at a genome-wide significance level (pgout cases, and NIPAL1 and FAM35A for the renal underexcretion gout subtype. While NIPAL1 encodes a magnesium transporter, functional analysis did not detect urate transport via NIPAL1, suggesting an indirect association with urate handling. Localisation analysis in the human kidney revealed expression of NIPAL1 and FAM35A mainly in the distal tubules, which suggests the involvement of the distal nephron in urate handling in humans. Clinically ascertained male patients with gout and controls of Caucasian and Polynesian ancestries were also genotyped, and FAM35A was associated with gout in all cases. A meta-analysis of the three populations revealed FAM35A to be associated with gout at a genome-wide level of significance (p meta =3.58×10 -8 ). Our findings including novel gout risk loci provide further understanding of the molecular pathogenesis of gout and lead to a novel concept for the therapeutic target of gout/hyperuricaemia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes

OpenAIRE

Nakayama, Akiyoshi; Nakaoka, Hirofumi; Yamamoto, Ken; Sakiyama, Masayuki; Shaukat, Amara; Toyoda, Yu; Okada, Yukinori; Kamatani, Yoichiro; Nakamura, Takahiro; Takada, Tappei; Inoue, Katsuhisa; Yasujima, Tomoya; Yuasa, Hiroaki; Shirahama, Yuko; Nakashima, Hiroshi

2016-01-01

Objective A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. Methods Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zeala...
Identifying the relevant dependencies of the neural network response on characteristics of the input space

CERN Multimedia

CERN. Geneva

2018-01-01

This talk presents an approach to identify those characteristics of the neural network inputs that are most relevant for the response and therefore provides essential information to determine the systematic uncertainties.
Targeted siRNA Screens Identify ER-to-Mitochondrial Calcium Exchange in Autophagy and Mitophagy Responses in RPE1 Cells

Directory of Open Access Journals (Sweden)

Thomas D. B. MacVicar

2015-06-01

Full Text Available Autophagy is an important stress response pathway responsible for the removal and recycling of damaged or redundant cytosolic constituents. Mitochondrial damage triggers selective mitochondrial autophagy (mitophagy, mediated by a variety of response factors including the Pink1/Parkin system. Using human retinal pigment epithelial cells stably expressing autophagy and mitophagy reporters, we have conducted parallel screens of regulators of endoplasmic reticulum (ER and mitochondrial morphology and function contributing to starvation-induced autophagy and damage-induced mitophagy. These screens identified the ER chaperone and Ca2+ flux modulator, sigma non-opioid intracellular receptor 1 (SIGMAR1, as a regulator of autophagosome expansion during starvation. Screens also identified phosphatidyl ethanolamine methyl transferase (PEMT and the IP3-receptors (IP3Rs as mediators of Parkin-induced mitophagy. Further experiments suggested that IP3R-mediated transfer of Ca2+ from the ER lumen to the mitochondrial matrix via the mitochondrial Ca2+ uniporter (MCU primes mitochondria for mitophagy. Importantly, recruitment of Parkin to damaged mitochondria did not require IP3R-mediated ER-to-mitochondrial Ca2+ transfer, but mitochondrial clustering downstream of Parkin recruitment was impaired, suggesting involvement of regulators of mitochondrial dynamics and/or transport. Our data suggest that Ca2+ flux between ER and mitochondria at presumed ER/mitochondrial contact sites is needed both for starvation-induced autophagy and for Parkin-mediated mitophagy, further highlighting the importance of inter-organellar communication for effective cellular homeostasis.
The transcriptional regulatory network in the drought response and its crosstalk in abiotic stress responses including drought, cold and heat

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Kazuo eNakashima

2014-05-01

Full Text Available Drought negatively impacts plant growth and the productivity of crops around the world. Understanding the molecular mechanisms in the drought response is important for improvement of drought tolerance using molecular techniques. In plants, abscisic acid (ABA is accumulated under osmotic stress conditions caused by drought, and has a key role in stress responses and tolerance. Comprehensive molecular analyses have shown that ABA regulates the expression of many genes under osmotic stress conditions, and the ABA-responsive element (ABRE is the major cis-element for ABA-responsive gene expression. Transcription factors (TFs are master regulators of gene expression. ABRE-binding protein (AREB and ABRE-binding factor (ABF TFs control gene expression in an ABA-dependent manner. SNF1-related protein kinases 2, group A 2C-type protein phosphatases, and ABA receptors were shown to control the ABA signaling pathway. ABA-independent signaling pathways such as dehydration-responsive element-binding protein (DREB TFs and NAC TFs are also involved in stress responses including drought, heat and cold. Recent studies have suggested that there are interactions between the major ABA signaling pathway and other signaling factors in stress responses. The important roles of these transcription factors in crosstalk among abiotic stress responses will be discussed. Control of ABA or stress signaling factor expression can improve tolerance to environmental stresses. Recent studies using crops have shown that stress-specific overexpression of TFs improves drought tolerance and grain yield compared with controls in the field.
The transcriptional regulatory network in the drought response and its crosstalk in abiotic stress responses including drought, cold, and heat.

Science.gov (United States)

Nakashima, Kazuo; Yamaguchi-Shinozaki, Kazuko; Shinozaki, Kazuo

2014-01-01

Drought negatively impacts plant growth and the productivity of crops around the world. Understanding the molecular mechanisms in the drought response is important for improvement of drought tolerance using molecular techniques. In plants, abscisic acid (ABA) is accumulated under osmotic stress conditions caused by drought, and has a key role in stress responses and tolerance. Comprehensive molecular analyses have shown that ABA regulates the expression of many genes under osmotic stress conditions, and the ABA-responsive element (ABRE) is the major cis-element for ABA-responsive gene expression. Transcription factors (TFs) are master regulators of gene expression. ABRE-binding protein and ABRE-binding factor TFs control gene expression in an ABA-dependent manner. SNF1-related protein kinases 2, group A 2C-type protein phosphatases, and ABA receptors were shown to control the ABA signaling pathway. ABA-independent signaling pathways such as dehydration-responsive element-binding protein TFs and NAC TFs are also involved in stress responses including drought, heat, and cold. Recent studies have suggested that there are interactions between the major ABA signaling pathway and other signaling factors in stress responses. The important roles of these TFs in crosstalk among abiotic stress responses will be discussed. Control of ABA or stress signaling factor expression can improve tolerance to environmental stresses. Recent studies using crops have shown that stress-specific overexpression of TFs improves drought tolerance and grain yield compared with controls in the field.
Systems approach identifies an organic nitrogen-responsive gene network that is regulated by the master clock control gene CCA1.

Science.gov (United States)

Gutiérrez, Rodrigo A; Stokes, Trevor L; Thum, Karen; Xu, Xiaodong; Obertello, Mariana; Katari, Manpreet S; Tanurdzic, Milos; Dean, Alexis; Nero, Damion C; McClung, C Robertson; Coruzzi, Gloria M

2008-03-25

Understanding how nutrients affect gene expression will help us to understand the mechanisms controlling plant growth and development as a function of nutrient availability. Nitrate has been shown to serve as a signal for the control of gene expression in Arabidopsis. There is also evidence, on a gene-by-gene basis, that downstream products of nitrogen (N) assimilation such as glutamate (Glu) or glutamine (Gln) might serve as signals of organic N status that in turn regulate gene expression. To identify genome-wide responses to such organic N signals, Arabidopsis seedlings were transiently treated with ammonium nitrate in the presence or absence of MSX, an inhibitor of glutamine synthetase, resulting in a block of Glu/Gln synthesis. Genes that responded to organic N were identified as those whose response to ammonium nitrate treatment was blocked in the presence of MSX. We showed that some genes previously identified to be regulated by nitrate are under the control of an organic N-metabolite. Using an integrated network model of molecular interactions, we uncovered a subnetwork regulated by organic N that included CCA1 and target genes involved in N-assimilation. We validated some of the predicted interactions and showed that regulation of the master clock control gene CCA1 by Glu or a Glu-derived metabolite in turn regulates the expression of key N-assimilatory genes. Phase response curve analysis shows that distinct N-metabolites can advance or delay the CCA1 phase. Regulation of CCA1 by organic N signals may represent a novel input mechanism for N-nutrients to affect plant circadian clock function.
Global Gene-Expression Analysis to Identify Differentially Expressed Genes Critical for the Heat Stress Response in Brassica rapa.

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Xiangshu Dong

Full Text Available Genome-wide dissection of the heat stress response (HSR is necessary to overcome problems in crop production caused by global warming. To identify HSR genes, we profiled gene expression in two Chinese cabbage inbred lines with different thermotolerances, Chiifu and Kenshin. Many genes exhibited >2-fold changes in expression upon exposure to 0.5- 4 h at 45°C (high temperature, HT: 5.2% (2,142 genes in Chiifu and 3.7% (1,535 genes in Kenshin. The most enriched GO (Gene Ontology items included 'response to heat', 'response to reactive oxygen species (ROS', 'response to temperature stimulus', 'response to abiotic stimulus', and 'MAPKKK cascade'. In both lines, the genes most highly induced by HT encoded small heat shock proteins (Hsps and heat shock factor (Hsf-like proteins such as HsfB2A (Bra029292, whereas high-molecular weight Hsps were constitutively expressed. Other upstream HSR components were also up-regulated: ROS-scavenging genes like glutathione peroxidase 2 (BrGPX2, Bra022853, protein kinases, and phosphatases. Among heat stress (HS marker genes in Arabidopsis, only exportin 1A (XPO1A (Bra008580, Bra006382 can be applied to B. rapa for basal thermotolerance (BT and short-term acquired thermotolerance (SAT gene. CYP707A3 (Bra025083, Bra021965, which is involved in the dehydration response in Arabidopsis, was associated with membrane leakage in both lines following HS. Although many transcription factors (TF genes, including DREB2A (Bra005852, were involved in HS tolerance in both lines, Bra024224 (MYB41 and Bra021735 (a bZIP/AIR1 [Anthocyanin-Impaired-Response-1] were specific to Kenshin. Several candidate TFs involved in thermotolerance were confirmed as HSR genes by real-time PCR, and these assignments were further supported by promoter analysis. Although some of our findings are similar to those obtained using other plant species, clear differences in Brassica rapa reveal a distinct HSR in this species. Our data could also provide a
Identifying At-Risk Individuals for Insomnia Using the Ford Insomnia Response to Stress Test

Science.gov (United States)

Kalmbach, David A.; Pillai, Vivek; Arnedt, J. Todd; Drake, Christopher L.

2016-01-01

Study Objectives: A primary focus of the National Institute of Mental Health's current strategic plan is “predicting” who is at risk for disease. As such, the current investigation examined the utility of premorbid sleep reactivity in identifying a specific and manageable population at elevated risk for future insomnia. Methods: A community-based sample of adults (n = 2,892; 59.3% female; 47.9 ± 13.3 y old) with no lifetime history of insomnia or depression completed web-based surveys across three annual assessments. Participants reported parental history of insomnia, demographic characteristics, sleep reactivity on the Ford Insomnia in Response to Stress Test (FIRST), and insomnia symptoms. DSM-IV diagnostic criteria were used to determine insomnia classification. Results: Baseline FIRST scores were used to predict incident insomnia at 1-y follow-up. Two clinically meaningful FIRST cutoff values were identified: FIRST ≥ 16 (sensitivity 77%; specificity 50%; odds ratio [OR] = 2.88, P insomnia onset, even after controlling for stress exposure and demographic characteristics. Of the incident cases, insomniacs with highly reactive sleep systems reported longer sleep onset latencies (FIRST ≥ 16: 65 min; FIRST ≥ 18: 68 min) than participants with nonreactive insomnia (FIRST insomnia based on trait sleep reactivity. The FIRST accurately identifies a focused target population in which the psychobiological processes complicit in insomnia onset and progression can be better investigated, thus improving future preventive efforts. Citation: Kalmbach DA, Pillai V, Arnedt JT, Drake CL. Identifying at-risk individuals for insomnia using the ford insomnia response to stress test. SLEEP 2016;39(2):449–456. PMID:26446111
Circulating RNA transcripts identify therapeutic response in cystic fibrosis lung disease.

Science.gov (United States)

Saavedra, Milene T; Hughes, Grant J; Sanders, Linda A; Carr, Michelle; Rodman, David M; Coldren, Christopher D; Geraci, Mark W; Sagel, Scott D; Accurso, Frank J; West, James; Nick, Jerry A

2008-11-01

Circulating leukocyte RNA transcripts are systemic markers of inflammation, which have not been studied in cystic fibrosis (CF) lung disease. Although the standard assessment of pulmonary treatment response is FEV(1), a measure of airflow limitation, the lack of systemic markers to reflect changes in lung inflammation critically limits the testing of proposed therapeutics. We sought to prospectively identify and validate peripheral blood leukocyte genes that could mark resolution of pulmonary infection and inflammation using a model by which RNA transcripts could increase the predictive value of spirometry. Peripheral blood mononuclear cells were isolated from 10 patients with CF and acute pulmonary exacerbations before and after therapy. RNA expression profiling revealed that 10 genes significantly changed with treatment when compared with matched non-CF and control subjects with stable CF to establish baseline transcript abundance. Peripheral blood mononuclear cell RNA transcripts were prospectively validated, using real-time polymerase chain reaction amplification, in an independent cohort of acutely ill patients with CF (n = 14). Patients who responded to therapy were analyzed using general estimating equations and multiple logistic regression, such that changes in FEV(1)% predicted were regressed with transcript changes. Three genes, CD64, ADAM9, and CD36, were significant and independent predictors of a therapeutic response beyond that of FEV(1) alone (P < 0.05). In both cohorts, receiver operating characteristic analysis revealed greater accuracy when genes were combined with FEV(1). Circulating mononuclear cell transcripts characterize a response to the treatment of pulmonary exacerbations. Even in small patient cohorts, changes in gene expression in conjunction with FEV(1) may enhance current outcomes measures for treatment response.
Characterization of the equine skeletal muscle transcriptome identifies novel functional responses to exercise training.

LENUS (Irish Health Repository)

McGivney, Beatrice A

2010-01-01

BACKGROUND: Digital gene expression profiling was used to characterize the assembly of genes expressed in equine skeletal muscle and to identify the subset of genes that were differentially expressed following a ten-month period of exercise training. The study cohort comprised seven Thoroughbred racehorses from a single training yard. Skeletal muscle biopsies were collected at rest from the gluteus medius at two time points: T(1) - untrained, (9 +\\/- 0.5 months old) and T(2) - trained (20 +\\/- 0.7 months old). RESULTS: The most abundant mRNA transcripts in the muscle transcriptome were those involved in muscle contraction, aerobic respiration and mitochondrial function. A previously unreported over-representation of genes related to RNA processing, the stress response and proteolysis was observed. Following training 92 tags were differentially expressed of which 74 were annotated. Sixteen genes showed increased expression, including the mitochondrial genes ACADVL, MRPS21 and SLC25A29 encoded by the nuclear genome. Among the 58 genes with decreased expression, MSTN, a negative regulator of muscle growth, had the greatest decrease.Functional analysis of all expressed genes using FatiScan revealed an asymmetric distribution of 482 Gene Ontology (GO) groups and 18 KEGG pathways. Functional groups displaying highly significant (P < 0.0001) increased expression included mitochondrion, oxidative phosphorylation and fatty acid metabolism while functional groups with decreased expression were mainly associated with structural genes and included the sarcoplasm, laminin complex and cytoskeleton. CONCLUSION: Exercise training in Thoroughbred racehorses results in coordinate changes in the gene expression of functional groups of genes related to metabolism, oxidative phosphorylation and muscle structure.
Compendium of Immune Signatures Identifies Conserved and Species-Specific Biology in Response to Inflammation.

Science.gov (United States)

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

2016-01-19

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

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Pablo Palma

Full Text Available Preoperative chemoradiation significantly improves oncological outcome in locally advanced rectal cancer. However there is no effective method of predicting tumor response to chemoradiation in these patients. Peripheral blood mononuclear cells have emerged recently as pathology markers of cancer and other diseases, making possible their use as therapy predictors. Furthermore, the importance of the immune response in radiosensivity of solid organs led us to hypothesized that microarray gene expression profiling of peripheral blood mononuclear cells could identify patients with response to chemoradiation in rectal cancer. Thirty five 35 patients with locally advanced rectal cancer were recruited initially to perform the study. Peripheral blood samples were obtained before neaodjuvant treatment. RNA was extracted and purified to obtain cDNA and cRNA for hybridization of microarrays included in Human WG CodeLink bioarrays. Quantitative real time PCR was used to validate microarray experiment data. Results were correlated with pathological response, according to Mandard´s criteria and final UICC Stage (patients with tumor regression grade 1-2 and downstaging being defined as responders and patients with grade 3-5 and no downstaging as non-responders. Twenty seven out of 35 patients were finally included in the study. We performed a multiple t-test using Significance Analysis of Microarrays, to find those genes differing significantly in expression, between responders (n = 11 and non-responders (n = 16 to CRT. The differently expressed genes were: BC 035656.1, CIR, PRDM2, CAPG, FALZ, HLA-DPB2, NUPL2, and ZFP36. The measurement of FALZ (p = 0.029 gene expression level determined by qRT-PCR, showed statistically significant differences between the two groups. Gene expression profiling reveals novel genes in peripheral blood samples of mononuclear cells that could predict responders and non-responders to chemoradiation in patients with
A predator-prey model with a holling type I functional response including a predator mutual interference

Science.gov (United States)

Seo, G.; DeAngelis, D.L.

2011-01-01

The most widely used functional response in describing predator-prey relationships is the Holling type II functional response, where per capita predation is a smooth, increasing, and saturating function of prey density. Beddington and DeAngelis modified the Holling type II response to include interference of predators that increases with predator density. Here we introduce a predator-interference term into a Holling type I functional response. We explain the ecological rationale for the response and note that the phase plane configuration of the predator and prey isoclines differs greatly from that of the Beddington-DeAngelis response; for example, in having three possible interior equilibria rather than one. In fact, this new functional response seems to be quite unique. We used analytical and numerical methods to show that the resulting system shows a much richer dynamical behavior than the Beddington-DeAngelis response, or other typically used functional responses. For example, cyclic-fold, saddle-fold, homoclinic saddle connection, and multiple crossing bifurcations can all occur. We then use a smooth approximation to the Holling type I functional response with predator mutual interference to show that these dynamical properties do not result from the lack of smoothness, but rather from subtle differences in the functional responses. ?? 2011 Springer Science+Business Media, LLC.
RNA-Seq Analysis of IL-1B and IL-36 Responses in Epidermal Keratinocytes Identifies a Shared MyD88-Dependent Gene Signature.

Science.gov (United States)

Swindell, William R; Beamer, Maria A; Sarkar, Mrinal K; Loftus, Shannon; Fullmer, Joseph; Xing, Xianying; Ward, Nicole L; Tsoi, Lam C; Kahlenberg, Michelle J; Liang, Yun; Gudjonsson, Johann E

2018-01-01

IL-36 cytokines have recently emerged as mediators of inflammation in autoimmune conditions including psoriasis vulgaris (PsV) and generalized pustular psoriasis (GPP). This study used RNA-seq to profile the transcriptome of primary epidermal keratinocytes (KCs) treated with IL-1B, IL-36A, IL-36B, or IL-36G. We identified some early IL-1B-specific responses (8 h posttreatment), but nearly all late IL-1B responses were replicated by IL-36 cytokines (24 h posttreatment). Type I and II interferon genes exhibited time-dependent response patterns, with early induction (8 h) followed by no response or repression (24 h). Altogether, we identified 225 differentially expressed genes (DEGs) with shared responses to all 4 cytokines at both time points (8 and 24 h). These involved upregulation of ligands ( IL1A, IL1B , and IL36G ) and activating proteases ( CTSS ) but also upregulation of inhibitors such as IL1RN and IL36RN . Shared IL-1B/IL-36 DEGs overlapped significantly with genes altered in PsV and GPP skin lesions, as well as genes near GWAS loci linked to autoimmune and autoinflammatory diseases (e.g., PsV, psoriatic arthritis, inflammatory bowel disease, and primary biliary cholangitis). Inactivation of MyD88 adapter protein using CRISPR/Cas9 completely abolished expression responses of such DEGs to IL-1B and IL-36G stimulation. These results provide a global view of IL-1B and IL-36 expression responses in epidermal KCs with fine-scale characterization of time-dependent and cytokine-specific response patterns. Our findings support an important role for IL-1B and IL-36 in autoimmune or autoinflammatory conditions and show that MyD88 adaptor protein mediates shared IL-1B/IL-36 responses.
Identifying Careless Responses in Survey Data

Science.gov (United States)

Meade, Adam W.; Craig, S. Bartholomew

2012-01-01

When data are collected via anonymous Internet surveys, particularly under conditions of obligatory participation (such as with student samples), data quality can be a concern. However, little guidance exists in the published literature regarding techniques for detecting careless responses. Previously several potential approaches have been…
"Everybody Identifies with Smokey the Bear": Employee Responses to Newsletter Identification Inducements at the U.S. Forest Service.

Science.gov (United States)

DiSanza, James R.; Bullis, Connie

1999-01-01

Contributes to scholarship on organizational identification (linked to decision making) by examining the identification rhetoric of an in-house newsletter at the U. S. Forest Service and by examining employee responses to newsletter content. Discusses the four responses to the newsletter that were identified: non identification, textual…
Identifying Links between Corporate Social Responsibility and Reputation: Some Considerations for Family Firms

Directory of Open Access Journals (Sweden)

Iguácel Melero-Polo

2017-07-01

To this end—following consultations with a panel of internationally recognized scholars—a selection of leading management, marketing and ethics, corporate governance and family firm management journals were reviewed. The results—based on a content analysis of 55 articles considering the global link between RSC and reputation—allowed us to identify, among others, topics related to consumer attitude and market response to CSR activities (via brand value, along with the impact of CSR on financial value and risk management.
Identifying behavioural differences in working donkeys in response to analgesic administration.

Science.gov (United States)

Regan, F H; Hockenhull, J; Pritchard, J C; Waterman-Pearson, A E; Whay, H R

2016-01-01

To identify pain-related behaviour in working donkeys in order to assist their owners and veterinarians to recognise and manage pain. To identify general and specific behaviours associated with pain or its relief using a trial with the nonsteroidal anti-inflammatory drug meloxicam (Metacam). Observer-blinded, placebo-controlled trial. Forty adult male working donkeys with common clinical abnormalities were randomly assigned to receive either a single loading dose of meloxicam (1.2 mg/kg bwt per os; n = 20) or a placebo (30 mg honey/250 ml water per os; n = 20). Observation of postural and event behaviours was undertaken at 2 pretreatment time points followed by 4 post treatment time points, using scan (instantaneous) and focal sampling. In comparison to pretreatment baselines, donkeys receiving meloxicam were more alert post treatment than the placebo group. They were observed lying down less frequently (P = 0.007), with their eyes closed less frequently (P = 0.04) and having a high head carriage more frequently (P = 0.02). Dozing behaviour decreased after meloxicam compared with the pretreatment baseline (P = 0.03). Donkeys given meloxicam also showed more interest in their environment, turning to look at environmental stimuli more frequently (P = 0.05) than those in the placebo group post treatment. Neither the meloxicam nor the placebo group showed a significant post treatment improvement in lameness scores. Working donkeys receiving meloxicam were more active and alert compared with their pretreatment behaviour, confirming the potential value of nonsteroidal anti-inflammatory drugs in identifying behaviours indicative of pain in working donkeys. Behavioural assessment of pain in working donkeys in field clinic conditions will enable veterinary staff and owners to identify welfare issues promptly and monitor response to analgesia. The Summary is available in Chinese--see Supporting information. © 2015 EVJ Ltd.

Maize MeJA-responsive proteins identified by high-resolution 2-DE PAGE

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Yuliang Zhang

2015-12-01

Full Text Available Exogenous methyl jasmonate (MeJA is well-known to induce plant defense mechanisms effective against a wide variety of insect and microbial pests. High-resolution 2-DE gel electrophoresis was used to discover changes in the leaf proteome of maize exposed to MeJA. We sequenced 62 MeJA-responsive proteins by tandem mass spectroscopy, and deposited the mass spectra and identities in the EMBL-EBI PRIDE repository under reference number PXD001793. An analysis and discussion of the identified proteins in relation to maize defense against Asian corn borer is published by Zhang et al. (2015 [1].
Investigation on plasmonic responses in multilayered nanospheres including asymmetry and spatial nonlocal effects

Science.gov (United States)

Dong, Tianyu; Shi, Yi; Liu, Hui; Chen, Feng; Ma, Xikui; Mittra, Raj

2017-12-01

In this work, we present a rigorous approach for analyzing the optical response of multilayered spherical nano-particles comprised of either plasmonic metal or dielectric, when there is no longer radial symmetry and when nonlocality is included. The Lorenz-Mie theory is applied, and a linearized hydrodynamic Drude model as well as the general nonlocal optical response model for the metals are employed. Additional boundary conditions, viz., the continuity of normal components of polarization current density and the continuity of first-order pressure of free electron density, respectively, are incorporated when handling interfaces involving metals. The application of spherical addition theorems, enables us to express a spherical harmonic about one origin to spherical harmonics about a different origin, and leads to a linear system of equations for the inward- and outward-field modal coefficients for all the layers in the nanoparticle. Scattering matrices at interfaces are obtained and cascaded to obtain the expansion coefficients, to yield the final solution. Through extensive modelling of stratified concentric and eccentric metal-involved spherical nanoshells illuminating by a plane wave, we show that, within a nonlocal description, significant modifications of plasmonic response appear, e.g. a blue-shift in the extinction / scattering spectrum and a broadening spectrum of the resonance. In addition, it has been demonstrated that core-shell nanostructures provide an option for tunable Fano-resonance generators. The proposed method shows its capability and flexibility to analyze the nonlocal response of eccentric hybrid metal-dielectric multilayer structures as well as adjoined metal-involved nanoparticles, even when the number of layers is large.
Posintro™-HBsAg, a modified ISCOM including HBsAg, induces strong cellular and humoral responses

DEFF Research Database (Denmark)

Schiött, Asa; Larsson, Kristina; Manniche, Søren

2011-01-01

HBsAg vaccine formulation, Posintro™-HBsAg, was compared to two commercial hepatitis B vaccines including aluminium or monophosphoryl lipid A (MPL) and the two adjuvant systems MF59 and QS21 in their efficiency to prime both cellular and humoral immune responses. The Posintro™-HBsAg induced...
Next-generation sequencing identifies deregulation of microRNAs involved in both innate and adaptive immune response in ALK+ ALCL.

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Julia Steinhilber

Full Text Available Anaplastic large cell lymphoma (ALCL is divided into two systemic diseases according to the expression of the anaplastic lymphoma kinase (ALK. We investigated the differential expression of miRNAs between ALK+ ALCL, ALK- ALCL cells and normal T-cells using next generation sequencing (NGS. In addition, a C/EBPβ-dependent miRNA profile was generated. The data were validated in primary ALCL cases. NGS identified 106 miRNAs significantly differentially expressed between ALK+ and ALK- ALCL and 228 between ALK+ ALCL and normal T-cells. We identified a signature of 56 miRNAs distinguishing ALK+ ALCL, ALK- ALCL and T-cells. The top candidates significant differentially expressed between ALK+ and ALK- ALCL included 5 upregulated miRNAs: miR-340, miR-203, miR-135b, miR-182, miR-183; and 7 downregulated: miR-196b, miR-155, miR-146a, miR-424, miR-503, miR-424*, miR-542-3p. The miR-17-92 cluster was also upregulated in ALK+ cells. Additionally, we identified a signature of 3 miRNAs significantly regulated by the transcription factor C/EBPβ, which is specifically overexpressed in ALK+ ALCL, including the miR-181 family. Of interest, miR-181a, which regulates T-cell differentiation and modulates TCR signalling strength, was significantly downregulated in ALK+ ALCL cases. In summary, our data reveal a miRNA signature linking ALK+ ALCL to a deregulated immune response and may reflect the abnormal TCR antigen expression known in ALK+ ALCL.
Tomato whole genome transcriptional response to Tetranychus urticae identifies divergence of spider mite-induced responses between tomato and Arabidopsis

NARCIS (Netherlands)

Martel, C.; Zhurov, V.; Navarro, M.; Martinez, M.; Cazaux, M.; Auger, P.; Migeon, A.; Santamaria, M.E.; Wybouw, N.; Diaz, I.; Van Leeuwen, T.; Navajas, M.; Grbic, M.; Grbic, V.

2015-01-01

The two-spotted spider mite Tetranychus urticae is one of the most significant mite pests in agriculture, feeding on more than 1,100 plant hosts, including model plants Arabidopsis thaliana and tomato, Solanum lycopersicum. Here, we describe timecourse tomato transcriptional responses to spider mite
Identifying the age cohort responsible for transmission in a natural outbreak of Bordetella bronchiseptica.

Directory of Open Access Journals (Sweden)

Gráinne H Long

2010-12-01

Full Text Available Identifying the major routes of disease transmission and reservoirs of infection are needed to increase our understanding of disease dynamics and improve disease control. Despite this, transmission events are rarely observed directly. Here we had the unique opportunity to study natural transmission of Bordetella bronchiseptica--a directly transmitted respiratory pathogen with a wide mammalian host range, including sporadic infection of humans--within a commercial rabbitry to evaluate the relative effects of sex and age on the transmission dynamics therein. We did this by developing an a priori set of hypotheses outlining how natural B. bronchiseptica infections may be transmitted between rabbits. We discriminated between these hypotheses by using force-of-infection estimates coupled with random effects binomial regression analysis of B. bronchiseptica age-prevalence data from within our rabbit population. Force-of-infection analysis allowed us to quantify the apparent prevalence of B. bronchiseptica while correcting for age structure. To determine whether transmission is largely within social groups (in this case litter, or from an external group, we used random-effect binomial regression to evaluate the importance of social mixing in disease spread. Between these two approaches our results support young weanlings--as opposed to, for example, breeder or maternal cohorts--as the age cohort primarily responsible for B. bronchiseptica transmission. Thus age-prevalence data, which is relatively easy to gather in clinical or agricultural settings, can be used to evaluate contact patterns and infer the likely age-cohort responsible for transmission of directly transmitted infections. These insights shed light on the dynamics of disease spread and allow an assessment to be made of the best methods for effective long-term disease control.
Expression Analysis of Immune Related Genes Identified from the Coelomocytes of Sea Cucumber (Apostichopus japonicus in Response to LPS Challenge

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Ying Dong

2014-10-01

Full Text Available The sea cucumber (Apostichopus japonicus occupies a basal position during the evolution of deuterostomes and is also an important aquaculture species. In order to identify more immune effectors, transcriptome sequencing of A. japonicus coelomocytes in response to lipopolysaccharide (LPS challenge was performed using the Illumina HiSeq™ 2000 platform. One hundred and seven differentially expressed genes were selected and divided into four functional categories including pathogen recognition (25 genes, reorganization of cytoskeleton (27 genes, inflammation (41 genes and apoptosis (14 genes. They were analyzed to elucidate the mechanisms of host-pathogen interactions and downstream signaling transduction. Quantitative real-time polymerase chain reactions (qRT-PCRs of 10 representative genes validated the accuracy and reliability of RNA sequencing results with the correlation coefficients from 0.88 to 0.98 and p-value <0.05. Expression analysis of immune-related genes after LPS challenge will be useful in understanding the immune response mechanisms of A. japonicus against pathogen invasion and developing strategies for resistant markers selection.
Bleaching response of coral species in the context of assemblage response

Science.gov (United States)

Swain, Timothy D.; DuBois, Emily; Goldberg, Scott J.; Backman, Vadim; Marcelino, Luisa A.

2017-06-01

Caribbean coral reefs are declining due to a mosaic of local and global stresses, including climate change-induced thermal stress. Species and assemblage responses differ due to factors that are not easily identifiable or quantifiable. We calculated a novel species-specific metric of coral bleaching response, taxon- α and - β, which relates the response of a species to that of its assemblages for 16 species over 18 assemblages. By contextualizing species responses within the response of their assemblages, the effects of environmental factors are removed and intrinsic differences among taxa are revealed. Most corals experience either a saturation response, overly sensitive to weak stress ( α > 0) but under-responsive compared to assemblage bleaching ( β bleaching ( β > 1). This metric may help reveal key factors of bleaching susceptibility and identify species as targets for conservation.
Factors that contribute to biomarker responses in humans including a study in individuals taking Vitamin C supplementation.

Science.gov (United States)

Anderson, D

2001-09-01

It is possible in many situations to identify humans exposed to potentially toxic materials in the workplace and in the environment. As in most human studies, there tends to be a high degree of interindividual variability in response to chemical insults. Some non-exposed control individuals exhibit as high a level of damage as some exposed individuals and some of these have levels of damage as low as many of the controls. Thus, it is only the mean values of the groups that can substantiate an exposure-related problem; the data on an individual basis are still of limited use. While human lymphocytes remain the most popular cell type for monitoring purposes, sperm, buccal, nasal, epithelial and placental cells are also used. However, for interpretation of responses, the issue of confounding factors must be addressed. There are endogenous confounding factors, such as age, gender, and genetic make-up and exogenous ones, including lifestyle habits (smoking, drinking, etc.) There are biomarkers of exposure, effect/response and susceptibility and the last may be influenced by the genotype and polymorphism genes existing in a population. From our own studies, confounding effects on cytogenetic damage and ras oncoproteins will be considered in relation to workers exposed to vinyl chloride and petroleum emissions and to volunteers taking Vitamin C supplementation. Smoking history, exposure and duration of employment affected the worker studies. For petroleum emissions, so did gender and season of exposure. For the non-smoking volunteer Vitamin C supplementation study, cholesterol levels, plasma Vitamin C levels, lipid peroxidation products and DNA damage in the Comet assay were also measured. Gender affected differences in Vitamin C levels, antioxidant capacity and the number of chromosome aberrations induced by bleomycin challenge in vitro. The results were the same for both high and low cholesterol subjects. The relationship between biomarkers and the various factors which
Hierarchical Energy Management of Microgrids including Storage and Demand Response

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Songli Fan

2018-05-01

Full Text Available Battery energy storage (BES and demand response (DR are considered to be promising technologies to cope with the uncertainty of renewable energy sources (RES and the load in the microgrid (MG. Considering the distinct prediction accuracies of the RES and load at different timescales, it is essential to incorporate the multi-timescale characteristics of BES and DR in MG energy management. Under this background, a hierarchical energy management framework is put forward for an MG including multi-timescale BES and DR to optimize operation with the uncertainty of RES as well as load. This framework comprises three stages of scheduling: day-ahead scheduling (DAS, hour-ahead scheduling (HAS, and real-time scheduling (RTS. In DAS, a scenario-based stochastic optimization model is established to minimize the expected operating cost of MG, while ensuring its safe operation. The HAS is utilized to bridge DAS and RTS. In RTS, a control strategy is proposed to eliminate the imbalanced power owing to the fluctuations of RES and load. Then, a decomposition-based algorithm is adopted to settle the models in DAS and HAS. Simulation results on a seven-bus MG validate the effectiveness of the proposed methodology.
Novel Method To Identify Source-Associated Phylogenetic Clustering Shows that Listeria monocytogenes Includes Niche-Adapted Clonal Groups with Distinct Ecological Preferences

DEFF Research Database (Denmark)

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

2006-01-01

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

Science.gov (United States)

Gunia, M; Phocas, F; Gourdine, J-L; Bijma, P; Mandonnet, N

2013-02-01

The Creole goat is a local breed used for meat production in Guadeloupe (French West Indies). As in other tropical countries, improvement of parasite resistance is needed. In this study, we compared predicted selection responses for alternative breeding programs with or without parasite resistance and resilience traits. The overall breeding goal included traits for production, reproduction, and parasite resilience and resistance to ensure a balanced selection outcome. The production traits were BW and dressing percentage (DP). The reproduction trait was fertility (FER), which was the number of doe kiddings per mating. The resistance trait was worm fecal egg count (FEC), which is a measurement of the number of gastro-intestinal parasite eggs found in the feces. The resilience trait was the packed cell volume (PCV), which is a measurement of the volume of red blood cells in the blood. Dressing percentage, BW, and FEC were measured at 11 mo of age, which is the mating or selling age. Fertility and PCV were measured on females at each kidding period. The breeding program accounting for the overall breeding goal and a selection index including all traits gave annual selection responses of 800 g for BW, 3.75% for FER, 0.08% for DP, -0.005 ln(eggs/g) for FEC, and 0.28% for PCV. The expected selection responses for BW and DP in this breeding program were reduced by 2% and 6%, respectively, compared with a breeding program not accounting for FEC and PCV. The overall breeding program, proposed for the Creole breed, offers the best breeding strategy in terms of expected selection responses, making it possible to improve all traits together. It offers a good balance between production and adaptation traits and may present some interest for the selection of other goat breeds in the tropics.
Identifying the nonlinear mechanical behaviour of micro-speakers from their quasi-linear electrical response

Science.gov (United States)

Zilletti, Michele; Marker, Arthur; Elliott, Stephen John; Holland, Keith

2017-05-01

In this study model identification of the nonlinear dynamics of a micro-speaker is carried out by purely electrical measurements, avoiding any explicit vibration measurements. It is shown that a dynamic model of the micro-speaker, which takes into account the nonlinear damping characteristic of the device, can be identified by measuring the response between the voltage input and the current flowing into the coil. An analytical formulation of the quasi-linear model of the micro-speaker is first derived and an optimisation method is then used to identify a polynomial function which describes the mechanical damping behaviour of the micro-speaker. The analytical results of the quasi-linear model are compared with numerical results. This study potentially opens up the possibility of efficiently implementing nonlinear echo cancellers.
Advanced neuroblastoma: improved response rate using a multiagent regimen (OPEC) including sequential cisplatin and VM-26.

Science.gov (United States)

Shafford, E A; Rogers, D W; Pritchard, J

1984-07-01

Forty-two children, all over one year of age, were given vincristine, cyclophosphamide, and sequentially timed cisplatin and VM-26 (OPEC) or OPEC and doxorubicin (OPEC-D) as initial treatment for newly diagnosed stage III or IV neuroblastoma. Good partial response was achieved in 31 patients (74%) overall and in 28 (78%) of 36 patients whose treatment adhered to the chemotherapy protocol, compared with a 65% response rate achieved in a previous series of children treated with pulsed cyclophosphamide and vincristine with or without doxorubicin. Only six patients, including two of the six children whose treatment did not adhere to protocol, failed to respond, but there were five early deaths from treatment-related complications. Tumor response to OPEC, which was the less toxic of the two regimens, was at least as good as tumor response to OPEC-D. Cisplatin-induced morbidity was clinically significant in only one patient and was avoided in others by careful monitoring of glomerular filtration rate and hearing. Other centers should test the efficacy of OPEC or equivalent regimens in the treatment of advanced neuroblastoma.
Study on the seismic response of reactor vessel of pool type LMFBR including fluid-structure interaction

International Nuclear Information System (INIS)

Tanimoto, K.; Ito, T.; Fujita, K.; Kurihara, C.; Sawada, Y.; Sakurai, A.

1988-01-01

The paper presents the seismic response of reactor vessel of pool type LMFBR with fluid-structure interaction. The reactor vessel has bottom support arrangement, the same core support system as Super-Phenix in France. Due to the bottom support arrangement, the level of core support is lower than that of the side support arrangement. So, in this reactor vessel, the displacement of the core top tends to increase because of the core's rocking. In this study, we investigated the vibration and seismic response characteristics of the reactor vessel. Therefore, the seismic experiments were carried out using one-eighth scale model and the seismic response including FSI and sloshing were investigated. From this study, the effect of liquid on the vibration characteristics and the seismic response characteristics of reactor vessel were clarified and sloshing characteristics were also clarified. It was confirmed that FEM analysis with FSI can reproduce the seismic behavior of the reactor vessel and is applicable to seismic design of the pool type LMFBR with bottom support arrangement. (author). 5 refs, 14 figs, 2 tabs
Method of identifying features in indexed data

Science.gov (United States)

Jarman, Kristin H [Richland, WA; Daly, Don Simone [Richland, WA; Anderson, Kevin K [Richland, WA; Wahl, Karen L [Richland, WA

2001-06-26

The present invention is a method of identifying features in indexed data, especially useful for distinguishing signal from noise in data provided as a plurality of ordered pairs. Each of the plurality of ordered pairs has an index and a response. The method has the steps of: (a) providing an index window having a first window end located on a first index and extending across a plurality of indices to a second window end; (b) selecting responses corresponding to the plurality of indices within the index window and computing a measure of dispersion of the responses; and (c) comparing the measure of dispersion to a dispersion critical value. Advantages of the present invention include minimizing signal to noise ratio, signal drift, varying baseline signal and combinations thereof.
Identifying response styles: A latent-class bilinear multinomial logit model

NARCIS (Netherlands)

van Rosmalen, J.; van Herk, H.; Groenen, P.J.F.

2010-01-01

Respondents can vary strongly in the way they use rating scales. Specifically, respondents can exhibit a variety of response styles, which threatens the validity of the responses. The purpose of this article Is to investigate how response style and content of the items affect rating scale responses.
Beyond imperviousness: A statistical approach to identifying functional differences between development morphologies on variable source area-type response in urbanized watersheds

Science.gov (United States)

Lim, T. C.

2016-12-01

Empirical evidence has shown linkages between urbanization, hydrological regime change, and degradation of water quality and aquatic habitat. Percent imperviousness, has long been suggested as the dominant source of these negative changes. However, recent research identifying alternative pathways of runoff production at the watershed scale have called into question percent impervious surface area's primacy in urban runoff production compared to other aspects of urbanization including change in vegetative cover, imported water and water leakages, and the presence of drainage infrastructure. In this research I show how a robust statistical methodology can detect evidence of variable source area (VSA)-type hydrologic response associated with incremental hydraulic connectivity in watersheds. I then use logistic regression to explore how evidence of VSA-type response relates to the physical and meterological characteristics of the watershed. I find that impervious surface area is highly correlated with development, but does not add significant explanatory power beyond percent developed in predicting VSA-type response. Other aspects of development morphology, including percent developed open space and type of drainage infrastructure also do not add to the explanatory power of undeveloped land in predicting VSA-type response. Within only developed areas, the effect of developed open space was found to be more similar to that of total impervious area than to undeveloped land. These findings were consistent when tested across a national cross-section of urbanized watersheds, a higher resolution dataset of Baltimore Metropolitan Area watersheds, and a subsample of watersheds confirmed not to be served by combined sewer systems. These findings suggest that land development policies that focus on lot coverage should be revisited, and more focus should be placed on preserving native vegetation and soil conditions alongside development.
Evaluation of Seismic Response Trends from Long-Term Monitoring of Two Instrumented RC Buildings Including Soil-Structure Interaction

Directory of Open Access Journals (Sweden)

Faheem Butt

2012-01-01

Full Text Available This paper presents analyses of the seismic responses of two reinforced concrete buildings monitored for a period of more than two years. One of the structures was a three-storey reinforced concrete (RC frame building with a shear core, while the other was a three-storey RC frame building without a core. Both buildings are part of the same large complex but are seismically separated from the rest of it. Statistical analysis of the relationships between maximum free field accelerations and responses at different points on the buildings was conducted and demonstrated strong correlation between those. System identification studies using recorded accelerations were undertaken and revealed that natural frequencies and damping ratios of the building structures vary during different earthquake excitations. This variation was statistically examined and relationships between identified natural frequencies and damping ratios, and the peak response acceleration at the roof level were developed. A general trend of decreasing modal frequencies and increasing damping ratios was observed with increased level of shaking and response. Moreover, the influence of soil structure interaction (SSI on the modal characteristics was evaluated. SSI effects decreased the modal frequencies and increased some of the damping ratios.
Transcriptome analysis identifies genes involved in ethanol response of Saccharomyces cerevisiae in Agave tequilana juice.

Science.gov (United States)

Ramirez-Córdova, Jesús; Drnevich, Jenny; Madrigal-Pulido, Jaime Alberto; Arrizon, Javier; Allen, Kirk; Martínez-Velázquez, Moisés; Alvarez-Maya, Ikuri

2012-08-01

During ethanol fermentation, yeast cells are exposed to stress due to the accumulation of ethanol, cell growth is altered and the output of the target product is reduced. For Agave beverages, like tequila, no reports have been published on the global gene expression under ethanol stress. In this work, we used microarray analysis to identify Saccharomyces cerevisiae genes involved in the ethanol response. Gene expression of a tequila yeast strain of S. cerevisiae (AR5) was explored by comparing global gene expression with that of laboratory strain S288C, both after ethanol exposure. Additionally, we used two different culture conditions, cells grown in Agave tequilana juice as a natural fermentation media or grown in yeast-extract peptone dextrose as artificial media. Of the 6368 S. cerevisiae genes in the microarray, 657 genes were identified that had different expression responses to ethanol stress due to strain and/or media. A cluster of 28 genes was found over-expressed specifically in the AR5 tequila strain that could be involved in the adaptation to tequila yeast fermentation, 14 of which are unknown such as yor343c, ylr162w, ygr182c, ymr265c, yer053c-a or ydr415c. These could be the most suitable genes for transforming tequila yeast to increase ethanol tolerance in the tequila fermentation process. Other genes involved in response to stress (RFC4, TSA1, MLH1, PAU3, RAD53) or transport (CYB2, TIP20, QCR9) were expressed in the same cluster. Unknown genes could be good candidates for the development of recombinant yeasts with ethanol tolerance for use in industrial tequila fermentation.

Developmental responses of bread wheat to changes in ambient temperature following deletion of a locus that includes FLOWERING LOCUS T1.

Science.gov (United States)

Dixon, Laura E; Farré, Alba; Finnegan, E Jean; Orford, Simon; Griffiths, Simon; Boden, Scott A

2018-01-04

FLOWERING LOCUS T (FT) is a central integrator of environmental signals that regulates the timing of vegetative to reproductive transition in flowering plants. In model plants, these environmental signals have been shown to include photoperiod, vernalization, and ambient temperature pathways, and in crop species, the integration of the ambient temperature pathway remains less well understood. In hexaploid wheat, at least 5 FT-like genes have been identified, each with a copy on the A, B, and D genomes. Here, we report the characterization of FT-B1 through analysis of FT-B1 null and overexpression genotypes under different ambient temperature conditions. This analysis has identified that the FT-B1 alleles perform differently under diverse environmental conditions; most notably, the FT-B1 null produces an increase in spikelet and tiller number when grown at lower temperature conditions. Additionally, absence of FT-B1 facilitates more rapid germination under both light and dark conditions. These results provide an opportunity to understand the FT-dependent pathways that underpin key responses of wheat development to changes in ambient temperature. This is particularly important for wheat, for which development and grain productivity are sensitive to changes in temperature. © 2018 The Authors Plant, Cell & Environment Published by John Wiley & Sons Ltd.
Unique genetic loci identified for emotional behavior in control and chronic stress conditions.

Directory of Open Access Journals (Sweden)

Kimberly AK Carhuatanta

2014-10-01

Full Text Available An individual’s genetic background affects their emotional behavior and response to stress. Although studies have been conducted to identify genetic predictors for emotional behavior or stress response, it remains unknown how prior stress history alters the interaction between an individual’s genome and their emotional behavior. Therefore, the purpose of this study is to identify chromosomal regions that affect emotional behavior and are sensitive to stress exposure. We utilized the BXD behavioral genetics mouse model to identify chromosomal regions that predict fear learning and emotional behavior following exposure to a control or chronic stress environment. 62 BXD recombinant inbred strains and C57BL/6 and DBA/2 parental strains underwent behavioral testing including a classical fear conditioning paradigm and the elevated plus maze. Distinct quantitative trait loci (QTLs were identified for emotional learning, anxiety and locomotion in control and chronic stress populations. Candidate genes, including those with already known functions in learning and stress were found to reside within the identified QTLs. Our data suggest that chronic stress history reveals novel genetic predictors of emotional behavior.
Wind-induced response analysis of a wind turbine tower including the blade-tower coupling effect

Institute of Scientific and Technical Information of China (English)

Xiao-bo CHEN; Jing LI; Jian-yun CHEN

2009-01-01

To analyze wind-induced response characteristics of a wind turbine tower more accurately, the blade-tower coupling effect was investigated. The mean wind velocity of the rotating blades and tower was simulated according to wind shear effects,and the fluctuating wind velocity time series of the wind turbine were simulated by a harmony superposition method. A dynamic finite element method (FEM) was used to calculate the wind-induced response of the blades and tower. Wind-induced responses of the tower were calculated in two cases (one included the blade-tower coupling effect, and the other only added the mass of blades and the hub at the top of the tower), and then the maximal displacements at the top of the tower of the tow cases were compared with each other. As a result of the influence of the blade-tower coupling effect and the total base shear of the blades, the maximal displacement of the first case increased nearly by 300% compared to the second case. To obtain more precise analysis, the blade-tower coupling effect and the total base shear of the blades should be considered simultaneously in the design of wind turbine towers.
Identifying and Prioritizing Information Needs and Research Priorities of Public Health Emergency Preparedness and Response Practitioners.

Science.gov (United States)

Siegfried, Alexa L; Carbone, Eric G; Meit, Michael B; Kennedy, Mallory J; Yusuf, Hussain; Kahn, Emily B

2017-10-01

This study describes findings from an assessment conducted to identify perceived knowledge gaps, information needs, and research priorities among state, territorial, and local public health preparedness directors and coordinators related to public health emergency preparedness and response (PHPR). The goal of the study was to gather information that would be useful for ensuring that future funding for research and evaluation targets areas most critical for advancing public health practice. We implemented a mixed-methods approach to identify and prioritize PHPR research questions. A web survey was sent to all state, city, and territorial health agencies funded through the Public Health Emergency Preparedness (PHEP) Cooperative Agreement program and a sample of local health departments (LHDs). Three focus groups of state and local practitioners and subject matter experts from the Centers for Disease Control and Prevention (CDC) were subsequently conducted, followed by 3 meetings of an expert panel of PHPR practitioners and CDC experts to prioritize and refine the research questions. We identified a final list of 44 research questions that were deemed by study participants as priority topics where future research can inform PHPR programs and practice. We identified differences in perceived research priorities between PHEP awardees and LHD survey respondents; the number of research questions rated as important was greater among LHDs than among PHEP awardees (75%, n=33, compared to 24%, n=15). The research questions identified provide insight into public health practitioners' perceived knowledge gaps and the types of information that would be most useful for informing and advancing PHPR practice. The study also points to a higher level of information need among LHDs than among PHEP awardees. These findings are important for CDC and the PHPR research community to ensure that future research studies are responsive to practitioners' needs and provide the information
SU-F-J-86: Method to Include Tissue Dose Response Effect in Deformable Image Registration

Energy Technology Data Exchange (ETDEWEB)

Zhu, J; Liang, J; Chen, S; Qin, A; Yan, D [Beaumont Health Systeml, Royal Oak, MI (United States)

2016-06-15

Purpose: Organ changes shape and size during radiation treatment due to both mechanical stress and radiation dose response. However, the dose response induced deformation has not been considered in conventional deformable image registration (DIR). A novel DIR approach is proposed to include both tissue elasticity and radiation dose induced organ deformation. Methods: Assuming that organ sub-volume shrinkage was proportional to the radiation dose induced cell killing/absorption, the dose induced organ volume change was simulated applying virtual temperature on each sub-volume. Hence, both stress and heterogeneity temperature induced organ deformation. Thermal stress finite element method with organ surface boundary condition was used to solve deformation. Initial boundary correspondence on organ surface was created from conventional DIR. Boundary condition was updated by an iterative optimization scheme to minimize elastic deformation energy. The registration was validated on a numerical phantom. Treatment dose was constructed applying both the conventional DIR and the proposed method using daily CBCT image obtained from HN treatment. Results: Phantom study showed 2.7% maximal discrepancy with respect to the actual displacement. Compared with conventional DIR, subvolume displacement difference in a right parotid had the mean±SD (Min, Max) to be 1.1±0.9(−0.4∼4.8), −0.1±0.9(−2.9∼2.4) and −0.1±0.9(−3.4∼1.9)mm in RL/PA/SI directions respectively. Mean parotid dose and V30 constructed including the dose response induced shrinkage were 6.3% and 12.0% higher than those from the conventional DIR. Conclusion: Heterogeneous dose distribution in normal organ causes non-uniform sub-volume shrinkage. Sub-volume in high dose region has a larger shrinkage than the one in low dose region, therefore causing more sub-volumes to move into the high dose area during the treatment course. This leads to an unfavorable dose-volume relationship for the normal organ
Assessment of Mobile Accident Response Capability

International Nuclear Information System (INIS)

1983-03-01

This report presents the results of a DOE-sponsored assessment of nuclear accident response resources. It identifies the mobile resources that could be required to respond to different types of nuclear accidents including major ones like TMI-2, identifies the resources currently available and makes recommendations for the design and construction of additional mobile accident response resources to supplement those already in existence. This project is referred to as the Mobile Accident Response Capability (MARC) program
Pareto Optimization Identifies Diverse Set of Phosphorylation Signatures Predicting Response to Treatment with Dasatinib.

Science.gov (United States)

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

2015-01-01

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

Science.gov (United States)

Pandey, Aarti; Chakraborty, Subhra; Datta, Asis; Chakraborty, Niranjan

2008-01-01

Dehydration or water-deficit is one of the most important environmental stress factors that greatly influences plant growth and development and limits crop productivity. Plants respond and adapt to such stress by altering their cellular metabolism and activating various defense machineries. Mechanisms that operate signal perception, transduction, and downstream regulatory events provide valuable information about the underlying pathways involved in environmental stress responses. The nuclear proteins constitute a highly organized, complex network that plays diverse roles during cellular development and other physiological processes. To gain a better understanding of dehydration response in plants, we have developed a comparative nuclear proteome in a food legume, chickpea (Cicer arietinum L.). Three-week-old chickpea seedlings were subjected to progressive dehydration by withdrawing water and the changes in the nuclear proteome were examined using two-dimensional gel electrophoresis. Approximately 205 protein spots were found to be differentially regulated under dehydration. Mass spectrometry analysis allowed the identification of 147 differentially expressed proteins, presumably involved in a variety of functions including gene transcription and replication, molecular chaperones, cell signaling, and chromatin remodeling. The dehydration responsive nuclear proteome of chickpea revealed a coordinated response, which involves both the regulatory as well as the functional proteins. This study, for the first time, provides an insight into the complex metabolic network operating in the nucleus during dehydration.
Identifying community thresholds for lotic benthic diatoms in response to human disturbance.

Science.gov (United States)

Tang, Tao; Tang, Ting; Tan, Lu; Gu, Yuan; Jiang, Wanxiang; Cai, Qinghua

2017-06-23

Although human disturbance indirectly influences lotic assemblages through modifying physical and chemical conditions, identifying thresholds of human disturbance would provide direct evidence for preventing anthropogenic degradation of biological conditions. In the present study, we used data obtained from tributaries of the Three Gorges Reservoir in China to detect effects of human disturbance on streams and to identify disturbance thresholds for benthic diatoms. Diatom species composition was significantly affected by three in-stream stressors including TP, TN and pH. Diatoms were also influenced by watershed % farmland and natural environmental variables. Considering three in-stream stressors, TP was positively influenced by % farmland and % impervious surface area (ISA). In contrast, TN and pH were principally affected by natural environmental variables. Among measured natural environmental variables, average annual air temperature, average annual precipitation, and topsoil % CaCO 3 , % gravel, and total exchangeable bases had significant effects on study streams. When effects of natural variables were accounted for, substantial compositional changes in diatoms occurred when farmland or ISA land use exceeded 25% or 0.3%, respectively. Our study demonstrated the rationale for identifying thresholds of human disturbance for lotic assemblages and addressed the importance of accounting for effects of natural factors for accurate disturbance thresholds.
Machine Learning Methods Improve Prognostication, Identify Clinically Distinct Phenotypes, and Detect Heterogeneity in Response to Therapy in a Large Cohort of Heart Failure Patients.

Science.gov (United States)

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

2018-04-12

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

Science.gov (United States)

Hewagalamulage, S D; Lee, T K; Clarke, I J; Henry, B A

2016-07-01

There is a strong inter-relationship between activation of the hypothalamo-pituitary-adrenal axis and energy homeostasis. Patients with abdominal obesity have elevated cortisol levels. Furthermore, stress and glucocorticoids act to control both food intake and energy expenditure. In particular, glucocorticoids are known to increase the consumption of foods enriched in fat and sugar. It is well-known that, in all species, the cortisol response to stress or adrenocorticotropin is highly variable. It has now emerged that cortisol responsiveness is an important determinant in the metabolic sequelae to stress. Sheep that are characterized as high-cortisol responders (HRs) have greater propensity to weight gain and obesity than low-cortisol responders (LRs). This difference in susceptibility to become obese is associated with a distinct metabolic, neuroendocrine, and behavioral phenotype. In women and ewes, HR individuals eat more in response to stress than LR. Furthermore, HR sheep have impaired melanocortin signaling and reduced skeletal muscle thermogenesis. High-cortisol responder sheep exhibit reactive coping strategies, whereas LRs exhibit proactive coping strategies. This complex set of traits leads to increased food intake and reduced energy expenditure in HR and thus, predisposition to obesity. We predict that cortisol responsiveness may be used as a marker to identify individuals who are at risk of weight gain and subsequent obesity. Copyright © 2016 Elsevier Inc. All rights reserved.
Gravimetric phenotyping of whole plant transpiration responses to atmospheric vapour pressure deficit identifies genotypic variation in water use efficiency.

Science.gov (United States)

Ryan, Annette C; Dodd, Ian C; Rothwell, Shane A; Jones, Ros; Tardieu, Francois; Draye, Xavier; Davies, William J

2016-10-01

There is increasing interest in rapidly identifying genotypes with improved water use efficiency, exemplified by the development of whole plant phenotyping platforms that automatically measure plant growth and water use. Transpirational responses to atmospheric vapour pressure deficit (VPD) and whole plant water use efficiency (WUE, defined as the accumulation of above ground biomass per unit of water used) were measured in 100 maize (Zea mays L.) genotypes. Using a glasshouse based phenotyping platform with naturally varying VPD (1.5-3.8kPa), a 2-fold variation in WUE was identified in well-watered plants. Regression analysis of transpiration versus VPD under these conditions, and subsequent whole plant gas exchange at imposed VPDs (0.8-3.4kPa) showed identical responses in specific genotypes. Genotype response of transpiration versus VPD fell into two categories: 1) a linear increase in transpiration rate with VPD with low (high WUE) or high (low WUE) transpiration rate at all VPDs, 2) a non-linear response with a pronounced change point at low VPD (high WUE) or high VPD (low WUE). In the latter group, high WUE genotypes required a significantly lower VPD before transpiration was restricted, and had a significantly lower rate of transpiration in response to VPD after this point, when compared to low WUE genotypes. Change point values were significantly positively correlated with stomatal sensitivity to VPD. A change point in stomatal response to VPD may explain why some genotypes show contradictory WUE rankings according to whether they are measured under glasshouse or field conditions. Furthermore, this novel use of a high throughput phenotyping platform successfully reproduced the gas exchange responses of individuals measured in whole plant chambers, accelerating the identification of plants with high WUE. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Including dynamic CO2 intensity with demand response

International Nuclear Information System (INIS)

Stoll, Pia; Brandt, Nils; Nordström, Lars

2014-01-01

Hourly demand response tariffs with the intention of reducing or shifting loads during peak demand hours are being intensively discussed among policy-makers, researchers and executives of future electricity systems. Demand response rates have still low customer acceptance, apparently because the consumption habits requires stronger incentive to change than any proposed financial incentive. An hourly CO 2 intensity signal could give customers an extra environmental motivation to shift or reduce loads during peak hours, as it would enable co-optimisation of electricity consumption costs and carbon emissions reductions. In this study, we calculated the hourly dynamic CO 2 signal and applied the calculation to hourly electricity market data in Great Britain, Ontario and Sweden. This provided a novel understanding of the relationships between hourly electricity generation mix composition, electricity price and electricity mix CO 2 intensity. Load shifts from high-price hours resulted in carbon emission reductions for electricity generation mixes where price and CO 2 intensity were positively correlated. The reduction can be further improved if the shift is optimised using both price and CO 2 intensity. The analysis also indicated that an hourly CO 2 intensity signal can help avoid carbon emissions increases for mixes with a negative correlation between electricity price and CO 2 intensity. - Highlights: • We present a formula for calculating hybrid dynamic CO 2 intensity of electricity generation mixes. • We apply the dynamic CO 2 Intensity on hourly electricity market prices and generation units for Great Britain, Ontario and Sweden. • We calculate the spearman correlation between hourly electricity market price and dynamic CO 2 intensity for Great Britain, Ontario and Sweden. • We calculate carbon footprint of shifting 1 kWh load daily from on-peak hours to off-peak hours using the dynamic CO 2 intensity. • We conclude that using dynamic CO 2 intensity for
Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates

Science.gov (United States)

Ances, Beau M.; Vitaliani, Roberta; Taylor, Robert A.; Liebeskind, David S.; Voloschin, Alfredo; Houghton, David J.; Galetta, Steven L.; Dichter, Marc; Alavi, Abass; Rosenfeld, Myrna R.; Dalmau, Josep

2007-01-01

had dramatic clinical and neuroimaging responses to immunotherapy or tumour resection; two patients had neurological relapse and improved with immunotherapy. Overall, the phenotype associated with the novel neuropil antibodies includes dominant behavioural and psychiatric symptoms and seizures that often interfere with the evaluation of cognition and memory, and brain MRI or FDG-PET abnormalities less frequently restricted to the medial temporal lobes than in patients with classical paraneoplastic or VGKC antibodies. When compared with patients with VGKC antibodies, patients with these novel antibodies are more likely to have CSF inflammatory abnormalities and systemic tumours (teratoma and thymoma), and they do not develop SIADH-like hyponatraemia. Although most autoantigens await characterization, all share intense expression by the neuropil of hippocampus, with patterns of immunolabelling characteristic enough to suggest the diagnosis of these disorders and predict response to treatment. PMID:15888538
A Transcriptomic Approach to Identify Novel Drug Efflux Pumps in Bacteria.

Science.gov (United States)

Li, Liping; Tetu, Sasha G; Paulsen, Ian T; Hassan, Karl A

2018-01-01

The core genomes of most bacterial species include a large number of genes encoding putative efflux pumps. The functional roles of most of these pumps are unknown, however, they are often under tight regulatory control and expressed in response to their substrates. Therefore, one way to identify pumps that function in antimicrobial resistance is to examine the transcriptional responses of efflux pump genes to antimicrobial shock. By conducting complete transcriptomic experiments following antimicrobial shock treatments, it may be possible to identify novel drug efflux pumps encoded in bacterial genomes. In this chapter we describe a complete workflow for conducting transcriptomic analyses by RNA sequencing, to determine transcriptional changes in bacteria responding to antimicrobials.
Identifying Unknown Response Styles: A Latent-Class Bilinear Multinomial Logit Model

NARCIS (Netherlands)

J.M. van Rosmalen (Joost); H. van Herk (Hester); P.J.F. Groenen (Patrick)

2007-01-01

textabstractRespondents can vary significantly in the way they use rating scales. Specifically, respondents can exhibit varying degrees of response style, which threatens the validity of the responses. The purpose of this article is to investigate to what extent rating scale responses show response
Using NMR metabolomics to identify responses of an environmental estrogen in blood plasma of fish

International Nuclear Information System (INIS)

Samuelsson, Linda M.; Foerlin, Lars; Karlsson, Goeran; Adolfsson-Erici, Margaretha; Larsson, D.G. Joakim

2006-01-01

Nuclear magnetic resonance (NMR) based metabolomics in combination with multivariate data analysis may become valuable tools to study environmental effects of pharmaceuticals and other chemicals in aquatic organisms. To explore the usefulness of this approach in fish, we have used 1 H NMR metabolomics to compare blood plasma and plasma lipid extracts from rainbow trout exposed to the synthetic contraceptive estrogen ethinylestradiol (EE 2 ) with plasma from control fish. The plasma metabolite profile was affected in fish exposed to 10 ng/L but not 0.87 ng/L of EE 2 , which was in agreement with an induced vitellogenin synthesis in the high dose group only, as measured by ELISA. The main affected metabolites were vitellogenin, alanine, phospholipids and cholesterol. The responses identified by this discovery-driven method could be put in context with previous knowledge of the effects of estrogens on fish. This adds confidence to the approach of using NMR metabolomics to identify environmental effects of pharmaceuticals and other contaminants
Identifying drought response of semi-arid aeolian systems using near-surface luminescence profiles and changepoint analysis, Nebraska Sandhills.

Science.gov (United States)

Buckland, Catherine; Bailey, Richard; Thomas, David

2017-04-01

Two billion people living in drylands are affected by land degradation. Sediment erosion by wind and water removes fertile soil and destabilises landscapes. Vegetation disturbance is a key driver of dryland erosion caused by both natural and human forcings: drought, fire, land use, grazing pressure. A quantified understanding of vegetation cover sensitivities and resultant surface change to forcing factors is needed if the vegetation and landscape response to future climate change and human pressure are to be better predicted. Using quartz luminescence dating and statistical changepoint analysis (Killick & Eckley, 2014) this study demonstrates the ability to identify step-changes in depositional age of near-surface sediments. Lx/Tx luminescence profiles coupled with statistical analysis show the use of near-surface sediments in providing a high-resolution record of recent system response and aeolian system thresholds. This research determines how the environment has recorded and retained sedimentary evidence of drought response and land use disturbances over the last two hundred years across both individual landforms and the wider Nebraska Sandhills. Identifying surface deposition and comparing with records of climate, fire and land use changes allows us to assess the sensitivity and stability of the surface sediment to a range of forcing factors. Killick, R and Eckley, IA. (2014) "changepoint: An R Package for Changepoint Analysis." Journal of Statistical Software, (58) 1-19.
Groundwater decline and tree change in floodplain landscapes: Identifying non-linear threshold responses in canopy condition

Directory of Open Access Journals (Sweden)

J. Kath

2014-12-01

Full Text Available Groundwater decline is widespread, yet its implications for natural systems are poorly understood. Previous research has revealed links between groundwater depth and tree condition; however, critical thresholds which might indicate ecological ‘tipping points’ associated with rapid and potentially irreversible change have been difficult to quantify. This study collated data for two dominant floodplain species, Eucalyptus camaldulensis (river red gum and E. populnea (poplar box from 118 sites in eastern Australia where significant groundwater decline has occurred. Boosted regression trees, quantile regression and Threshold Indicator Taxa Analysis were used to investigate the relationship between tree condition and groundwater depth. Distinct non-linear responses were found, with groundwater depth thresholds identified in the range from 12.1 m to 22.6 m for E. camaldulensis and 12.6 m to 26.6 m for E. populnea beyond which canopy condition declined abruptly. Non-linear threshold responses in canopy condition in these species may be linked to rooting depth, with chronic groundwater decline decoupling trees from deep soil moisture resources. The quantification of groundwater depth thresholds is likely to be critical for management aimed at conserving groundwater dependent biodiversity. Identifying thresholds will be important in regions where water extraction and drying climates may contribute to further groundwater decline. Keywords: Canopy condition, Dieback, Drought, Tipping point, Ecological threshold, Groundwater dependent ecosystems
Cross-species multiple environmental stress responses: An integrated approach to identify candidate genes for multiple stress tolerance in sorghum (Sorghum bicolor (L. Moench and related model species.

Directory of Open Access Journals (Sweden)

Adugna Abdi Woldesemayat

Full Text Available Crop response to the changing climate and unpredictable effects of global warming with adverse conditions such as drought stress has brought concerns about food security to the fore; crop yield loss is a major cause of concern in this regard. Identification of genes with multiple responses across environmental stresses is the genetic foundation that leads to crop adaptation to environmental perturbations.In this paper, we introduce an integrated approach to assess candidate genes for multiple stress responses across-species. The approach combines ontology based semantic data integration with expression profiling, comparative genomics, phylogenomics, functional gene enrichment and gene enrichment network analysis to identify genes associated with plant stress phenotypes. Five different ontologies, viz., Gene Ontology (GO, Trait Ontology (TO, Plant Ontology (PO, Growth Ontology (GRO and Environment Ontology (EO were used to semantically integrate drought related information.Target genes linked to Quantitative Trait Loci (QTLs controlling yield and stress tolerance in sorghum (Sorghum bicolor (L. Moench and closely related species were identified. Based on the enriched GO terms of the biological processes, 1116 sorghum genes with potential responses to 5 different stresses, such as drought (18%, salt (32%, cold (20%, heat (8% and oxidative stress (25% were identified to be over-expressed. Out of 169 sorghum drought responsive QTLs associated genes that were identified based on expression datasets, 56% were shown to have multiple stress responses. On the other hand, out of 168 additional genes that have been evaluated for orthologous pairs, 90% were conserved across species for drought tolerance. Over 50% of identified maize and rice genes were responsive to drought and salt stresses and were co-located within multifunctional QTLs. Among the total identified multi-stress responsive genes, 272 targets were shown to be co-localized within QTLs

Identifying At-Risk Individuals for Insomnia Using the Ford Insomnia Response to Stress Test.

Science.gov (United States)

Kalmbach, David A; Pillai, Vivek; Arnedt, J Todd; Drake, Christopher L

2016-02-01

A primary focus of the National Institute of Mental Health's current strategic plan is "predicting" who is at risk for disease. As such, the current investigation examined the utility of premorbid sleep reactivity in identifying a specific and manageable population at elevated risk for future insomnia. A community-based sample of adults (n = 2,892; 59.3% female; 47.9 ± 13.3 y old) with no lifetime history of insomnia or depression completed web-based surveys across three annual assessments. Participants reported parental history of insomnia, demographic characteristics, sleep reactivity on the Ford Insomnia in Response to Stress Test (FIRST), and insomnia symptoms. DSM-IV diagnostic criteria were used to determine insomnia classification. Baseline FIRST scores were used to predict incident insomnia at 1-y follow-up. Two clinically meaningful FIRST cutoff values were identified: FIRST ≥ 16 (sensitivity 77%; specificity 50%; odds ratio [OR] = 2.88, P insomnia onset, even after controlling for stress exposure and demographic characteristics. Of the incident cases, insomniacs with highly reactive sleep systems reported longer sleep onset latencies (FIRST ≥ 16: 65 min; FIRST ≥ 18: 68 min) than participants with nonreactive insomnia (FIRST insomnia based on trait sleep reactivity. The FIRST accurately identifies a focused target population in which the psychobiological processes complicit in insomnia onset and progression can be better investigated, thus improving future preventive efforts. © 2016 Associated Professional Sleep Societies, LLC.
Global mapping of protein phosphorylation events identifies novel signalling hubs mediating fatty acid starvation responses in Saccharomyces cerevisiae

DEFF Research Database (Denmark)

Pultz, Dennis; Bennetzen, Martin; Rødkær, Steven Vestergaard

2011-01-01

Dietary restriction (DR) extends the life span of multiple species, ranging from single-celled organisms like yeast to mammals. This increase in longevity by dietary restriction is coupled to profound beneficial effects on age-related pathology. Despite the number of studies on DR...... and the physiological changes DR induces, only little is known about the genetics and signalling networks, which regulate the DR response. We have recently shown that inhibition of fatty acid synthesis in Saccharomyces cerevisiae induces autophagy mediated by TORC1 signalling and affects life span. In the present study...... in a temporal manner in response to inhibition of fatty acid synthesis by cerulenin. By in silico analysis of these phosphorylation events, we have identified the major downstream regulated processes and signalling networks mediating the cellular response to fatty acid starvation. The analysis further...
Genome-wide analysis identifies chickpea (Cicer arietinum) heat stress transcription factors (Hsfs) responsive to heat stress at the pod development stage.

Science.gov (United States)

Chidambaranathan, Parameswaran; Jagannadham, Prasanth Tej Kumar; Satheesh, Viswanathan; Kohli, Deshika; Basavarajappa, Santosh Halasabala; Chellapilla, Bharadwaj; Kumar, Jitendra; Jain, Pradeep Kumar; Srinivasan, R

2018-05-01

The heat stress transcription factors (Hsfs) play a prominent role in thermotolerance and eliciting the heat stress response in plants. Identification and expression analysis of Hsfs gene family members in chickpea would provide valuable information on heat stress responsive Hsfs. A genome-wide analysis of Hsfs gene family resulted in the identification of 22 Hsf genes in chickpea in both desi and kabuli genome. Phylogenetic analysis distinctly separated 12 A, 9 B, and 1 C class Hsfs, respectively. An analysis of cis-regulatory elements in the upstream region of the genes identified many stress responsive elements such as heat stress elements (HSE), abscisic acid responsive element (ABRE) etc. In silico expression analysis showed nine and three Hsfs were also expressed in drought and salinity stresses, respectively. Q-PCR expression analysis of Hsfs under heat stress at pod development and at 15 days old seedling stage showed that CarHsfA2, A6, and B2 were significantly upregulated in both the stages of crop growth and other four Hsfs (CarHsfA2, A6a, A6c, B2a) showed early transcriptional upregulation for heat stress at seedling stage of chickpea. These subclasses of Hsfs identified in this study can be further evaluated as candidate genes in the characterization of heat stress response in chickpea.
Quantitative analysis of biological responses to low dose-rate γ-radiation, including dose, irradiation time, and dose-rate

International Nuclear Information System (INIS)

Magae, J.; Furukawa, C.; Kawakami, Y.; Hoshi, Y.; Ogata, H.

2003-01-01

Full text: Because biological responses to radiation are complex processes dependent on irradiation time as well as total dose, it is necessary to include dose, dose-rate and irradiation time simultaneously to predict the risk of low dose-rate irradiation. In this study, we analyzed quantitative relationship among dose, irradiation time and dose-rate, using chromosomal breakage and proliferation inhibition of human cells. For evaluation of chromosome breakage we assessed micronuclei induced by radiation. U2OS cells, a human osteosarcoma cell line, were exposed to gamma-ray in irradiation room bearing 50,000 Ci 60 Co. After the irradiation, they were cultured for 24 h in the presence of cytochalasin B to block cytokinesis, cytoplasm and nucleus were stained with DAPI and propidium iodide, and the number of binuclear cells bearing micronuclei was determined by fluorescent microscopy. For proliferation inhibition, cells were cultured for 48 h after the irradiation and [3H] thymidine was pulsed for 4 h before harvesting. Dose-rate in the irradiation room was measured with photoluminescence dosimeter. While irradiation time less than 24 h did not affect dose-response curves for both biological responses, they were remarkably attenuated as exposure time increased to more than 7 days. These biological responses were dependent on dose-rate rather than dose when cells were irradiated for 30 days. Moreover, percentage of micronucleus-forming cells cultured continuously for more than 60 days at the constant dose-rate, was gradually decreased in spite of the total dose accumulation. These results suggest that biological responses at low dose-rate, are remarkably affected by exposure time, that they are dependent on dose-rate rather than total dose in the case of long-term irradiation, and that cells are getting resistant to radiation after the continuous irradiation for 2 months. It is necessary to include effect of irradiation time and dose-rate sufficiently to evaluate risk
Directional response of identifier Micro Detective ORTEC, N-type with 15% of detection efficiency

International Nuclear Information System (INIS)

Arbach, Mayara Nascimento; Karam, Rudnei M.; Cardoso, Domingos D.O.; Sant'anna, Viviane C.; Vellozo, Sergio de O.; Gomes, Renato G.; Amorim, Aneuri S. de; Oliveira, Luciano S.R.

2016-01-01

It was characterized the directional response of identifier Micro Detective ORTEC, N-type with 15% of detection efficiency by using sources of Cesium ("1"3"7Cs) with activity of 37,4 kBq and Cobalt ("6"0Co) with an activity of 41 kBq, manufactured on 04/17/2007. The work took place in distances (0,5m, 1,0m, 1,5m e 2,0m) and for the angles (0°, 45°, 60° e 90°), and the measure found in angle 0° of said evaluation was adopted as reference value; this same procedure was adopted for other distances evaluated in this work. The results achieved are provided in charts 1, 2 and 3. (author)
Identifying attentional bias and emotional response after appearance-related stimuli exposure.

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Cho, Ara; Kwak, Soo-Min; Lee, Jang-Han

2013-01-01

The effect of media images has been regarded as a significant variable in the construction or in the activation of body images. Individuals who have a negative body image use avoidance coping strategies to minimize damage to their body image. We identified attentional biases and negative emotional responses following exposure to body stimuli. Female university students were divided into two groups based on their use of avoidance coping strategies (high-level group: high avoidance [HA]; low-group: low avoidance [LA]), and were assigned to two different conditions (exposure to thin body pictures, ET, and exposure to oversized body pictures, EO). Results showed that the HA group paid more attention to slim bodies and reported more negative emotions than the LA group, and that the EO had more negative effects than the ET. We suggest that HAs may attend more to slim bodies as a way of avoiding overweight bodies, influenced by social pressure, and in the search for a compensation of a positive emotional balance. However, attentional bias toward slim bodies can cause an upward comparison process, leading to increased body dissatisfaction, which is the main factor in the development of eating disorders (EDs). Therefore, altering avoidance coping strategies should be considered for people at risk of EDs.
Optimization of Gluten-Free Tulumba Dessert Formulation Including Corn Flour: Response Surface Methodology Approach

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Yildiz Önder

2017-03-01

Full Text Available Tulumba dessert is widely preferred in Turkey; however, it cannot be consumed by celiac patients because it includes gluten. The diversity of gluten-free products should be expanded so that celiac patients may meet their daily needs regularly. In this study, corn flour (CF / potato starch (PS blend to be used in the gluten-free tulumba dessert formulation was optimized using the Response Surface Methodology (RSM. Increasing ratio of PS in the CF-PS led to a decrease in hardness of the dessert and to an increase in expansion, viscosity, adhesiveness, yield of dessert both with and without syrup (P0.05, additionally these desserts had a much higher sensory score compared to the control sample in terms of the overall quality and pore structure (P<0.05.
Difficulty identifying feelings and automatic activation in the fusiform gyrus in response to facial emotion.

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Eichmann, Mischa; Kugel, Harald; Suslow, Thomas

2008-12-01

Difficulties in identifying and differentiating one's emotions are a central characteristic of alexithymia. In the present study, automatic activation of the fusiform gyrus to facial emotion was investigated as a function of alexithymia as assessed by the 20-item Toronto Alexithymia Scale. During 3 Tesla fMRI scanning, pictures of faces bearing sad, happy, and neutral expressions masked by neutral faces were presented to 22 healthy adults who also responded to the Toronto Alexithymia Scale. The fusiform gyrus was selected as the region of interest, and voxel values of this region were extracted, summarized as means, and tested among the different conditions (sad, happy, and neutral faces). Masked sad facial emotions were associated with greater bilateral activation of the fusiform gyrus than masked neutral faces. The subscale, Difficulty Identifying Feelings, was negatively correlated with the neural response of the fusiform gyrus to masked sad faces. The correlation results suggest that automatic hyporesponsiveness of the fusiform gyrus to negative emotion stimuli may reflect problems in recognizing one's emotions in everyday life.
Experience from the Inspection of Licensees' Outage Activities, Including Fire Protection Programmes, Event Response Inspections, and the Impact of the Fukushima Daiichi NPP Accident on Inspection Programmes. Workshop Proceedings, Chattanooga, Tennessee, United States, 7-10 April 2014 - Appendix: Compilation of Survey Responses

International Nuclear Information System (INIS)

2014-10-01

This appendix provides the complete compilation of responses received to the questionnaire issued in conjunction with the workshop announcements. The responses are provided as received, with changes made only to the formatting. The OECD Nuclear Energy Agency (NEA) Committee on Nuclear Regulatory Activities (CNRA) Working Group on Inspection Practices (WGIP) sponsored the 12. International Workshop on Nuclear Regulatory Inspection Activities. The workshop was hosted by the U.S. NRC, in Chattanooga, Tennessee, United States of America on 7 -10 April 2014. The three workshop topics that were addressed were as follows: - Inspection of Outage Activities Including Fire Protection Programmes. - Event Response Inspections. - The Impact of Inspection Programmes of the Fukushima Daiichi NPP Accident. Each of the respondents was given the following instructions in relation to their response: - Only one response per country is required. If more than one person from your country is participating, please co-ordinate the responses accordingly. - Please provide responses on separate sheet and clearly identify the questionnaire part and topic. For preparation of the workshop, participants are invited to supply their national inspection approaches used in inspection of events and incidents according to the surveys. Actual issues that were discussed during the workshop were generated by the topic leaders based on the responses submitted by participants with their registration forms. This formats helps to ensure that issues considered most important by the workshop participants are covered during the group discussions. (authors)
Identifying the Factors Influence Turkish Deposit Banks to Join Corporate Social Responsibility Activities by Using Panel Probit Method

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Serhat Yuksel

2017-02-01

Full Text Available This study aims to determine the influencing factors of the banks to join corporate social responsibility activities. Within this scope, annual data of 23 deposit banks in Turkey for the periods between 2005 and 2015 was taken into the consideration. In addition to this situation, panel probit model was used in the analysis so as to achieve this objective. According to the results of the analysis, it was determined that there is a negative relationship between CSR activities and nonperforming loans ratio. This situation shows that banks do not prefer to make social responsibility activities in case of higher financial losses. In addition to this situation, it was also identified that there is a positive relationship between return on asset and corporate social responsibility activities of the banks. In other words, it can be understood that Turkish deposit banks, which have higher profitability, joint more CSR activities in comparison with others.
Chemical fingerprinting identifies Echium vulgare, Eupatorium cannabinum and Senecio spp. as plant species mainly responsible for pyrrolizidine alkaloids in bee-collected pollen.

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Kast, Christina; Kilchenmann, Verena; Reinhard, Hans; Droz, Benoit; Lucchetti, Matteo Angelo; Dübecke, Arne; Beckh, Gudrun; Zoller, Otmar

2018-02-01

Various studies have shown that bee-collected pollen sold as nutritional supplements may contain toxic pyrrolizidine alkaloids (PAs) and, thus, pose a potential health risk for consumers. The level of contamination may vary according to its geographical and botanical origin. Here, the PA content of pollen produced in Switzerland was studied and 32 commercially available bee-collected pollen supplements produced between 2010 and 2014 were analysed. In addition, at what time period bees collect PA-containing pollen was investigated. Hence, this study looked into the occurrence of PAs in pollen samples collected daily during two-to-three consecutive seasons. Furthermore, the PA spectrum in pollen was compared to the spectrum found in flower heads of PA-plants to unambiguously identify plants responsible for PA contamination of pollen. The PA concentration of commercial and daily collected pollen was determined by target analysis using an HPLC-MS/MS system, allowing the detection of 18 different PAs and PA N-oxides found in the genera Echium, Eupatorium and Senecio, while the comparison of the PA spectrum in pollen and flower heads was performed by LC-HR-MS, allowing the detection of all PA types in a sample, including saturated, non-carcinogenic PAs. Of the commercially available pollen, 31% contained PAs with a mean concentration of 319 ng/g, mainly Echium- and Eupatorium-type PAs, while the PA concentrations were below the limit of quantitation (LOQ) in 69% of the pollen samples. Bees collected pollen containing Echium-type PAs mainly in June and July, while they gathered pollen containing Eupatorium-type PAs from mid-July to August. Senecio-type PAs appeared from June to September. Comparison of the PA array in pollen and plants identified E. vulgare and E. cannabinum as the main plants responsible for PA contamination of Swiss bee-collected pollen, and to a lesser extent also identified plants belonging to the genus Senecio.
G2 Checkpoint Responses in Arabidopsis

Energy Technology Data Exchange (ETDEWEB)

Britt, Anne [Univ. of California, Davis, CA (United States)

2013-03-18

This project focused on the mechanism and biological significance of the G2 arrest response to replication stress in plants. We employed both forward and reverse genetic approaches to identify genes required for this response. A total of 3 different postdocs, 5 undergraduates, and 2 graduate students participated in the project. We identified several genes required for damage response in plants, including homologs of genes previously identified in animals (ATM and ATR), novel, a plant-specific genes (SOG1) and a gene known in animals but previously thought to be missing from the Arabidopsis genome (ATRIP). We characterized the transcriptome of gamma-irradiated plants, and found that plants, unlike animals, express a robust transcriptional response to damage, involving genes that regulate the cell cycle and DNA metabolism. This response requires both ATM and the transcription factor SOG1. We found that both ATM and ATR play a role in meiosis in plants. We also found that plants have a cell-type-specific programmed cell death response to ionizing radiation and UV light, and that this response requires ATR, ATM, and SOG1. These results were published in a series of 5 papers.
Identifying genes that mediate anthracyline toxicity in immune cells

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Amber eFrick

2015-04-01

Full Text Available The role of the immune system in response to chemotherapeutic agents remains elusive. The interpatient variability observed in immune and chemotherapeutic cytotoxic responses is likely, at least in part, due to complex genetic differences. Through the use of a panel of genetically diverse mouse inbred strains, we developed a drug screening platform aimed at identifying genes underlying these chemotherapeutic cytotoxic effects on immune cells. Using genome-wide association studies (GWAS, we identified four genome-wide significant quantitative trait loci (QTL that contributed to the sensitivity of doxorubicin and idarubicin in immune cells. Of particular interest, a locus on chromosome 16 was significantly associated with cell viability following idarubicin administration (p = 5.01x10-8. Within this QTL lies App, which encodes amyloid beta precursor protein. Comparison of dose-response curves verified that T-cells in App knockout mice were more sensitive to idarubicin than those of C57BL/6J control mice (p < 0.05.In conclusion, the cellular screening approach coupled with GWAS led to the identification and subsequent validation of a gene involved in T-cell viability after idarubicin treatment. Previous studies have suggested a role for App in in vitro and in vivo cytotoxicity to anticancer agents; the overexpression of App enhances resistance, while the knockdown of this gene is deleterious to cell viability. Thus, further investigations should include performing mechanistic studies, validating additional genes from the GWAS, including Ppfia1 and Ppfibp1, and ultimately translating the findings to in vivo and human studies.
A genetic screen in Myxococcus xanthus identifies mutants that uncouple outer membrane exchange from a downstream cellular response.

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Dey, Arup; Wall, Daniel

2014-12-01

Upon physical contact with sibling cells, myxobacteria transiently fuse their outer membranes (OMs) and exchange OM proteins and lipids. From previous work, TraA and TraB were identified to be essential factors for OM exchange (OME) in donor and recipient cells. To define the genetic complexity of OME, we carried out a comprehensive forward genetic screen. The screen was based on the observation that Myxococcus xanthus nonmotile cells, by a Tra-dependent mechanism, block swarm expansion of motile cells when mixed. Thus, mutants defective in OME or a downstream responsive pathway were readily identified as escape flares from mixed inocula seeded on agar. This screen was surprisingly powerful, as we found >50 mutants defective in OME. Importantly, all of the mutations mapped to the traAB operon, suggesting that there may be few, if any, proteins besides TraA and TraB directly required for OME. We also found a second and phenotypically different class of mutants that exhibited wild-type OME but were defective in a responsive pathway. This pathway is postulated to control inner membrane homeostasis by covalently attaching amino acids to phospholipids. The identified proteins are homologous to the Staphylococcus aureus MprF protein, which is involved in membrane adaptation and antibiotic resistance. Interestingly, we also found that a small number of nonmotile cells were sufficient to block the swarming behavior of a large gliding-proficient population. This result suggests that an OME-derived signal could be amplified from a few nonmotile producers to act on many responder cells. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Hombres Sanos: exposure and response to a social marketing HIV prevention campaign targeting heterosexually identified Latino men who have sex with men and women.

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Martínez-Donate, Ana P; Zellner, Jennifer A; Fernández-Cerdeño, Araceli; Sañudo, Fernando; Hovell, Melbourne F; Sipan, Carol L; Engelberg, Moshe; Ji, Ming

2009-10-01

This study examined the reach and impact of a social marketing intervention to reduce HIV risk among heterosexually identified (HI) Latino men who have sex with men and women (MSMW). Repeated cross-sectional intercept surveys were conducted in selected community venues during and after the campaign with 1,137 HI Latino men. Of them, 6% were classified as HI Latino MSMW. On average, 85.9% of the heterosexual respondents and 86.8% of the HI MSMW subsample reported exposure to the campaign. Responses to the campaign included having made an appointment for a male health exam that included HIV testing and using condoms. Campaign exposure was significantly associated with HIV testing behavior and intentions and with knowledge of where to get tested. The campaign reached its underserved target audience and stimulated preventive behaviors. Social marketing represents a promising approach for HIV prevention among HI Latinos, in general, and HI Latino MSMW, in particular.
Genome-Wide Transcriptome Analysis of Cotton (Gossypium hirsutum L. Identifies Candidate Gene Signatures in Response to Aflatoxin Producing Fungus Aspergillus flavus.

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Renesh Bedre

Full Text Available Aflatoxins are toxic and potent carcinogenic metabolites produced from the fungi Aspergillus flavus and A. parasiticus. Aflatoxins can contaminate cottonseed under conducive preharvest and postharvest conditions. United States federal regulations restrict the use of aflatoxin contaminated cottonseed at >20 ppb for animal feed. Several strategies have been proposed for controlling aflatoxin contamination, and much success has been achieved by the application of an atoxigenic strain of A. flavus in cotton, peanut and maize fields. Development of cultivars resistant to aflatoxin through overexpression of resistance associated genes and/or knocking down aflatoxin biosynthesis of A. flavus will be an effective strategy for controlling aflatoxin contamination in cotton. In this study, genome-wide transcriptome profiling was performed to identify differentially expressed genes in response to infection with both toxigenic and atoxigenic strains of A. flavus on cotton (Gossypium hirsutum L. pericarp and seed. The genes involved in antifungal response, oxidative burst, transcription factors, defense signaling pathways and stress response were highly differentially expressed in pericarp and seed tissues in response to A. flavus infection. The cell-wall modifying genes and genes involved in the production of antimicrobial substances were more active in pericarp as compared to seed. The genes involved in auxin and cytokinin signaling were also induced. Most of the genes involved in defense response in cotton were highly induced in pericarp than in seed. The global gene expression analysis in response to fungal invasion in cotton will serve as a source for identifying biomarkers for breeding, potential candidate genes for transgenic manipulation, and will help in understanding complex plant-fungal interaction for future downstream research.
Identifying the Source of Misfit in Item Response Theory Models.

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Liu, Yang; Maydeu-Olivares, Alberto

2014-01-01

When an item response theory model fails to fit adequately, the items for which the model provides a good fit and those for which it does not must be determined. To this end, we compare the performance of several fit statistics for item pairs with known asymptotic distributions under maximum likelihood estimation of the item parameters: (a) a mean and variance adjustment to bivariate Pearson's X(2), (b) a bivariate subtable analog to Reiser's (1996) overall goodness-of-fit test, (c) a z statistic for the bivariate residual cross product, and (d) Maydeu-Olivares and Joe's (2006) M2 statistic applied to bivariate subtables. The unadjusted Pearson's X(2) with heuristically determined degrees of freedom is also included in the comparison. For binary and ordinal data, our simulation results suggest that the z statistic has the best Type I error and power behavior among all the statistics under investigation when the observed information matrix is used in its computation. However, if one has to use the cross-product information, the mean and variance adjusted X(2) is recommended. We illustrate the use of pairwise fit statistics in 2 real-data examples and discuss possible extensions of the current research in various directions.
Practical aids for freshwater spill response

International Nuclear Information System (INIS)

Steen, A.E.; Walker, A.H.

1993-01-01

The current research program at API is focused on the environmental and human health effects from oil spills in freshwater habitats. Components of the program include lessons learned from spill response, development of decision-making protocols for the use of chemicals during initial response operations, preparation of a manual for spill response and contingency planning, and a review of the literature on environmental and human health effects from inland spills. API has reviewed past inland spill responses to identify lessons learned. A survey questionnaire has been developed to collect information from freshwater spill responders on their successes and difficulties in response operations. The questionnaire is tailored to focus on the impact to the operations from the absence of technical/scientific data on environmental effects or operation effectiveness/efficiency as well as to identify situations in which the use of particular response or cleanup options is likely to be effective. The questionnaires will be available at the Conference. Published case studies also will be examined for lessons-learned information. The results will be used to identify and prioritize API research needs in freshwater spill response. General concerns about the effectiveness of the toxicity associated with chemicals in spill response has prevented their use in fresh water. API has begun a detailed survey and interview process with state and federal regulatory personnel to identify their concerns and decision criteria to evaluate the use of chemicals in initial spill response. Ten classes of chemicals were identified for consideration: dispersants, shoreline cleaners, shoreline protection agents, herding agents, solidifiers, demulsifiers, emulsion inhibitors, foaming agents, oxidizing agents, and burning agents
Parametric Response Maps of Perfusion MRI May Identify Recurrent Glioblastomas Responsive to Bevacizumab and Irinotecan

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Aquino, Domenico; Cuppini, Lucia; Anghileri, Elena; Finocchiaro, Gaetano; Bruzzone, Maria Grazia; Eoli, Marica

2014-01-01

Background Perfusion weighted imaging (PWI) can be used to measure key aspects of tumor vascularity in vivo and recent studies suggest that perfusion imaging may be useful in the early assessment of response to angiogenesis inhibitors. Aim of this work is to compare Parametric Response Maps (PRMs) with the Region Of Interest (ROI) approach in the analysis of tumor changes induced by bevacizumab and irinotecan in recurrent glioblastomas (rGBM), and to evaluate if changes in tumor blood volume measured by perfusion MRI may predict clinical outcome. Methods 42 rGBM patients with KPS ≥50 were treated until progression, as defined by MRI with RANO criteria. Relative cerebral blood volume (rCBV) variation after 8 weeks of treatment was calculated through semi-automatic ROI placement in the same anatomic region as in baseline. Alternatively, rCBV variations with respect to baseline were calculated into the evolving tumor region using a voxel-by-voxel difference. PRMs were created showing where rCBV significantly increased, decreased or remained unchanged. Results An increased blood volume in PRM (PRMCBV+) higher than 18% (first quartile) after 8 weeks of treatment was associated with increased progression free survival (PFS; 24 versus 13 weeks, p = 0.045) and overall survival (OS; 38 versus 25 weeks, p = 0.016). After 8 weeks of treatment ROI analysis showed that mean rCBV remained elevated in non responsive patients (4.8±0.9 versus 5.1±1.2, p = 0.38), whereas decreased in responsive patients (4.2±1.3 versus 3.8±1.6 p = 0.04), and re-increased progressively when patients approached tumor progression. Conclusions Our data suggest that PRMs can provide an early marker of response to antiangiogenic treatment and warrant further confirmation in a larger cohort of GBM patients. PMID:24675671
Transcriptome analysis of the spalax hypoxia survival response includes suppression of apoptosis and tight control of angiogenesis

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Malik Assaf

2012-11-01

Full Text Available Abstract Background The development of complex responses to hypoxia has played a key role in the evolution of mammals, as inadequate response to this condition is frequently associated with cardiovascular diseases, developmental disorders, and cancers. Though numerous studies have used mice and rats in order to explore mechanisms that contribute to hypoxia tolerance, these studies are limited due to the high sensitivity of most rodents to severe hypoxia. The blind subterranean mole rat Spalax is a hypoxia tolerant rodent, which exhibits unique longevity and therefore has invaluable potential in hypoxia and cancer research. Results Using microarrays, transcript abundance was measured in brain and muscle tissues from Spalax and rat individuals exposed to acute and chronic hypoxia for varying durations. We found that Spalax global gene expression response to hypoxia differs from that of rat and is characterized by the activation of functional groups of genes that have not been strongly associated with the response to hypoxia in hypoxia sensitive mammals. Using functional enrichment analysis of Spalax hypoxia induced genes we found highly significant overrepresentation of groups of genes involved in anti apoptosis, cancer, embryonic/sexual development, epidermal growth factor receptor binding, coordinated suppression and activation of distinct groups of transcription factors and membrane receptors, in addition to angiogenic related processes. We also detected hypoxia induced increases of different critical Spalax hub gene transcripts, including antiangiogenic genes associated with cancer tolerance in Down syndrome human individuals. Conclusions This is the most comprehensive study of Spalax large scale gene expression response to hypoxia to date, and the first to use custom Spalax microarrays. Our work presents novel patterns that may underlie mechanisms with critical importance to the evolution of hypoxia tolerance, with special relevance to

The primary immune response to Vaccinia virus vaccination includes cells with a distinct cytotoxic effector CD4 T-cell phenotype.

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Munier, C Mee Ling; van Bockel, David; Bailey, Michelle; Ip, Susanna; Xu, Yin; Alcantara, Sheilajen; Liu, Sue Min; Denyer, Gareth; Kaplan, Warren; Suzuki, Kazuo; Croft, Nathan; Purcell, Anthony; Tscharke, David; Cooper, David A; Kent, Stephen J; Zaunders, John J; Kelleher, Anthony D

2016-10-17

Smallpox was eradicated by a global program of inoculation with Vaccinia virus (VV). Robust VV-specific CD4 T-cell responses during primary infection are likely essential to controlling VV replication. Although there is increasing interest in cytolytic CD4 T-cells across many viral infections, the importance of these cells during acute VV infection is unclear. We undertook a detailed functional and genetic characterization of CD4 T-cells during acute VV-infection of humans. VV-specific T-cells were identified by up-regulation of activation markers directly ex vivo and through cytokine and co-stimulatory molecule expression. At day-13-post primary inoculation with VV, CD38highCD45RO+ CD4 T-cells were purified by cell sorting, RNA isolated and analysed by microarray. Differential expression of up-regulated genes in activated CD4 T-cells was confirmed at the mRNA and protein levels. We compared analyses of VV-specific CD4 T-cells to studies on 12 subjects with primary HIV infection (PHI). VV-specific T-cells lines were established from PBMCs collected post vaccination and checked for cytotoxicity potential. A median 11.9% CD4 T-cells were CD38highCD45RO+ at day-13 post-VV inoculation, compared to 3.0% prior and 10.4% during PHI. Activated CD4 T-cells had an up-regulation of genes related to cytolytic function, including granzymes K and A, perforin, granulysin, TIA-1, and Rab27a. No difference was seen between CD4 T-cell expression of perforin or TIA-1 to VV and PHI, however granzyme k was more dominant in the VV response. At 25:1 effector to target ratio, two VV-specific T-cell lines exhibited 62% and 30% cytotoxicity respectively and CD107a degranulation. We show for the first time that CD4 CTL are prominent in the early response to VV. Understanding the role of CD4 CTL in the generation of an effective anti-viral memory may help develop more effective vaccines for diseases such as HIV. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.
Computer incident response and forensics team management conducting a successful incident response

CERN Document Server

Johnson, Leighton

2013-01-01

Computer Incident Response and Forensics Team Management provides security professionals with a complete handbook of computer incident response from the perspective of forensics team management. This unique approach teaches readers the concepts and principles they need to conduct a successful incident response investigation, ensuring that proven policies and procedures are established and followed by all team members. Leighton R. Johnson III describes the processes within an incident response event and shows the crucial importance of skillful forensics team management, including when and where the transition to forensics investigation should occur during an incident response event. The book also provides discussions of key incident response components. Provides readers with a complete handbook on computer incident response from the perspective of forensics team management Identify the key steps to completing a successful computer incident response investigation Defines the qualities necessary to become a succ...
Anesthesiology leadership rounding: identifying opportunities for improvement.

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Gravenstein, Dietrich; Ford, Susan; Enneking, F Kayser

2012-01-01

Rounding that includes participation of individuals with authority to implement changes has been advocated as important to the transformation of an institution into a high-quality and safe organization. We describe a Department of Anesthesiology's experience with leadership rounding. The Department Chair or other senior faculty designate, a quality coordinator, up to four residents, the ward charge nurse, and patient nurses participated in rounds at bedsides. During a 23-month period, 14 significant opportunities to improve care were identified. Nurses identified 5 of these opportunities, primary team physicians 2, the rounding team 4, and patients or their family members another 3. The anesthesiology service had sole or shared responsibility for 10 improvements. A variety of organizations track specific measures across all phases of the patient experience to gauge quality of care. Chart auditing tools for detecting threats to safety are often used. These measures and tools missed opportunities for improvement that were discovered only through rounding. We conclude that the introduction of leadership rounding by an anesthesiology service can identify opportunities for improving quality that are not captured by conventional efforts.
A proteomic study to identify soya allergens--the human response to transgenic versus non-transgenic soya samples.

Science.gov (United States)

Batista, Rita; Martins, Isabel; Jeno, Paul; Ricardo, Cândido Pinto; Oliveira, Maria Margarida

2007-01-01

In spite of being among the main foods responsible for allergic reactions worldwide, soybean (Glycine max)-derived products continue to be increasingly widespread in a variety of food products due to their well-documented health benefits. Soybean also continues to be one of the elected target crops for genetic modification. The aim of this study was to characterize the soya proteome and, specifically, IgE-reactive proteins as well as to compare the IgE response in soya-allergic individuals to genetically modified Roundup Ready soya versus its non-transgenic control. We performed two-dimensional gel electrophoresis of protein extracts from a 5% genetically modified Roundup Ready flour sample and its non-transgenic control followed by Western blotting with plasma from 5 soya-sensitive individuals. We used peptide tandem mass spectrometry to identify soya proteins (55 protein matches), specifically IgE-binding ones, and to evaluate differences between transgenic and non-transgenic samples. We identified 2 new potential soybean allergens--one is maturation associated and seems to be part of the late embryogenesis abundant proteins group and the other is a cysteine proteinase inhibitor. None of the individuals tested reacted differentially to the transgenic versus non-transgenic samples under study. Soybean endogenous allergen expression does not seem to be altered after genetic modification. Proteomics should be considered a powerful tool for functional characterization of plants and for food safety assessment. Copyright (c) 2007 S. Karger AG, Basel.
Identifying environmental safety and health requirements for an Environmental Restoration Management Contractor

International Nuclear Information System (INIS)

Beckman, W.H.; Cossel, S.C.; Alhadeff, N.; Lindamood, S.B.; Beers, J.A.

1993-10-01

The purpose of the Standards/Requirements Identification Program, developed partially in response to the Defense Nuclear Facilities Safety Board Recommendation 90-2, was to identify applicable requirements that established the Environmental Restoration Management Contractor's (ERMC) responsibilities and authorities under the Environmental Restoration Management Contract, determine the adequacy of these requirements, ascertain a baseline level of compliance with them, and implement a maintenance program that would keep the program current as requirements or compliance levels change. The resultant Standards/Requirements Identification Documents (S/RIDs) consolidate the applicable requirements. These documents govern the development of procedures and manuals to ensure compliance with the requirements. Twenty-four such documents, corresponding with each functional area identified at the site, are to be issued. These requirements are included in the contractor's management plan
Genetic differences in transcript responses to low-dose ionizing radiation identify tissue functions associated with breast cancer susceptibility.

Science.gov (United States)

Snijders, Antoine M; Marchetti, Francesco; Bhatnagar, Sandhya; Duru, Nadire; Han, Ju; Hu, Zhi; Mao, Jian-Hua; Gray, Joe W; Wyrobek, Andrew J

2012-01-01

High dose ionizing radiation (IR) is a well-known risk factor for breast cancer but the health effects after low-dose (LD, differences in their sensitivity to radiation-induced mammary cancer (BALB/c and C57BL/6) for the purpose of identifying mechanisms of mammary cancer susceptibility. Unirradiated mammary and blood tissues of these strains differed significantly in baseline expressions of DNA repair, tumor suppressor, and stress response genes. LD exposures of 7.5 cGy (weekly for 4 weeks) did not induce detectable genomic instability in either strain. However, the mammary glands of the sensitive strain but not the resistant strain showed early transcriptional responses involving: (a) diminished immune response, (b) increased cellular stress, (c) altered TGFβ-signaling, and (d) inappropriate expression of developmental genes. One month after LD exposure, the two strains showed opposing responses in transcriptional signatures linked to proliferation, senescence, and microenvironment functions. We also discovered a pre-exposure expression signature in both blood and mammary tissues that is predictive for poor survival among human cancer patients (p = 0.0001), and a post-LD-exposure signature also predictive for poor patient survival (pidentify genetic features that predispose or protect individuals from LD-induced breast cancer.
The Role of the Pulmonary Embolism Response Team: How to Build One, Who to Include, Scenarios, Organization, and Algorithms.

Science.gov (United States)

Galmer, Andrew; Weinberg, Ido; Giri, Jay; Jaff, Michael; Weinberg, Mitchell

2017-09-01

Pulmonary embolism response teams (PERTs) are multidisciplinary response teams aimed at delivering a range of diagnostic and therapeutic modalities to patients with pulmonary embolism. These teams have gained traction on a national scale. However, despite sharing a common goal, individual PERT programs are quite individualized-varying in their methods of operation, team structures, and practice patterns. The tendency of such response teams is to become intensely structured, algorithmic, and inflexible. However, in their current form, PERT programs are quite the opposite. They are being creatively customized to meet the needs of the individual institution based on available resources, skills, personnel, and institutional goals. After a review of the essential core elements needed to create and operate a PERT team in any form, this article will discuss the more flexible feature development of the nascent PERT team. These include team planning, member composition, operational structure, benchmarking, market analysis, and rudimentary financial operations. Copyright © 2017 Elsevier Inc. All rights reserved.
Airfoil wake and linear theory gust response including sub and superresonant flow conditions

Science.gov (United States)

Henderson, Gregory H.; Fleeter, Sanford

1992-01-01

The unsteady aerodynamic gust response of a high solidity stator vane row is examined in terms of the fundamental gust modeling assumptions with particular attention given to the effects near an acoustic resonance. A series of experiments was performed with gusts generated by rotors comprised of perforated plates and airfoils. It is concluded that, for both the perforated plate and airfoil wake generated gusts, the unsteady pressure responses do not agree with the linear-theory gust predictions near an acoustic resonance. The effects of the acoustic resonance phenomena are clearly evident on the airfoil surface unsteady pressure responses. The transition of the measured lift coefficients across the acoustic resonance from the subresonant regime to the superresonant regime occurs in a simple linear fashion.
Systematic review including re-analyses of 1148 individual data sets of central venous pressure as a predictor of fluid responsiveness

DEFF Research Database (Denmark)

Eskesen, T G; Wetterslev, M; Perner, A

2016-01-01

PURPOSE: Central venous pressure (CVP) has been shown to have poor predictive value for fluid responsiveness in critically ill patients. We aimed to re-evaluate this in a larger sample subgrouped by baseline CVP values. METHODS: In April 2015, we systematically searched and included all clinical...
Evaluation of the angular response of LaBr{sub 3}(Ce) and NaI(Tl) radiological identifiers for emergency situations attendance

Energy Technology Data Exchange (ETDEWEB)

Izidório, Ana C.A.C.; Cardoso, Domingos D’O.; Oliveira, Luciano S.R.; Balthar, Mario C.V.; Amorim, Aneuri S. de; Santos, Avelino dos; Guimarães Junior, Walter J.; Arbach, Mayara N., E-mail: carolizidorio@hotmail.com, E-mail: domingos.oliveiralvr71@gmail.com, E-mail: walter_guimaraes@ime.eb.br, E-mail: lucianosantarita@gmail.com, E-mail: mariobalthar@gmail.com, E-mail: aneurideamorim@gmail.com, E-mail: hiperav@gmail.com, E-mail: mayaraarbach@gmail.com [Instituto Militar de Engenharia (IME), Rio de Janeiro, RJ (Brazil); Instituto de Defesa Química, Biológica, Radiológica e Nuclear (IDQBRN/CTEx), Barra de Guaratiba, RJ (Brazil); Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

2017-11-01

The Institute of Chemical, Biological, Radiological and Nuclear Defense (IDQBRN) of the Brazilian Army has been developing activities aimed at characterizing radiological detectors for use during emergency situations and radiological incidents and also for research and academic activities. This work describes the experiments performed in order to evaluate the angular response of LaBr{sub 3}(Ce) and NaI(Tl) portable radiological identifiers (PRI) with scintillator crystal detectors measuring 1.5” x 1.5” and 3.0” x 1.5”, respectively. A {sup 137}Cs source with corrected activity of 2.623 GBq (July 29, 2017) supplied the beam for the experiments. It was positioned at a distance of 1.00 m from the PRIs, together with attenuators, in order to yield different ambient dose equivalent rate, H⁎(10), thus allowing the adjustment of the counting statistics and the analysis of the responses obtained. The objective of this work was to evaluate the angular dependence of the response of LaBr{sub 3}(Ce) and NaI(Tl) PRIs exposed to a {sup 137}Cs source by azimuthally varying the angle of incidence of the primary beam within the 0° ± 30° range, measured from the center of the sensitive volume of the scintillators. The PRIs were programmed to reach a maximum count of 10{sup 6} in order to ensure that the relative uncertainty of the measured data would be negligible which led to improved angular response data, in addition to higher correlation factors and greater reliability in the responses obtained with LaBr{sub 3}(Ce) and NaI(T1) portable radiological identifiers. (author)
Habituation of the cold shock response may include a significant perceptual component.

Science.gov (United States)

Barwood, Martin J; Corbett, Jo; Wagstaff, Christopher R D

2014-02-01

Accidental immersion in cold water is a risk factor for many occupations. Habituation to cold-water immersion (CWI) is one practical means of reducing the cold shock response (CSR) on immersion. We investigated whether repeated thermoneutral water immersion (TWI) induced a perceptual habituation (i.e., could lessen perceived threat and anxiety) and consequently reduce the CSR on subsequent CWI. There were 12 subjects who completed seven 7-min head-out immersions. Immersions one and seven were CWls [15.0 (0.1) degrees C], and immersions two to six were TWI [34.9 (0.10) degrees C]. Anxiety 120-cm visual analogue scale) and the cardiorespiratory responses [heart rate (f(C)), respiratory frequency (f(R)), tidal volume (V(T)), and minute ventilation (V(E))] to immersion were measured throughout. Data were compared within subject between conditions using ANOVA to an alpha level of 0.05. Acute anxiety was significantly reduced after repeated exposure to the immersion scenario (i.e., TWI): CWI-1: 6.3 (4.4) cm; and CWI-2: 4.5 (4.0) cm [condition mean (SD)]. These differences did not influence the peak in the CSR. The f(C), f(R), and V(E) responses were similar between CWI-1 and CWI-2. V(T) response was significantly lower in CWI-2; mean (SD) across the immersion: CWI-1 1.27 (0.17) vs. CWI-2 1.11 0.21 L. Repeated TWI lessened the anxiety associated with CWI (perceptual habituation). This had a negligible effect on the primary components of the CSR, but did lower VT, which may reduce the volume of any aspirated water in an emergency situation. Reducing the threat appraisal of an environmental stressor may be a useful biproduct of survival training, thereby minimizing psychophysiological strain.
Survey of innate immune responses to Burkholderia pseudomallei in human blood identifies a central role for lipopolysaccharide.

Directory of Open Access Journals (Sweden)

Narisara Chantratita

Full Text Available B. pseudomallei is a gram-negative bacterium that causes the tropical infection melioidosis. In northeast Thailand, mortality from melioidosis approaches 40%. As exemplified by the lipopolysaccharide-Toll-like receptor 4 interaction, innate immune responses to invading bacteria are precipitated by activation of host pathogen recognition receptors by pathogen associated molecular patterns. Human melioidosis is characterized by up-regulation of pathogen recognition receptors and pro-inflammatory cytokine release. In contrast to many gram-negative pathogens, however, the lipopolysaccharide of B. pseudomallei is considered only weakly inflammatory. We conducted a study in 300 healthy Thai subjects to investigate the ex vivo human blood response to various bacterial pathogen associated molecular patterns, including lipopolysaccharide from several bacteria, and to two heat-killed B. pseudomallei isolates. We measured cytokine levels after stimulation of fresh whole blood with a panel of stimuli. We found that age, sex, and white blood cell count modulate the innate immune response to B. pseudomallei. We further observed that, in comparison to other stimuli, the innate immune response to B. pseudomallei is most highly correlated with the response to lipopolysaccharide. The magnitude of cytokine responses induced by B. pseudomallei lipopolysaccharide was significantly greater than those induced by lipopolysaccharide from Escherichia coli and comparable to many responses induced by lipopolysaccharide from Salmonella minnesota despite lower amounts of lipid A in the B. pseudomallei lipopolysaccharide preparation. In human monocytes stimulated with B. pseudomallei, addition of polymyxin B or a TLR4/MD-2 neutralizing antibody inhibited the majority of TNF-α production. Challenging existing views, our data indicate that the innate immune response to B. pseudomallei in human blood is largely driven by lipopolysaccharide, and that the response to B
Identifying and validating a combined mRNA and microRNA signature in response to imatinib treatment in a chronic myeloid leukemia cell line.

Directory of Open Access Journals (Sweden)

Steven Bhutra

Full Text Available Imatinib, a targeted tyrosine kinase inhibitor, is the gold standard for managing chronic myeloid leukemia (CML. Despite its wide application, imatinib resistance occurs in 20-30% of individuals with CML. Multiple potential biomarkers have been identified to predict imatinib response; however, the majority of them remain externally uncorroborated. In this study, we set out to systematically identify gene/microRNA (miRNA whose expression changes are related to imatinib response. Through a Gene Expression Omnibus search, we identified two genome-wide expression datasets that contain expression changes in response to imatinib treatment in a CML cell line (K562: one for mRNA and the other for miRNA. Significantly differentially expressed transcripts/miRNAs post imatinib treatment were identified from both datasets. Three additional filtering criteria were applied 1 miRbase/miRanda predictive algorithm; 2 opposite direction of imatinib effect for genes and miRNAs; and 3 literature support. These criteria narrowed our candidate gene-miRNA to a single pair: IL8 and miR-493-5p. Using PCR we confirmed the significant up-regulation and down-regulation of miR-493-5p and IL8 by imatinib treatment, respectively in K562 cells. In addition, IL8 expression was significantly down-regulated in K562 cells 24 hours after miR-493-5p mimic transfection (p = 0.002. Furthermore, we demonstrated significant cellular growth inhibition after IL8 inhibition through either gene silencing or by over-expression of miR-493-5p (p = 0.0005 and p = 0.001 respectively. The IL8 inhibition also further sensitized K562 cells to imatinib cytotoxicity (p < 0.0001. Our study combined expression changes in transcriptome and miRNA after imatinib exposure to identify a potential gene-miRNA pair that is a critical target in imatinib response. Experimental validation supports the relationships between IL8 and miR-493-5p and between this gene-miRNA pair and imatinib sensitivity in a CML cell
Use of amplified fragment length polymorphism analysis to identify medically important Candida spp., including C-dubliniensis

NARCIS (Netherlands)

Borst, A; Theelen, B; Reinders, E; Boekhout, T; Fluit, AC; Savelkoul, PHM

Non-Candida albicans Candida species are increasingly being isolated. These species show differences in levels of resistance to antimycotic agents and mortality. Therefore, it is important to be able to correctly identify the causative organism to the species level. Identification of C. dubliniensis
Use of amplified fragment length polymorphism analysis to identify medically important Candida spp., including C. dubliniensis.

NARCIS (Netherlands)

Borst, A; Theelen, B; Reinders, E; Boekhout, T; Fluit, AC; Savelkoul, P.H.M.

2003-01-01

Non-Candida albicans Candida species are increasingly being isolated. These species show differences in levels of resistance to antimycotic agents and mortality. Therefore, it is important to be able to correctly identify the causative organism to the species level. Identification of C. dubliniensis
Validation of ATR FT-IR to identify polymers of plastic marine debris, including those ingested by marine organisms

Science.gov (United States)

Jung, Melissa R.; Horgen, F. David; Orski, Sara V.; Rodriguez, Viviana; Beers, Kathryn L.; Balazs, George H.; Jones, T. Todd; Work, Thierry M.; Brignac, Kayla C.; Royer, Sarah-Jeanne; Hyrenbach, David K.; Jensen, Brenda A.; Lynch, Jennifer M.

2018-01-01

Polymer identification of plastic marine debris can help identify its sources, degradation, and fate. We optimized and validated a fast, simple, and accessible technique, attenuated total reflectance Fourier transform infrared spectroscopy (ATR FT-IR), to identify polymers contained in plastic ingested by sea turtles. Spectra of consumer good items with known resin identification codes #1–6 and several #7 plastics were compared to standard and raw manufactured polymers. High temperature size exclusion chromatography measurements confirmed ATR FT-IR could differentiate these polymers. High-density (HDPE) and low-density polyethylene (LDPE) discrimination is challenging but a clear step-by-step guide is provided that identified 78% of ingested PE samples. The optimal cleaning methods consisted of wiping ingested pieces with water or cutting. Of 828 ingested plastics pieces from 50 Pacific sea turtles, 96% were identified by ATR FT-IR as HDPE, LDPE, unknown PE, polypropylene (PP), PE and PP mixtures, polystyrene, polyvinyl chloride, and nylon.
Transcriptome profiling to identify ATRA-responsive genes in human iPSC-derived endoderm for high-throughput point of departure analysis (SOT Annual Meeting)

Science.gov (United States)

Toxicological tipping points occur at chemical concentrations that overwhelm a cell’s adaptive response leading to permanent effects. We focused on retinoid signaling in differentiating endoderm to identify developmental pathways for tipping point analysis. Human induced pluripot...
Rapid response systems.

Science.gov (United States)

Lyons, Patrick G; Edelson, Dana P; Churpek, Matthew M

2018-07-01

Rapid response systems are commonly employed by hospitals to identify and respond to deteriorating patients outside of the intensive care unit. Controversy exists about the benefits of rapid response systems. We aimed to review the current state of the rapid response literature, including evolving aspects of afferent (risk detection) and efferent (intervention) arms, outcome measurement, process improvement, and implementation. Articles written in English and published in PubMed. Rapid response systems are heterogeneous, with important differences among afferent and efferent arms. Clinically meaningful outcomes may include unexpected mortality, in-hospital cardiac arrest, length of stay, cost, and processes of care at end of life. Both positive and negative interventional studies have been published, although the two largest randomized trials involving rapid response systems - the Medical Early Response and Intervention Trial (MERIT) and the Effect of a Pediatric Early Warning System on All-Cause Mortality in Hospitalized Pediatric Patients (EPOCH) trial - did not find a mortality benefit with these systems, albeit with important limitations. Advances in monitoring technologies, risk assessment strategies, and behavioral ergonomics may offer opportunities for improvement. Rapid responses may improve some meaningful outcomes, although these findings remain controversial. These systems may also improve care for patients at the end of life. Rapid response systems are expected to continue evolving with novel developments in monitoring technologies, risk prediction informatics, and work in human factors. Copyright © 2018 Elsevier B.V. All rights reserved.
41 CFR 301-74.4 - What should cost comparisons include?

Science.gov (United States)

2010-07-01

... comparisons include? 301-74.4 Section 301-74.4 Public Contracts and Property Management Federal Travel Regulation System TEMPORARY DUTY (TDY) TRAVEL ALLOWANCES AGENCY RESPONSIBILITIES 74-CONFERENCE PLANNING Agency Responsibilities § 301-74.4 What should cost comparisons include? Cost comparisons should include...
A meta-analysis including dose-response relationship between night shift work and the risk of colorectal cancer.

Science.gov (United States)

Wang, Xiao; Ji, Alin; Zhu, Yi; Liang, Zhen; Wu, Jian; Li, Shiqi; Meng, Shuai; Zheng, Xiangyi; Xie, Liping

2015-09-22

A meta-analysis was conducted to quantitatively evaluate the correlation between night shift work and the risk of colorectal cancer. We searched for publications up to March 2015 using PubMed, Web of Science, Cochrane Library, EMBASE and the Chinese National Knowledge Infrastructure databases, and the references of the retrieved articles and relevant reviews were also checked. OR and 95% CI were used to assess the degree of the correlation between night shift work and risk of colorectal cancer via fixed- or random-effect models. A dose-response meta-analysis was performed as well. The pooled OR estimates of the included studies illustrated that night shift work was correlated with an increased risk of colorectal cancer (OR = 1.318, 95% CI 1.121-1.551). No evidence of publication bias was detected. In the dose-response analysis, the rate of colorectal cancer increased by 11% for every 5 years increased in night shift work (OR = 1.11, 95% CI 1.03-1.20). In conclusion, this meta-analysis indicated that night shift work was associated with an increased risk of colorectal cancer. Further researches should be conducted to confirm our findings and clarify the potential biological mechanisms.

Taming Trojan Horses: Identifying and Mitigating Corporate Social Responsibility Risks

NARCIS (Netherlands)

P.P.M.A.R. Heugens (Pursey); N.A. Dentchev (Nikolay)

2007-01-01

textabstractOrganizations are exposed to increasing pressures from their constituents to integrate corporate social responsibility (CSR) principles into their ongoing business practices. But accepting new and potentially open-ended commitments is not a harmless exercise, and companies may well
Use of signature-tagged mutagenesis to identify virulence determinants in Haemophilus ducreyi responsible for ulcer formation.

Science.gov (United States)

Yeung, Angela; Cameron, D William; Desjardins, Marc; Lee, B Craig

2011-02-01

Elucidating the molecular mechanisms responsible for chancroid, a genital ulcer disease caused by Haemophilus ducreyi, has been hampered in part by the relative genetic intractability of the organism. A whole genome screen using signature-tagged mutagenesis in the temperature-dependent rabbit model (TDRM) of H. ducreyi infection uncovered 26 mutants with a presumptive attenuated phenotype. Insertions in two previously recognized virulence determinants, hgbA and lspA1, validated this genome scanning technique. Database interrogation allowed assignment of 24 mutants to several functional classes, including transport, metabolism, DNA repair, stress response and gene regulation. The attenuated virulence for a 3 strain with a mutation in hicB was confirmed by individual infection in the TDRM. The results from this preliminary study indicate that this high throughput strategy will further the understanding of the pathogenesis of H. ducreyi infection. Copyright © 2010 Elsevier B.V. All rights reserved.
Validation of search filters for identifying pediatric studies in PubMed.

Science.gov (United States)

Leclercq, Edith; Leeflang, Mariska M G; van Dalen, Elvira C; Kremer, Leontien C M

2013-03-01

To identify and validate PubMed search filters for retrieving studies including children and to develop a new pediatric search filter for PubMed. We developed 2 different datasets of studies to evaluate the performance of the identified pediatric search filters, expressed in terms of sensitivity, precision, specificity, accuracy, and number needed to read (NNR). An optimal search filter will have a high sensitivity and high precision with a low NNR. In addition to the PubMed Limits: All Child: 0-18 years filter (in May 2012 renamed to PubMed Filter Child: 0-18 years), 6 search filters for identifying studies including children were identified: 3 developed by Kastner et al, 1 developed by BestBets, one by the Child Health Field, and 1 by the Cochrane Childhood Cancer Group. Three search filters (Cochrane Childhood Cancer Group, Child Health Field, and BestBets) had the highest sensitivity (99.3%, 99.5%, and 99.3%, respectively) but a lower precision (64.5%, 68.4%, and 66.6% respectively) compared with the other search filters. Two Kastner search filters had a high precision (93.0% and 93.7%, respectively) but a low sensitivity (58.5% and 44.8%, respectively). They failed to identify many pediatric studies in our datasets. The search terms responsible for false-positive results in the reference dataset were determined. With these data, we developed a new search filter for identifying studies with children in PubMed with an optimal sensitivity (99.5%) and precision (69.0%). Search filters to identify studies including children either have a low sensitivity or a low precision with a high NNR. A new pediatric search filter with a high sensitivity and a low NNR has been developed. Copyright © 2013 Mosby, Inc. All rights reserved.
Interprofessional non-technical skills for surgeons in disaster response: a literature review.

Science.gov (United States)

Willems, Anneliese; Waxman, Bruce; Bacon, Andrew K; Smith, Julian; Kitto, Simon

2013-09-01

Natural disasters impose a significant burden on society. Current disaster training programmes do not place an emphasis on equipping surgeons with non-technical skills for disaster response. This literature review sought to identify non-technical skills required of surgeons in disaster response through an examination of four categories of literature: "disaster"; "surgical"; "organisational management"; and "interprofessional". Literature search criteria included electronic database searches, internet searches, hand searching, ancestry searching and networking strategies. Various potential non-technical skills for surgeons in disaster response were identified including: interpersonal skills such as communication, teamwork and leadership; cognitive strategies such flexibility, adaptability, innovation, improvisation and creativity; physical and psychological self-care; conflict management, collaboration, professionalism, health advocacy and teaching. Such skills and the role of interprofessionalism should be considered for inclusion in surgical disaster response training course curricula.
Thoughts on identifiers

CERN Multimedia

CERN. Geneva

2005-01-01

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

DEFF Research Database (Denmark)

Brunskog, Jonas; Hwang, Ha Dong; Jeong, Cheol-Ho

2011-01-01

annoyance, using simulated binaural room impulse responses, with sources being a moving point source or a nonmoving surface source, and rooms being a room with a reverberation time of 0.5 s or an anechoic room. The paper concludes that no strong effect of the source localization on the annoyance can...
Integrated physiological, biochemical and molecular analysis identifies important traits and mechanisms associated with differential response of rice genotypes to elevated temperature

Directory of Open Access Journals (Sweden)

Boghireddy eSailaja

2015-11-01

Full Text Available In changing climate, heat stress caused by high temperature poses a serious threat to rice cultivation. A multiple organizational analysis at physiological, biochemical and molecular level is required to fully understand the impact of elevated temperature in rice. This study was aimed at deciphering the elevated temperature response in eleven popular and mega rice cultivars widely grown in India. Physiological and biochemical traits specifically membrane thermostability (MTS, antioxidants, and photosynthesis were studied at vegetative and reproductive phases which were used to establish a correlation with grain yield under stress. Several useful traits in different genotypes were identified which will be important resource to develop high temperature tolerant rice cultivars. Interestingly, Nagina22 emerged as best performer in terms of yield as well as expression of physiological and biochemical traits at elevated temperature. It showed lesser relative injury, lesser reduction in chlorophyll content, increased super oxide dismutase, catalase and peroxidase activity, lesser reduction in net photosynthetic rate (PN, high transpiration rate (E and other photosynthetic/ fluorescence parameters contributing to least reduction in spikelet fertility and grain yield at elevated temperature. Further, expression of 14 genes including heat shock transcription factors and heat shock proteins was analyzed in Nagina22 (tolerant and Vandana (susceptible at flowering phase, strengthening the fact that N22 performs better at molecular level also during elevated temperature. This study shows that elevated temperature response is complex and involves multiple biological processes which are needed to be characterized to address the challenges of future climate extreme conditions.
University Social Responsibility (USR): Identifying an Ethical Foundation within Higher Education Institutions

Science.gov (United States)

Chen, Shu-Hsiang; Nasongkhla, Jaitip; Donaldson, J. Ana

2015-01-01

Social responsibility is a responsibility not a requirement, of an organization for the impact of its decisions and activities on society and the environment, through transparent and ethical behavior that contributes to sustainable development, health and the welfare of society; which takes into account the expectations of stakeholders, is in…
Developing an explicit strategy towards social responsibility in the NHS: a case for including NHS managers in this strategy.

Science.gov (United States)

Merali, Faruk

2006-01-01

To explore the concept of corporate social responsibility (CSR) within the UK National Health Service (NHS) and to examine how it may be developed to positively influence the psyche, behaviour and performance of NHS managers. Primary research based upon semi-structured individual face to face interviews with 20 NHS managers. Theoretical frameworks and concepts relating to organisational culture and CSR are drawn upon to discuss the findings. The NHS managers see themselves as being driven by altruistic core values. However, they feel that the public does not believe that they share the altruistic NHS value system. The study is based on a relatively small sample of NHS managers working exclusively in London and may not necessarily represent the views of managers either London-wide or nation-wide. It is suggested that an explicit recognition by the NHS of the socially responsible commitment of its managers within its CSR strategy would help challenge the existing negative public image of NHS managers and in turn improve the managers' self esteem and morale. This paper addresses the relative lacunae in research relating to public sector organisations (such as the NHS) explicitly including the role and commitment of its staff within the way it publicises its CSR strategy. This paper would be of interest to a wide readership including public sector and NHS policy formulators, NHS practitioners, academics and students.
Discord of response

International Nuclear Information System (INIS)

Roga, W; Illuminati, F; Giampaolo, S M

2014-01-01

The presence of quantum correlations in a quantum state is related to the state's response to local unitary perturbations. Such a response is quantified by the distance between the unperturbed and perturbed states, minimized with respect to suitably identified sets of local unitary operations. In order to be a bona fide measure of quantum correlations, the distance function must be chosen among those that are contractive under completely positive and trace preserving (CPTP) maps. The most relevant instances of such physically well-behaved metrics include the trace, the Bures, and the Hellinger distance. To each of these metrics one can associate the corresponding discord of response, namely the trace, or Hellinger, or Bures minimum distance from the set of unitarily perturbed states. All these three discords of response satisfy the basic axioms for a proper measure of quantum correlations. In the present work we focus in particular on the Bures distance, which enjoys the unique property of being both Riemannian and contractive under CPTP maps, and admits important operational interpretations in terms of state distinguishability. We compute analytically the Bures discord of response for two-qubit states with maximally mixed marginals and we compare it with the corresponding Bures geometric discord, namely the geometric measure of quantum correlations defined as the Bures distance from the set of classical-quantum states. Finally, we investigate and identify the maximally quantum correlated two-qubit states according to the Bures discord of response. These states exhibit a remarkable nonlinear dependence on the global state purity. (paper)
Microarray analysis and scale-free gene networks identify candidate regulators in drought-stressed roots of loblolly pine (P. taeda L.

Directory of Open Access Journals (Sweden)

Bordeaux John M

2011-05-01

Full Text Available Abstract Background Global transcriptional analysis of loblolly pine (Pinus taeda L. is challenging due to limited molecular tools. PtGen2, a 26,496 feature cDNA microarray, was fabricated and used to assess drought-induced gene expression in loblolly pine propagule roots. Statistical analysis of differential expression and weighted gene correlation network analysis were used to identify drought-responsive genes and further characterize the molecular basis of drought tolerance in loblolly pine. Results Microarrays were used to interrogate root cDNA populations obtained from 12 genotype × treatment combinations (four genotypes, three watering regimes. Comparison of drought-stressed roots with roots from the control treatment identified 2445 genes displaying at least a 1.5-fold expression difference (false discovery rate = 0.01. Genes commonly associated with drought response in pine and other plant species, as well as a number of abiotic and biotic stress-related genes, were up-regulated in drought-stressed roots. Only 76 genes were identified as differentially expressed in drought-recovered roots, indicating that the transcript population can return to the pre-drought state within 48 hours. Gene correlation analysis predicts a scale-free network topology and identifies eleven co-expression modules that ranged in size from 34 to 938 members. Network topological parameters identified a number of central nodes (hubs including those with significant homology (E-values ≤ 2 × 10-30 to 9-cis-epoxycarotenoid dioxygenase, zeatin O-glucosyltransferase, and ABA-responsive protein. Identified hubs also include genes that have been associated previously with osmotic stress, phytohormones, enzymes that detoxify reactive oxygen species, and several genes of unknown function. Conclusion PtGen2 was used to evaluate transcriptome responses in loblolly pine and was leveraged to identify 2445 differentially expressed genes responding to severe drought stress in
Microarray analysis and scale-free gene networks identify candidate regulators in drought-stressed roots of loblolly pine (P. taeda L.)

Science.gov (United States)

2011-01-01

Background Global transcriptional analysis of loblolly pine (Pinus taeda L.) is challenging due to limited molecular tools. PtGen2, a 26,496 feature cDNA microarray, was fabricated and used to assess drought-induced gene expression in loblolly pine propagule roots. Statistical analysis of differential expression and weighted gene correlation network analysis were used to identify drought-responsive genes and further characterize the molecular basis of drought tolerance in loblolly pine. Results Microarrays were used to interrogate root cDNA populations obtained from 12 genotype × treatment combinations (four genotypes, three watering regimes). Comparison of drought-stressed roots with roots from the control treatment identified 2445 genes displaying at least a 1.5-fold expression difference (false discovery rate = 0.01). Genes commonly associated with drought response in pine and other plant species, as well as a number of abiotic and biotic stress-related genes, were up-regulated in drought-stressed roots. Only 76 genes were identified as differentially expressed in drought-recovered roots, indicating that the transcript population can return to the pre-drought state within 48 hours. Gene correlation analysis predicts a scale-free network topology and identifies eleven co-expression modules that ranged in size from 34 to 938 members. Network topological parameters identified a number of central nodes (hubs) including those with significant homology (E-values ≤ 2 × 10-30) to 9-cis-epoxycarotenoid dioxygenase, zeatin O-glucosyltransferase, and ABA-responsive protein. Identified hubs also include genes that have been associated previously with osmotic stress, phytohormones, enzymes that detoxify reactive oxygen species, and several genes of unknown function. Conclusion PtGen2 was used to evaluate transcriptome responses in loblolly pine and was leveraged to identify 2445 differentially expressed genes responding to severe drought stress in roots. Many of the
Extracting gene expression patterns and identifying co-expressed genes from microarray data reveals biologically responsive processes

Directory of Open Access Journals (Sweden)

Paules Richard S

2007-11-01

Full Text Available Abstract Background A common observation in the analysis of gene expression data is that many genes display similarity in their expression patterns and therefore appear to be co-regulated. However, the variation associated with microarray data and the complexity of the experimental designs make the acquisition of co-expressed genes a challenge. We developed a novel method for Extracting microarray gene expression Patterns and Identifying co-expressed Genes, designated as EPIG. The approach utilizes the underlying structure of gene expression data to extract patterns and identify co-expressed genes that are responsive to experimental conditions. Results Through evaluation of the correlations among profiles, the magnitude of variation in gene expression profiles, and profile signal-to-noise ratio's, EPIG extracts a set of patterns representing co-expressed genes. The method is shown to work well with a simulated data set and microarray data obtained from time-series studies of dauer recovery and L1 starvation in C. elegans and after ultraviolet (UV or ionizing radiation (IR-induced DNA damage in diploid human fibroblasts. With the simulated data set, EPIG extracted the appropriate number of patterns which were more stable and homogeneous than the set of patterns that were determined using the CLICK or CAST clustering algorithms. However, CLICK performed better than EPIG and CAST with respect to the average correlation between clusters/patterns of the simulated data. With real biological data, EPIG extracted more dauer-specific patterns than CLICK. Furthermore, analysis of the IR/UV data revealed 18 unique patterns and 2661 genes out of approximately 17,000 that were identified as significantly expressed and categorized to the patterns by EPIG. The time-dependent patterns displayed similar and dissimilar responses between IR and UV treatments. Gene Ontology analysis applied to each pattern-related subset of co-expressed genes revealed underlying
Whole exome sequencing identifies novel genes for fetal hemoglobin response to hydroxyurea in children with sickle cell anemia.

Science.gov (United States)

Sheehan, Vivien A; Crosby, Jacy R; Sabo, Aniko; Mortier, Nicole A; Howard, Thad A; Muzny, Donna M; Dugan-Perez, Shannon; Aygun, Banu; Nottage, Kerri A; Boerwinkle, Eric; Gibbs, Richard A; Ware, Russell E; Flanagan, Jonathan M

2014-01-01

Hydroxyurea has proven efficacy in children and adults with sickle cell anemia (SCA), but with considerable inter-individual variability in the amount of fetal hemoglobin (HbF) produced. Sibling and twin studies indicate that some of that drug response variation is heritable. To test the hypothesis that genetic modifiers influence pharmacological induction of HbF, we investigated phenotype-genotype associations using whole exome sequencing of children with SCA treated prospectively with hydroxyurea to maximum tolerated dose (MTD). We analyzed 171 unrelated patients enrolled in two prospective clinical trials, all treated with dose escalation to MTD. We examined two MTD drug response phenotypes: HbF (final %HbF minus baseline %HbF), and final %HbF. Analyzing individual genetic variants, we identified multiple low frequency and common variants associated with HbF induction by hydroxyurea. A validation cohort of 130 pediatric sickle cell patients treated to MTD with hydroxyurea was genotyped for 13 non-synonymous variants with the strongest association with HbF response to hydroxyurea in the discovery cohort. A coding variant in Spalt-like transcription factor, or SALL2, was associated with higher final HbF in this second independent replication sample and SALL2 represents an outstanding novel candidate gene for further investigation. These findings may help focus future functional studies and provide new insights into the pharmacological HbF upregulation by hydroxyurea in patients with SCA.
Identifying artificial selection signals in the chicken genome.

Directory of Open Access Journals (Sweden)

Yunlong Ma

Full Text Available Identifying the signals of artificial selection can contribute to further shaping economically important traits. Here, a chicken 600k SNP-array was employed to detect the signals of artificial selection using 331 individuals from 9 breeds, including Jingfen (JF, Jinghong (JH, Araucanas (AR, White Leghorn (WL, Pekin-Bantam (PB, Shamo (SH, Gallus-Gallus-Spadiceus (GA, Rheinlander (RH and Vorwerkhuhn (VO. Per the population genetic structure, 9 breeds were combined into 5 breed-pools, and a 'two-step' strategy was used to reveal the signals of artificial selection. GA, which has little artificial selection, was defined as the reference population, and a total of 204, 155, 305 and 323 potential artificial selection signals were identified in AR_VO, PB, RH_WL and JH_JF, respectively. We also found signals derived from standing and de-novo genetic variations have contributed to adaptive evolution during artificial selection. Further enrichment analysis suggests that the genomic regions of artificial selection signals harbour genes, including THSR, PTHLH and PMCH, responsible for economic traits, such as fertility, growth and immunization. Overall, this study found a series of genes that contribute to the improvement of chicken breeds and revealed the genetic mechanisms of adaptive evolution, which can be used as fundamental information in future chicken functional genomics study.
The transcriptional regulatory network in the drought response and its crosstalk in abiotic stress responses including drought, cold, and heat

OpenAIRE

Nakashima, Kazuo; Yamaguchi-Shinozaki, Kazuko; Shinozaki, Kazuo

2014-01-01

Drought negatively impacts plant growth and the productivity of crops around the world. Understanding the molecular mechanisms in the drought response is important for improvement of drought tolerance using molecular techniques. In plants, abscisic acid (ABA) is accumulated under osmotic stress conditions caused by drought, and has a key role in stress responses and tolerance. Comprehensive molecular analyses have shown that ABA regulates the expression of many genes under osmotic stress cond...
Extreme wave and wind response predictions

DEFF Research Database (Denmark)

Jensen, Jørgen Juncher; Olsen, Anders S.; Mansour, Alaa E.

2011-01-01

codes and the short duration of the time domain simulations needed (typically 60–300s to cover the hydro- and aerodynamic memory effects in the response) the calculation of the mean out-crossing rates of a given response is fast. Thus non-linear effects can be included. Furthermore, the FORM analysis...... also identifies the most probable wave episodes leading to given responses.Because of the linearization of the failure surface in the FORM procedure the results are only asymptotically exact and thus MCS often also needs to be performed. In the present paper a scaling property inherent in the FORM...
Exome and Transcriptome Sequencing of Aedes aegypti Identifies a Locus That Confers Resistance to Brugia malayi and Alters the Immune Response

KAUST Repository

Juneja, Punita

2015-03-27

Many mosquito species are naturally polymorphic for their abilities to transmit parasites, a feature which is of great interest for controlling vector-borne disease. Aedes aegypti, the primary vector of dengue and yellow fever and a laboratory model for studying lymphatic filariasis, is genetically variable for its capacity to harbor the filarial nematode Brugia malayi. The genome of Ae. aegypti is large and repetitive, making genome resequencing difficult and expensive. We designed exome captures to target protein-coding regions of the genome, and used association mapping in a wild Kenyan population to identify a single, dominant, sex-linked locus underlying resistance. This falls in a region of the genome where a resistance locus was previously mapped in a line established in 1936, suggesting that this polymorphism has been maintained in the wild for the at least 80 years. We then crossed resistant and susceptible mosquitoes to place both alleles of the gene into a common genetic background, and used RNA-seq to measure the effect of this locus on gene expression. We found evidence for Toll, IMD, and JAK-STAT pathway activity in response to early stages of B. malayi infection when the parasites are beginning to die in the resistant genotype. We also found that resistant mosquitoes express anti-microbial peptides at the time of parasite-killing, and that this expression is suppressed in susceptible mosquitoes. Together, we have found that a single resistance locus leads to a higher immune response in resistant mosquitoes, and we identify genes in this region that may be responsible for this trait.
Cytokines in the host response to Candida vaginitis: Identifying a role for non-classical immune mediators, S100 alarmins

Science.gov (United States)

Yano, Junko; Noverr, Mairi C.; Fidel, Paul L.

2011-01-01

Vulvovaginal candidiasis (VVC), caused by Candida albicans, affects a significant number of women during their reproductive years. More than two decades of research have been focused on the mechanisms associated with susceptibility or resistance to symptomatic infection. Adaptive immunity by Th1-type CD4+ T cells and downstream cytokine responses are considered the predominant host defense mechanisms against mucosal Candida infections. However, numerous clinical and animal studies have indicated no or limited protective role of cells and cytokines of the Th1 or Th2 lineage against vaginal infection. The role for Th17 is only now begun to be investigated in-depth for VVC with results already showing significant controversy. On the other hand, a clinical live-challenge study and an established animal model have shown that a symptomatic condition is intimately associated with the vaginal infiltration of polymorphonuclear leukocytes (PMNs) but with no effect on vaginal fungal burden. Subsequent studies identified S100A8 and S100A9 Alarmins as key chemotactic mediators of the acute PMN response. These chemotactic danger signals appear to be secreted by vaginal epithelial cells upon interaction and early adherence of Candida. Thus, instead of a putative immunodeficiency against Candida involving classical immune cells and cytokines of the adaptive response, the pathological inflammation in VVC is now considered a consequence of a non-productive innate response initiated by non-classical immune mediators. PMID:22182685
ROS-activated ATM-dependent phosphorylation of cytoplasmic substrates identified by large scale phosphoproteomics screen

DEFF Research Database (Denmark)

Kozlov, Sergei V; Waardenberg, Ashley J; Engholm-Keller, Kasper

2016-01-01

ATM (ataxia-telangiectasia, mutated) protein plays a central role in phosphorylating a network of proteins in response to DNA damage. These proteins function in signalling pathways designed to maintain the stability of the genome and minimize the risk of disease by controlling cell cycle checkpoi......ATM (ataxia-telangiectasia, mutated) protein plays a central role in phosphorylating a network of proteins in response to DNA damage. These proteins function in signalling pathways designed to maintain the stability of the genome and minimize the risk of disease by controlling cell cycle...... checkpoints, initiating DNA repair and regulating gene expression. ATM kinase can be activated by a variety of stimuli, including oxidative stress. Here we confirmed activation of cytoplasmic ATM by autophosphorylation at multiple sites. Then we employed a global quantitative phosphoproteomics approach...... to identify cytoplasmic proteins altered in their phosphorylation state in control and A-T (ataxia-telangiectasia) cells in response to oxidative damage. We demonstrated that ATM was activated by oxidative damage in the cytoplasm as well as in the nucleus and identified a total of 9,833 phosphorylation sites...

Indoctrination and Social Context: A System-Based Approach to Identifying the Threat of Indoctrination and the Responsibilities of Educators

Science.gov (United States)

Taylor, Rebecca M.

2017-01-01

Debates about indoctrination raise fundamental questions about the ethics of teaching. This paper presents a philosophical analysis of indoctrination, including 1) an account of what indoctrination is and why it is harmful, and 2) a framework for understanding the responsibilities of teachers and other educational actors to avoid its negative…
Reactive Oxygen Species (ROS)-Activated ATM-Dependent Phosphorylation of Cytoplasmic Substrates Identified by Large-Scale Phosphoproteomics Screen*

Science.gov (United States)

Kozlov, Sergei V.; Waardenberg, Ashley J.; Engholm-Keller, Kasper; Arthur, Jonathan W.; Graham, Mark E.; Lavin, Martin

2016-01-01

Ataxia-telangiectasia, mutated (ATM) protein plays a central role in phosphorylating a network of proteins in response to DNA damage. These proteins function in signaling pathways designed to maintain the stability of the genome and minimize the risk of disease by controlling cell cycle checkpoints, initiating DNA repair, and regulating gene expression. ATM kinase can be activated by a variety of stimuli, including oxidative stress. Here, we confirmed activation of cytoplasmic ATM by autophosphorylation at multiple sites. Then we employed a global quantitative phosphoproteomics approach to identify cytoplasmic proteins altered in their phosphorylation state in control and ataxia-telangiectasia (A-T) cells in response to oxidative damage. We demonstrated that ATM was activated by oxidative damage in the cytoplasm as well as in the nucleus and identified a total of 9,833 phosphorylation sites, including 6,686 high-confidence sites mapping to 2,536 unique proteins. A total of 62 differentially phosphorylated peptides were identified; of these, 43 were phosphorylated in control but not in A-T cells, and 19 varied in their level of phosphorylation. Motif enrichment analysis of phosphopeptides revealed that consensus ATM serine glutamine sites were overrepresented. When considering phosphorylation events, only observed in control cells (not observed in A-T cells), with predicted ATM sites phosphoSerine/phosphoThreonine glutamine, we narrowed this list to 11 candidate ATM-dependent cytoplasmic proteins. Two of these 11 were previously described as ATM substrates (HMGA1 and UIMCI/RAP80), another five were identified in a whole cell extract phosphoproteomic screens, and the remaining four proteins had not been identified previously in DNA damage response screens. We validated the phosphorylation of three of these proteins (oxidative stress responsive 1 (OSR1), HDGF, and ccdc82) as ATM dependent after H2O2 exposure, and another protein (S100A11) demonstrated ATM
The experiences and support needs of people with intellectual disabilities who identify as LGBT: A review of the literature.

Science.gov (United States)

McCann, Edward; Lee, Regina; Brown, Michael

2016-10-01

People who identify as lesbian, gay, bisexual and transgender (LGBT) can face many challenges in society including accessing education, care and support appropriate to individual needs. However, there is a growing and evolving evidence base about the specific needs of people with intellectual disabilities (ID) in this regard. The aim of this review was to explore the experiences of people with ID who identified as LGBT through an examination of studies that addressed their views and highlighted specific issues, concerns and service responses. A comprehensive search of relevant databases from February 1995 to February 2015 was conducted. Studies were identified that met specific criteria that included: empirical peer reviewed studies, the use of recognised research methods and focused on people with ID whom identified as LGBT. The search yielded 161 papers in total. The search was narrowed and 37 papers were screened using rigorous inclusion and exclusion criteria. Finally, 14 papers were considered suitable for the review. The data were analysed and key themes identified that included accessing health services, gender and sexual identity, attitudes of people with ID regarding their LGBT status, and education, supports and therapeutic interventions. There is a need for service providers and carers to be more responsive to the concerns of people with ID who identify as LGBT to improve their health and well-being by reducing stigma and discrimination and by increasing awareness of their care and support needs. The implications are discussed in terms of policy, education, research and practice developments. Copyright © 2016 Elsevier Ltd. All rights reserved.
A review of sex differences in sexual jealousy, including self-report data, psychophysiological responses, interpersonal violence, and morbid jealousy.

Science.gov (United States)

Harris, Christine R

2003-01-01

The specific innate modular theory of jealousy hypothesizes that natural selection shaped sexual jealousy as a mechanism to prevent cuckoldry, and emotional jealousy as a mechanism to prevent resource loss. Therefore, men should be primarily jealous over a mate's sexual infidelity and women over a mate's emotional infidelity. Five lines of evidence have been offered as support: self-report responses, psychophysiological data, domestic violence (including spousal abuse and homicide), and morbid jealousy cases. This article reviews each line of evidence and finds only one hypothetical measure consistent with the hypothesis. This, however, is contradicted by a variety of other measures (including reported reactions to real infidelity). A meta-analysis of jealousy-inspired homicides, taking into account base rates for murder, found no evidence that jealousy disproportionately motivates men to kill. The findings are discussed from a social-cognitive theoretical perspective.
Stimulation of demand response through evaluation and training

International Nuclear Information System (INIS)

Encinas, N.; Alfonso, D.; Alvarez, C.; Mendez, C.; Rodriguez, J.; Perez-Navarro, A.; Gabaldon, A.

2004-01-01

The objective of Demand Response is to enhance customer choice opportunities by means of price-responsive mechanisms in contrast to direct load control practices and associated revenues based on fixed incentives. In this way, the new approach complements the traditional concept of Demand Side Management by including the voluntary nature to customer participation. This voluntary feature implies a change in customers' traditional behaviour and therefore stimulation and training is needed to achieve an optimal participation. This paper presents a methodology developed to stimulate and train customers for Demand Response practices as well as to identify the suitable products for different customers. Finally, the paper includes an example of the methodology considering a university as a customer. (au)
Finite Element Modeling and Analysis of Nonlinear Impact and Frictional Motion Responses Including Fluid—Structure Coupling Effects

Directory of Open Access Journals (Sweden)

Yong Zhao

1997-01-01

Full Text Available A nonlinear three dimensional (3D single rack model and a nonlinear 3D whole pool multi-rack model are developed for the spent fuel storage racks of a nuclear power plant (NPP to determine impacts and frictional motion responses when subjected to 3D excitations from the supporting building floor. The submerged free standing rack system and surrounding water are coupled due to hydrodynamic fluid-structure interaction (FSI using potential theory. The models developed have features that allow consideration of geometric and material nonlinearities including (1 the impacts of fuel assemblies to rack cells, a rack to adjacent racks or pool walls, and rack support legs to the pool floor; (2 the hydrodynamic coupling of fuel assemblies with their storing racks, and of a rack with adjacent racks, pool walls, and the pool floor; and (3 the dynamic motion behavior of rocking, twisting, and frictional sliding of rack modules. Using these models 3D nonlinear time history dynamic analyses are performed per the U.S. Nuclear Regulatory Commission (USNRC criteria. Since few such modeling, analyses, and results using both the 3D single and whole pool multiple rack models are available in the literature, this paper emphasizes description of modeling and analysis techniques using the SOLVIA general purpose nonlinear finite element code. Typical response results with different Coulomb friction coefficients are presented and discussed.
CORPORATE SOCIAL RESPONSIBILITY AS CONDITION OF INCLUDING UKRAINE IN EUROPE AND WORLD ECONOMIC SPACE

Directory of Open Access Journals (Sweden)

T. Lytvynenko

2013-09-01

Full Text Available The thesis that companies’ activities for introduction of corporate social responsibility stimulates the speed of to the processes of the technical upgrade, modernization of company’s activity and increase of its profitability is proved within the article. Those Ukrainian companies, which have high index of activities transparency, are also the most profitable. However, we can’t observe any significant increment of number of companies joining the Global agreement. One of the explanations we could name is the unproved idea supported by some politicians and economists about a shadow (‘black’ market that allegedly allows creating workplaces and taking off social tension in society on the certain stage. Insignificant values of index of citizens’ trust to activity of industries holds on the development socially of responsible business. Trust considered as a part of the general social capital. The Government of Ukraine must support initiative of companies to introduce social responsibility of business, as many European governments do it. It is also important to inform society of advantages of CSR.
Proteomic analysis of barley response during early spot blotch infection

International Nuclear Information System (INIS)

Al-Daoude, A.; Jawhar, M.; Shoaib, A.; Arabi, M.I.E.

2015-01-01

Spot blotch (SB), caused by the fungus Cochliobolus sativus, is a common foliar disease of barley worldwide, but little is known about the host response to infection at the protein level. In this study, a systematic shotgun proteomics approach was chosen to document the early barley response to C. sativus infection. Overall, 28 protein spots were consistently observed as differential in the proteome profiles of the challenged and unchallenged plants. After tryptic digestion, MALDI-TOF/MS analysis and MASCOT database searching identified proteins associated with the defense response including resistance proteins, putative hydrolase, proteinase, kinase and general metabolism and transport proteins. These afford important functions in host resistance and pathogen's inhibition in plants. One of the identified products is a putative NBS-LRR protein which is considered one of the major plant disease resistance proteins identified to date. This work indicates that, in combination with functional genomics, response of barley to challenge by C. sativus involved the recruitment of proteins from various defense pathways.(author)
High Throughput Sequencing of Small RNAs in the Two Cucurbita Germplasm with Different Sodium Accumulation Patterns Identifies Novel MicroRNAs Involved in Salt Stress Response.

Science.gov (United States)

Xie, Junjun; Lei, Bo; Niu, Mengliang; Huang, Yuan; Kong, Qiusheng; Bie, Zhilong

2015-01-01

MicroRNAs (miRNAs), a class of small non-coding RNAs, recognize their mRNA targets based on perfect sequence complementarity. MiRNAs lead to broader changes in gene expression after plants are exposed to stress. High-throughput sequencing is an effective method to identify and profile small RNA populations in non-model plants under salt stresses, significantly improving our knowledge regarding miRNA functions in salt tolerance. Cucurbits are sensitive to soil salinity, and the Cucurbita genus is used as the rootstock of other cucurbits to enhance salt tolerance. Several cucurbit crops have been used for miRNA sequencing but salt stress-related miRNAs in cucurbit species have not been reported. In this study, we subjected two Cucurbita germplasm, namely, N12 (Cucurbita. maxima Duch.) and N15 (Cucurbita. moschata Duch.), with different sodium accumulation patterns, to Illumina sequencing to determine small RNA populations in root tissues after 4 h of salt treatment and control. A total of 21,548,326 and 19,394,108 reads were generated from the control and salt-treated N12 root tissues, respectively. By contrast, 19,108,240 and 20,546,052 reads were obtained from the control and salt-treated N15 root tissues, respectively. Fifty-eight conserved miRNA families and 33 novel miRNAs were identified in the two Cucurbita germplasm. Seven miRNAs (six conserved miRNAs and one novel miRNAs) were up-regulated in salt-treated N12 and N15 samples. Most target genes of differentially expressed novel miRNAs were transcription factors and salt stress-responsive proteins, including dehydration-induced protein, cation/H+ antiporter 18, and CBL-interacting serine/threonine-protein kinase. The differential expression of miRNAs between the two Cucurbita germplasm under salt stress conditions and their target genes demonstrated that novel miRNAs play an important role in the response of the two Cucurbita germplasm to salt stress. The present study initially explored small RNAs in the
High Throughput Sequencing of Small RNAs in the Two Cucurbita Germplasm with Different Sodium Accumulation Patterns Identifies Novel MicroRNAs Involved in Salt Stress Response.

Directory of Open Access Journals (Sweden)

Junjun Xie

Full Text Available MicroRNAs (miRNAs, a class of small non-coding RNAs, recognize their mRNA targets based on perfect sequence complementarity. MiRNAs lead to broader changes in gene expression after plants are exposed to stress. High-throughput sequencing is an effective method to identify and profile small RNA populations in non-model plants under salt stresses, significantly improving our knowledge regarding miRNA functions in salt tolerance. Cucurbits are sensitive to soil salinity, and the Cucurbita genus is used as the rootstock of other cucurbits to enhance salt tolerance. Several cucurbit crops have been used for miRNA sequencing but salt stress-related miRNAs in cucurbit species have not been reported. In this study, we subjected two Cucurbita germplasm, namely, N12 (Cucurbita. maxima Duch. and N15 (Cucurbita. moschata Duch., with different sodium accumulation patterns, to Illumina sequencing to determine small RNA populations in root tissues after 4 h of salt treatment and control. A total of 21,548,326 and 19,394,108 reads were generated from the control and salt-treated N12 root tissues, respectively. By contrast, 19,108,240 and 20,546,052 reads were obtained from the control and salt-treated N15 root tissues, respectively. Fifty-eight conserved miRNA families and 33 novel miRNAs were identified in the two Cucurbita germplasm. Seven miRNAs (six conserved miRNAs and one novel miRNAs were up-regulated in salt-treated N12 and N15 samples. Most target genes of differentially expressed novel miRNAs were transcription factors and salt stress-responsive proteins, including dehydration-induced protein, cation/H+ antiporter 18, and CBL-interacting serine/threonine-protein kinase. The differential expression of miRNAs between the two Cucurbita germplasm under salt stress conditions and their target genes demonstrated that novel miRNAs play an important role in the response of the two Cucurbita germplasm to salt stress. The present study initially explored small
High-throughput matrix screening identifies synergistic and antagonistic antimalarial drug combinations

Science.gov (United States)

Mott, Bryan T.; Eastman, Richard T.; Guha, Rajarshi; Sherlach, Katy S.; Siriwardana, Amila; Shinn, Paul; McKnight, Crystal; Michael, Sam; Lacerda-Queiroz, Norinne; Patel, Paresma R.; Khine, Pwint; Sun, Hongmao; Kasbekar, Monica; Aghdam, Nima; Fontaine, Shaun D.; Liu, Dongbo; Mierzwa, Tim; Mathews-Griner, Lesley A.; Ferrer, Marc; Renslo, Adam R.; Inglese, James; Yuan, Jing; Roepe, Paul D.; Su, Xin-zhuan; Thomas, Craig J.

2015-01-01

Drug resistance in Plasmodium parasites is a constant threat. Novel therapeutics, especially new drug combinations, must be identified at a faster rate. In response to the urgent need for new antimalarial drug combinations we screened a large collection of approved and investigational drugs, tested 13,910 drug pairs, and identified many promising antimalarial drug combinations. The activity of known antimalarial drug regimens was confirmed and a myriad of new classes of positively interacting drug pairings were discovered. Network and clustering analyses reinforced established mechanistic relationships for known drug combinations and identified several novel mechanistic hypotheses. From eleven screens comprising >4,600 combinations per parasite strain (including duplicates) we further investigated interactions between approved antimalarials, calcium homeostasis modulators, and inhibitors of phosphatidylinositide 3-kinases (PI3K) and the mammalian target of rapamycin (mTOR). These studies highlight important targets and pathways and provide promising leads for clinically actionable antimalarial therapy. PMID:26403635
Emergency response facilities including primary and secondary prevention strategies across 79 professional football clubs in England.

Science.gov (United States)

Malhotra, Aneil; Dhutia, Harshil; Gati, Sabiha; Yeo, Tee-Joo; Finocchiaro, Gherardo; Keteepe-Arachi, Tracey; Richards, Thomas; Walker, Mike; Birt, Robin; Stuckey, David; Robinson, Laurence; Tome, Maite; Beasley, Ian; Papadakis, Michael; Sharma, Sanjay

2017-06-14

To assess the emergency response planning and prevention strategies for sudden cardiac arrest (SCA) across a wide range of professional football clubs in England. A written survey was sent to all professional clubs in the English football league, namely the Premiership, Championship, League 1 and League 2. Outcomes included: (1) number of clubs performing cardiac screening and frequency of screening; (2) emergency planning and documentation; (3) automated external defibrillator (AED) training and availability; and (4) provision of emergency services at sporting venues. 79 clubs (86%) responded to the survey. 100% clubs participated in cardiac screening. All clubs had AEDs available on match days and during training sessions. 100% Premiership clubs provided AED training to designated staff. In contrast, 30% of lower division clubs with AEDs available did not provide formal training. Most clubs (n=66; 83%) reported the existence of an emergency action plan for SCA but formal documentation was variable. All clubs in the Premiership and League 1 provided an ambulance equipped for medical emergencies on match days compared with 75% of clubs in the Championship and 66% in League 2. The majority of football clubs in England have satisfactory prevention strategies and emergency response planning in line with European recommendations. Additional improvements such as increasing awareness of European guidelines for emergency planning, AED training and mentorship with financial support to lower division clubs are necessary to further enhance cardiovascular safety of athletes and spectators and close the gap between the highest and lower divisions. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Harnessing genomics to identify environmental determinants of heritable disease

Science.gov (United States)

Yauk, Carole Lyn; Argueso, J. Lucas; Auerbach, Scott S.; Awadalla, Philip; Davis, Sean R.; DeMarini, David M.; Douglas, George R.; Dubrova, Yuri E.; Elespuru, Rosalie K.; Glover, Thomas W.; Hales, Barbara F.; Hurles, Matthew E.; Klein, Catherine B.; Lupski, James R.; Manchester, David K.; Marchetti, Francesco; Montpetit, Alexandre; Mulvihill, John J.; Robaire, Bernard; Robbins, Wendie A.; Rouleau, Guy A.; Shaughnessy, Daniel T.; Somers, Christopher M.; Taylor, James G.; Trasler, Jacquetta; Waters, Michael D.; Wilson, Thomas E.; Witt, Kristine L.; Bishop, Jack B.

2012-01-01

Next-generation sequencing technologies can now be used to directly measure heritable de novo DNA sequence mutations in humans. However, these techniques have not been used to examine environmental factors that induce such mutations and their associated diseases. To address this issue, a working group on environmentally induced germline mutation analysis (ENIGMA) met in October 2011 to propose the necessary foundational studies, which include sequencing of parent–offspring trios from highly exposed human populations, and controlled dose–response experiments in animals. These studies will establish background levels of variability in germline mutation rates and identify environmental agents that influence these rates and heritable disease. Guidance for the types of exposures to examine come from rodent studies that have identified agents such as cancer chemotherapeutic drugs, ionizing radiation, cigarette smoke, and air pollution as germ-cell mutagens. Research is urgently needed to establish the health consequences of parental exposures on subsequent generations. PMID:22935230
Research Resource: A Dual Proteomic Approach Identifies Regulated Islet Proteins During β-Cell Mass Expansion In Vivo

DEFF Research Database (Denmark)

Horn, Signe; Kirkegaard, Jeannette S.; Hoelper, Soraya

2016-01-01

to be up regulated as a response to pregnancy. These included several proteins, not previously associated with pregnancy-induced islet expansion, such as CLIC1, STMN1, MCM6, PPIB, NEDD4, and HLTF. Confirming the validity of our approach, we also identified proteins encoded by genes known to be associated...
IFNL4 ss469415590 Variant Is Associated with Treatment Response in Japanese HCV Genotype 1 Infected Individuals Treated with IFN-Including Regimens

Directory of Open Access Journals (Sweden)

Tatsuo Miyamura

2014-01-01

Full Text Available Aim. Eradication of hepatitis C virus (HCV is still challenging even if interferon- (IFN- free regimens with direct-acting antiviral agents (DAAs for HCV-infected individuals are available in clinical practice. IFNL4 is a newly described protein, associated with human antiviral defenses. We investigated whether IFNL4 ss469415590 variant has an effect on the prediction of treatment response in HCV-infected patients treated with IFN-including regimens. Patients and Methods. In all, 185 patients infected with HCV genotype 1 treated with peg-IFN plus ribavirin, with or without telaprevir, were genotyped for IFNL4 ss469415590. We retrospectively investigated whether the role of IFNL4 ss469415590 variant and other factors could predict sustained virological response (SVR in Japanese patients infected with HCV genotype 1. Results. There were 65.7%, 31.5%, and 2.8% patients in the IFNL4 ss469415590 TT/TT, TT/-G, and -G/-G groups, respectively. SVR rates were 82.1% or 49.3% in patients treated with peg-IFN plus ribavirin with or without telaprevir, respectively. IFNL4 ss469415590 variant and HCV viral loads or IFNL4 ss469415590 variant and early virological response were better predictors of SVR in patients treated with peg-IFN plus ribavirin with or without telaprevir, respectively. Conclusion. In the era of DAAs, measurement of IFNL4 ss469415590 variant could help the prediction of SVR in Japanese HCV genotype 1 infected individuals treated with IFN-including regimens.
Seismic response of nuclear reactors in layered liquefiable soil deposits including nonlinear soil-structure interaction

International Nuclear Information System (INIS)

Zaman, M.; Mamoon, S.M.

1989-01-01

Analysis of seismic response of structures located at a site with potential for soil liquefaction has drawn attention of many researchers. The topic is particularly important in the design of critical facilities like nuclear reactors and defense installations. This paper presents the results of a study involving evaluation of coupled seismic response of structures (model nuclear reactors) and characteristics of soil liquefaction at a site. The analysis procedure employed is based on the nonlinear finite element (FE) technique and accounts for the interaction effects due to a neighboring structure. Emphasis is given to the following features: prediction of spatial and temporal variation of pore water pressure; identification of the on-set of liquefaction based on the effective stress approach, and tracing the propagation of the liquefied zones with time and resulting response of the structures
Systems biology approach identifies the kinase Csnk1a1 as a regulator of the DNA damage response in embryonic stem cells.

Science.gov (United States)

Carreras Puigvert, Jordi; von Stechow, Louise; Siddappa, Ramakrishnaiah; Pines, Alex; Bahjat, Mahnoush; Haazen, Lizette C J M; Olsen, Jesper V; Vrieling, Harry; Meerman, John H N; Mullenders, Leon H F; van de Water, Bob; Danen, Erik H J

2013-01-22

In pluripotent stem cells, DNA damage triggers loss of pluripotency and apoptosis as a safeguard to exclude damaged DNA from the lineage. An intricate DNA damage response (DDR) signaling network ensures that the response is proportional to the severity of the damage. We combined an RNA interference screen targeting all kinases, phosphatases, and transcription factors with global transcriptomics and phosphoproteomics to map the DDR in mouse embryonic stem cells treated with the DNA cross-linker cisplatin. Networks derived from canonical pathways shared in all three data sets were implicated in DNA damage repair, cell cycle and survival, and differentiation. Experimental probing of these networks identified a mode of DNA damage-induced Wnt signaling that limited apoptosis. Silencing or deleting the p53 gene demonstrated that genotoxic stress elicited Wnt signaling in a p53-independent manner. Instead, this response occurred through reduced abundance of Csnk1a1 (CK1α), a kinase that inhibits β-catenin. Together, our findings reveal a balance between p53-mediated elimination of stem cells (through loss of pluripotency and apoptosis) and Wnt signaling that attenuates this response to tune the outcome of the DDR.
A PR-4 gene identified from Malus domestica is involved in the defense responses against Botryosphaeria dothidea.

Science.gov (United States)

Bai, Suhua; Dong, Chaohua; Li, Baohua; Dai, Hongyi

2013-01-01

Pathogenesis-related protein-4 (PR-4) family is a group of proteins with a Barwin domain in C-terminus and generally thought to be involved in plant defense responses. However, their detailed roles are poorly understood in defense of apple plant against pathogenic infection. In the present study, a new PR-4 gene (designated as MdPR-4) was identified from Malus domestica, and its roles in defense responses of apple were investigated. The open reading frame of MdPR-4 gene is of 447 bp encoding a protein of 148 amino acids with a Barwin domain in C-terminus and a signal peptide of 26 amino acids in N-terminus. Sequence and structural analysis indicated that MdPR-4 protein belongs to class II of PR-4 family. The high-level expression of MdPR-4 was observed in flowers and leaves as revealed by quantitative real time PCR. The temporal expression analysis demonstrated that MdPR-4 expression could be up-regulated by Botryosphaeria dothidea infection and salicylic acid (SA) or methyl jasmonate (MeJA) treatment, but suppressed by diethyldithiocarbamic acid (DIECA). In vitro assays, recombinant MdPR-4 protein exhibited ribonuclease activity specific for single strand RNA and significant inhibition to hyphal growth of three apple pathogenic fungi B. dothidea, Valsa ceratosperma and Glomerella cingulata. Moreover, the inhibition was reduced by the presence of 5'-ADP. Taken all together, the results indicate that MdPR-4 protein is involved in the defense responses of apple against pathogenic attack by directly inhibiting hyphal growth, and the inhibition is correlated with its ribonuclease activity, where as MdPR-4 expression is regulated by both SA and JA signaling pathway. Copyright © 2012 Elsevier Masson SAS. All rights reserved.
Identifying bully victims: definitional versus behavioral approaches.

Science.gov (United States)

Green, Jennifer Greif; Felix, Erika D; Sharkey, Jill D; Furlong, Michael J; Kras, Jennifer E

2013-06-01

Schools frequently assess bullying and the Olweus Bully/Victimization Questionnaire (BVQ; Olweus, 1996) is the most widely adopted tool for this purpose. The BVQ is a self-report survey that uses a definitional measurement method--describing "bullying" as involving repeated, intentional aggression in a relationship where there is an imbalance of power and then asking respondents to indicate how frequently they experienced this type of victimization. Few studies have examined BVQ validity and whether this definitional method truly identifies the repetition and power differential that distinguish bullying from other forms of peer victimization. This study examined the concurrent validity of the BVQ definitional question among 435 students reporting peer victimization. BVQ definitional responses were compared with responses to a behavioral measure that did not use the term "bullying" but, instead, included items that asked about its defining characteristics (repetition, intentionality, power imbalance). Concordance between the two approaches was moderate, with an area under the receiver operating curve of .72. BVQ responses were more strongly associated with students indicating repeated victimization and multiple forms of victimization, than with power imbalance in their relationship with the bully. Findings indicate that the BVQ is a valid measure of repeated victimization and a broad range of victimization experiences but may not detect the more subtle and complex power imbalances that distinguish bullying from other forms of peer victimization. PsycINFO Database Record (c) 2013 APA, all rights reserved.
A simple method to identify radiation and annealing biases that lead to worst-case CMOS static RAM postirradiation response

International Nuclear Information System (INIS)

Fleetwood, D.M.; Dressendorfer, P.V.

1987-01-01

The authors illustrate a simple method to identify bias conditions that lead to worst-case postirradiation speed and timing response for SRAMs. Switching cell states between radiation and anneal should lead to maximum speed and timing degradation for many hardened designs and technologies. The greatest SRAM cell imbalance is also established by these radiation and annealing conditions for the hardened and commercial parts that we have examined. These results should provide insight into the behavior of SRAMs during and after irradiation. The results should also be useful to establishing guidelines for integrated-circuit functionality testing, and SEU and dose-rate upset testing, after total-dose irradiation

Gene-based association identifies SPATA13-AS1 as a pharmacogenomic predictor of inhaled short-acting beta-agonist response in multiple population groups.

Science.gov (United States)

Padhukasahasram, B; Yang, J J; Levin, A M; Yang, M; Burchard, E G; Kumar, R; Kwok, P-Y; Seibold, M A; Lanfear, D E; Williams, L K

2014-08-01

Inhaled short-acting beta-agonist (SABA) medication is commonly used in asthma patients to rapidly reverse airway obstruction and improve acute symptoms. We performed a genome-wide association study of SABA medication response using gene-based association tests. A linear mixed model approach was first used for single-nucleotide polymorphism associations, and the results were later combined using GATES to generate gene-based associations. Our results identified SPATA13-AS1 as being significantly associated with SABA bronchodilator response in 328 healthy African Americans. In replication, this gene was associated with SABA response among the two separate groups of African Americans with asthma (n=1073, P=0.011 and n=1968, P=0.014), 149 healthy African Americans (P=0.003) and 556 European Americans with asthma (P=0.041). SPATA13-AS1 was also associated with longitudinal SABA medication usage in the two separate groups of African Americans with asthma (n=658, P=0.047 and n=1968, P=0.025). Future studies are needed to delineate the precise mechanism by which SPATA13-AS1 may influence SABA response.
T-cell activation and early gene response in dogs.

Directory of Open Access Journals (Sweden)

Sally-Anne Mortlock

Full Text Available T-cells play a crucial role in canine immunoregulation and defence against invading pathogens. Proliferation is fundamental to T-cell differentiation, homeostasis and immune response. Initiation of proliferation following receptor mediated stimuli requires a temporally programmed gene response that can be identified as immediate-early, mid- and late phases. The immediate-early response genes in T-cell activation engage the cell cycle machinery and promote subsequent gene activation events. Genes involved in this immediate-early response in dogs are yet to be identified. The present study was undertaken to characterise the early T-cell gene response in dogs to improve understanding of the genetic mechanisms regulating immune function. Gene expression profiles were characterised using canine gene expression microarrays and quantitative reverse transcription PCR (qRT-PCR, and paired samples from eleven dogs. Significant functional annotation clusters were identified following stimulation with phytohemagluttinin (PHA (5μg/ml, including the Toll-like receptor signaling pathway and phosphorylation pathways. Using strict statistical criteria, 13 individual genes were found to be differentially expressed, nine of which have ontologies that relate to proliferation and cell cycle control. These included, prostaglandin-endoperoxide synthase 2 (PTGS2/COX2, early growth response 1 (EGR1, growth arrest and DNA damage-inducible gene (GADD45B, phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1, V-FOS FBJ murine osteosarcoma viral oncogene homolog (FOS, early growth response 2 (EGR2, hemogen (HEMGN, polo-like kinase 2 (PLK2 and polo-like kinase 3 (PLK3. Differential gene expression was re-examined using qRT-PCR, which confirmed that EGR1, EGR2, PMAIP1, PTGS2, FOS and GADD45B were significantly upregulated in stimulated cells and ALAS2 downregulated. PTGS2 and EGR1 showed the highest levels of response in these dogs. Both of these genes are involved in
Using Persuasion Models to Identify Givers.

Science.gov (United States)

Ferguson, Mary Ann; And Others

1986-01-01

Assesses the feasibility of and suggests using W. J. McGuire's information processing theory and cognitive response analysis theory in research studies to identify "givers"--those who are likely to contribute money and resources to charities or volunteer to aid philanthropic organizations. (SRT)
The study of using earth tide response of groundwater level and rainfall recharge to identify groundwater aquifer

Science.gov (United States)

Huang, W. J.; Hsu, C. H.; Chang, L. C.; Chiang, C. J.; Wang, Y. S.; Lu, W. C.

2017-12-01

Hydrogeological framework is the most important basis for groundwater analysis and simulation. Conventionally, the core drill is a most commonly adopted skill to acquire the core's data with the help of other research methods to artificially determine the result. Now, with the established groundwater station network, there are a lot of groundwater level information available. Groundwater level is an integrated presentation of the hydrogeological framework and the external pumping and recharge system. Therefore, how to identify the hydrogeological framework from a large number of groundwater level data is an important subject. In this study, the frequency analysis method and rainfall recharge mechanism were used to identify the aquifer where the groundwater level's response frequency and amplitude react to the earth tide. As the earth tide change originates from the gravity caused by the paths of sun and moon, it leads to soil stress and strain changes, which further affects the groundwater level. The scale of groundwater level's change varies with the influence of aquifer pressure systems such as confined or unconfined aquifers. This method has been applied to the identification of aquifers in the Cho-Shui River Alluvial Fan. The results of the identification are compared to the records of core drill and they both are quite consistent. It is shown that the identification methods developed in this study can considerably contribute to the identification of hydrogeological framework.
New families of human regulatory RNA structures identified by comparative analysis of vertebrate genomes.

Science.gov (United States)

Parker, Brian J; Moltke, Ida; Roth, Adam; Washietl, Stefan; Wen, Jiayu; Kellis, Manolis; Breaker, Ronald; Pedersen, Jakob Skou

2011-11-01

Regulatory RNA structures are often members of families with multiple paralogous instances across the genome. Family members share functional and structural properties, which allow them to be studied as a whole, facilitating both bioinformatic and experimental characterization. We have developed a comparative method, EvoFam, for genome-wide identification of families of regulatory RNA structures, based on primary sequence and secondary structure similarity. We apply EvoFam to a 41-way genomic vertebrate alignment. Genome-wide, we identify 220 human, high-confidence families outside protein-coding regions comprising 725 individual structures, including 48 families with known structural RNA elements. Known families identified include both noncoding RNAs, e.g., miRNAs and the recently identified MALAT1/MEN β lincRNA family; and cis-regulatory structures, e.g., iron-responsive elements. We also identify tens of new families supported by strong evolutionary evidence and other statistical evidence, such as GO term enrichments. For some of these, detailed analysis has led to the formulation of specific functional hypotheses. Examples include two hypothesized auto-regulatory feedback mechanisms: one involving six long hairpins in the 3'-UTR of MAT2A, a key metabolic gene that produces the primary human methyl donor S-adenosylmethionine; the other involving a tRNA-like structure in the intron of the tRNA maturation gene POP1. We experimentally validate the predicted MAT2A structures. Finally, we identify potential new regulatory networks, including large families of short hairpins enriched in immunity-related genes, e.g., TNF, FOS, and CTLA4, which include known transcript destabilizing elements. Our findings exemplify the diversity of post-transcriptional regulation and provide a resource for further characterization of new regulatory mechanisms and families of noncoding RNAs.
Searching for Moral Dumbfounding: Identifying Measurable Indicators of Moral Dumbfounding

Directory of Open Access Journals (Sweden)

Cillian McHugh

2017-10-01

Full Text Available Moral dumbfounding is defined as maintaining a moral judgement, without supporting reasons. The most cited demonstration of dumbfounding does not identify a specific measure of dumbfounding and has not been published in peer-review form, or directly replicated. Despite limited empirical examination, dumbfounding has been widely discussed in moral psychology. The present research examines the reliability with which dumbfounding can be elicited, and aims to identify measureable indicators of dumbfounding. Study 1 aimed at establishing the effect that is reported in the literature. Participants read four scenarios and judged the actions described. An Interviewer challenged participants’ stated reasons for judgements. Dumbfounding was evoked, as measured by two indicators, admissions of not having reasons (17%, unsupported declarations (9% with differences between scenarios. Study 2 measured dumbfounding as the selecting of an unsupported declaration as part of a computerised task. We observed high rates of dumbfounding across all scenarios. Studies 3a (college sample and 3b (MTurk sample, addressing limitations in Study 2, replaced the unsupported declaration with an admission of having no reason, and included open-ended responses that were coded for unsupported declarations. As predicted, lower rates of dumbfounding were observed (3a 20%; 3b 16%; or 3a 32%; 3b 24% including unsupported declarations in open-ended responses. Two measures provided evidence for dumbfounding across three studies; rates varied with task type (interview/computer task, and with the particular measure being employed (admissions of not having reasons/unsupported declarations. Possible cognitive processes underlying dumbfounding and limitations of methodologies used are discussed as a means to account for this variability.
Post discharge issues identified by a call-back program: identifying improvement opportunities.

Science.gov (United States)

Ojeda, Patricia I; Kara, Areeba

2017-12-01

The period following discharge from the hospital is one of heightened vulnerability. Discharge instructions serve as a guide during this transition. Yet, clinicians receive little feedback on the quality of this document that ties into the patients' experience. We reviewed the issues voiced by discharged patients via a call-back program and compared them to the discharge instructions they had received. At our institution, patients receive an automated call forty-eight hours following discharge inquiring about progress. If indicated by the response to the call, they are directed to a nurse who assists with problem solving. We reviewed the nursing documentation of these encounters for a period of nine months. The issues voiced were grouped into five categories: communication, medications, durable medical equipment/therapies, follow up and new or ongoing symptoms. The discharge instructions given to each patient were reviewed. We retrieved data on the number of discharges from each specialty from the hospital over the same period. A total of 592 patients voiced 685 issues. The numbers of patients discharged from medical or surgical services identified as having issues via the call-back line paralleled the proportions discharged from medical and surgical services from the hospital during the same period. Nearly a quarter of the issues discussed had been addressed in the discharge instructions. The most common category of issues was related to communication deficits including missing or incomplete information which made it difficult for the patient to enact or understand the plan of care. Medication prescription related issues were the next most common. Resource barriers and questions surrounding medications were often unaddressed. Post discharge issues affect patients discharged from all services equally. Data from call back programs may provide actionable targets for improvement, identify the inpatient team's 'blind spots' and be used to provide feedback to clinicians.
British Columbia inland oil spill response plan

International Nuclear Information System (INIS)

2005-01-01

This paper presents an outline of the organization, procedures and duties of the provincial government in response to inland oil spills stemming from pipeline or tank-farm rupture, train derailment and vehicle accidents in British Columbia. Provincial response strategies were reviewed, along with their relationships to various policies and standards. Public, infrastructure and environmental protection were identified as key factors. Incident notification procedures were detailed, including outlines of roles, event criteria and call for incident management teams. Agreements and cost recovery issues were examined. The characteristics of site response were reviewed, including details of communications, tactical planning, and unified command among local and federal governments. The role of First Nations and responsible parties was also addressed. Details of shore cleanup, wildlife rescue, decontamination, and waste handling strategies were presented. The organization, missions and duties for an incident management team were outlined, along with a summary of operational guidelines and information on team positions and the establishment of joint information centres. The involvement of cooperating agencies was examined. An incident command system was also presented, including details of planning, operations, logistics, and organization. A checklist of individual duties was provided, with details of responsibilities, safety issues and general instructions for all team members. tabs., figs
Improving applicant selection: identifying qualities of the unsuccessful otolaryngology resident.

Science.gov (United States)

Badran, Karam W; Kelley, Kanwar; Conderman, Christian; Mahboubi, Hossein; Armstrong, William B; Bhandarkar, Naveen D

2015-04-01

To identify the prevalence and management of problematic residents. Additionally, we hope to identify the factors associated with successful remediation of unsuccessful otolaryngology residents. Self-reported Internet and paper-based survey. An anonymous survey was distributed to 152 current and former program directors (PDs) in 2012. The factors associated with unsuccessful otolaryngology residents and those associated with the successful remediation of problematic residents were investigated. An unsuccessful resident is defined as one who quit or was removed from the program for any reason, or one whose actions resulted in criminal action or citation against their medical license after graduation from residency. Remediation is defined as an individualized program implemented to correct documented weaknesses. The overall response rate was 26% (40 PDs). Seventy-three unsuccessful or problematic residents were identified. Sixty-six problematic or unsuccessful residents were identified during residency, with 58 of 66 (88%) undergoing remediation. Thirty-one (47%) residents did not graduate. The most commonly identified factors of an unsuccessful resident were: change in specialty (21.5%), interpersonal and communication skills with health professionals (13.9%), and clinical judgment (10.1%). Characteristics of those residents who underwent successful remediation include: poor performance on in-training examination (17%, P otolaryngology PDs in this sample identified at least one unsuccessful resident. Improved methods of applicant screening may assist in optimizing otolaryngology resident selection. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.
Identifying serotonergic mechanisms underlying the corticolimbic response to threat in humans

DEFF Research Database (Denmark)

Fisher, Patrick M; Hariri, Ahmad R

2013-01-01

. Integrating these methodological approaches offers novel opportunities to identify mechanisms through which serotonin signalling contributes to differences in brain function and behaviour, which in turn can illuminate factors that confer risk for illness and inform the development of more effective treatment...
Risk Management and Crisis Response: Are You Prepared?

Science.gov (United States)

Schirick, Ed

2002-01-01

How a camp responds to a crisis may determine whether it can survive financially. Effective risk management requires total commitment from ownership and management, and staff involvement. Steps in formulating a risk management plan include identifying all potential crises and their frequency and severity potential, developing responses,…
Using a Delphi Method to Identify Human Factors Contributing to Nursing Errors.

Science.gov (United States)

Roth, Cheryl; Brewer, Melanie; Wieck, K Lynn

2017-07-01

The purpose of this study was to identify human factors associated with nursing errors. Using a Delphi technique, this study used feedback from a panel of nurse experts (n = 25) on an initial qualitative survey questionnaire followed by summarizing the results with feedback and confirmation. Synthesized factors regarding causes of errors were incorporated into a quantitative Likert-type scale, and the original expert panel participants were queried a second time to validate responses. The list identified 24 items as most common causes of nursing errors, including swamping and errors made by others that nurses are expected to recognize and fix. The responses provided a consensus top 10 errors list based on means with heavy workload and fatigue at the top of the list. The use of the Delphi survey established consensus and developed a platform upon which future study of nursing errors can evolve as a link to future solutions. This list of human factors in nursing errors should serve to stimulate dialogue among nurses about how to prevent errors and improve outcomes. Human and system failures have been the subject of an abundance of research, yet nursing errors continue to occur. © 2016 Wiley Periodicals, Inc.
Genomic Characterization of Metformin Hepatic Response.

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Marcelo R Luizon

2016-11-01

Full Text Available Metformin is used as a first-line therapy for type 2 diabetes (T2D and prescribed for numerous other diseases. However, its mechanism of action in the liver has yet to be characterized in a systematic manner. To comprehensively identify genes and regulatory elements associated with metformin treatment, we carried out RNA-seq and ChIP-seq (H3K27ac, H3K27me3 on primary human hepatocytes from the same donor treated with vehicle control, metformin or metformin and compound C, an AMP-activated protein kinase (AMPK inhibitor (allowing to identify AMPK-independent pathways. We identified thousands of metformin responsive AMPK-dependent and AMPK-independent differentially expressed genes and regulatory elements. We functionally validated several elements for metformin-induced promoter and enhancer activity. These include an enhancer in an ataxia telangiectasia mutated (ATM intron that has SNPs in linkage disequilibrium with a metformin treatment response GWAS lead SNP (rs11212617 that showed increased enhancer activity for the associated haplotype. Expression quantitative trait locus (eQTL liver analysis and CRISPR activation suggest that this enhancer could be regulating ATM, which has a known role in AMPK activation, and potentially also EXPH5 and DDX10, its neighboring genes. Using ChIP-seq and siRNA knockdown, we further show that activating transcription factor 3 (ATF3, our top metformin upregulated AMPK-dependent gene, could have an important role in gluconeogenesis repression. Our findings provide a genome-wide representation of metformin hepatic response, highlight important sequences that could be associated with interindividual variability in glycemic response to metformin and identify novel T2D treatment candidates.
Angiotensinogen and HLA class II predict bevacizumab response in recurrent glioblastoma patients

DEFF Research Database (Denmark)

Urup, Thomas; Michaelsen, Signe Regner; Olsen, Lars Rønn

2016-01-01

Background: Bevacizumab combination therapy is among the most frequently used treatments in recurrent glioblastoma and patients who achieve response to bevacizumab have improved survival as well as quality of life. Accordingly, the aim of this study was to identify predictive biomarkers for bevac......Background: Bevacizumab combination therapy is among the most frequently used treatments in recurrent glioblastoma and patients who achieve response to bevacizumab have improved survival as well as quality of life. Accordingly, the aim of this study was to identify predictive biomarkers...... for bevacizumab response in recurrent glioblastoma patients. Methods: The study included a total of 82 recurrent glioblastoma patients treated with bevacizumab combination therapy whom were both response and biomarker evaluable. Gene expression of tumor tissue was analyzed by using a customized Nano...
The use of source memory to identify one's own episodic confusion errors.

Science.gov (United States)

Smith, S M; Tindell, D R; Pierce, B H; Gilliland, T R; Gerkens, D R

2001-03-01

In 4 category cued recall experiments, participants falsely recalled nonlist common members, a semantic confusion error. Errors were more likely if critical nonlist words were presented on an incidental task, causing source memory failures called episodic confusion errors. Participants could better identify the source of falsely recalled words if they had deeply processed the words on the incidental task. For deep but not shallow processing, participants could reliably include or exclude incidentally shown category members in recall. The illusion that critical items actually appeared on categorized lists was diminished but not eradicated when participants identified episodic confusion errors post hoc among their own recalled responses; participants often believed that critical items had been on both the incidental task and the study list. Improved source monitoring can potentially mitigate episodic (but not semantic) confusion errors.
Using Opinions and Knowledge to Identify Natural Groups of Gambling Employees.

Science.gov (United States)

Gray, Heather M; Tom, Matthew A; LaPlante, Debi A; Shaffer, Howard J

2015-12-01

Gaming industry employees are at higher risk than the general population for health conditions including gambling disorder. Responsible gambling training programs, which train employees about gambling and gambling-related problems, might be a point of intervention. However, such programs tend to use a "one-size-fits-all" approach rather than multiple tiers of instruction. We surveyed employees of one Las Vegas casino (n = 217) and one online gambling operator (n = 178) regarding their gambling-related knowledge and opinions prior to responsible gambling training, to examine the presence of natural knowledge groups among recently hired employees. Using k-means cluster analysis, we observed four natural groups within the Las Vegas casino sample and two natural groups within the online operator sample. We describe these natural groups in terms of opinion/knowledge differences as well as distributions of demographic/occupational characteristics. Gender and language spoken at home were correlates of cluster group membership among the sample of Las Vegas casino employees, but we did not identify demographic or occupational correlates of cluster group membership among the online gambling operator employees. Gambling operators should develop more sophisticated training programs that include instruction that targets different natural knowledge groups.
Abia State HIV epidemic and response: challenges and prospects.

Science.gov (United States)

Onyeonoro, Ugochukwu Uchenna; Emelumadu, Obiageli Fidelia; Nwamoh, Uche Ngozi; Ukegbu, Andrew Ugwunna; Okafor, Godwin Oc

2014-11-13

Since the first seroprevalence survey in 1999, the HIV prevalence in Abia State has increased from 1.8% to 7.3% in 2010. The state is currently experiencing a generalized epidemic, with most transmission occurring through heterosexual low-risk sex. Drivers of the epidemic include low knowledge of HIV prevention, low risk perception, predominantly male factor-driven risky sexual behavior, and low condom use. This study reviewed the state HIV epidemic trend in relation to response, sought to identify the gaps between the epidemic and response, and recommended measures to strengthen the state response.
Proteomic analysis identifies galectin-1 as a predictive biomarker for relapsed/refractory disease in classical Hodgkin lymphoma

DEFF Research Database (Denmark)

Kamper, Peter; Ludvigsen, Maja; Bendix, Knud

2011-01-01

Considerable effort has been spent identifying prognostic biomarkers in classic Hodgkin lymphoma (cHL). The aim of our study was to search for possible prognostic parameters in advanced-stage cHL using a proteomics-based strategy. A total of 14 cHL pretreatment tissue samples from younger, advanced......-stage patients were included. Patients were grouped according to treatment response. Proteins that were differentially expressed between the groups were analyzed using 2D-PAGE and identified by liquid chromatography mass spectrometry. Selected proteins were validated using Western blot analysis. One...
Identifying the Impact of Individual Differences on the Basis of Affect Intensity Measure on Consumers Response to Advertising Appeals

OpenAIRE

Santosh Kumar

2013-01-01

This study aims (i) to find out the individuals scoring on Larsen Affect intensity measurement Scale (AIM) for emotional ads and (ii) to know whether the individual differences of response diminishes when they are exposed to the nonemotional (rational) advertisements, (iii) to know whether the cultural differences among other countries and Pakistan mediate the applicability and implications of AIM scale in the field of advertising research. Variety of researchers including consumers behavior,...
Interprofessional non-technical skills for surgeons in disaster response: a qualitative study of the Australian perspective.

Science.gov (United States)

Willems, Anneliese; Waxman, Buce; Bacon, Andrew K; Smith, Julian; Peller, Jennifer; Kitto, Simon

2013-03-01

Interprofessional non-technical skills for surgeons in disaster response have not yet been developed. The aims of this study were to identify the non-technical skills required of surgeons in disaster response and training for disaster response and to explore the barriers and facilitators to interprofessional practice in surgical teams responding to disasters. Twenty health professionals, with prior experience in natural disaster response or education, participated in semi-structured in-depth interviews. A qualitative matrix analysis design was used to thematically analyze the data. Non-technical skills for surgeons in disaster response identified in this study included skills for austere environments, cognitive strategies and interprofessional skills. Skills for austere environments were physical self-care including survival skills, psychological self-care, flexibility, adaptability, innovation and improvisation. Cognitive strategies identified in this study were "big picture" thinking, situational awareness, critical thinking, problem solving and creativity. Interprofessional attributes include communication, team-player, sense of humor, cultural competency and conflict resolution skills. "Interprofessionalism" in disaster teams also emerged as a key factor in this study and incorporated elements of effective teamwork, clear leadership, role adjustment and conflict resolution. The majority of participants held the belief that surgeons needed training in non-technical skills in order to achieve best practice in disaster response. Surgeons considerring becoming involved in disaster management should be trained in these skills, and these skills should be incorporated into disaster preparation courses with an interprofessional focus.

Dam owner floodplain management: responsibility, consequences and strategies in a competitive environment

International Nuclear Information System (INIS)

Joyner, J.B.; Lence, B.J.

1999-01-01

Dam owners responsibilities regarding dam construction, operation, maintenance, and eventual decommissioning, as imposed by various statutes in British Columbia, are discussed. The discussion includes consideration of consequences of failure to meet mandated responsibilities, and technical, legal and educational strategies to avoid exposure to risk. Recent court decisions are examined to identify common areas of risk. 9 refs., 1 fig
A two-dimensional simulation model of phosphorus uptake including crop growth and P-response

NARCIS (Netherlands)

Mollier, A.; Willigen, de P.; Heinen, M.; Morel, C.; Schneider, A.; Pellerin, S.

2008-01-01

Modelling nutrient uptake by crops implies considering and integrating the processes controlling the soil nutrient supply, the uptake by the root system and relationships between the crop growth response and the amount of nutrient absorbed. We developed a model that integrates both dynamics of maize
Genetic Influences on Response to Alcohol and Response to Pharmacotherapies for Alcoholism

Science.gov (United States)

Enoch, Mary-Anne

2014-01-01

Although very many individuals drink alcohol at safe levels, a significant proportion escalates their consumption with addiction as the end result. Alcoholism is a common, moderately heritable, psychiatric disorder that is accompanied by considerable morbidity and mortality. Variation in clinical presentation suggests inter-individual variation in mechanisms of vulnerability including genetic risk factors. The development of addiction is likely to involve numerous functional genetic variants of small effects. The first part of this review will focus on genetic factors underlying inter-individual variability in response to alcohol consumption, including variants in alcohol metabolizing genes that produce an aversive response (the flushing syndrome) and variants that predict the level of subjective and physiological response to alcohol. The second part of this review will report on genetic variants that identify subgroups of alcoholics who are more likely to respond to pharmacotherapy to reduce levels of drinking or maintain abstinence. Genetic analyses of the level of response to alcohol, particularly of the functional OPRM1 A118G polymorphism and 5′ and 3′ functional polymorphisms in SLC6A4, are beginning to provide insights into the etiology of alcoholism and also genotype-stratified subgroup responses to naltrexone and SSRIs / ondansetron respectively. Because of large inter-ethnic variation in allele frequencies, the relevance of these functional polymorphisms will vary between ethnic groups. However there are relatively few published studies in this field, particularly with large sample sizes in pharmacogenetic studies, therefore it is premature to draw any conclusions at this stage. PMID:24220019
Heterogeneity in glucose response curves during an oral glucose tolerance test and associated cardiometabolic risk

DEFF Research Database (Denmark)

Hulman, Adam; Simmons, Rebecca Kate; Vistisen, Dorte

2017-01-01

patterns of plasma glucose change during the oral glucose tolerance test. Cardiometabolic risk factor profiles were compared between the identified groups. Using latent class trajectory analysis, five glucose response curves were identified. Despite similar fasting and 2-h values, glucose peaks and peak......We aimed to examine heterogeneity in glucose response curves during an oral glucose tolerance test with multiple measurements and to compare cardiometabolic risk profiles between identified glucose response curve groups. We analyzed data from 1,267 individuals without diabetes from five studies...... in Denmark, the Netherlands and the USA. Each study included between 5 and 11 measurements at different time points during a 2-h oral glucose tolerance test, resulting in 9,602 plasma glucose measurements. Latent class trajectories with a cubic specification for time were fitted to identify different...
Social Responsibility of Hospitality Industry Enterprises

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Nuray Türker

2013-09-01

Full Text Available The main aim of this study is to determine the views of employees and managers working at the hospitality industry in Safranbolu towards the social responsibility of tourism enterprises, social responsibility activities carried out by the hotel enterprises, and their views on the advantages and contributions of social responsibility projects to the hotel business. This study will make contributions to the related literature on social responsibility at the hospitality industry by means of identifying the social responsibility activities of hotel enterprises, of which there is relatively limited number of studies.Within this context, a structured survey was conducted with 152 respondents including employees, managers and owners of the hotel enterprises through face to face interviews in order to determine the perceptions of employees towards social responsibility. SPSS 15 for Windows was used to analyze the data. The research has found that the employees working at hospitality industry in Safranbolu are sensitive to the social responsibilities and they act socially responsible in their activities. Additionally the results show that the respondents behave socially responsible towards guests, society and natural environment, but that they are less responsible towards the suppliers.
A water-based training program that include perturbation exercises to improve stepping responses in older adults: study protocol for a randomized controlled cross-over trial

Directory of Open Access Journals (Sweden)

Tsedek Irit

2008-08-01

Full Text Available Abstract Background Gait and balance impairments may increase the risk of falls, the leading cause of accidental death in the elderly population. Fall-related injuries constitute a serious public health problem associated with high costs for society as well as human suffering. A rapid step is the most important protective postural strategy, acting to recover equilibrium and prevent a fall from initiating. It can arise from large perturbations, but also frequently as a consequence of volitional movements. We propose to use a novel water-based training program which includes specific perturbation exercises that will target the stepping responses that could potentially have a profound effect in reducing risk of falling. We describe the water-based balance training program and a study protocol to evaluate its efficacy (Trial registration number #NCT00708136. Methods/Design The proposed water-based training program involves use of unpredictable, multi-directional perturbations in a group setting to evoke compensatory and volitional stepping responses. Perturbations are made by pushing slightly the subjects and by water turbulence, in 24 training sessions conducted over 12 weeks. Concurrent cognitive tasks during movement tasks are included. Principles of physical training and exercise including awareness, continuity, motivation, overload, periodicity, progression and specificity were used in the development of this novel program. Specific goals are to increase the speed of stepping responses and improve the postural control mechanism and physical functioning. A prospective, randomized, cross-over trial with concealed allocation, assessor blinding and intention-to-treat analysis will be performed to evaluate the efficacy of the water-based training program. A total of 36 community-dwelling adults (age 65–88 with no recent history of instability or falling will be assigned to either the perturbation-based training or a control group (no training
Identifying and quantifying heterogeneity in high content analysis: application of heterogeneity indices to drug discovery.

Directory of Open Access Journals (Sweden)

Albert H Gough

Full Text Available One of the greatest challenges in biomedical research, drug discovery and diagnostics is understanding how seemingly identical cells can respond differently to perturbagens including drugs for disease treatment. Although heterogeneity has become an accepted characteristic of a population of cells, in drug discovery it is not routinely evaluated or reported. The standard practice for cell-based, high content assays has been to assume a normal distribution and to report a well-to-well average value with a standard deviation. To address this important issue we sought to define a method that could be readily implemented to identify, quantify and characterize heterogeneity in cellular and small organism assays to guide decisions during drug discovery and experimental cell/tissue profiling. Our study revealed that heterogeneity can be effectively identified and quantified with three indices that indicate diversity, non-normality and percent outliers. The indices were evaluated using the induction and inhibition of STAT3 activation in five cell lines where the systems response including sample preparation and instrument performance were well characterized and controlled. These heterogeneity indices provide a standardized method that can easily be integrated into small and large scale screening or profiling projects to guide interpretation of the biology, as well as the development of therapeutics and diagnostics. Understanding the heterogeneity in the response to perturbagens will become a critical factor in designing strategies for the development of therapeutics including targeted polypharmacology.
Proteomic Assessment of Biochemical Pathways That Are Critical to Nickel-Induced Toxicity Responses in Human Epithelial Cells

Science.gov (United States)

Ge, Yue; Bruno, Maribel; Haykal-Coates, Najwa; Wallace, Kathleen; Andrews, Debora; Swank, Adam; Winnik, Witold; Ross, Jeffrey A.

2016-01-01

Understanding the mechanisms underlying toxicity initiated by nickel, a ubiquitous environmental contaminant and known human carcinogen is necessary for proper assessment of its risks to human and environment. Among a variety of toxic mechanisms, disruption of protein responses and protein response-based biochemical pathways represents a key mechanism through which nickel induces cytotoxicity and carcinogenesis. To identify protein responses and biochemical pathways that are critical to nickel-induced toxicity responses, we measured cytotoxicity and changes in expression and phosphorylation status of 14 critical biochemical pathway regulators in human BEAS-2B cells exposed to four concentrations of nickel using an integrated proteomic approach. A subset of the pathway regulators, including interleukin-6, and JNK, were found to be linearly correlated with cell viability, and may function as molecular determinants of cytotoxic responses of BEAS-2B cells to nickel exposures. In addition, 128 differentially expressed proteins were identified by two dimensional electrophoresis (2-DE) and mass spectrometry. Principal component analysis, hierarchical cluster analyses, and ingenuity signaling pathway analysis (IPA) identified putative nickel toxicity pathways. Some of the proteins and pathways identified have not previously been linked to nickel toxicity. Based on the consistent results obtained from both ELISA and 2-DE proteomic analysis, we propose a core signaling pathway regulating cytotoxic responses of human BEAS-2B cells to nickel exposures, which integrates a small set of proteins involved in glycolysis and gluconeogenesis pathways, apoptosis, protein degradation, and stress responses including inflammation and oxidative stress. PMID:27626938
Resolution of Chlamydia trachomatis Infection Is Associated with a Distinct T Cell Response Profile.

Science.gov (United States)

Picard, Michele D; Bodmer, Jean-Luc; Gierahn, Todd M; Lee, Alexander; Price, Jessica; Cohane, Kenya; Clemens, Veronica; DeVault, Victoria L; Gurok, Galina; Kohberger, Robert; Higgins, Darren E; Siber, George R; Flechtner, Jessica Baker; Geisler, William M

2015-11-01

Chlamydia trachomatis is the causative agent of the most frequently reported bacterial sexually transmitted infection, the total burden of which is underestimated due to the asymptomatic nature of the infection. Untreated C. trachomatis infections can cause significant morbidities, including pelvic inflammatory disease and tubal factor infertility (TFI). The human immune response against C. trachomatis, an obligate intracellular bacterium, is poorly characterized but is thought to rely on cell-mediated immunity, with CD4(+) and CD8(+) T cells implicated in protection. In this report, we present immune profiling data of subjects enrolled in a multicenter study of C. trachomatis genital infection. CD4(+) and CD8(+) T cells from subjects grouped into disease-specific cohorts were screened using a C. trachomatis proteomic library to identify the antigen specificities of recall T cell responses after natural exposure by measuring interferon gamma (IFN-γ) levels. We identified specific T cell responses associated with the resolution of infection, including unique antigens identified in subjects who spontaneously cleared infection and different antigens associated with C. trachomatis-related sequelae, such as TFI. These data suggest that novel and unique C. trachomatis T cell antigens identified in individuals with effective immune responses can be considered as targets for vaccine development, and by excluding antigens associated with deleterious sequelae, immune-mediated pathologies may be circumvented. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Integrative analysis of deep sequencing data identifies estrogen receptor early response genes and links ATAD3B to poor survival in breast cancer.

Directory of Open Access Journals (Sweden)

Kristian Ovaska

Full Text Available Identification of responsive genes to an extra-cellular cue enables characterization of pathophysiologically crucial biological processes. Deep sequencing technologies provide a powerful means to identify responsive genes, which creates a need for computational methods able to analyze dynamic and multi-level deep sequencing data. To answer this need we introduce here a data-driven algorithm, SPINLONG, which is designed to search for genes that match the user-defined hypotheses or models. SPINLONG is applicable to various experimental setups measuring several molecular markers in parallel. To demonstrate the SPINLONG approach, we analyzed ChIP-seq data reporting PolII, estrogen receptor α (ERα, H3K4me3 and H2A.Z occupancy at five time points in the MCF-7 breast cancer cell line after estradiol stimulus. We obtained 777 ERa early responsive genes and compared the biological functions of the genes having ERα binding within 20 kb of the transcription start site (TSS to genes without such binding site. Our results show that the non-genomic action of ERα via the MAPK pathway, instead of direct ERa binding, may be responsible for early cell responses to ERα activation. Our results also indicate that the ERα responsive genes triggered by the genomic pathway are transcribed faster than those without ERα binding sites. The survival analysis of the 777 ERα responsive genes with 150 primary breast cancer tumors and in two independent validation cohorts indicated the ATAD3B gene, which does not have ERα binding site within 20 kb of its TSS, to be significantly associated with poor patient survival.
Metabolomics Analysis of Hormone-Responsive and Triple-Negative Breast Cancer Cell Responses to Paclitaxel Identify Key Metabolic Differences.

Science.gov (United States)

Stewart, Delisha A; Winnike, Jason H; McRitchie, Susan L; Clark, Robert F; Pathmasiri, Wimal W; Sumner, Susan J

2016-09-02

To date, no targeted therapies are available to treat triple negative breast cancer (TNBC), while other breast cancer subtypes are responsive to current therapeutic treatment. Metabolomics was conducted to reveal differences in two hormone receptor-negative TNBC cell lines and two hormone receptor-positive Luminal A cell lines. Studies were conducted in the presence and absence of paclitaxel (Taxol). TNBC cell lines had higher levels of amino acids, branched-chain amino acids, nucleotides, and nucleotide sugars and lower levels of proliferation-related metabolites like choline compared with Luminal A cell lines. In the presence of paclitaxel, each cell line showed unique metabolic responses, with some similarities by type. For example, in the Luminal A cell lines, levels of lactate and creatine decreased while certain choline metabolites and myo-inositol increased with paclitaxel. In the TNBC cell lines levels of glutamine, glutamate, and glutathione increased, whereas lysine, proline, and valine decreased in the presence of drug. Profiling secreted inflammatory cytokines in the conditioned media demonstrated a greater response to paclitaxel in the hormone-positive Luminal cells compared with a secretion profile that suggested greater drug resistance in the TNBC cells. The most significant differences distinguishing the cell types based on pathway enrichment analyses were related to amino acid, lipid and carbohydrate metabolism pathways, whereas several biological pathways were differentiated between the cell lines following treatment.
On-line method to identify control rod drops in Pressurized Water Reactors

International Nuclear Information System (INIS)

Souza, T.J.; Martinez, A.S.; Medeiros, J.A.C.C.; Palma, D.A.P.; Gonçalves, A.C.

2014-01-01

Highlights: • On-line method to identify control rod drops in PWR reactors. • Identification method based on the readings of the ex-core detector. • Recognition of the patterns in the ex-core detector responses. - Abstract: A control rod drop event in PWR reactors leads to an unsafe operating condition. It is important to quickly identify the rod to minimise undesirable effects in such a scenario. The goal of this work is to develop an online method to identify control rod drops in PWR reactors. The method entails the construction of a tool based on ex-core detector responses. It proposes to recognize patterns in the neutron ex-core detectors responses and thus to make an online identification of a control rod drop in the core during the reactor operation. The results of the study, as well as the behaviour of the detector responses demonstrated the feasibility of this method
Patient- and Family-Identified Problems of Traumatic Brain Injury: Value and Utility of a Target Outcome Approach to Identifying the Worst Problems

Directory of Open Access Journals (Sweden)

Laraine Winter

2016-01-01

Full Text Available Purpose: This study aimed to identify the sequelae of traumatic brain injury (TBI that are most troubling to veterans with TBI and their families and identify veteran-family differences in content and ranking. Instead of standardized measures of symptom frequency or severity, which may be insensitive to change or intervention effects, we used a target outcome measure for veterans with TBI and their key family members, which elicited open-ended reports concerning the three most serious TBI-related problems. This was followed by Likert-scaled ratings of difficulty in managing the problem. Methods: In this cross-sectional study, interviews were conducted in veterans’ homes. Participants included 83 veterans with TBI diagnosed at a Veterans Affairs medical rehabilitation service and a key family member of each veteran. We utilized open-ended questions to determine the problems caused by TBI within the last month. Sociodemographic characteristics of veterans and family members, and veterans’ military and medical characteristics were collected. A coding scheme was developed to categorize open-ended responses. Results: Families identified nearly twice as many categories of problems as did veterans, and veterans and families ranked problem categories very differently. Veterans ranked cognitive and physical problems worst; families ranked emotional and interpersonal problems worst. Conclusions: Easily administered open-ended questions about the most troubling TBI-related problems yield novel insights and reveal important veteran-family discrepancies.
A Systems Biology Framework Identifies Molecular Underpinnings of Coronary Heart Disease

Science.gov (United States)

Huan, Tianxiao; Zhang, Bin; Wang, Zhi; Joehanes, Roby; Zhu, Jun; Johnson, Andrew D.; Ying, Saixia; Munson, Peter J.; Raghavachari, Nalini; Wang, Richard; Liu, Poching; Courchesne, Paul; Hwang, Shih-Jen; Assimes, Themistocles L.; McPherson, Ruth; Samani, Nilesh J.; Schunkert, Heribert; Meng, Qingying; Suver, Christine; O'Donnell, Christopher J.; Derry, Jonathan; Yang, Xia; Levy, Daniel

2013-01-01

Objective Genetic approaches have identified numerous loci associated with coronary heart disease (CHD). The molecular mechanisms underlying CHD gene-disease associations, however, remain unclear. We hypothesized that genetic variants with both strong and subtle effects drive gene subnetworks that in turn affect CHD. Approach and Results We surveyed CHD-associated molecular interactions by constructing coexpression networks using whole blood gene expression profiles from 188 CHD cases and 188 age- and sex-matched controls. 24 coexpression modules were identified including one case-specific and one control-specific differential module (DM). The DMs were enriched for genes involved in B-cell activation, immune response, and ion transport. By integrating the DMs with altered gene expression associated SNPs (eSNPs) and with results of GWAS of CHD and its risk factors, the control-specific DM was implicated as CHD-causal based on its significant enrichment for both CHD and lipid eSNPs. This causal DM was further integrated with tissue-specific Bayesian networks and protein-protein interaction networks to identify regulatory key driver (KD) genes. Multi-tissue KDs (SPIB and TNFRSF13C) and tissue-specific KDs (e.g. EBF1) were identified. Conclusions Our network-driven integrative analysis not only identified CHD-related genes, but also defined network structure that sheds light on the molecular interactions of genes associated with CHD risk. PMID:23539213
Vegetation response to invasive Tamarix control in southwestern U.S. rivers: a collaborative study including 416 sites.

Science.gov (United States)

González, Eduardo; Sher, Anna A; Anderson, Robert M; Bay, Robin F; Bean, Daniel W; Bissonnete, Gabriel J; Bourgeois, Bérenger; Cooper, David J; Dohrenwend, Kara; Eichhorst, Kim D; El Waer, Hisham; Kennard, Deborah K; Harms-Weissinger, Rebecca; Henry, Annie L; Makarick, Lori J; Ostoja, Steven M; Reynolds, Lindsay V; Robinson, W Wright; Shafroth, Patrick B

2017-09-01

Most studies assessing vegetation response following control of invasive Tamarix trees along southwestern U.S. rivers have been small in scale (e.g., river reach), or at a regional scale but with poor spatial-temporal replication, and most have not included testing the effects of a now widely used biological control. We monitored plant composition following Tamarix control along hydrologic, soil, and climatic gradients in 244 treated and 172 reference sites across six U.S. states. This represents the largest comprehensive assessment to date on the vegetation response to the four most common Tamarix control treatments. Biocontrol by a defoliating beetle (treatment 1) reduced the abundance of Tamarix less than active removal by mechanically using hand and chain-saws (2), heavy machinery (3) or burning (4). Tamarix abundance also decreased with lower temperatures, higher precipitation, and follow-up treatments for Tamarix resprouting. Native cover generally increased over time in active Tamarix removal sites, however, the increases observed were small and was not consistently increased by active revegetation. Overall, native cover was correlated to permanent stream flow, lower grazing pressure, lower soil salinity and temperatures, and higher precipitation. Species diversity also increased where Tamarix was removed. However, Tamarix treatments, especially those generating the highest disturbance (burning and heavy machinery), also often promoted secondary invasions of exotic forbs. The abundance of hydrophytic species was much lower in treated than in reference sites, suggesting that management of southwestern U.S. rivers has focused too much on weed control, overlooking restoration of fluvial processes that provide habitat for hydrophytic and floodplain vegetation. These results can help inform future management of Tamarix-infested rivers to restore hydrogeomorphic processes, increase native biodiversity and reduce abundance of noxious species. © 2017 by the
An affinity pull-down approach to identify the plant cyclic nucleotide interactome

KAUST Repository

Donaldson, Lara Elizabeth; Meier, Stuart Kurt

2013-01-01

Cyclic nucleotides (CNs) are intracellular second messengers that play an important role in mediating physiological responses to environmental and developmental signals, in species ranging from bacteria to humans. In response to these signals, CNs are synthesized by nucleotidyl cyclases and then act by binding to and altering the activity of downstream target proteins known as cyclic nucleotide-binding proteins (CNBPs). A number of CNBPs have been identified across kingdoms including transcription factors, protein kinases, phosphodiesterases, and channels, all of which harbor conserved CN-binding domains. In plants however, few CNBPs have been identified as homology searches fail to return plant sequences with significant matches to known CNBPs. Recently, affinity pull-down techniques have been successfully used to identify CNBPs in animals and have provided new insights into CN signaling. The application of these techniques to plants has not yet been extensively explored and offers an alternative approach toward the unbiased discovery of novel CNBP candidates in plants. Here, an affinity pull-down technique for the identification of the plant CN interactome is presented. In summary, the method involves an extraction of plant proteins which is incubated with a CN-bait, followed by a series of increasingly stringent elutions that eliminates proteins in a sequential manner according to their affinity to the bait. The eluted and bait-bound proteins are separated by one-dimensional gel electrophoresis, excised, and digested with trypsin after which the resultant peptides are identified by mass spectrometry - techniques that are commonplace in proteomics experiments. The discovery of plant CNBPs promises to provide valuable insight into the mechanism of CN signal transduction in plants. © Springer Science+Business Media New York 2013.
An affinity pull-down approach to identify the plant cyclic nucleotide interactome

KAUST Repository

Donaldson, Lara Elizabeth

2013-09-03

Cyclic nucleotides (CNs) are intracellular second messengers that play an important role in mediating physiological responses to environmental and developmental signals, in species ranging from bacteria to humans. In response to these signals, CNs are synthesized by nucleotidyl cyclases and then act by binding to and altering the activity of downstream target proteins known as cyclic nucleotide-binding proteins (CNBPs). A number of CNBPs have been identified across kingdoms including transcription factors, protein kinases, phosphodiesterases, and channels, all of which harbor conserved CN-binding domains. In plants however, few CNBPs have been identified as homology searches fail to return plant sequences with significant matches to known CNBPs. Recently, affinity pull-down techniques have been successfully used to identify CNBPs in animals and have provided new insights into CN signaling. The application of these techniques to plants has not yet been extensively explored and offers an alternative approach toward the unbiased discovery of novel CNBP candidates in plants. Here, an affinity pull-down technique for the identification of the plant CN interactome is presented. In summary, the method involves an extraction of plant proteins which is incubated with a CN-bait, followed by a series of increasingly stringent elutions that eliminates proteins in a sequential manner according to their affinity to the bait. The eluted and bait-bound proteins are separated by one-dimensional gel electrophoresis, excised, and digested with trypsin after which the resultant peptides are identified by mass spectrometry - techniques that are commonplace in proteomics experiments. The discovery of plant CNBPs promises to provide valuable insight into the mechanism of CN signal transduction in plants. © Springer Science+Business Media New York 2013.
Enhancing 'Whole-of-Government' Response to Biological Events in Korea: Able Response 2014.

Science.gov (United States)

Tak, Sangwoo; Jareb, Anton; Choi, Suon; Sikes, Marvin; Choi, Yeon Hwa; Boo, Hyeong-Wook

2018-01-01

Since 2011, the Republic of Korea (ROK) and United States (U.S.) have been collaborating to conduct inter- and intra-governmental exercises to jointly respond to biological events in Korea. These exercises highlight U.S. interest in increasing its global biosurveillance capability and the ROK's interest in improving cooperation among ministries to respond to crises. With Able Response (AR) exercises, the ROK and U.S. have improved coordination among US and ROK government and defense agencies responding to potential bio-threats and identified additional areas on which to apply refinements in policies and practices. In 2014, the AR exercise employed a Biosurveillance Portal (BSP) to facilitate more effective communication among participating agencies and countries including Australia. In the present paper, we seek to provide a comprehensive assessment of the AR 2014 (AR14) exercise and make recommendations for future improvements. Incorporating a more realistic response in future scenarios by integrating a tactical response episode in the exercise is recommended.
Autonomous Sensory Meridian Response (ASMR): a flow-like mental state

OpenAIRE

Emma L. Barratt; Nick J. Davis

2015-01-01

Autonomous Sensory Meridian Response (ASMR) is a previously unstudied sensory phenomenon, in which individuals experience a tingling, static-like sensation across the scalp, back of the neck and at times further areas in response to specific triggering audio and visual stimuli. This sensation is widely reported to be accompanied by feelings of relaxation and well-being. The current study identifies several common triggers used to achieve ASMR, including whispering, personal attention, crisp s...
Evaluating alternative responses to safeguards alarms

International Nuclear Information System (INIS)

Al-Ayat, R.A.; Judd, B.R.; McCord, R.K.

1982-01-01

This paper describes a quantitative approach to help evaluate and respond to safeguards alarms. These alarms may be generated internally by a facility's safeguards systems or externally by individuals claiming to have stolen special nuclear material (SNM). This approach can be used to identify the most likely cause of an alarm - theft, hoax, or error - and to evaluate alternative responses to alarms. Possible responses include conducting investigations, initiating measures to recover stolen SNM, and replying to external threats. Based on the results of each alarm investigation step, the evaluation revises the likelihoods of possible causes of an alarm, and uses this information to determine the optimal sequence of further responses. The choice of an optimal sequence of responses takes into consideration the costs and benefits of successful thefts or hoaxes. These results provide an analytical basis for setting priorities and developing contingency plans for responding to safeguards alarms

Rice Transcriptome Analysis to Identify Possible Herbicide Quinclorac Detoxification Genes

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Wenying eXu

2015-09-01

Full Text Available Quinclorac is a highly selective auxin-type herbicide, and is widely used in the effective control of barnyard grass in paddy rice fields, improving the world’s rice yield. The herbicide mode of action of quinclorac has been proposed and hormone interactions affect quinclorac signaling. Because of widespread use, quinclorac may be transported outside rice fields with the drainage waters, leading to soil and water pollution and environmental health problems.In this study, we used 57K Affymetrix rice whole-genome array to identify quinclorac signaling response genes to study the molecular mechanisms of action and detoxification of quinclorac in rice plants. Overall, 637 probe sets were identified with differential expression levels under either 6 or 24 h of quinclorac treatment. Auxin-related genes such as GH3 and OsIAAs responded to quinclorac treatment. Gene Ontology analysis showed that genes of detoxification-related family genes were significantly enriched, including cytochrome P450, GST, UGT, and ABC and drug transporter genes. Moreover, real-time RT-PCR analysis showed that top candidate P450 families such as CYP81, CYP709C and CYP72A genes were universally induced by different herbicides. Some Arabidopsis genes for the same P450 family were up-regulated under quinclorac treatment.We conduct rice whole-genome GeneChip analysis and the first global identification of quinclorac response genes. This work may provide potential markers for detoxification of quinclorac and biomonitors of environmental chemical pollution.
Novel Harmful Recessive Haplotypes Identified for Fertility Traits in Nordic Holstein Cattle

Science.gov (United States)

Sahana, Goutam; Nielsen, Ulrik Sander; Aamand, Gert Pedersen; Lund, Mogens Sandø; Guldbrandtsen, Bernt

2013-01-01

Using genomic data, lethal recessives may be discovered from haplotypes that are common in the population but never occur in the homozygote state in live animals. This approach only requires genotype data from phenotypically normal (i.e. live) individuals and not from the affected embryos that die. A total of 7,937 Nordic Holstein animals were genotyped with BovineSNP50 BeadChip and haplotypes including 25 consecutive markers were constructed and tested for absence of homozygotes states. We have identified 17 homozygote deficient haplotypes which could be loosely clustered into eight genomic regions harboring possible recessive lethal alleles. Effects of the identified haplotypes were estimated on two fertility traits: non-return rates and calving interval. Out of the eight identified genomic regions, six regions were confirmed as having an effect on fertility. The information can be used to avoid carrier-by-carrier mattings in practical animal breeding. Further, identification of causative genes/polymorphisms responsible for lethal effects will lead to accurate testing of the individuals carrying a lethal allele. PMID:24376603
Transcriptional profiling of Medicago truncatula under salt stress identified a novel CBF transcription factor MtCBF4 that plays an important role in abiotic stress responses

Directory of Open Access Journals (Sweden)

Su Zhen

2011-07-01

Full Text Available Abstract Background Salt stress hinders the growth of plants and reduces crop production worldwide. However, different plant species might possess different adaptive mechanisms to mitigate salt stress. We conducted a detailed pathway analysis of transcriptional dynamics in the roots of Medicago truncatula seedlings under salt stress and selected a transcription factor gene, MtCBF4, for experimental validation. Results A microarray experiment was conducted using root samples collected 6, 24, and 48 h after application of 180 mM NaCl. Analysis of 11 statistically significant expression profiles revealed different behaviors between primary and secondary metabolism pathways in response to external stress. Secondary metabolism that helps to maintain osmotic balance was induced. One of the highly induced transcription factor genes was successfully cloned, and was named MtCBF4. Phylogenetic analysis revealed that MtCBF4, which belongs to the AP2-EREBP transcription factor family, is a novel member of the CBF transcription factor in M. truncatula. MtCBF4 is shown to be a nuclear-localized protein. Expression of MtCBF4 in M. truncatula was induced by most of the abiotic stresses, including salt, drought, cold, and abscisic acid, suggesting crosstalk between these abiotic stresses. Transgenic Arabidopsis over-expressing MtCBF4 enhanced tolerance to drought and salt stress, and activated expression of downstream genes that contain DRE elements. Over-expression of MtCBF4 in M. truncatula also enhanced salt tolerance and induced expression level of corresponding downstream genes. Conclusion Comprehensive transcriptomic analysis revealed complex mechanisms exist in plants in response to salt stress. The novel transcription factor gene MtCBF4 identified here played an important role in response to abiotic stresses, indicating that it might be a good candidate gene for genetic improvement to produce stress-tolerant plants.
Transcriptional profiling of Medicago truncatula under salt stress identified a novel CBF transcription factor MtCBF4 that plays an important role in abiotic stress responses

Science.gov (United States)

2011-01-01

Background Salt stress hinders the growth of plants and reduces crop production worldwide. However, different plant species might possess different adaptive mechanisms to mitigate salt stress. We conducted a detailed pathway analysis of transcriptional dynamics in the roots of Medicago truncatula seedlings under salt stress and selected a transcription factor gene, MtCBF4, for experimental validation. Results A microarray experiment was conducted using root samples collected 6, 24, and 48 h after application of 180 mM NaCl. Analysis of 11 statistically significant expression profiles revealed different behaviors between primary and secondary metabolism pathways in response to external stress. Secondary metabolism that helps to maintain osmotic balance was induced. One of the highly induced transcription factor genes was successfully cloned, and was named MtCBF4. Phylogenetic analysis revealed that MtCBF4, which belongs to the AP2-EREBP transcription factor family, is a novel member of the CBF transcription factor in M. truncatula. MtCBF4 is shown to be a nuclear-localized protein. Expression of MtCBF4 in M. truncatula was induced by most of the abiotic stresses, including salt, drought, cold, and abscisic acid, suggesting crosstalk between these abiotic stresses. Transgenic Arabidopsis over-expressing MtCBF4 enhanced tolerance to drought and salt stress, and activated expression of downstream genes that contain DRE elements. Over-expression of MtCBF4 in M. truncatula also enhanced salt tolerance and induced expression level of corresponding downstream genes. Conclusion Comprehensive transcriptomic analysis revealed complex mechanisms exist in plants in response to salt stress. The novel transcription factor gene MtCBF4 identified here played an important role in response to abiotic stresses, indicating that it might be a good candidate gene for genetic improvement to produce stress-tolerant plants. PMID:21718548
Responsible Reporting: Neuroimaging News in the Age of Responsible Research and Innovation.

Science.gov (United States)

de Jong, Irja Marije; Kupper, Frank; Arentshorst, Marlous; Broerse, Jacqueline

2016-08-01

Besides offering opportunities in both clinical and non-clinical domains, the application of novel neuroimaging technologies raises pressing dilemmas. 'Responsible Research and Innovation' (RRI) aims to stimulate research and innovation activities that take ethical and social considerations into account from the outset. We previously identified that Dutch neuroscientists interpret "responsible innovation" as educating the public on neuroimaging technologies via the popular press. Their aim is to mitigate (neuro)hype, an aim shared with the wider emerging RRI community. Here, we present results of a media-analysis undertaken to establish whether the body of articles in the Dutch popular press presents balanced conversations on neuroimaging research to the public. We found that reporting was mostly positive and framed in terms of (healthcare) progress. There was rarely a balance between technology opportunities and limitations, and even fewer articles addressed societal or ethical aspects of neuroimaging research. Furthermore, neuroimaging metaphors seem to favour oversimplification. Current reporting is therefore more likely to enable hype than to mitigate it. How can neuroscientists, given their self-ascribed social responsibility, address this conundrum? We make a case for a collective and shared responsibility among neuroscientists, journalists and other stakeholders, including funders, committed to responsible reporting on neuroimaging research.
Corporate Social Responsability: Selected Theoretical and Empirical Aspects

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Witkowska Janina

2016-03-01

Full Text Available The notion of Corporate social responsibility (CSR is still stirring debate over how it should be interpreted, what models of CSR dominate in business practice, and consequences of enterprises’ engagement into socially responsible actions. While business practice demonstrates that companies voluntarily include social and environmental issues into their activities and into their relations with stakeholders, it is hard to determine what intentions motivate them to do so. This paper analyses selected aspects of discussions focused on the notion of CSR and identifies controversies over the standardisation of ethical and social business activities.
Treatment response in psychotic patients classified according to social and clinical needs, drug side effects, and previous treatment; a method to identify functional remission

DEFF Research Database (Denmark)

Alenius, Malin; Hammarlund-Udenaes, Margareta; Honoré, Per Gustaf Hartvig

2009-01-01

, fewer psychotic symptoms, and higher rate of workers than those with the worst treatment outcome. CONCLUSION: In the evaluation, CANSEPT showed validity in discriminating the patients of interest and was well tolerated by the patients. CANSEPT could secure inclusion of correct patients in the clinic......BACKGROUND: Various approaches have been made over the years to classify psychotic patients according to inadequate treatment response, using terms such as treatment resistant or treatment refractory. Existing classifications have been criticized for overestimating positive symptoms......; underestimating residual symptoms, negative symptoms, and side effects; or being to open for individual interpretation. The aim of this study was to present and evaluate a new method of classification according to treatment response and, thus, to identify patients in functional remission. METHOD: A naturalistic...
Identifying Information Focuses in Listening Comprehension

Science.gov (United States)

Zhang, Hong-yan

2011-01-01

The study explains the process of learners' listening comprehension within Halliday's information theory in functional grammar, including the skills of identifying focuses while listening in college English teaching. Identifying information focuses in listening is proved to improve the students' communicative listening ability by the means of a…
De novo RNA sequencing transcriptome of Rhododendron obtusum identified the early heat response genes involved in the transcriptional regulation of photosynthesis.

Directory of Open Access Journals (Sweden)

Linchuan Fang

Full Text Available Rhododendron spp. is an important ornamental species that is widely cultivated for landscape worldwide. Heat stress is a major obstacle for its cultivation in south China. Previous studies on rhododendron principally focused on its physiological and biochemical processes, which are involved in a series of stress tolerance. However, molecular or genetic properties of rhododendron's response to heat stress are still poorly understood. The phenotype and chlorophyll fluorescence kinetics parameters of four rhododendron cultivars were compared under normal or heat stress conditions, and a cultivar with highest heat tolerance, "Yanzhimi" (R. obtusum was selected for transcriptome sequencing. A total of 325,429,240 high quality reads were obtained and assembled into 395,561 transcripts and 92,463 unigenes. Functional annotation showed that 38,724 unigenes had sequence similarity to known genes in at least one of the proteins or nucleotide databases used in this study. These 38,724 unigenes were categorized into 51 functional groups based on Gene Ontology classification and were blasted to 24 known cluster of orthologous groups. A total of 973 identified unigenes belonged to 57 transcription factor families, including the stress-related HSF, DREB, ZNF, and NAC genes. Photosynthesis was significantly enriched in the Kyoto Encyclopedia of Genes and Genomes pathway, and the changed expression pattern was illustrated. The key pathways and signaling components that contribute to heat tolerance in rhododendron were revealed. These results provide a potentially valuable resource that can be used for heat-tolerance breeding.
De novo RNA sequencing transcriptome of Rhododendron obtusum identified the early heat response genes involved in the transcriptional regulation of photosynthesis

Science.gov (United States)

Tong, Jun; Dong, Yanfang; Xu, Dongyun; Mao, Jing; Zhou, Yuan

2017-01-01

Rhododendron spp. is an important ornamental species that is widely cultivated for landscape worldwide. Heat stress is a major obstacle for its cultivation in south China. Previous studies on rhododendron principally focused on its physiological and biochemical processes, which are involved in a series of stress tolerance. However, molecular or genetic properties of rhododendron’s response to heat stress are still poorly understood. The phenotype and chlorophyll fluorescence kinetics parameters of four rhododendron cultivars were compared under normal or heat stress conditions, and a cultivar with highest heat tolerance, “Yanzhimi” (R. obtusum) was selected for transcriptome sequencing. A total of 325,429,240 high quality reads were obtained and assembled into 395,561 transcripts and 92,463 unigenes. Functional annotation showed that 38,724 unigenes had sequence similarity to known genes in at least one of the proteins or nucleotide databases used in this study. These 38,724 unigenes were categorized into 51 functional groups based on Gene Ontology classification and were blasted to 24 known cluster of orthologous groups. A total of 973 identified unigenes belonged to 57 transcription factor families, including the stress-related HSF, DREB, ZNF, and NAC genes. Photosynthesis was significantly enriched in the Kyoto Encyclopedia of Genes and Genomes pathway, and the changed expression pattern was illustrated. The key pathways and signaling components that contribute to heat tolerance in rhododendron were revealed. These results provide a potentially valuable resource that can be used for heat-tolerance breeding. PMID:29059200
Identifying domestic and international sex-trafficking victims during human service provision.

Science.gov (United States)

Macy, Rebecca J; Graham, Laurie M

2012-04-01

Children, youth, and adults of both genders are sex trafficked into and throughout the United States every day. Regrettably, little attention has been given to how human service providers might identify the sex-trafficking victims they are likely to encounter. To address this knowledge gap, the authors review 20 documents with the aim of detecting and synthesizing service identification recommendations in the scientific literature, government reports, and documents produced by organizations working with sex-trafficking victims. The review shows consensus regarding identification recommendations, including (a) trafficking indicators, (b) victim interaction strategies, (c) immediate response strategies, and (d) child-specific information. The review also shows consensus regarding screening questions that are important for service providers to use in identifying sex-trafficking victims. These questions relate to the victims' safety, employment, living environment, and travel and immigration status in addition to specific questions used with children and youth. The review results offer human service providers a preliminary set of screening strategies and questions that can be used to identify sex-trafficking victims in the context of human services. Building on the review findings, the authors offer policy and research recommendations.
Identifying content for simulation-based curricula in urology: a national needs assessment.

Science.gov (United States)

Nayahangan, Leizl Joy; Bølling Hansen, Rikke; Gilboe Lindorff-Larsen, Karen; Paltved, Charlotte; Nielsen, Bjørn Ulrik; Konge, Lars

2017-12-01

Simulation-based training is well recognized in the transforming field of urological surgery; however, integration into the curriculum is often unstructured. Development of simulation-based curricula should follow a stepwise approach starting with a needs assessment. This study aimed to identify technical procedures in urology that should be included in a simulation-based curriculum for residency training. A national needs assessment was performed using the Delphi method involving 56 experts with significant roles in the education of urologists. Round 1 identified technical procedures that newly qualified urologists should perform. Round 2 included a survey using an established needs assessment formula to explore: the frequency of procedures; the number of physicians who should be able to perform the procedure; the risk and/or discomfort to patients when a procedure is performed by an inexperienced physician; and the feasibility of simulation training. Round 3 involved elimination and reranking of procedures according to priority. The response rates for the three Delphi rounds were 70%, 55% and 67%, respectively. The 34 procedures identified in Round 1 were reduced to a final prioritized list of 18 technical procedures for simulation-based training. The five procedures that reached the highest prioritization were cystoscopy, transrectal ultrasound-guided biopsy of the prostate, placement of ureteral stent, insertion of urethral and suprapubic catheter, and transurethral resection of the bladder. The prioritized list of technical procedures in urology that were identified as highly suitable for simulation can be used as an aid in the planning and development of simulation-based training programs.
Effectiveness of Tuned Mass Dampers in Seismic Response Control of Isolated Bridges Including Soil-Structure Interaction

Directory of Open Access Journals (Sweden)

Said Elias

Full Text Available Abstract The effect of soil-structure interaction (SSI on the dynamic responses of seismically isolated three-span continuous reinforced concrete (RC bridge is investigated. Also, tuned mass damper(s (TMD/s is/are installed to control undesirable bearing displacement, even under the SSI effect. The TMDs are placed at the mid-span of the bridge and each tuned with a modal frequency, while controlling up to first few modes as desirable. The soil surrounding the foundation of pier is modeled by frequency independent coefficients. Dynamic analysis is carried out in time domain using direct integration method. In order to specify the effects of the SSI, the responses of the non-isolated, isolated, and controlled isolated bridge are compared. It is observed that the soil surrounding the pier has significant effects on the bearing displacement of the isolated RC bridges. In addition, it is observed that the seismic responses of isolated RC bridge reduced significantly with installation of the TMDs.
The case of cholera preparedness, response and prevention in the ...

African Journals Online (AJOL)

In this paper the authors seek to identify the most appropriate model for a regional co-ordination mechanism for cholera preparedness, response and prevention. The qualitative mixed-method data collection approach that was followed revealed the need for alternative solutions, including a socio-political understanding of ...
Comparison study of time history and response spectrum responses for multiply supported piping systems

International Nuclear Information System (INIS)

Wang, Y.K.; Subudhi, M.; Bezler, P.

1983-01-01

In the past decade, several investigators have studied the problem of independent support excitation of a multiply supported piping system to identify the real need for such an analysis. This approach offers an increase in accuracy at a small increase in computational costs. To assess the method, studies based on the response spectrum approach using independent support motions for each group of commonly connected supports were performed. The results obtained from this approach were compared with the conventional envelope spectrum and time history solutions. The present study includes a mathematical formulation of the independent support motion analysis method suitable for implementation into an existing all purpose piping code PSAFE2 and a comparison of the solutions for some typical piping system using both Time History and Response Spectrum Methods. The results obtained from the Response Spectrum Methods represent the upper bound solution at most points in the piping system. Similarly, the Seismic Anchor Movement analysis based on the SRP method over predicts the responses near the support points and under predicts at points away from the supports
Straight but Not Narrow; Within-Gender Variation in the Gender-Specificity of Women's Sexual Response.

Science.gov (United States)

Chivers, Meredith L; Bouchard, Katrina N; Timmers, Amanda D

2015-01-01

Gender differences in the specificity of sexual response have been a primary focus in sexual psychophysiology research, however, within-gender variability suggests sexual orientation moderates category-specific responding among women; only heterosexual women show gender-nonspecific genital responses to sexual stimuli depicting men and women. But heterosexually-identified or "straight" women are heterogeneous in their sexual attractions and include women who are exclusively androphilic (sexually attracted to men) and women who are predominantly androphilic with concurrent gynephilia (sexually attracted to women). It is therefore unclear if gender-nonspecific responding is found in both exclusively and predominantly androphilic women. The current studies investigated within-gender variability in the gender-specificity of women's sexual response. Two samples of women reporting concurrent andro/gynephilia viewed (Study 1, n = 29) or listened (Study 2, n = 30) to erotic stimuli varying by gender of sexual partner depicted while their genital and subjective sexual responses were assessed. Data were combined with larger datasets of predominantly gyne- and androphilic women (total N = 78 for both studies). In both studies, women reporting any degree of gynephilia, including those who self-identified as heterosexual, showed significantly greater genital response to female stimuli, similar to predominantly gynephilic women; gender-nonspecific genital response was observed for exclusively androphilic women only. Subjective sexual arousal patterns were more variable with respect to sexual attractions, likely reflecting stimulus intensity effects. Heterosexually-identified women are therefore not a homogenous group with respect to sexual responses to gender cues. Implications for within-gender variation in women's sexual orientation and sexual responses are discussed.
Identifying the core competencies of mental health telephone triage.

Science.gov (United States)

Sands, Natisha; Elsom, Stephen; Gerdtz, Marie; Henderson, Kathryn; Keppich-Arnold, Sandra; Droste, Nicolas; Prematunga, Roshani K; Wereta, Zewdu W

2013-11-01

The primary aim of this study was to identify the core competencies of mental health telephone triage, including key role tasks, skills, knowledge and responsibilities, in which clinicians are required to be competent to perform safe and effective triage. Recent global trends indicate an increased reliance on telephone-based health services to facilitate access to health care across large populations. The trend towards telephone-based health services has also extended to mental health settings, evidenced by the growing number of mental health telephone triage services providing 24-hour access to specialist mental health assessment and treatment. Mental health telephone triage services are critical to the early identification of mental health problems and the provision of timely, appropriate interventions. In spite of the rapid growth in mental health telephone triage and the important role these services play in the assessment and management of mental illness and related risks, there has been very little research investigating this area of practice. An observational design was employed to address the research aims. Structured observations (using dual wireless headphones) were undertaken on 197 occasions of mental health telephone triage over a three-month period from January to March 2011. The research identified seven core areas of mental health telephone triage practice in which clinicians are required to be competent in to perform effective mental health telephone triage, including opening the call; performing mental status examination; risk assessment; planning and action; termination of call; referral and reporting; and documentation. The findings of this research contribute to the evidence base for mental health telephone triage by articulating the core competencies for practice. The mental health telephone triage competencies identified in this research may be used to define an evidence-based framework for mental health telephone triage practice that aims to
Omics Approaches for Identifying Physiological Adaptations to Genome Instability in Aging.

Science.gov (United States)

Edifizi, Diletta; Schumacher, Björn

2017-11-04

DNA damage causally contributes to aging and age-related diseases. The declining functioning of tissues and organs during aging can lead to the increased risk of succumbing to aging-associated diseases. Congenital syndromes that are caused by heritable mutations in DNA repair pathways lead to cancer susceptibility and accelerated aging, thus underlining the importance of genome maintenance for withstanding aging. High-throughput mass-spectrometry-based approaches have recently contributed to identifying signalling response networks and gaining a more comprehensive understanding of the physiological adaptations occurring upon unrepaired DNA damage. The insulin-like signalling pathway has been implicated in a DNA damage response (DDR) network that includes epidermal growth factor (EGF)-, AMP-activated protein kinases (AMPK)- and the target of rapamycin (TOR)-like signalling pathways, which are known regulators of growth, metabolism, and stress responses. The same pathways, together with the autophagy-mediated proteostatic response and the decline in energy metabolism have also been found to be similarly regulated during natural aging, suggesting striking parallels in the physiological adaptation upon persistent DNA damage due to DNA repair defects and long-term low-level DNA damage accumulation occurring during natural aging. These insights will be an important starting point to study the interplay between signalling networks involved in progeroid syndromes that are caused by DNA repair deficiencies and to gain new understanding of the consequences of DNA damage in the aging process.
Identifying psychological contract breaches to guide improvements in faculty recruitment, retention, and development.

Science.gov (United States)

Peirce, Gretchen L; Desselle, Shane P; Draugalis, JoLaine R; Spies, Alan R; Davis, Tamra S; Bolino, Mark

2012-08-10

To identify pharmacy faculty members' perceptions of psychological contract breaches that can be used to guide improvements in faculty recruitment, retention, and development. A list of psychological contract breaches was developed using a Delphi procedure involving a panel of experts assembled through purposive sampling. The Delphi consisted of 4 rounds, the first of which elicited examples of psychological contract breaches in an open-ended format. The ensuing 3 rounds consisting of a survey and anonymous feedback on aggregated group responses. Usable responses were obtained from 11 of 12 faculty members who completed the Delphi procedure. The final list of psychological contract breaches included 27 items, after modifications based on participant feedback in subsequent rounds. The psychological contract breach items generated in this study provide guidance for colleges and schools of pharmacy regarding important aspects of faculty recruitment, retention, and development.
Hospital to Post-Acute Care Facility Transfers: Identifying Targets for Information Exchange Quality Improvement.

Science.gov (United States)

Jones, Christine D; Cumbler, Ethan; Honigman, Benjamin; Burke, Robert E; Boxer, Rebecca S; Levy, Cari; Coleman, Eric A; Wald, Heidi L

2017-01-01

Information exchange is critical to high-quality care transitions from hospitals to post-acute care (PAC) facilities. We conducted a survey to evaluate the completeness and timeliness of information transfer and communication between a tertiary-care academic hospital and its related PAC facilities. This was a cross-sectional Web-based 36-question survey of 110 PAC clinicians and staff representing 31 PAC facilities conducted between October and December 2013. We received responses from 71 of 110 individuals representing 29 of 31 facilities (65% and 94% response rates). We collapsed 4-point Likert responses into dichotomous variables to reflect completeness (sufficient vs insufficient) and timeliness (timely vs not timely) for information transfer and communication. Among respondents, 32% reported insufficient information about discharge medical conditions and management plan, and 83% reported at least occasionally encountering problems directly related to inadequate information from the hospital. Hospital clinician contact information was the most common insufficient domain. With respect to timeliness, 86% of respondents desired receipt of a discharge summary on or before the day of discharge, but only 58% reported receiving the summary within this time frame. Through free-text responses, several participants expressed the need for paper prescriptions for controlled pain medications to be sent with patients at the time of transfer. Staff and clinicians at PAC facilities perceive substantial deficits in content and timeliness of information exchange between the hospital and facilities. Such deficits are particularly relevant in the context of the increasing prevalence of bundled payments for care across settings as well as forthcoming readmissions penalties for PAC facilities. Targets identified for quality improvement include structuring discharge summary information to include information identified as deficient by respondents, completion of discharge summaries

STUDY OF THE PRESENCE OF THE CORPORATE SOCIAL RESPONSIBILITY CHIEF OFFICER IN BANKING SYSTEM

OpenAIRE

MIHAELA DUMITRASCU

2014-01-01

We present a study regarding the banking system from Romania with the aim to identify corporations that have a position of „Corporate Social Responsibility Cheif Officer” or „Corporate Social Responsibility Synonym: Citizenship/ Sustainability” included in the position title. To achieve this objective, we present some preliminary findings. Our first hypothesis was that there are a number of positions of Chief Officers of Corporate Social Responsibility in banking system. After...
Electrophysiological and biochemical studies of slow responses to serotonin and dopamine of snail identified neurons. Mediating role of the cyclic AMP

International Nuclear Information System (INIS)

Deterre, Philippe

1983-01-01

In this research thesis, the electrophysiological study of slow incoming currents induced in some identified neurons of the Helix aspersa snail by serotonin and dopamine shows that they are associated with a decrease of a potassium conductance involved in the modulation of the action potential duration. By means of enzymatic tests performed on a single cell, and of electrophysiological experiments, the author shows that the cyclic AMP is an intracellular mediator involved in the genesis of these slow responses. Moreover, the obtained results show that serotonin and dopamine act by binding to specific receptors, and that these receptors activate the adenylate-cyclase through a GTP binding protein [fr
Lessons from the domestic Ebola response: Improving health care system resilience to high consequence infectious diseases.

Science.gov (United States)

Meyer, Diane; Kirk Sell, Tara; Schoch-Spana, Monica; Shearer, Matthew P; Chandler, Hannah; Thomas, Erin; Rose, Dale A; Carbone, Eric G; Toner, Eric

2018-05-01

The domestic response to the West Africa Ebola virus disease (EVD) epidemic from 2014-2016 provides a unique opportunity to distill lessons learned about health sector planning and operations from those individuals directly involved. This research project aimed to identify and integrate these lessons into an actionable checklist that can improve health sector resilience to future high-consequence infectious disease (HCID) events. Interviews (N = 73) were completed with individuals involved in the domestic EVD response in 4 cities (Atlanta, Dallas, New York, and Omaha), and included individuals who worked in academia, emergency management, government, health care, law, media, and public health during the response. Interviews were transcribed and analyzed qualitatively. Two focus groups were then conducted to expand on themes identified in the interviews. Using these themes, an evidence-informed checklist was developed and vetted for completeness and feasibility by an expert advisory group. Salient themes identified included health care facility issues-specifically identifying assessment and treatment hospitals, isolation and treatment unit layout, waste management, community relations, patient identification, patient isolation, limitations on treatment, laboratories, and research considerations-and health care workforce issues-specifically psychosocial impact, unit staffing, staff training, and proper personal protective equipment. The experiences of those involved in the domestic Ebola response provide critical lessons that can help strengthen resilience of health care systems and improve future responses to HCID events. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.
Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysis

Science.gov (United States)

Malhotra, Deepti; Portales-Casamar, Elodie; Singh, Anju; Srivastava, Siddhartha; Arenillas, David; Happel, Christine; Shyr, Casper; Wakabayashi, Nobunao; Kensler, Thomas W.; Wasserman, Wyeth W.; Biswal, Shyam

2010-01-01

The Nrf2 (nuclear factor E2 p45-related factor 2) transcription factor responds to diverse oxidative and electrophilic environmental stresses by circumventing repression by Keap1, translocating to the nucleus, and activating cytoprotective genes. Nrf2 responses provide protection against chemical carcinogenesis, chronic inflammation, neurodegeneration, emphysema, asthma and sepsis in murine models. Nrf2 regulates the expression of a plethora of genes that detoxify oxidants and electrophiles and repair or remove damaged macromolecules, such as through proteasomal processing. However, many direct targets of Nrf2 remain undefined. Here, mouse embryonic fibroblasts (MEF) with either constitutive nuclear accumulation (Keap1−/−) or depletion (Nrf2−/−) of Nrf2 were utilized to perform chromatin-immunoprecipitation with parallel sequencing (ChIP-Seq) and global transcription profiling. This unique Nrf2 ChIP-Seq dataset is highly enriched for Nrf2-binding motifs. Integrating ChIP-Seq and microarray analyses, we identified 645 basal and 654 inducible direct targets of Nrf2, with 244 genes at the intersection. Modulated pathways in stress response and cell proliferation distinguish the inducible and basal programs. Results were confirmed in an in vivo stress model of cigarette smoke-exposed mice. This study reveals global circuitry of the Nrf2 stress response emphasizing Nrf2 as a central node in cell survival response. PMID:20460467
Physiological genomics of response to soil drying in diverse Arabidopsis accessions.

Science.gov (United States)

Des Marais, David L; McKay, John K; Richards, James H; Sen, Saunak; Wayne, Tierney; Juenger, Thomas E

2012-03-01

Arabidopsis thaliana, like many species, is characterized by abundant genetic variation. This variation is rapidly being cataloged at the sequence level, but careful dissection of genetic variation in whole-organism responses to stresses encountered in the natural environment are lacking; this functional variation can be exploited as a natural mutant screen to determine gene function. Here, we document physiological and transcriptomic response to soil drying in 17 natural accessions of Arabidopsis. By imposing ecologically realistic stress conditions, we found that acclimation in Arabidopsis involved a strong signature of increased investment in photosynthesis, carbohydrate turnover, and root growth. Our results extend previous work in the Columbia accession suggesting that abscisic acid signaling pathways play an important role in drought stress response. We also identified several mechanisms, including an increase in leaf nitrogen concentration and upregulation of two-component signaling relays, that were common to most natural accessions but had not been identified in studies using only the Columbia accession. Principal component analysis reveals strong correlations between suites of genes and specific physiological responses to stress. The functional variants we identified may represent adaptive mutations in natural habitats and useful variants for agronomic improvement of crop species.
Building resilience into practical conservation: identifying local management responses to global climate change in the southern Great Barrier Reef

Science.gov (United States)

Maynard, J. A.; Marshall, P. A.; Johnson, J. E.; Harman, S.

2010-06-01

Climate change is now considered the greatest long-term threat to coral reefs, with some future change inevitable despite mitigation efforts. Managers must therefore focus on supporting the natural resilience of reefs, requiring that resilient reefs and reef regions be identified. We develop a framework for assessing resilience and trial it by applying the framework to target management responses to climate change on the southern Great Barrier Reef. The framework generates a resilience score for a site based on the evaluation of 19 differentially weighted indicators known or thought to confer resilience to coral reefs. Scores are summed, and sites within a region are ranked in terms of (1) their resilience relative to the other sites being assessed, and (2) the extent to which managers can influence their resilience. The framework was applied to 31 sites in Keppel Bay of the southern Great Barrier Reef, which has a long history of disturbance and recovery. Resilience and ‘management influence potential’ were both found to vary widely in Keppel Bay, informing site selection for the staged implementation of resilience-based management strategies. The assessment framework represents a step towards making the concept of resilience operational to reef managers and conservationists. Also, it is customisable, easy to teach and implement and effective in building support among local communities and stakeholders for management responses to climate change.
Emergency response packaging: A conceptual outline

International Nuclear Information System (INIS)

Luna, R.E.; McClure, J.D.; Bennett, P.C.; Wheeler, T.A.

1992-01-01

The Packaging and Transportation Needs in the 1990's (PATN) component of the Transportation Assessment and Integration (TRAIN) program (DOE Nov. 1991) was designed to survey United States Department of Energy programs, both ongoing and planned, to identify needs for packaging and transportation services over the next decade. PATN also identified transportation elements that should be developed by the DOE Office of Environmental Restoration and Waste Management (DOE EM) Transportation Management Program (TMP). As a result of the predominant involvement of the TMP in radioactive material shipment issues and DOE EM's involvement with waste management issues, the primary focus of PATN was on waste packaging issues. Pending DOE regulations will formalize federal guidelines and regulations for transportation of hazardous and radioactive materials within the boundaries of DOE reservations and facilities and reflect a growing awareness of concern regarding safety environmental responsibility activities on DOE reservations. Future practices involving the transportation of radioactive material within DOE reservations will closely parallel those used for commercial and governmental transportation across the United States. This has added to the perceived need for emergency recovery packaging and emergency response features on primary packaging, for both on-site shipments and shipments between DOE facilities (off-site). Historically, emergency response and recovery functions of packaging have not been adequately considered in packaging design and construction concepts. This paper develops the rationale for emergency response packaging, including both overpack concepts for repackaging compromised packaging and primary packaging redesign to facilitate the recovery of packages via mobile remote handling equipment. The rationale will examine concepts for determination of likely use patterns to identify types of shipments where recovery packaging may have the most favorable payoff
ORCID: Author Identifiers for Librarians

Directory of Open Access Journals (Sweden)

Robyn B. Reed

2017-10-01

Full Text Available Generating accurate publication lists by researchers can be challenging when faced with scholars who have common names or who have published under name variations. This article describes ORCID and the goal of generating author identifiers for scholars to connect their research outputs. Included are the reasons for having author identifiers as well as the types of information within individual profiles. This article includes information on how academic libraries are playing a role with ORCID initiatives as well as describing how publishers, institutions, and funders are employing ORCID in their workflows. Highlighted is material on academic institutions in Pennsylvania using ORCID. The purpose of the article is to provide an overview of ORCID and its uses to inform librarians about this important initiative.
Global miRNA expression analysis of serous and clear cell ovarian carcinomas identifies differentially expressed miRNAs including miR-200c-3p as a prognostic marker

International Nuclear Information System (INIS)

Vilming Elgaaen, Bente; Olstad, Ole Kristoffer; Haug, Kari Bente Foss; Brusletto, Berit; Sandvik, Leiv; Staff, Anne Cathrine; Gautvik, Kaare M; Davidson, Ben

2014-01-01

Improved insight into the molecular characteristics of the different ovarian cancer subgroups is needed for developing a more individualized and optimized treatment regimen. The aim of this study was to a) identify differentially expressed miRNAs in high-grade serous ovarian carcinoma (HGSC), clear cell ovarian carcinoma (CCC) and ovarian surface epithelium (OSE), b) evaluate selected miRNAs for association with clinical parameters including survival and c) map miRNA-mRNA interactions. Differences in miRNA expression between HGSC, CCC and OSE were analyzed by global miRNA expression profiling (Affymetrix GeneChip miRNA 2.0 Arrays, n = 12, 9 and 9, respectively), validated by RT-qPCR (n = 35, 19 and 9, respectively), and evaluated for associations with clinical parameters. For HGSC, differentially expressed miRNAs were linked to differentially expressed mRNAs identified previously. Differentially expressed miRNAs (n = 78) between HGSC, CCC and OSE were identified (FDR < 0.01%), of which 18 were validated (p < 0.01) using RT-qPCR in an extended cohort. Compared with OSE, miR-205-5p was the most overexpressed miRNA in HGSC. miR-200 family members and miR-182-5p were the most overexpressed in HGSC and CCC compared with OSE, whereas miR-383 was the most underexpressed. miR-205-5p and miR-200 members target epithelial-mesenchymal transition (EMT) regulators, apparently being important in tumor progression. miR-509-3-5p, miR-509-5p, miR-509-3p and miR-510 were among the strongest differentiators between HGSC and CCC, all being significantly overexpressed in CCC compared with HGSC. High miR-200c-3p expression was associated with poor progression-free (p = 0.031) and overall (p = 0.026) survival in HGSC patients. Interacting miRNA and mRNA targets, including those of a TP53-related pathway presented previously, were identified in HGSC. Several miRNAs differentially expressed between HGSC, CCC and OSE have been identified, suggesting a carcinogenetic role for these mi
Mouse preimplantation embryo responses to culture medium osmolarity include increased expression of CCM2 and p38 MAPK activation

Directory of Open Access Journals (Sweden)

Watson Andrew J

2007-01-01

Full Text Available Abstract Background Mechanisms that confer an ability to respond positively to environmental osmolarity are fundamental to ensuring embryo survival during the preimplantation period. Activation of p38 mitogen-activated protein kinase (MAPK occurs following exposure to hyperosmotic treatment. Recently, a novel scaffolding protein called Osmosensing Scaffold for MEKK3 (OSM was linked to p38 MAPK activation in response to sorbitol-induced hypertonicity. The human ortholog of OSM is cerebral cavernous malformation 2 (CCM2. The present study was conducted to investigate whether CCM2 is expressed during mouse preimplantation development and to determine whether this scaffolding protein is associated with p38 MAPK activation following exposure of preimplantation embryos to hyperosmotic environments. Results Our results indicate that Ccm2 along with upstream p38 MAPK pathway constituents (Map3k3, Map2k3, Map2k6, and Map2k4 are expressed throughout mouse preimplantation development. CCM2, MAP3K3 and the phosphorylated forms of MAP2K3/MAP2K6 and MAP2K4 were also detected throughout preimplantation development. Embryo culture in hyperosmotic media increased p38 MAPK activity in conjunction with elevated CCM2 levels. Conclusion These results define the expression of upstream activators of p38 MAPK during preimplantation development and indicate that embryo responses to hyperosmotic environments include elevation of CCM2 and activation of p38 MAPK.
Ethical responsibilities in nursing: research findings and issues.

Science.gov (United States)

Cassidy, V R

1991-01-01

Discussions in the literature assert that nurses are becoming increasingly cognizant of their ethical responsibilities, but that they are often ill prepared to participate in ethical decision making. A review of selected research literature from 1970 to 1987 was undertaken to validate these assertions. A total of 12 studies related to ethical responsibilities was identified in the review; all studies were published between 1980 and 1987. The majority of studies were at the descriptive and exploratory levels and employed Kohlberg's cognitive theory of moral development as their conceptual framework. Significant findings related to educational level and ethical responsibilities were consistent across studies. Findings related to age and clinical experience were mixed; the effects of economic level, religion-religiosity, ethnicity, and other variables on ethical responsibilities were not significant. Issues raised in the light of the existing research include the use of Kohlberg's theory as a conceptual orientation in nursing groups and limited data on the reliability and validity of instruments used in measuring ethical constructs. Recommendations for future research on ethical responsibilities include the validation of Kohlberg's theory for nursing investigations, exploration of other frameworks for developing a multidimensional view of ethical responsibilities, and the use of qualitative research designs.
A framework to identify gene expression profiles in a model of inflammation induced by lipopolysaccharide after treatment with thalidomide

Directory of Open Access Journals (Sweden)

Paiva Renata T

2012-06-01

Full Text Available Abstract Background Thalidomide is an anti-inflammatory and anti-angiogenic drug currently used for the treatment of several diseases, including erythema nodosum leprosum, which occurs in patients with lepromatous leprosy. In this research, we use DNA microarray analysis to identify the impact of thalidomide on gene expression responses in human cells after lipopolysaccharide (LPS stimulation. We employed a two-stage framework. Initially, we identified 1584 altered genes in response to LPS. Modulation of this set of genes was then analyzed in the LPS stimulated cells treated with thalidomide. Results We identified 64 genes with altered expression induced by thalidomide using the rank product method. In addition, the lists of up-regulated and down-regulated genes were investigated by means of bioinformatics functional analysis, which allowed for the identification of biological processes affected by thalidomide. Confirmatory analysis was done in five of the identified genes using real time PCR. Conclusions The results showed some genes that can further our understanding of the biological mechanisms in the action of thalidomide. Of the five genes evaluated with real time PCR, three were down regulated and two were up regulated confirming the initial results of the microarray analysis.
Simulation of spatially varying ground motions including incoherence, wave‐passage and differential site‐response effects

DEFF Research Database (Denmark)

Konakli, Katerina; Der Kiureghian, Armen

2012-01-01

A method is presented for simulating arrays of spatially varying ground motions, incorporating the effects of incoherence, wave passage, and differential site response. Non‐stationarity is accounted for by considering the motions as consisting of stationary segments. Two approaches are developed....
Extending Vulnerability Assessment to Include Life Stages Considerations.

Science.gov (United States)

Hodgson, Emma E; Essington, Timothy E; Kaplan, Isaac C

2016-01-01

Species are experiencing a suite of novel stressors from anthropogenic activities that have impacts at multiple scales. Vulnerability assessment is one tool to evaluate the likely impacts that these stressors pose to species so that high-vulnerability cases can be identified and prioritized for monitoring, protection, or mitigation. Commonly used semi-quantitative methods lack a framework to explicitly account for differences in exposure to stressors and organism responses across life stages. Here we propose a modification to commonly used spatial vulnerability assessment methods that includes such an approach, using ocean acidification in the California Current as an illustrative case study. Life stage considerations were included by assessing vulnerability of each life stage to ocean acidification and were used to estimate population vulnerability in two ways. We set population vulnerability equal to: (1) the maximum stage vulnerability and (2) a weighted mean across all stages, with weights calculated using Lefkovitch matrix models. Vulnerability was found to vary across life stages for the six species explored in this case study: two krill-Euphausia pacifica and Thysanoessa spinifera, pteropod-Limacina helicina, pink shrimp-Pandalus jordani, Dungeness crab-Metacarcinus magister and Pacific hake-Merluccius productus. The maximum vulnerability estimates ranged from larval to subadult and adult stages with no consistent stage having maximum vulnerability across species. Similarly, integrated vulnerability metrics varied greatly across species. A comparison showed that some species had vulnerabilities that were similar between the two metrics, while other species' vulnerabilities varied substantially between the two metrics. These differences primarily resulted from cases where the most vulnerable stage had a low relative weight. We compare these methods and explore circumstances where each method may be appropriate.
Crossing Thresholds: Identifying conceptual transitions in postsecondary teaching

Directory of Open Access Journals (Sweden)

Susan Wilcox

2013-12-01

Full Text Available In this paper we report on research we conducted to begin the process of identifying threshold concepts in the field of postsecondary teaching. Meyer & Land (2006 propose that within all disciplinary fields there seem to be particular threshold concepts that serve as gateways, opening up new and previously inaccessible ways of thinking and practicing. We developed a series of questions focusing on the “troublesome” and “transformative” characteristics of threshold concepts and asked these questions of several constituent groups, including those who are new to practice and the body of knowledge in postsecondary teaching and those who are already knowledgeable and/or experienced in the field. Based on our interpretation of participants’ responses, we identified four recognized concepts in the field of postsecondary teaching as potential threshold concepts in this field: Assessment for/as learning; Learning-centred teaching; Accommodation for diversity; and, Context-driven practice. Our findings suggest that threshold concepts are relevant to the field of postsecondary teaching. Through this work, we hope to help educational developers and faculty members consider what is involved in learning to teach and developing teaching expertise, and to encourage critical discussion about the teaching development “curriculum” in postsecondary settings. Threshold concepts arise as a field develops and are defined as practitioners and scholars in the field define their field. At this stage, we believe the real value of threshold concepts for postsecondary teaching lies in the discussion that arises in the process of identifying and naming the concepts.
Identifying patient-centred recommendations for improving patient safety in General Practices in England: a qualitative content analysis of free-text responses using the Patient Reported Experiences and Outcomes of Safety in Primary Care (PREOS-PC) questionnaire.

Science.gov (United States)

Ricci-Cabello, Ignacio; Saletti-Cuesta, Lorena; Slight, Sarah P; Valderas, Jose M

2017-10-01

There is a growing interest in identifying strategies to achieve safer primary health-care provision. However, most of the research conducted so far in this area relies on information supplied by health-care providers, and limited attention has been paid to patients' perspectives. To explore patients' experiences and perceptions of patient safety in English general practices with the aim of eliciting patient-centred recommendations for improving patient safety. The Patient Reported Experiences and Outcomes of Safety in Primary Care questionnaire was sent to a random sample of 6736 primary care users registered in 45 English practices. We conducted a qualitative content analysis of responses to seven open-ended items addressing patients' experiences of safety problems, lessons learnt as a result of such experiences and recommendations for safer health care. A total of 1244 (18.4%) participants returned completed questionnaires. Of those, 678 (54.5%) responded to at least one open-ended question. Two main themes emerged as follows: (i) experiences of safety problems and (ii) good practices and recommendations to improve patient safety in primary care. Most frequent experiences of safety problems were related to appointments, coordination between providers, tests, medication and diagnosis. Patients' responses to these problems included increased patient activation (eg speaking up about concerns with their health care) and avoidance of unnecessary health care. Recommendations for safer health care included improvements in patient-centred communication, continuity of care, timely appointments, technical quality of care, active monitoring, teamwork, health records and practice environment. This study identified a number of patient-centred recommendations for improving patient safety in English general practices. © 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.
Identifying Clusters with Mixture Models that Include Radial Velocity Observations

Science.gov (United States)

Czarnatowicz, Alexis; Ybarra, Jason E.

2018-01-01

The study of stellar clusters plays an integral role in the study of star formation. We present a cluster mixture model that considers radial velocity data in addition to spatial data. Maximum likelihood estimation through the Expectation-Maximization (EM) algorithm is used for parameter estimation. Our mixture model analysis can be used to distinguish adjacent or overlapping clusters, and estimate properties for each cluster.Work supported by awards from the Virginia Foundation for Independent Colleges (VFIC) Undergraduate Science Research Fellowship and The Research Experience @Bridgewater (TREB).
Straight but Not Narrow; Within-Gender Variation in the Gender-Specificity of Women’s Sexual Response

Science.gov (United States)

Chivers, Meredith L.; Bouchard, Katrina N.; Timmers, Amanda D.

2015-01-01

Gender differences in the specificity of sexual response have been a primary focus in sexual psychophysiology research, however, within-gender variability suggests sexual orientation moderates category-specific responding among women; only heterosexual women show gender-nonspecific genital responses to sexual stimuli depicting men and women. But heterosexually-identified or “straight” women are heterogeneous in their sexual attractions and include women who are exclusively androphilic (sexually attracted to men) and women who are predominantly androphilic with concurrent gynephilia (sexually attracted to women). It is therefore unclear if gender-nonspecific responding is found in both exclusively and predominantly androphilic women. The current studies investigated within-gender variability in the gender-specificity of women’s sexual response. Two samples of women reporting concurrent andro/gynephilia viewed (Study 1, n = 29) or listened (Study 2, n = 30) to erotic stimuli varying by gender of sexual partner depicted while their genital and subjective sexual responses were assessed. Data were combined with larger datasets of predominantly gyne- and androphilic women (total N = 78 for both studies). In both studies, women reporting any degree of gynephilia, including those who self-identified as heterosexual, showed significantly greater genital response to female stimuli, similar to predominantly gynephilic women; gender-nonspecific genital response was observed for exclusively androphilic women only. Subjective sexual arousal patterns were more variable with respect to sexual attractions, likely reflecting stimulus intensity effects. Heterosexually-identified women are therefore not a homogenous group with respect to sexual responses to gender cues. Implications for within-gender variation in women’s sexual orientation and sexual responses are discussed. PMID:26629910
Inflammatory response in laparoscopic vs. open surgery for gastric cancer

DEFF Research Database (Denmark)

Okholm, Cecilie; Goetze, Jens Peter; Svendsen, Lars Bo

2014-01-01

lead to an increased susceptibility to complications and morbidity. The aim of this review was to investigate if laparoscopic surgery reduces the immunological response compared to open surgery in gastric cancer. METHODS: We conducted a literature search identifying relevant studies comparing...... laparoscopy or laparoscopic-assisted surgery with open gastric surgery. The main outcome was postoperative immunological status defined as surgical stress parameters, including inflammatory cytokines and blood parameters. RESULTS: We identified seven studies that addressed the immunological status in patients...... laparotomy. Finally, most studies reported lower levels of white blood cell count in laparoscopic patients, although this result did not reach statistical significance in a small number of studies. CONCLUSIONS: Laparoscopy-assisted gastric surgery seems to attenuate the immune response compared to open...
Metabolome Integrated Analysis of High-Temperature Response in Pinus radiata

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Mónica Escandón

2018-04-01

Full Text Available The integrative omics approach is crucial to identify the molecular mechanisms underlying high-temperature response in non-model species. Based on future scenarios of heat increase, Pinus radiata plants were exposed to a temperature of 40°C for a period of 5 days, including recovered plants (30 days after last exposure to 40°C in the analysis. The analysis of the metabolome using complementary mass spectrometry techniques (GC-MS and LC-Orbitrap-MS allowed the reliable quantification of 2,287 metabolites. The analysis of identified metabolites and highlighter metabolic pathways across heat time exposure reveal the dynamism of the metabolome in relation to high-temperature response in P. radiata, identifying the existence of a turning point (on day 3 at which P. radiata plants changed from an initial stress response program (shorter-term response to an acclimation one (longer-term response. Furthermore, the integration of metabolome and physiological measurements, which cover from the photosynthetic state to hormonal profile, suggests a complex metabolic pathway interaction network related to heat-stress response. Cytokinins (CKs, fatty acid metabolism and flavonoid and terpenoid biosynthesis were revealed as the most important pathways involved in heat-stress response in P. radiata, with zeatin riboside (ZR and isopentenyl adenosine (iPA as the key hormones coordinating these multiple and complex interactions. On the other hand, the integrative approach allowed elucidation of crucial metabolic mechanisms involved in heat response in P. radiata, as well as the identification of thermotolerance metabolic biomarkers (L-phenylalanine, hexadecanoic acid, and dihydromyricetin, crucial metabolites which can reschedule the metabolic strategy to adapt to high temperature.

Simulated selection responses for breeding programs including resistance and resilience to parasites in Creole goats

NARCIS (Netherlands)

Gunia, M.; Phocas, F.; Gourdine, J.L.; Bijma, P.; Mandonnet, N.

2013-01-01

The Creole goat is a local breed used for meat production in Guadeloupe (French West Indies). As in other tropical countries, improvement of parasite resistance is needed. In this study, we compared predicted selection responses for alternative breeding programs with or without parasites resistance
Jasmonate-responsive transcription factors regulating plant secondary metabolism.

Science.gov (United States)

Zhou, Meiliang; Memelink, Johan

2016-01-01

Plants produce a large variety of secondary metabolites including alkaloids, glucosinolates, terpenoids and phenylpropanoids. These compounds play key roles in plant-environment interactions and many of them have pharmacological activity in humans. Jasmonates (JAs) are plant hormones which induce biosynthesis of many secondary metabolites. JAs-responsive transcription factors (TFs) that regulate the JAs-induced accumulation of secondary metabolites belong to different families including AP2/ERF, bHLH, MYB and WRKY. Here, we give an overview of the types and functions of TFs that have been identified in JAs-induced secondary metabolite biosynthesis, and highlight their similarities and differences in regulating various biosynthetic pathways. We review major recent developments regarding JAs-responsive TFs mediating secondary metabolite biosynthesis, and provide suggestions for further studies. Copyright © 2016 Elsevier Inc. All rights reserved.
Large-scale functional RNAi screen in C. elegans identifies genes that regulate the dysfunction of mutant polyglutamine neurons.

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Lejeune, François-Xavier; Mesrob, Lilia; Parmentier, Frédéric; Bicep, Cedric; Vazquez-Manrique, Rafael P; Parker, J Alex; Vert, Jean-Philippe; Tourette, Cendrine; Neri, Christian

2012-03-13

A central goal in Huntington's disease (HD) research is to identify and prioritize candidate targets for neuroprotective intervention, which requires genome-scale information on the modifiers of early-stage neuron injury in HD. Here, we performed a large-scale RNA interference screen in C. elegans strains that express N-terminal huntingtin (htt) in touch receptor neurons. These neurons control the response to light touch. Their function is strongly impaired by expanded polyglutamines (128Q) as shown by the nearly complete loss of touch response in adult animals, providing an in vivo model in which to manipulate the early phases of expanded-polyQ neurotoxicity. In total, 6034 genes were examined, revealing 662 gene inactivations that either reduce or aggravate defective touch response in 128Q animals. Several genes were previously implicated in HD or neurodegenerative disease, suggesting that this screen has effectively identified candidate targets for HD. Network-based analysis emphasized a subset of high-confidence modifier genes in pathways of interest in HD including metabolic, neurodevelopmental and pro-survival pathways. Finally, 49 modifiers of 128Q-neuron dysfunction that are dysregulated in the striatum of either R/2 or CHL2 HD mice, or both, were identified. Collectively, these results highlight the relevance to HD pathogenesis, providing novel information on the potential therapeutic targets for neuroprotection in HD. © 2012 Lejeune et al; licensee BioMed Central Ltd.
Hybridising Sport Education and Teaching for Personal and Social Responsibility to Include Students with Disabilities

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Menendez, Jose Ignacio; Fernandez-Rio, Javier

2017-01-01

The present study aimed to explore the impact of the combination of two pedagogical models, Sport Education and Teaching for Personal and Social Responsibility, for learners with disabilities experiencing a contactless kickboxing learning unit. Twelve secondary education students agreed to participate. Five had disabilities (intellectual and…
Epidemiological and Clinical Baseline Characteristics as Predictive Biomarkers of Response to Anti-VEGF Treatment in Patients with Neovascular AMD

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Miltiadis K. Tsilimbaris

2016-01-01

Full Text Available Purpose. To review the current literature investigating patient response to antivascular endothelial growth factor-A (VEGF therapy in the treatment of neovascular age-related macular degeneration (nAMD and to identify baseline characteristics that might predict response. Method. A literature search of the PubMed database was performed, using the keywords: AMD, anti-VEGF, biomarker, optical coherence tomography, treatment outcome, and predictor. The search was limited to articles published from 2006 to date. Exclusion criteria included phase 1 trials, case reports, studies focusing on indications other than nAMD, and oncology. Results. A total of 1467 articles were identified, of which 845 were excluded. Of the 622 remaining references, 47 met all the search criteria and were included in this review. Conclusion. Several baseline characteristics correlated with anti-VEGF treatment response, including best-corrected visual acuity, age, lesion size, and retinal thickness. The majority of factors were associated with disease duration, suggesting that longer disease duration before treatment results in worse treatment outcomes. This highlights the need for early treatment for patients with nAMD to gain optimal treatment outcomes. Many of the identified baseline characteristics are interconnected and cannot be evaluated in isolation; therefore multivariate analyses will be required to determine any specific relationship with treatment response.
Seismic response and fragility evaluation for an Eastern US NPP including soil-structure interaction effects

International Nuclear Information System (INIS)

Ghiocel, Dan M.; Wilson, Paul R.; Thomas, Gary G.; Stevenson, John D.

1998-01-01

The paper discusses methodological aspects involved in a probabilistic seismic soil-structure interaction (SSI) analysis for a Seismic Probabilistic Risk Assessment (SPRA) review. An example of an Eastern US nuclear power plant (NPP) is presented. The approach presented herein follows the current practice of the Individual Plant Examination for External Events (IPEEE) program in the US. The NPP is founded on a relatively soft soil deposit, and thus the SSI effects on seismic responses are significant. Probabilistic models used for the idealization of the seismic excitation and the surrounding soil deposit are described. Using a lognormal format, computed random variability effects were combined with those proposed in the SPRA methodology guidelines. Probabilistic floor response spectra and structural fragilities for different NPP buildings were computed. Structural capacities were determined following the current practice which assumes independent median safety factors for strength and inelastic absorption. Limitations of the IPEEE practice for performing SPRA are discussed and alternate procedures, more rigorous and simple to implement, are suggested
Playful hyper responsibility

DEFF Research Database (Denmark)

Knudsen, Hanne; Andersen, Niels Åkerstrøm

2014-01-01

Over the past 10–15 years, state-funded schools have begun to require parents to assume an undefined and infinite personal responsibility. In this article, we investigate how schools organize responsibility games to respond to this challenge and how these games affect the concept of responsibility....... We point to a dislocation in the way parents are assigned responsibility, because the definition of responsibility is not only a question of formulating rules or providing advice. We argue that what emerges is a kind of playful hyper responsibility that identifies responsibility as the participation...
Common Allergens Identified Based on Patch Test Results in Patients with Suspected Contact Dermatitis of the Scalp.

Science.gov (United States)

Aleid, Nouf M; Fertig, Raymond; Maddy, Austin; Tosti, Antonella

2017-03-01

Contact dermatitis of the scalp is common and might be caused by many chemicals including metals, ingredients of shampoos and conditioners, dyes, or other hair treatments. Eliciting a careful history and patch tests are necessary to identify the responsible allergen and prevent relapses. To identify allergens that may cause contact dermatitis of the scalp by reviewing patch test results. We reviewed the records of 1,015 patients referred for patch testing at the Dermatology Department of the University of Miami. A total of 226 patients (205 females and 21 males) with suspected scalp contact dermatitis were identified, and the patch test results and clinical data for those patients were analyzed. Most patients were referred for patch testing from a specialized hair clinic at our institution. The most common allergens in our study population were nickel (23.8%), cobalt (21.0%), balsam of Peru (18.2%), fragrance mix (14.4%), carba mix (11.6%), and propylene glycol (PG) (8.8%). The majority of patients were females aged 40-59 years, and scalp itching or burning were reported as the most common symptom. Frequent sources of allergens for metals include hair clasps, pins, and brushes, while frequent sources of allergens for preservatives, fragrance mix, and balsam of Peru include shampoos, conditioners, and hair gels. Frequent sources of allergens for PG include topical medications.
Common Allergens Identified Based on Patch Test Results in Patients with Suspected Contact Dermatitis of the Scalp

Science.gov (United States)

Aleid, Nouf M.; Fertig, Raymond; Maddy, Austin; Tosti, Antonella

2017-01-01

Background Contact dermatitis of the scalp is common and might be caused by many chemicals including metals, ingredients of shampoos and conditioners, dyes, or other hair treatments. Eliciting a careful history and patch tests are necessary to identify the responsible allergen and prevent relapses. Objectives To identify allergens that may cause contact dermatitis of the scalp by reviewing patch test results. Methods We reviewed the records of 1,015 patients referred for patch testing at the Dermatology Department of the University of Miami. A total of 226 patients (205 females and 21 males) with suspected scalp contact dermatitis were identified, and the patch test results and clinical data for those patients were analyzed. Most patients were referred for patch testing from a specialized hair clinic at our institution. Results The most common allergens in our study population were nickel (23.8%), cobalt (21.0%), balsam of Peru (18.2%), fragrance mix (14.4%), carba mix (11.6%), and propylene glycol (PG) (8.8%). The majority of patients were females aged 40–59 years, and scalp itching or burning were reported as the most common symptom. Conclusion Frequent sources of allergens for metals include hair clasps, pins, and brushes, while frequent sources of allergens for preservatives, fragrance mix, and balsam of Peru include shampoos, conditioners, and hair gels. Frequent sources of allergens for PG include topical medications. PMID:28611994
Probe train including a flaw detector and a radiation responsive recording means with alignment means having a natural curved cast

International Nuclear Information System (INIS)

Stone, R.M.

1975-01-01

An inspection system for a multitube steam generator comprising a probe train for insertion in a tube to be inspected is described. The probe train includes, in series, directional probe means, such as an eddy current probe, for indicating the longitudinal and angular location of an irregularity at or in the wall of the tube, and radiation responsive recording means nonrotatable relative to the eddy current probe during operation and in substantially close longitudinal relationship thereto for receiving an image of the irregularity when laterally adjacent thereto; elongated alignment means joined to at least one end of the probe train against rotation relative thereto and insertable in the tube for controlling or determining the angular orientation of the probe train within the tube; means for propelling the probe train longitudinally within the tube; and a source of radiation insertable in another tube of the steam generator to a position therealong laterally adjacent the indicated irregularity for irradiation of the irregularity to project said image on the recording means. The directional probe means may preferably be an eddy current probe and the radiation responsive recording means may preferably be a film bearing cassette probe. The alignment means may be provided by a resilient naturally curved plastic cable, which cable might also be used to propel the probe train. (auth)
Identifying management competencies for health care executives: review of a series of Delphi studies.

Science.gov (United States)

Hudak, R P; Brooke, P P; Finstuen, K

2000-01-01

This analysis reviews a selected body of research that identifies the essential areas of management expertise required of future health care executives. To ensure consistency, six studies are analyzed, utilizing the Delphi technique, to query a broad spectrum of experts in different fields and sites of health care management. The analysis identifies a number of management competencies, i.e., managerial capabilities, which current and aspiring health care executives, in various settings and with differing educational backgrounds, should possess to enhance the probability of their success in current and future positions of responsibility. In addition, this review identifies the skills (technical expertise), knowledge (facts and principles) and abilities (physical, mental or legal power) required to support achievement of these competencies. Leadership and resource management, including cost and finance dimensions, are the highest-rated requisite management competencies. The dominant skills, knowledge and abilities (SKAs) are related to interpersonal skills. The lowest-rated SKAs are related to job-specific, technical skills. Recommendations include the review of this research by formal and continuing education programs to determine the content of their courses and areas for future research. Similarly, current health care executives should assess this research to assist in identifying competency gaps. Lastly, this analysis recommends that the Delphi technique, as a valid and replicable methodology, be applied toward the study of non-executive health care managers, e.g., students, clinicians, mid-level managers and integrated systems administrators, to determine their requisite management competencies and SKAs.
An assessment of two methods for identifying undocumented levees using remotely sensed data

Science.gov (United States)

Czuba, Christiana R.; Williams, Byron K.; Westman, Jack; LeClaire, Keith

2015-01-01

Many undocumented and commonly unmaintained levees exist in the landscape complicating flood forecasting, risk management, and emergency response. This report describes a pilot study completed by the U.S. Geological Survey in cooperation with the U.S. Army Corps of Engineers to assess two methods to identify undocumented levees by using remotely sensed, high-resolution topographic data. For the first method, the U.S. Army Corps of Engineers examined hillshades computed from a digital elevation model that was derived from light detection and ranging (lidar) to visually identify potential levees and then used detailed site visits to assess the validity of the identifications. For the second method, the U.S. Geological Survey applied a wavelet transform to a lidar-derived digital elevation model to identify potential levees. The hillshade method was applied to Delano, Minnesota, and the wavelet-transform method was applied to Delano and Springfield, Minnesota. Both methods were successful in identifying levees but also identified other features that required interpretation to differentiate from levees such as constructed barriers, high banks, and bluffs. Both methods are complementary to each other, and a potential conjunctive method for testing in the future includes (1) use of the wavelet-transform method to rapidly identify slope-break features in high-resolution topographic data, (2) further examination of topographic data using hillshades and aerial photographs to classify features and map potential levees, and (3) a verification check of each identified potential levee with local officials and field visits.
Justification of response time testing requirements for pressure and differential pressure sensors

International Nuclear Information System (INIS)

Weiss, J.M.; Mayo, C.; Swisher, V.

1991-01-01

This paper reports on response time testing (RTT) requirements that were imposed on pressure, differential pressure sensors as a conservative approach to insure that assumptions in the plant safety analyses were met. The purpose of this project has been to identify the need for response time testing using the bases identified in IEEE Standard 338. A combination of plant data analyses, failure modes, and effects analyses (FMEAs) was performed. Eighteen currently qualified sensor models were utilized. The results of these analyses indicate that there are only two failure modes that affect response time, not sensor output concurrently. For these failure modes, appropriate plant actions and testing techniques were identified. Safety system RTT requirements were established by IEEE Standard 338-1975. Criteria for the Periodic Testing of Class IE Power, Protection Systems, presuming the need existed for this testing. This standard established guidelines for periodic testing to verify that loop response times of installed nuclear safety-related equipment were within the limits presumed by the design basis plant transient, accident analyses. The requirements covered all passive, active components in an instrument loop, including sensors. Individual components could be tested either in groups or separately to determine the overall loop response time
The Role of IL-33 in Host Response to Candida albicans

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C. Rodríguez-Cerdeira

2014-01-01

Full Text Available Background. Interleukin (IL 33 is a recently identified pleiotropic cytokine that influences the activity of multiple cell types and orchestrates complex innate and adaptive immune responses. Methods. We performed an extensive review of the literature published between 2005 and 2013 on IL-33 and related cytokines, their functions, and their regulation of the immune system following Candida albicans colonization. Our literature review included cross-references from retrieved articles and specific data from our own studies. Results. IL-33 (IL-1F11 is a recently identified member of the IL-1 family of cytokines. Accumulating evidence suggests a pivotal role of the IL-33/ST2 axis in host immune defense against fungal pathogens, including C. albicans. IL-33 induces a Th2-type inflammatory response and activates both innate and adaptive immunity. Studies in animal models have shown that Th2 inflammatory responses have a beneficial role in immunity against gastrointestinal and systemic infections by Candida spp. Conclusions. This review summarizes the most important clinical studies and case reports describing the beneficial role of IL-33 in immunity and host defense mechanisms against pathogenic fungi. The finding that the IL-33/ST2 axis is involved in therapeutic target has implications for the prevention and treatment of inflammatory diseases, including acute or chronic candidiasis.
SPARQL-enabled identifier conversion with Identifiers.org.

Science.gov (United States)

Wimalaratne, Sarala M; Bolleman, Jerven; Juty, Nick; Katayama, Toshiaki; Dumontier, Michel; Redaschi, Nicole; Le Novère, Nicolas; Hermjakob, Henning; Laibe, Camille

2015-06-01

On the semantic web, in life sciences in particular, data is often distributed via multiple resources. Each of these sources is likely to use their own International Resource Identifier for conceptually the same resource or database record. The lack of correspondence between identifiers introduces a barrier when executing federated SPARQL queries across life science data. We introduce a novel SPARQL-based service to enable on-the-fly integration of life science data. This service uses the identifier patterns defined in the Identifiers.org Registry to generate a plurality of identifier variants, which can then be used to match source identifiers with target identifiers. We demonstrate the utility of this identifier integration approach by answering queries across major producers of life science Linked Data. The SPARQL-based identifier conversion service is available without restriction at http://identifiers.org/services/sparql. © The Author 2015. Published by Oxford University Press.
SPARQL-enabled identifier conversion with Identifiers.org

Science.gov (United States)

Wimalaratne, Sarala M.; Bolleman, Jerven; Juty, Nick; Katayama, Toshiaki; Dumontier, Michel; Redaschi, Nicole; Le Novère, Nicolas; Hermjakob, Henning; Laibe, Camille

2015-01-01

Motivation: On the semantic web, in life sciences in particular, data is often distributed via multiple resources. Each of these sources is likely to use their own International Resource Identifier for conceptually the same resource or database record. The lack of correspondence between identifiers introduces a barrier when executing federated SPARQL queries across life science data. Results: We introduce a novel SPARQL-based service to enable on-the-fly integration of life science data. This service uses the identifier patterns defined in the Identifiers.org Registry to generate a plurality of identifier variants, which can then be used to match source identifiers with target identifiers. We demonstrate the utility of this identifier integration approach by answering queries across major producers of life science Linked Data. Availability and implementation: The SPARQL-based identifier conversion service is available without restriction at http://identifiers.org/services/sparql. Contact: sarala@ebi.ac.uk PMID:25638809
A Reply to ''Reinterpretation of Students' Ideas When Reasoning about Particle Model Illustrations. A Response to ''Using Animations in Identifying General Chemistry Students' Misconceptions and Evaluating Their Knowledge Transfer Relating to Particle Position in Physical Changes'' by Smith and Villarreal (2015)''

Science.gov (United States)

Smith, K. Christopher; Villarreal, Savannah

2015-01-01

In this reply to Elon Langbeheim's response to an article recently published in this journal, authors Smith and Villarreal identify several types of general chemistry students' misconceptions concerning the concept of particle position during physical change. They focus their response on one of the misconceptions identified as such: Given a solid…
Identifying indicators of illegal behaviour: carnivore killing in human-managed landscapes.

Science.gov (United States)

St John, Freya A V; Keane, Aidan M; Edwards-Jones, Gareth; Jones, Lauren; Yarnell, Richard W; Jones, Julia P G

2012-02-22

Managing natural resources often depends on influencing people's behaviour, however effectively targeting interventions to discourage environmentally harmful behaviours is challenging because those involved may be unwilling to identify themselves. Non-sensitive indicators of sensitive behaviours are therefore needed. Previous studies have investigated people's attitudes, assuming attitudes reflect behaviour. There has also been interest in using people's estimates of the proportion of their peers involved in sensitive behaviours to identify those involved, since people tend to assume that others behave like themselves. However, there has been little attempt to test the potential of such indicators. We use the randomized response technique (RRT), designed for investigating sensitive behaviours, to estimate the proportion of farmers in north-eastern South Africa killing carnivores, and use a modified logistic regression model to explore relationships between our best estimates of true behaviour (from RRT) and our proposed non-sensitive indicators (including farmers' attitudes, and estimates of peer-behaviour). Farmers' attitudes towards carnivores, question sensitivity and estimates of peers' behaviour, predict the likelihood of farmers killing carnivores. Attitude and estimates of peer-behaviour are useful indicators of involvement in illicit behaviours and may be used to identify groups of people to engage in interventions aimed at changing behaviour.
Stages of Formation of the Strategy of Social Responsibility of Business

Directory of Open Access Journals (Sweden)

Zatieyshchykova Olha O.

2014-02-01

Full Text Available The article studies existing approaches to formulation of stages of the strategy, according to which a list of stages of formation of the strategy of social responsibility (SSR is formed, including: identification of the mission and vision of SSR, formation of the system of goals of SSR, assessment of influence of factors of external environment, assessment of the level of social responsibility, analysis of alternatives and selection of strategies. The article identifies SSR mission for Ukrainian enterprises, which lies in increase of the quality of life of employees, local society and society in general. SSR vision – improvement of effectiveness of business and profitability indicators on the basis of creation of trustworthy relations between business, society and state. The article develops the goals tree of SSR that has goals of three levels. It identifies a list of factors of external environment, including: growing anxiety about the state of environment and demographic situation, level of education and culture, growing intensity of competition, level of income and wellbeing, active participation of the state policy in the use of principles of social responsibility, propaganda of social responsibility within the impact area, fast change of technologies, fair marketing practice, informing and executing agreements. The article offers to assess the level of social responsibility on the basis of calculation of indicators of social investments both by quantitative and qualitative methods and calculation of indicators of voluntary social responsibility of business. It also offers main components of the essence of the SSR strategy.
Child-Level Predictors of Responsiveness to Evidence-Based Mathematics Intervention.

Science.gov (United States)

Powell, Sarah R; Cirino, Paul T; Malone, Amelia S

2017-07-01

We identified child-level predictors of responsiveness to 2 types of mathematics (calculation and word-problem) intervention among 2nd-grade children with mathematics difficulty. Participants were 250 children in 107 classrooms in 23 schools pretested on mathematics and general cognitive measures and posttested on mathematics measures. We assigned classrooms randomly assigned to calculation intervention, word-problem intervention, or business-as-usual control. Intervention lasted 17 weeks. Path analyses indicated that scores on working memory and language comprehension assessments moderated responsiveness to calculation intervention. No moderators were identified for responsiveness to word-problem intervention. Across both intervention groups and the control group, attentive behavior predicted both outcomes. Initial calculation skill predicted the calculation outcome, and initial language comprehension predicted word-problem outcomes. These results indicate that screening for calculation intervention should include a focus on working memory, language comprehension, attentive behavior, and calculations. Screening for word-problem intervention should focus on attentive behavior and word problems.

Omics Approaches for Identifying Physiological Adaptations to Genome Instability in Aging

Directory of Open Access Journals (Sweden)

Diletta Edifizi

2017-11-01

Full Text Available DNA damage causally contributes to aging and age-related diseases. The declining functioning of tissues and organs during aging can lead to the increased risk of succumbing to aging-associated diseases. Congenital syndromes that are caused by heritable mutations in DNA repair pathways lead to cancer susceptibility and accelerated aging, thus underlining the importance of genome maintenance for withstanding aging. High-throughput mass-spectrometry-based approaches have recently contributed to identifying signalling response networks and gaining a more comprehensive understanding of the physiological adaptations occurring upon unrepaired DNA damage. The insulin-like signalling pathway has been implicated in a DNA damage response (DDR network that includes epidermal growth factor (EGF-, AMP-activated protein kinases (AMPK- and the target of rapamycin (TOR-like signalling pathways, which are known regulators of growth, metabolism, and stress responses. The same pathways, together with the autophagy-mediated proteostatic response and the decline in energy metabolism have also been found to be similarly regulated during natural aging, suggesting striking parallels in the physiological adaptation upon persistent DNA damage due to DNA repair defects and long-term low-level DNA damage accumulation occurring during natural aging. These insights will be an important starting point to study the interplay between signalling networks involved in progeroid syndromes that are caused by DNA repair deficiencies and to gain new understanding of the consequences of DNA damage in the aging process.
Survey indicated that core outcome set development is increasingly including patients, being conducted internationally and using Delphi surveys.

Science.gov (United States)

Biggane, Alice M; Brading, Lucy; Ravaud, Philippe; Young, Bridget; Williamson, Paula R

2018-02-17

There are numerous challenges in including patients in a core outcome set (COS) study, these can vary depending on the patient group. This study describes current efforts to include patients in the development of COS, with the aim of identifying areas for further improvement and study. Using the COMET database, corresponding authors of COS projects registered or published from 1 January 2013 to 2 February 2017 were invited via a personalised email to participate in a short online survey. The survey and emails were constructed to maximise the response rate by following the academic literature on enhancing survey responses. Personalised reminder emails were sent to non-responders. This survey explored the frequency of patient input in COS studies, who was involved, what methods were used and whether or not the COS development was international. One hundred and ninety-two COS developers were sent the survey. Responses were collected from 21 February 2017 until 7 May 2017. One hundred and forty-six unique developers responded, yielding a 76% response rate and data in relation to 195 unique COSs (as some developers had worked on multiple COSs). Of focus here are their responses regarding 162 COSs at the published, completed or ongoing stages of development. Inclusion of patient participants was indicated in 87% (141/162) of COSs in the published completed or ongoing stages and over 94% (65/69) of ongoing COS projects. Nearly half (65/135) of COSs included patient participants from two or more countries and 22% (30/135) included patient participants from five or more countries. The Delphi survey was reported as being used singularly or in combination with other methods in 85% (119/140) of projects. Almost a quarter (16/65) of ongoing studies reported using a combination of qualitative interviews, Delphi survey and consensus meeting. These findings indicated that the Delphi survey is the most popular method of facilitating patient participation, while the combination of
A protocol for a systematic review to identify allergenic tree nuts and the molecules responsible for their allergenic properties.

Science.gov (United States)

Javed, Bushra; Padfield, Philip; Sperrin, Matthew; Simpson, Angela; Mills, E N Clare

2017-08-01

Food regulations require that tree nuts and derived ingredients are included on food labels in order to help individuals with IgE-mediated allergies to avoid them. However, there is no consensus regarding which tree nut species should be included in this definition and specified on food labels. Allergen detection methods used for monitoring foods target allergen molecules, but it not clear which are the most relevant molecules to choose. A modified population-exposure-comparators-outcome (PECO) approach has been developed to systematically review the evidence regarding (1) which allergenic tree nuts should be included in food allergen labelling lists and (2) which are the clinically relevant allergens which should be used as analytical targets. A search strategy and criteria against which the evidence will be evaluated have been developed. The resulting evidence will be used to rank tree nuts with regards their ability to cause IgE-mediated allergies, and allergen molecules regarding their capacity to elicit an allergic reaction. The results of the systematic review will enable risk assessors and managers to identify tree nut species that should be included in food allergen labelling lists and ensure analytical methods for determination of allergens in foods are targeting appropriate molecules. Copyright © 2017. Published by Elsevier Ltd.
Unique genetic loci identified for emotional behavior in control and chronic stress conditions

OpenAIRE

Carhuatanta, Kimberly A. K.; Shea, Chloe J. A.; Herman, James P.; Jankord, Ryan

2014-01-01

An individual's genetic background affects their emotional behavior and response to stress. Although studies have been conducted to identify genetic predictors for emotional behavior or stress response, it remains unknown how prior stress history alters the interaction between an individual's genome and their emotional behavior. Therefore, the purpose of this study is to identify chromosomal regions that affect emotional behavior and are sensitive to stress exposure. We utilized the BXD behav...
Insights into salicylic acid responses in cucumber (Cucumis sativus L.) cotyledons based on a comparative proteomic analysis.

Science.gov (United States)

Hao, J H; Dong, C J; Zhang, Z G; Wang, X L; Shang, Q M

2012-05-01

To investigate the response of cucumber seedlings to exogenous salicylic acid (SA) and gain a better understanding of SA action mechanism, we generated a proteomic profile of cucumber (Cucumis sativus L.) cotyledons treated with exogenous SA. Analysis of 1500 protein spots from each gel revealed 63 differentially expressed proteins, 59 of which were identified successfully. Of the identified proteins, 97% matched cucumber proteins using a whole cucumber protein database based on the newly completed genome established by our laboratory. The identified proteins were involved in various cellular responses and metabolic processes, including antioxidative reactions, cell defense, photosynthesis, carbohydrate metabolism, respiration and energy homeostasis, protein folding and biosynthesis. The two largest functional categories included proteins involved in antioxidative reactions (23.7%) and photosynthesis (18.6%). Furthermore, the SA-responsive protein interaction network revealed 13 key proteins, suggesting that the expression changes of these proteins could be critical for SA-induced resistance. An analysis of these changes suggested that SA-induced resistance and seedling growth might be regulated in part through pathways involving antioxidative reactions and photosynthesis. © 2012 Elsevier Ireland Ltd. All rights reserved.
Reliability of estimating the room volume from a single room impulse response

OpenAIRE

Kuster, M.

2008-01-01

The methods investigated for the room volume estimation are based on geometrical acoustics, eigenmode, and diffuse field models and no data other than the room impulse response are available. The measurements include several receiver positions in a total of 12 rooms of vastly different sizes and acoustic characteristics. The limitations in identifying the pivotal specular reflections of the geometrical acoustics model in measured room impulse responses are examined both theoretically and expe...
How to include the variability of TMS responses in simulations: a speech mapping case study

Science.gov (United States)

De Geeter, N.; Lioumis, P.; Laakso, A.; Crevecoeur, G.; Dupré, L.

2016-11-01

When delivered over a specific cortical site, TMS can temporarily disrupt the ongoing process in that area. This allows mapping of speech-related areas for preoperative evaluation purposes. We numerically explore the observed variability of TMS responses during a speech mapping experiment performed with a neuronavigation system. We selected four cases with very small perturbations in coil position and orientation. In one case (E) a naming error occurred, while in the other cases (NEA, B, C) the subject appointed the images as smoothly as without TMS. A realistic anisotropic head model was constructed of the subject from T1-weighted and diffusion-weighted MRI. The induced electric field distributions were computed, associated to the coil parameters retrieved from the neuronavigation system. Finally, the membrane potentials along relevant white matter fibre tracts, extracted from DTI-based tractography, were computed using a compartmental cable equation. While only minor differences could be noticed between the induced electric field distributions of the four cases, computing the corresponding membrane potentials revealed different subsets of tracts were activated. A single tract was activated for all coil positions. Another tract was only triggered for case E. NEA induced action potentials in 13 tracts, while NEB stimulated 11 tracts and NEC one. The calculated results are certainly sensitive to the coil specifications, demonstrating the observed variability in this study. However, even though a tract connecting Broca’s with Wernicke’s area is only triggered for the error case, further research is needed on other study cases and on refining the neural model with synapses and network connections. Case- and subject-specific modelling that includes both electromagnetic fields and neuronal activity enables demonstration of the variability in TMS experiments and can capture the interaction with complex neural networks.
Comparative metatranscriptomics identifies molecular bases for the physiological responses of phytoplankton to varying iron availability.

Science.gov (United States)

Marchetti, Adrian; Schruth, David M; Durkin, Colleen A; Parker, Micaela S; Kodner, Robin B; Berthiaume, Chris T; Morales, Rhonda; Allen, Andrew E; Armbrust, E Virginia

2012-02-07

In vast expanses of the oceans, growth of large phytoplankton such as diatoms is limited by iron availability. Diatoms respond almost immediately to the delivery of iron and rapidly compose the majority of phytoplankton biomass. The molecular bases underlying the subsistence of diatoms in iron-poor waters and the plankton community dynamics that follow iron resupply remain largely unknown. Here we use comparative metatranscriptomics to identify changes in gene expression associated with iron-stimulated growth of diatoms and other eukaryotic plankton. A microcosm iron-enrichment experiment using mixed-layer waters from the northeastern Pacific Ocean resulted in increased proportions of diatom transcripts and reduced proportions of transcripts from most other taxa within 98 h after iron addition. Hundreds of diatom genes were differentially expressed in the iron-enriched community compared with the iron-limited community; transcripts of diatom genes required for synthesis of photosynthesis and chlorophyll components, nitrate assimilation and the urea cycle, and synthesis of carbohydrate storage compounds were significantly overrepresented. Transcripts of genes encoding rhodopsins in eukaryotic phytoplankton were significantly underrepresented following iron enrichment, suggesting rhodopsins help cells cope with low-iron conditions. Oceanic diatoms appear to display a distinctive transcriptional response to iron enrichment that allows chemical reduction of available nitrogen and carbon sources along with a continued dependence on iron-free photosynthetic proteins rather than substituting for iron-containing functional equivalents present within their gene repertoire. This ability of diatoms to divert their newly acquired iron toward nitrate assimilation may underlie why diatoms consistently dominate iron enrichments in high-nitrate, low-chlorophyll regions.
33 CFR 155.1050 - Response plan development and evaluation criteria for vessels carrying groups I through IV...

Science.gov (United States)

2010-07-01

... qualified individual; and (2) Within 30 minutes of a discovery of a discharge or substantial threat of... a discharge in advance of the arrival of response resources identified in the plan for tiers 1, 2... shoreline protection operations. (1) The response resources must include the quantities of boom listed in...
Reliability evaluation of containments including soil-structure interaction

International Nuclear Information System (INIS)

Pires, J.; Hwang, H.; Reich, M.

1985-12-01

Soil-structure interaction effects on the reliability assessment of containment structures are examined. The probability-based method for reliability evaluation of nuclear structures developed at Brookhaven National Laboratory is extended to include soil-structure interaction effects. In this method, reliability of structures is expressed in terms of limit state probabilities. Furthermore, random vibration theory is utilized to calculate limit state probabilities under random seismic loads. Earthquake ground motion is modeled by a segment of a zero-mean, stationary, filtered Gaussian white noise random process, represented by its power spectrum. All possible seismic hazards at a site, represented by a hazard curve, are also included in the analysis. The soil-foundation system is represented by a rigid surface foundation on an elastic halfspace. Random and other uncertainties in the strength properties of the structure, in the stiffness and internal damping of the soil, are also included in the analysis. Finally, a realistic reinforced concrete containment is analyzed to demonstrate the application of the method. For this containment, the soil-structure interaction effects on; (1) limit state probabilities, (2) structural fragility curves, (3) floor response spectra with probabilistic content, and (4) correlation coefficients for total acceleration response at specified structural locations, are examined in detail. 25 refs., 21 figs., 12 tabs
Expression of diverse neuropeptide cotransmitters by identified motor neurons in Aplysia

International Nuclear Information System (INIS)

Church, P.J.; Lloyd, P.E.

1991-01-01

Neuropeptide synthesis was determined for individual identified ventral-cluster neurons in the buccal ganglia of Aplysia. Each of these cells was shown to be a motor neuron that innervates buccal muscles that generate biting and swallowing movements during feeding. Individual neurons were identified by a battery of physiological criteria and stained with intracellular injection of a vital dye, and the ganglia were incubated in 35S-methionine. Peptide synthesis was determined by measuring labeled peptides in extracts from individually dissected neuronal cell bodies analyzed by HPLC. Previously characterized peptides found to be synthesized included buccalin, FMRFamide, myomodulin, and the 2 small cardioactive peptides (SCPs). Each of these neuropeptides has been shown to modulate buccal muscle responses to motor neuron stimulation. Two other peptides were found to be synthesized in individual motor neurons. One peptide, which was consistently observed in neurons that also synthesized myomodulin, is likely to be the recently sequenced myomodulin B. The other peptide was observed in a subset of the neurons that synthesize FMRFamide. While identified motor neurons consistently synthesized the same peptide(s), neurons that innervate the same muscle often express different peptides. Neurons that synthesized the SCPs also contained SCP-like activity, as determined by snail heart bioassay. Our results indicate that every identified motor neuron synthesizes a subset of these methionine-containing peptides, and that several neurons consistently synthesize peptides that are likely to be processed from multiple precursors
Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

DEFF Research Database (Denmark)

Justice, Anne E; Winkler, Thomas W; Feitosa, Mary F

2017-01-01

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87......% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent...... direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting...
Hydrodynamic theory for quantum plasmonics: Linear-response dynamics of the inhomogeneous electron gas

DEFF Research Database (Denmark)

Yan, Wei

2015-01-01

We investigate the hydrodynamic theory of metals, offering systematic studies of the linear-response dynamics for an inhomogeneous electron gas. We include the quantum functional terms of the Thomas-Fermi kinetic energy, the von Weizsa¨cker kinetic energy, and the exchange-correlation Coulomb...... energies under the local density approximation. The advantages, limitations, and possible improvements of the hydrodynamic theory are transparently demonstrated. The roles of various parameters in the theory are identified. We anticipate that the hydrodynamic theory can be applied to investigate the linear...... response of complex metallic nanostructures, including quantum effects, by adjusting theory parameters appropriately....
Food allergy: a clinician's criteria for including sera in a serum bank.

Science.gov (United States)

Ballmer-Weber, B K; Fernández-Rivas, M

2008-10-01

Safety assessment for genetically-engineered crop plants includes assessment for allergic responses. To facilitate this assessment, serum banks should contain well-characterised sera from patients with confirmed food allergies. A serum is defined as well-characterised if it is taken from a patient who has a convincing history of allergic responses to a known allergen or an allergen-containing food, a positive skin prick test (or elevated IgE response), and a positive response in a clinical food challenge.
Integrated mRNA and microRNA analysis identifies genes and small miRNA molecules associated with transcriptional and post-transcriptional-level responses to both drought stress and re-watering treatment in tobacco.

Science.gov (United States)

Chen, Qiansi; Li, Meng; Zhang, Zhongchun; Tie, Weiwei; Chen, Xia; Jin, Lifeng; Zhai, Niu; Zheng, Qingxia; Zhang, Jianfeng; Wang, Ran; Xu, Guoyun; Zhang, Hui; Liu, Pingping; Zhou, Huina

2017-01-10

Drought stress is one of the most severe problem limited agricultural productivity worldwide. It has been reported that plants response to drought-stress by sophisticated mechanisms at both transcriptional and post-transcriptional levels. However, the precise molecular mechanisms governing the responses of tobacco leaves to drought stress and water status are not well understood. To identify genes and miRNAs involved in drought-stress responses in tobacco, we performed both mRNA and small RNA sequencing on tobacco leaf samples from the following three treatments: untreated-control (CL), drought stress (DL), and re-watering (WL). In total, we identified 798 differentially expressed genes (DEGs) between the DL and CL (DL vs. CL) treatments and identified 571 DEGs between the WL and DL (WL vs. DL) treatments. Further analysis revealed 443 overlapping DEGs between the DL vs. CL and WL vs. DL comparisons, and, strikingly, all of these genes exhibited opposing expression trends between these two comparisons, strongly suggesting that these overlapping DEGs are somehow involved in the responses of tobacco leaves to drought stress. Functional annotation analysis showed significant up-regulation of genes annotated to be involved in responses to stimulus and stress, (e.g., late embryogenesis abundant proteins and heat-shock proteins) antioxidant defense (e.g., peroxidases and glutathione S-transferases), down regulation of genes related to the cell cycle pathway, and photosynthesis processes. We also found 69 and 56 transcription factors (TFs) among the DEGs in, respectively, the DL vs. CL and the WL vs. DL comparisons. In addition, small RNA sequencing revealed 63 known microRNAs (miRNA) from 32 families and 368 novel miRNA candidates in tobacco. We also found that five known miRNA families (miR398, miR390, miR162, miR166, and miR168) showed differential regulation under drought conditions. Analysis to identify negative correlations between the differentially expressed mi
Identifying the Misconceptions of Natural Science (IPA Using CRI (Certanty of Response Index at the Primary School Students in Tarakan

Directory of Open Access Journals (Sweden)

Muhsinah Annisa

2017-10-01

Full Text Available The objective of this study is to identify the misconceptions of Natural Science (IPA on primary school students in Tarakan. The output of this study is presented into a national scientific journal with ISSN. This study absolutely contributes to the schools and the education providers (universities. This study can identify the misconceptions of what happens to the students, so that teachers know how to handle and remediate these misconceptions. This study employs quantitative descriptive research. The population is the sixth grade students of primary schools in Tarakan. It is because the students of this grade have got the learning material on force, light, and simple machine. The technique.;s used in taking the sample is cluster sampling by considering on the three criteria, namely: superior, medium, and low school category which is based on the mean scores of final test (UAS on natural science subject. So, the sixth grade students of SDN A, SDN B Tarakan, and SDN C Tarakan are chosen as the sample of this study. The instrument of this research is a written test in a form of multiple choice test equiped with the CRI (certainty of response index answer sheet. The data are collected by distributing multiple-choice test which is consisted of 40 questions that are equipped with the CRI answer sheet.
Rate of Clinical Complete Response for 1 Year or More in Bone-Metastatic Breast Cancer after Comprehensive Treatments including Autologous Formalin-Fixed Tumor Vaccine.

Science.gov (United States)

Kuranishi, Fumito; Imaoka, Yuki; Sumi, Yuusuke; Uemae, Yoji; Yasuda-Kurihara, Hiroko; Ishihara, Takeshi; Miyazaki, Tsubasa; Ohno, Tadao

2018-01-01

No effective treatment has been developed for bone-metastatic breast cancer. We found 3 cases with clinical complete response (cCR) of the bone metastasis and longer overall survival of the retrospectively examined cohort treated comprehensively including autologous formalin-fixed tumor vaccine (AFTV). AFTV was prepared individually for each patient from their own formalin-fixed and paraffin-embedded breast cancer tissues. Three patients maintained cCR status of the bone metastasis for 17 months or more. Rate of cCR for 1 year or more appeared to be 15% (3/20) after comprehensive treatments including AFTV. The median overall survival time (60.0 months) and the 3- to 8-year survival rates after diagnosis of bone metastasis were greater than those of historical control cohorts in Japan (1988-2002) and in the nationwide population-based cohort study of Denmark (1999-2007). Bone-metastatic breast cancer may be curable after comprehensive treatments including AFTV, although larger scale clinical trial is required.
Proteomics analysis of alfalfa response to heat stress.

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Weimin Li

Full Text Available The proteome responses to heat stress have not been well understood. In this study, alfalfa (Medicago sativa L. cv. Huaiyin seedlings were exposed to 25 °C (control and 40 °C (heat stress in growth chambers, and leaves were collected at 24, 48 and 72 h after treatment, respectively. The morphological, physiological and proteomic processes were negatively affected under heat stress. Proteins were extracted and separated by two-dimensional polyacrylamide gel electrophoresis (2-DE, and differentially expressed protein spots were identified by mass spectrometry (MS. Totally, 81 differentially expressed proteins were identified successfully by MALDI-TOF/TOF. These proteins were categorized into nine classes: including metabolism, energy, protein synthesis, protein destination/storage, transporters, intracellular traffic, cell structure, signal transduction and disease/defence. Five proteins were further analyzed for mRNA levels. The results of the proteomics analyses provide a better understanding of the molecular basis of heat-stress responses in alfalfa.
Tracking micro-optical resonances for identifying and sensing novel procaspase-3 protein marker released from cell cultures in response to toxins

International Nuclear Information System (INIS)

Chen, Ying-Jen; Vollmer, Frank; Xiang, Wei; Klucken, Jochen

2016-01-01

The response of cells to toxins is commonly investigated by detecting intracellular markers for cell death, such as caspase proteins. This requires the introduction of labels by the permeabilization or complete lysis of cells. Here we introduce a non-invasive tool for monitoring a caspase protein in the extracellular medium. The tool is based on highly sensitive optical micro-devices, referred to as whispering-gallery mode biosensors (WGMBs). WGMBs are functionalized with antibodies for the specific and label-free detection of procaspase-3 released from human embryonic kidney HEK293 and neuroglioma H4 cells after introducing staurosporine and rotenone toxins, respectively. Additional tests show that the extracellular accumulation of procaspase-3 is concomitant with a decrease in cell viability. The hitherto unknown release of procaspase-3 from cells in response to toxins and its accumulation in the medium is further investigated by Western blot, showing that the extracellular detection of procaspase-3 is interrelated with cytotoxicity of alpha-synuclein protein (aSyn) overexpressed in H4 cells. These studies provide evidence for procaspase-3 as a novel extracellular biomarker for cell death, with applications in cytotoxicity tests. Such WGMBs could be applied to further identify as-yet unknown extracellular biomarkers using established antibodies against intracellular antigens. (paper)
Response Properties of a Newly Identified Tristratified Narrow Field Amacrine Cell in the Mouse Retina.

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G S Newkirk

Full Text Available Amacrine cells were targeted for whole cell recording using two-photon fluorescence microscopy in a transgenic mouse line in which the promoter for dopamine receptor 2 drove expression of green fluorescent protein in a narrow field tristratified amacrine cell (TNAC that had not been studied previously. Light evoked a multiphasic response that was the sum of hyperpolarizing and depolarization synaptic inputs consistent with distinct dendritic ramifications in the off and on sublamina of the inner plexiform layer. The amplitude and waveform of the response, which consisted of an initial brief hyperpolarization at light onset followed by recovery to a plateau potential close to dark resting potential and a hyperpolarizing response at the light offset varied little over an intensity range from 0.4 to ~10^6 Rh*/rod/s. This suggests that the cell functions as a differentiator that generates an output signal (a transient reduction in inhibitory input to downstream retina neurons that is proportional to the derivative of light input independent of its intensity. The underlying circuitry appears to consist of rod and cone driven on and off bipolar cells that provide direct excitatory input to the cell as well as to GABAergic amacrine cells that are synaptically coupled to TNAC. Canonical reagents that blocked excitatory (glutamatergic and inhibitory (GABA and glycine synaptic transmission had effects on responses to scotopic stimuli consistent with the rod driven component of the proposed circuit. However, responses evoked by photopic stimuli were paradoxical and could not be interpreted on the basis of conventional thinking about the neuropharmacology of synaptic interactions in the retina.

The transcriptional response of Drosophila melanogaster to infection with the sigma virus (Rhabdoviridae.

Directory of Open Access Journals (Sweden)

Jennifer Carpenter

2009-08-01

Full Text Available Bacterial and fungal infections induce a potent immune response in Drosophila melanogaster, but it is unclear whether viral infections induce an antiviral immune response. Using microarrays, we examined the changes in gene expression in Drosophila that occur in response to infection with the sigma virus, a negative-stranded RNA virus (Rhabdoviridae that occurs in wild populations of D. melanogaster.We detected many changes in gene expression in infected flies, but found no evidence for the activation of the Toll, IMD or Jak-STAT pathways, which control immune responses against bacteria and fungi. We identified a number of functional categories of genes, including serine proteases, ribosomal proteins and chorion proteins that were overrepresented among the differentially expressed genes. We also found that the sigma virus alters the expression of many more genes in males than in females.These data suggest that either Drosophila do not mount an immune response against the sigma virus, or that the immune response is not controlled by known immune pathways. If the latter is true, the genes that we identified as differentially expressed after infection are promising candidates for controlling the host's response to the sigma virus.
The transcriptional response of Drosophila melanogaster to infection with the sigma virus (Rhabdoviridae).

Science.gov (United States)

Carpenter, Jennifer; Hutter, Stephan; Baines, John F; Roller, Julia; Saminadin-Peter, Sarah S; Parsch, John; Jiggins, Francis M

2009-08-31

Bacterial and fungal infections induce a potent immune response in Drosophila melanogaster, but it is unclear whether viral infections induce an antiviral immune response. Using microarrays, we examined the changes in gene expression in Drosophila that occur in response to infection with the sigma virus, a negative-stranded RNA virus (Rhabdoviridae) that occurs in wild populations of D. melanogaster. We detected many changes in gene expression in infected flies, but found no evidence for the activation of the Toll, IMD or Jak-STAT pathways, which control immune responses against bacteria and fungi. We identified a number of functional categories of genes, including serine proteases, ribosomal proteins and chorion proteins that were overrepresented among the differentially expressed genes. We also found that the sigma virus alters the expression of many more genes in males than in females. These data suggest that either Drosophila do not mount an immune response against the sigma virus, or that the immune response is not controlled by known immune pathways. If the latter is true, the genes that we identified as differentially expressed after infection are promising candidates for controlling the host's response to the sigma virus.
The Transcriptional Response of Drosophila melanogaster to Infection with the Sigma Virus (Rhabdoviridae)

Science.gov (United States)

Baines, John F.; Roller, Julia; Saminadin-Peter, Sarah S.; Parsch, John; Jiggins, Francis M.

2009-01-01

Background Bacterial and fungal infections induce a potent immune response in Drosophila melanogaster, but it is unclear whether viral infections induce an antiviral immune response. Using microarrays, we examined the changes in gene expression in Drosophila that occur in response to infection with the sigma virus, a negative-stranded RNA virus (Rhabdoviridae) that occurs in wild populations of D. melanogaster. Principal Findings We detected many changes in gene expression in infected flies, but found no evidence for the activation of the Toll, IMD or Jak-STAT pathways, which control immune responses against bacteria and fungi. We identified a number of functional categories of genes, including serine proteases, ribosomal proteins and chorion proteins that were overrepresented among the differentially expressed genes. We also found that the sigma virus alters the expression of many more genes in males than in females. Conclusions These data suggest that either Drosophila do not mount an immune response against the sigma virus, or that the immune response is not controlled by known immune pathways. If the latter is true, the genes that we identified as differentially expressed after infection are promising candidates for controlling the host's response to the sigma virus. PMID:19718442
Pleural fluid cell-free DNA integrity index to identify cytologically negative malignant pleural effusions including mesotheliomas

International Nuclear Information System (INIS)

Sriram, Krishna B; Courtney, Deborah; Yang, Ian A; Bowman, Rayleen V; Fong, Kwun M; Relan, Vandana; Clarke, Belinda E; Duhig, Edwina E; Windsor, Morgan N; Matar, Kevin S; Naidoo, Rishendran; Passmore, Linda; McCaul, Elizabeth

2012-01-01

The diagnosis of malignant pleural effusions (MPE) is often clinically challenging, especially if the cytology is negative for malignancy. DNA integrity index has been reported to be a marker of malignancy. The aim of this study was to evaluate the utility of pleural fluid DNA integrity index in the diagnosis of MPE. We studied 75 pleural fluid and matched serum samples from consecutive subjects. Pleural fluid and serum ALU DNA repeats [115bp, 247bp and 247bp/115bp ratio (DNA integrity index)] were assessed by real-time quantitative PCR. Pleural fluid and serum mesothelin levels were quantified using ELISA. Based on clinico-pathological evaluation, 52 subjects had MPE (including 16 mesotheliomas) and 23 had benign effusions. Pleural fluid DNA integrity index was higher in MPE compared with benign effusions (1.2 vs. 0.8; p<0.001). Cytology had a sensitivity of 55% in diagnosing MPE. If cytology and pleural fluid DNA integrity index were considered together, they exhibited 81% sensitivity and 87% specificity in distinguishing benign and malignant effusions. In cytology-negative pleural effusions (35 MPE and 28 benign effusions), elevated pleural fluid DNA integrity index had an 81% positive predictive value in detecting MPEs. In the detection of mesothelioma, at a specificity of 90%, pleural fluid DNA integrity index had similar sensitivity to pleural fluid and serum mesothelin (75% each respectively). Pleural fluid DNA integrity index is a promising diagnostic biomarker for identification of MPEs, including mesothelioma. This biomarker may be particularly useful in cases of MPE where pleural aspirate cytology is negative, and could guide the decision to undertake more invasive definitive testing. A prospective validation study is being undertaken to validate our findings and test the clinical utility of this biomarker for altering clinical practice
Framework for analyzing safeguards alarms and response decisions

International Nuclear Information System (INIS)

Al-Ayat, R.A.; Judd, B.R.; McCord, R.K.

1982-01-01

This paper describes a quantitative approach to help evaluate and respond to safeguards alarms. These alrms may be generated internally by a facility's safeguards systems or externally by individuals claiming to possess stolen Special Nuclear Material (SNM). This approach can be used to identify the most likely cause of an alarm - theft, hoax, or error - and to evaluate alternative responses to alarms. Possible responses include conducting investigations, initiating measures to recover stolen SNM, and replying to external threats. Based on the results of each alarm investigation step, the evaluation revises the likelihoods of possible causes of an alarm, and uses this information to determine the optimal sequence of further responses. The choice of an optimal sequence of responses takes into consideration the costs and benefits of successful thefts or hoaxes. These results provide an analytical basis for setting priorities and developing contingency plans for responding to safeguards alarms
Objective Model Selection for Identifying the Human Feedforward Response in Manual Control

OpenAIRE

Drop, F.M.; Pool, D.M.; van Paassen, M.M.; Mulder, M.; Bülthoff, Heinrich H.

2017-01-01

Realistic manual control tasks typically involve predictable target signals and random disturbances. The human controller (HC) is hypothesized to use a feedforward control strategy for target-following, in addition to feedback control for disturbance-rejection. Little is known about human feedforward control, partly because common system identification methods have difficulty in identifying whether, and (if so) how, the HC applies a feedforward strategy. In this paper, an identification proce...
The Silence of Corruption : Identifying Underreporting of Business Corruption through Randomized Response Techniques

OpenAIRE

Jensen, Nathan M.; Rahman, Aminur

2011-01-01

Research on the economic consequences of corruption has been hampered by the inability to directly measure corruption. Using an innovative methodology that allows respondents to report individual experiences with corruption while minimizing self-incrimination and an objective diagnostic to evaluate lying (false responses), this paper explores the extent of business corruption in Bangladesh...
Adolescent Concepts of Responsibility in Different Typesof Moral Dilemmas

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Molchanov S.V.

2017-12-01

Full Text Available The paper presents results of an empirical study of adolescents' concepts of responsibility in different types of moral dilemmas characterized by violations of moral norms. The study proved that the type of moral dilemma and the context of interaction of its participants determine the adolescents' readiness to recognize the responsibility of the main character of the dilemma for violating the norm. In dilemmas of asocial type adolescents are more willing to recognize the responsibility of the offender whose behavior leads to obvious damage for one of the participants in the interaction. As for prosocial dilemmas and dilemmas of confronting norms, adolescents tend to deny the responsibility of the offender. The paper provides a comparative analysis of empirically identified types of adolescent concepts of responsibility, including the differentiated responsibility with egoistic orientation, high responsibility, low responsibility and ‘polar’ responsibility. The authors highlight the ambiguity of the relationship between adolescents’ evaluation of behavior, their readiness to recognize responsibility in moral transgression, and their judgment about the necessity of punishment. The paper concludes with the discussion concerning the relationship between the level of development of moral judgments/moral reasoning and the concepts of responsibility in adolescents.
Statistical determination of significant curved I-girder bridge seismic response parameters

Science.gov (United States)

Seo, Junwon

2013-06-01

Curved steel bridges are commonly used at interchanges in transportation networks and more of these structures continue to be designed and built in the United States. Though the use of these bridges continues to increase in locations that experience high seismicity, the effects of curvature and other parameters on their seismic behaviors have been neglected in current risk assessment tools. These tools can evaluate the seismic vulnerability of a transportation network using fragility curves. One critical component of fragility curve development for curved steel bridges is the completion of sensitivity analyses that help identify influential parameters related to their seismic response. In this study, an accessible inventory of existing curved steel girder bridges located primarily in the Mid-Atlantic United States (MAUS) was used to establish statistical characteristics used as inputs for a seismic sensitivity study. Critical seismic response quantities were captured using 3D nonlinear finite element models. Influential parameters from these quantities were identified using statistical tools that incorporate experimental Plackett-Burman Design (PBD), which included Pareto optimal plots and prediction profiler techniques. The findings revealed that the potential variation in the influential parameters included number of spans, radius of curvature, maximum span length, girder spacing, and cross-frame spacing. These parameters showed varying levels of influence on the critical bridge response.
Predicting response to incretin-based therapy

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Agrawal N

2011-04-01

Full Text Available Sanjay Kalra1, Bharti Kalra2, Rakesh Sahay3, Navneet Agrawal41Department of Endocrinology, 2Department of Diabetology, Bharti Hospital, Karnal, India; 3Department of Endocrinology, Osmania Medical College, Hyderabad, India; 4Department of Medicine, GR Medical College, Gwalior, IndiaAbstract: There are two important incretin hormones, glucose-dependent insulin tropic polypeptide (GIP and glucagon-like peptide-1 (GLP-1. The biological activities of GLP-1 include stimulation of glucose-dependent insulin secretion and insulin biosynthesis, inhibition of glucagon secretion and gastric emptying, and inhibition of food intake. GLP-1 appears to have a number of additional effects in the gastrointestinal tract and central nervous system. Incretin based therapy includes GLP-1 receptor agonists like human GLP-1 analogs (liraglutide and exendin-4 based molecules (exenatide, as well as DPP-4 inhibitors like sitagliptin, vildagliptin and saxagliptin. Most of the published studies showed a significant reduction in HbA1c using these drugs. A critical analysis of reported data shows that the response rate in terms of target achievers of these drugs is average. One of the first actions identified for GLP-1 was the glucose-dependent stimulation of insulin secretion from islet cell lines. Following the detection of GLP-1 receptors on islet beta cells, a large body of evidence has accumulated illustrating that GLP-1 exerts multiple actions on various signaling pathways and gene products in the ß cell. GLP-1 controls glucose homeostasis through well-defined actions on the islet ß cell via stimulation of insulin secretion and preservation and expansion of ß cell mass. In summary, there are several factors determining the response rate to incretin therapy. Currently minimal clinical data is available to make a conclusion. Key factors appear to be duration of diabetes, obesity, presence of autonomic neuropathy, resting energy expenditure, plasma glucagon levels and
Setting Priorities for Diabetic Retinopathy Clinical Research and Identifying Evidence Gaps.

Science.gov (United States)

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

2017-01-01

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

Science.gov (United States)

Rees, Vaughan W; Kreslake, Jennifer M; Cummings, K Michael; O'Connor, Richard J; Hatsukami, Dorothy K; Parascandola, Mark; Shields, Peter G; Connolly, Gregory N

2009-12-01

Internal tobacco industry documents and the mainstream literature are reviewed to identify methods and measures for evaluating tobacco consumer response. The review aims to outline areas in which established methods exist, identify gaps in current methods for assessing consumer response, and consider how these methods might be applied to evaluate potentially reduced exposure tobacco products and new products. Internal industry research reviewed included published articles, manuscript drafts, presentations, protocols, and instruments relating to consumer response measures were identified and analyzed. Peer-reviewed research was identified using PubMed and Scopus. Industry research on consumer response focuses on product development and marketing. To develop and refine new products, the tobacco industry has developed notable strategies for assessing consumers' sensory and subjective responses to product design characteristics. Independent research is often conducted to gauge the likelihood of future product adoption by measuring consumers' risk perceptions, responses to product, and product acceptability. A model that conceptualizes consumer response as comprising the separate, but interacting, domains of product perceptions and response to product is outlined. Industry and independent research supports the dual domain model and provides a wide range of methods for assessment of the construct components of consumer response. Further research is needed to validate consumer response constructs, determine the relationship between consumer response and tobacco user behavior, and improve reliability of consumer response measures. Scientifically rigorous consumer response assessment methods will provide a needed empirical basis for future regulation of potentially reduced-exposure tobacco products and new products, to counteract tobacco industry influence on consumers, and enhance the public health.
Plant transducers of the endoplasmic reticulum unfolded protein response

KAUST Repository

Iwata, Yuji; Koizumi, Nozomu

2012-01-01

The unfolded protein response (UPR) activates a set of genes to overcome accumulation of unfolded proteins in the endoplasmic reticulum (ER), a condition termed ER stress, and constitutes an essential part of ER protein quality control that ensures efficient maturation of secretory and membrane proteins in eukaryotes. Recent studies on Arabidopsis and rice identified the signaling pathway in which the ER membrane-localized ribonuclease IRE1 (inositol-requiring enzyme 1) catalyzes unconventional cytoplasmic splicing of mRNA, thereby producing the active transcription factor Arabidopsis bZIP60 (basic leucine zipper 60) and its ortholog in rice. Here we review recent findings identifying the molecular components of the plant UPR, including IRE1/bZIP60 and the membrane-bound transcription factors bZIP17 and bZIP28, and implicating its importance in several physiological phenomena such as pathogen response. © 2012 Elsevier Ltd.
Plant transducers of the endoplasmic reticulum unfolded protein response

KAUST Repository

Iwata, Yuji

2012-12-01

The unfolded protein response (UPR) activates a set of genes to overcome accumulation of unfolded proteins in the endoplasmic reticulum (ER), a condition termed ER stress, and constitutes an essential part of ER protein quality control that ensures efficient maturation of secretory and membrane proteins in eukaryotes. Recent studies on Arabidopsis and rice identified the signaling pathway in which the ER membrane-localized ribonuclease IRE1 (inositol-requiring enzyme 1) catalyzes unconventional cytoplasmic splicing of mRNA, thereby producing the active transcription factor Arabidopsis bZIP60 (basic leucine zipper 60) and its ortholog in rice. Here we review recent findings identifying the molecular components of the plant UPR, including IRE1/bZIP60 and the membrane-bound transcription factors bZIP17 and bZIP28, and implicating its importance in several physiological phenomena such as pathogen response. © 2012 Elsevier Ltd.
Characterization and evaluation of controls on post-fire streamflow response across western US watersheds

Science.gov (United States)

Saxe, Samuel; Hogue, Terri S.; Hay, Lauren

2018-02-01

This research investigates the impact of wildfires on watershed flow regimes, specifically focusing on evaluation of fire events within specified hydroclimatic regions in the western United States, and evaluating the impact of climate and geophysical variables on response. Eighty-two watersheds were identified with at least 10 years of continuous pre-fire daily streamflow records and 5 years of continuous post-fire daily flow records. Percent change in annual runoff ratio, low flows, high flows, peak flows, number of zero flow days, baseflow index, and Richards-Baker flashiness index were calculated for each watershed using pre- and post-fire periods. Independent variables were identified for each watershed and fire event, including topographic, vegetation, climate, burn severity, percent area burned, and soils data. Results show that low flows, high flows, and peak flows increase in the first 2 years following a wildfire and decrease over time. Relative response was used to scale response variables with the respective percent area of watershed burned in order to compare regional differences in watershed response. To account for variability in precipitation events, runoff ratio was used to compare runoff directly to PRISM precipitation estimates. To account for regional differences in climate patterns, watersheds were divided into nine regions, or clusters, through k-means clustering using climate data, and regression models were produced for watersheds grouped by total area burned. Watersheds in Cluster 9 (eastern California, western Nevada, Oregon) demonstrate a small negative response to observed flow regimes after fire. Cluster 8 watersheds (coastal California) display the greatest flow responses, typically within the first year following wildfire. Most other watersheds show a positive mean relative response. In addition, simple regression models show low correlation between percent watershed burned and streamflow response, implying that other watershed factors
Humanitarian response: improving logistics to save lives.

Science.gov (United States)

McCoy, Jessica

2008-01-01

Each year, millions of people worldwide are affected by disasters, underscoring the importance of effective relief efforts. Many highly visible disaster responses have been inefficient and ineffective. Humanitarian agencies typically play a key role in disaster response (eg, procuring and distributing relief items to an affected population, assisting with evacuation, providing healthcare, assisting in the development of long-term shelter), and thus their efficiency is critical for a successful disaster response. The field of disaster and emergency response modeling is well established, but the application of such techniques to humanitarian logistics is relatively recent. This article surveys models of humanitarian response logistics and identifies promising opportunities for future work. Existing models analyze a variety of preparation and response decisions (eg, warehouse location and the distribution of relief supplies), consider both natural and manmade disasters, and typically seek to minimize cost or unmet demand. Opportunities to enhance the logistics of humanitarian response include the adaptation of models developed for general disaster response; the use of existing models, techniques, and insights from the literature on commercial supply chain management; the development of working partnerships between humanitarian aid organizations and private companies with expertise in logistics; and the consideration of behavioral factors relevant to a response. Implementable, realistic models that support the logistics of humanitarian relief can improve the preparation for and the response to disasters, which in turn can save lives.
Sequencing illustrates the transcriptional response of Legionella pneumophila during infection and identifies seventy novel small non-coding RNAs.

LENUS (Irish Health Repository)

Weissenmayer, Barbara A

2011-01-01

Second generation sequencing has prompted a number of groups to re-interrogate the transcriptomes of several bacterial and archaeal species. One of the central findings has been the identification of complex networks of small non-coding RNAs that play central roles in transcriptional regulation in all growth conditions and for the pathogen\\'s interaction with and survival within host cells. Legionella pneumophila is a gram-negative facultative intracellular human pathogen with a distinct biphasic lifestyle. One of its primary environmental hosts in the free-living amoeba Acanthamoeba castellanii and its infection by L. pneumophila mimics that seen in human macrophages. Here we present analysis of strand specific sequencing of the transcriptional response of L. pneumophila during exponential and post-exponential broth growth and during the replicative and transmissive phase of infection inside A. castellanii. We extend previous microarray based studies as well as uncovering evidence of a complex regulatory architecture underpinned by numerous non-coding RNAs. Over seventy new non-coding RNAs could be identified; many of them appear to be strain specific and in configurations not previously reported. We discover a family of non-coding RNAs preferentially expressed during infection conditions and identify a second copy of 6S RNA in L. pneumophila. We show that the newly discovered putative 6S RNA as well as a number of other non-coding RNAs show evidence for antisense transcription. The nature and extent of the non-coding RNAs and their expression patterns suggests that these may well play central roles in the regulation of Legionella spp. specific traits and offer clues as to how L. pneumophila adapts to its intracellular niche. The expression profiles outlined in the study have been deposited into Genbank\\'s Gene Expression Omnibus (GEO) database under the series accession GSE27232.
Treatment response in psychotic patients classified according to social and clinical needs, drug side effects, and previous treatment; a method to identify functional remission.

Science.gov (United States)

Alenius, Malin; Hammarlund-Udenaes, Margareta; Hartvig, Per; Sundquist, Staffan; Lindström, Leif

2009-01-01

Various approaches have been made over the years to classify psychotic patients according to inadequate treatment response, using terms such as treatment resistant or treatment refractory. Existing classifications have been criticized for overestimating positive symptoms; underestimating residual symptoms, negative symptoms, and side effects; or being to open for individual interpretation. The aim of this study was to present and evaluate a new method of classification according to treatment response and, thus, to identify patients in functional remission. A naturalistic, cross-sectional study was performed using patient interviews and information from patient files. The new classification method CANSEPT, which combines the Camberwell Assessment of Need rating scale, the Udvalg for Kliniske Undersøgelser side effect rating scale (SE), and the patient's previous treatment history (PT), was used to group the patients according to treatment response. CANSEPT was evaluated by comparison of expected and observed results. In the patient population (n = 123), the patients in functional remission, as defined by CANSEPT, had higher quality of life, fewer hospitalizations, fewer psychotic symptoms, and higher rate of workers than those with the worst treatment outcome. In the evaluation, CANSEPT showed validity in discriminating the patients of interest and was well tolerated by the patients. CANSEPT could secure inclusion of correct patients in the clinic or in research.
Identifying the essential components of cultural competence in a Chinese nursing context: A qualitative study.

Science.gov (United States)

Cai, Duanying; Kunaviktikul, Wipada; Klunklin, Areewan; Sripusanapan, Acharaporn; Avant, Patricia Kay

2017-06-01

This qualitative study using semi-structured interviews was conducted to identify the essential components of cultural competence from the perspective of Chinese nurses. A purposive sample of 20 nurse experts, including senior clinical nurses, nurse administrators, and educators in transcultural nursing, was recruited. Using thematic analysis, four themes: awareness, attitudes, knowledge, and skills, with two subthemes for each, were identified. Notably, culture in China was understood in a broad way. The participants' responses focused upon demographic attributes, individuality, and efforts to facilitate quality care rather than on the cultural differences of ethnicity and race and developing the capacity to change discrimination or health disparities. A greater understanding of cultural competence in the Chinese nursing context, in which a dominant cultural group exists, is essential to facilitate the provision of culturally competent care to diverse populations. © 2016 John Wiley & Sons Australia, Ltd.
Identifying a predictive model for response to atypical antipsychotic monotherapy treatment in south Indian schizophrenia patients.

Science.gov (United States)

Gupta, Meenal; Moily, Nagaraj S; Kaur, Harpreet; Jajodia, Ajay; Jain, Sanjeev; Kukreti, Ritushree

2013-08-01

Atypical antipsychotic (AAP) drugs are the preferred choice of treatment for schizophrenia patients. Patients who do not show favorable response to AAP monotherapy are subjected to random prolonged therapeutic treatment with AAP multitherapy, typical antipsychotics or a combination of both. Therefore, prior identification of patients' response to drugs can be an important step in providing efficacious and safe therapeutic treatment. We thus attempted to elucidate a genetic signature which could predict patients' response to AAP monotherapy. Our logistic regression analyses indicated the probability that 76% patients carrying combination of four SNPs will not show favorable response to AAP therapy. The robustness of this prediction model was assessed using repeated 10-fold cross validation method, and the results across n-fold cross-validations (mean accuracy=71.91%; 95%CI=71.47-72.35) suggest high accuracy and reliability of the prediction model. Further validations of these results in large sample sets are likely to establish their clinical applicability. Copyright © 2013 Elsevier Inc. All rights reserved.

In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target.

Science.gov (United States)

Manguso, Robert T; Pope, Hans W; Zimmer, Margaret D; Brown, Flavian D; Yates, Kathleen B; Miller, Brian C; Collins, Natalie B; Bi, Kevin; LaFleur, Martin W; Juneja, Vikram R; Weiss, Sarah A; Lo, Jennifer; Fisher, David E; Miao, Diana; Van Allen, Eliezer; Root, David E; Sharpe, Arlene H; Doench, John G; Haining, W Nicholas

2017-07-27

Immunotherapy with PD-1 checkpoint blockade is effective in only a minority of patients with cancer, suggesting that additional treatment strategies are needed. Here we use a pooled in vivo genetic screening approach using CRISPR-Cas9 genome editing in transplantable tumours in mice treated with immunotherapy to discover previously undescribed immunotherapy targets. We tested 2,368 genes expressed by melanoma cells to identify those that synergize with or cause resistance to checkpoint blockade. We recovered the known immune evasion molecules PD-L1 and CD47, and confirmed that defects in interferon-γ signalling caused resistance to immunotherapy. Tumours were sensitized to immunotherapy by deletion of genes involved in several diverse pathways, including NF-κB signalling, antigen presentation and the unfolded protein response. In addition, deletion of the protein tyrosine phosphatase PTPN2 in tumour cells increased the efficacy of immunotherapy by enhancing interferon-γ-mediated effects on antigen presentation and growth suppression. In vivo genetic screens in tumour models can identify new immunotherapy targets in unanticipated pathways.
IDENTIFYING COMPETENCIES OF VOLUNTEER BOARD MEMBERS OF COMMUNITY SPORTS CLUBS

OpenAIRE

A. BALDUCK; A. VAN ROSSEM; M. BUELENS

2009-01-01

This study contributes to the emerging empirical studies on roles and responsibilities of boards in nonprofit organizations by identifying competencies of volunteer board members. We identified how two types of constituents—volunteer board members and sports members—perceived competencies of volunteer board members in community sports clubs. We used the repertory grid technique to draw cognitive maps and to reveal the perceived reality of these constituents. Our results suggest that constitue...
IEA Wind Task 32: Wind lidar identifying and mitigating barriers to the adoption of wind lidar

DEFF Research Database (Denmark)

Clifton, Andrew; Clive, Peter; Gottschall, Julia

2018-01-01

IEA Wind Task 32 exists to identify and mitigate barriers to the adoption of lidar for wind energy applications. It leverages ongoing international research and development activities in academia and industry to investigate site assessment, power performance testing, controls and loads, and complex...... flows. Since its initiation in 2011, Task 32 has been responsible for several recommended practices and expert reports that have contributed to the adoption of ground-based, nacelle-based, and floating lidar by the wind industry. Future challenges include the development of lidar uncertainty models......, best practices for data management, and developing community-based tools for data analysis, planning of lidar measurements and lidar configuration. This paper describes the barriers that Task 32 identified to the deployment of wind lidar in each of these application areas, and the steps that have been...
Global Microbial Identifier

DEFF Research Database (Denmark)

Wielinga, Peter; Hendriksen, Rene S.; Aarestrup, Frank Møller

2017-01-01

) will likely also enable a much better understanding of the pathogenesis of the infection and the molecular basis of the host response to infection. But the full potential of these advances will only transpire if the data in this area become transferable and thereby comparable, preferably in open-source...... of microorganisms, for the identification of relevant genes and for the comparison of genomes to detect outbreaks and emerging pathogens. To harness the full potential of WGS, a shared global database of genomes linked to relevant metadata and the necessary software tools needs to be generated, hence the global...... microbial identifier (GMI) initiative. This tool will ideally be used in amongst others in the diagnosis of infectious diseases in humans and animals, in the identification of microorganisms in food and environment, and to track and trace microbial agents in all arenas globally. This will require...
Identifying research priorities for public health research to address health inequalities: use of Delphi-like survey methods.

Science.gov (United States)

Turner, S; Ollerhead, E; Cook, A

2017-10-09

In the funding of health research and public health research it is vital that research questions posed are important and that funded research meets a research need or a gap in evidence. Many methods are used in the identification of research priorities, however, these can be resource intensive, costly and logistically challenging. Identifying such research priorities can be particularly challenging for complex public health problems as there is a need to consult a number of experts across disciplines and with a range of expertise. This study investigated the use of Delphi-like survey methods in identifying important research priorities relating to health inequalities and framing tractable research questions for topic areas identified. The study was conducted in two phases, both using Delphi-like survey methods. Firstly, public health professionals with an interest in health inequalities were asked to identify research priorities. Secondly academic researchers were asked to frame tractable research questions relating to the priorities identified. These research priorities identified using Delphi-like survey methods were subsequently compared to those identified using different methods. A total of 52 public health professionals and 21 academics across the United Kingdom agreed to take part. The response rates were high, from public health professionals across three survey rounds (69%, 50% and 40%) and from academics across one round (52%), indicating that participants were receptive to the method and motivated to respond. The themes identified as encompassing the most important research priorities were mental health, healthy environment and health behaviours. Within these themes, the topic areas that emerged most strongly included community interventions for prevention of mental health problems and the food and alcohol environment. Some responses received from academic researchers were (as requested) in the form of tractable research questions, whereas others
The Lifecycles of Drought: Informing Responses Across Timescales

Science.gov (United States)

Pulwarty, R. S.; Schubert, S. D.

2014-12-01

Drought is a slow-onset hazard that is a normal part of climate. Drought onset and demise are difficult to determine. Impacts are mostly nonstructural, spread over large geographical areas, and can persist long after precipitation deficits end. These factors hinder development of accurate, timely estimates of drought severity and resultant responses. Drivers of drought range from SST anomalies and global scale atmospheric response, through regional forcing and local land-surface feedbacks. Key climatological questions related to drought risk assessment, perception and management include, "Does a drought end by a return to normal precipitation; how much moisture is required and over what period; can the end of a drought be defined by the diminishing impacts e.g. soil moisture, reservoir volumes; will precipitation patterns on which management systems rely, change in the future?" Effective early warning systems inform strategic responses that anticipate crises and crisis evolution across climate timescales. While such "early information" is critical for defining event onset, it is even more critical for identifying the potential for increases in severity. Many social and economic systems have buffers in place to respond to onset (storage, transfers and purchase of grain) but lack response capabilities as drought intensifies, as buffers are depleted. Throughout the drought lifecycle (and between events), monitoring, research and risk assessments are required to: Map decision-making processes and resource capabilities including degradation of water and ecosystems Place multiple climate and land surface indicators within a consistent triggering framework (e.g. climate and vegetation mapping) before critical thresholds are reached Identify policies and practices that impede or enable the flow of information, through policy gaming and other exercises The presentation will outline the capabilities and framework needed to ensure improved scientific inputs to preparedness
Characteristics and treatment response of self-identified problematic Internet users in a behavioral addiction outpatient clinic.

Science.gov (United States)

Thorens, Gabriel; Achab, Sophia; Billieux, Joël; Khazaal, Yasser; Khan, Riaz; Pivin, Edward; Gupta, Vishal; Zullino, Daniel

2014-03-01

Controversies remain about the validity of the diagnosis of problematic Internet use. This might be due in part to the lack of longitudinal naturalistic studies that have followed a cohort of patients who self-identify as having Internet-related problems. This retrospective study included 57 patients who consulted the Geneva Addiction Outpatient Clinic from January 1, 2007, to January 1, 2010. Patients underwent an initial clinical psychiatric evaluation that included collection of data on socio-demographics, method of referral, specific Internet usage, psychiatric diagnosis, and Internet Addiction Test (IAT) and Clinical Global Impression Scale (CGI) scores. Treatment consisted of individual psychotherapeutic sessions. Of these patients, 98% were male and 37% were 18 years or younger. Most patients were online gamers (46% playing massively multiplayer online role-playing games). The mean IAT score was 52.9 (range 20-90). Sixty-eight percent of patients had a co-morbid psychiatric diagnosis, with social phobia being the most prevalent (17.8%). Patients who remained in treatment (dropout rate 24%) showed an overall improvement of symptoms: 38.6% showed significant or average improvement on their CGI score, 26.3% showed minimal improvement, and 14% showed no change. Our results support the hypothesis that there are specific types of Internet use, with online gaming mainly affecting young male patients. As Internet addiction is not yet an official diagnosis, better instruments are needed to screen patients and to avoid false-negative and false-positive diagnoses. Successful care should integrate the treatment of co-morbid symptoms and involve families and relatives in the therapeutic process.
Manual of functions, assignments, and responsibilities for nuclear safety: Revision 2

Energy Technology Data Exchange (ETDEWEB)

1994-10-15

The FAR Manual is a convenient easy-to-use collection of the functions, assignments, and responsibilities (FARs) of DOE nuclear safety personnel. Current DOE directives, including Orders, Secretary of Energy Notices, and other assorted policy memoranda, are the source of this information and form the basis of the FAR Manual. Today, the majority of FARs for DOE personnel are contained in DOE`s nuclear safety Orders. As these Orders are converted to rules in the Code of Federal Regulations, the FAR Manual will become the sole source for information relating to the functions, assignments, responsibilities of DOE nuclear safety personnel. The FAR Manual identifies DOE directives that relate to nuclear safety and the specific DOE personnel who are responsible for implementing them. The manual includes only FARs that have been extracted from active directives that have been approved in accordance with the procedures contained in DOE Order 1321.1B.
Key Characteristics of Combined Accident including TLOFW accident for PSA Modeling

Energy Technology Data Exchange (ETDEWEB)

Kim, Bo Gyung; Kang, Hyun Gook [KAIST, Daejeon (Korea, Republic of); Yoon, Ho Joon [Khalifa University of Science, Technology and Research, Abu Dhabi (United Arab Emirates)

2015-05-15

The conventional PSA techniques cannot adequately evaluate all events. The conventional PSA models usually focus on single internal events such as DBAs, the external hazards such as fire, seismic. However, the Fukushima accident of Japan in 2011 reveals that very rare event is necessary to be considered in the PSA model to prevent the radioactive release to environment caused by poor treatment based on lack of the information, and to improve the emergency operation procedure. Especially, the results from PSA can be used to decision making for regulators. Moreover, designers can consider the weakness of plant safety based on the quantified results and understand accident sequence based on human actions and system availability. This study is for PSA modeling of combined accidents including total loss of feedwater (TLOFW) accident. The TLOFW accident is a representative accident involving the failure of cooling through secondary side. If the amount of heat transfer is not enough due to the failure of secondary side, the heat will be accumulated to the primary side by continuous core decay heat. Transients with loss of feedwater include total loss of feedwater accident, loss of condenser vacuum accident, and closure of all MSIVs. When residual heat removal by the secondary side is terminated, the safety injection into the RCS with direct primary depressurization would provide alternative heat removal. This operation is called feed and bleed (F and B) operation. Combined accidents including TLOFW accident are very rare event and partially considered in conventional PSA model. Since the necessity of F and B operation is related to plant conditions, the PSA modeling for combined accidents including TLOFW accident is necessary to identify the design and operational vulnerabilities.The PSA is significant to assess the risk of NPPs, and to identify the design and operational vulnerabilities. Even though the combined accident is very rare event, the consequence of combined
The NOAA Dataset Identifier Project

Science.gov (United States)

de la Beaujardiere, J.; Mccullough, H.; Casey, K. S.

2013-12-01

The US National Oceanic and Atmospheric Administration (NOAA) initiated a project in 2013 to assign persistent identifiers to datasets archived at NOAA and to create informational landing pages about those datasets. The goals of this project are to enable the citation of datasets used in products and results in order to help provide credit to data producers, to support traceability and reproducibility, and to enable tracking of data usage and impact. A secondary goal is to encourage the submission of datasets for long-term preservation, because only archived datasets will be eligible for a NOAA-issued identifier. A team was formed with representatives from the National Geophysical, Oceanographic, and Climatic Data Centers (NGDC, NODC, NCDC) to resolve questions including which identifier scheme to use (answer: Digital Object Identifier - DOI), whether or not to embed semantics in identifiers (no), the level of granularity at which to assign identifiers (as coarsely as reasonable), how to handle ongoing time-series data (do not break into chunks), creation mechanism for the landing page (stylesheet from formal metadata record preferred), and others. Decisions made and implementation experience gained will inform the writing of a Data Citation Procedural Directive to be issued by the Environmental Data Management Committee in 2014. Several identifiers have been issued as of July 2013, with more on the way. NOAA is now reporting the number as a metric to federal Open Government initiatives. This paper will provide further details and status of the project.
Functional response to cholinesterase inhibitor therapy in a naturalistic Alzheimer’s disease cohort

Directory of Open Access Journals (Sweden)

Wattmo Carina

2012-11-01

Full Text Available Abstract Background Activities of daily living (ADL are an essential part of the diagnostic criteria for Alzheimer’s disease (AD. A decline in ADL affects independent living and has a strong negative impact on caregiver burden. Functional response to cholinesterase inhibitor (ChEI treatment and factors that might influence this response in naturalistic AD patients need investigating. The aim of this study was to identify the socio-demographic and clinical factors that affect the functional response after 6 months of ChEI therapy. Methods This prospective, non-randomised, multicentre study in a routine clinical setting included 784 AD patients treated with donepezil, rivastigmine or galantamine. At baseline and after 6 months of treatment, patients were assessed using several rating scales, including the Instrumental Activities of Daily Living (IADL scale, Physical Self-Maintenance Scale (PSMS and Mini-Mental State Examination (MMSE. Demographic and clinical characteristics were investigated at baseline. The functional response and the relationships of potential predictors were analysed using general linear models. Results After 6 months of ChEI treatment, 49% and 74% of patients showed improvement/no change in IADL and in PSMS score, respectively. The improved/unchanged patients exhibited better cognitive status at baseline; regarding improved/unchanged PSMS, patients were younger and used fewer anti-depressants. A more positive functional response to ChEI was observed in younger individuals or among those having the interaction effect of better preserved cognition and lower ADL ability. Patients with fewer concomitant medications or those using NSAIDs/acetylsalicylic acid showed a better PSMS response. Conclusions Critical characteristics that may influence the functional response to ChEI in AD were identified. Some predictors differed from those previously shown to affect cognitive response, e.g., lower cognitive ability and older age
Leptin regulates dopamine responses to sustained stress in humans

OpenAIRE

Burghardt, Paul R; Love, Tiffany M; Stohler, Christian S.; Hodgkinson, Colin; Shen, Pei-Hong; Enoch, Mary Ann; Goldman, David; Zubieta, Jon-Kar

2012-01-01

Neural systems that identify and respond to salient stimuli are critical for survival in a complex and changing environment. In addition, interindividual differences, including genetic variation, hormonal, and metabolic status likely influence the behavioral strategies and neuronal responses to environmental challenges. Here we examined the relationship between leptin allelic variation and plasma leptin levels with DAD2/3R availability in vivo as measured with [11C]raclopride Positron Emissio...
Identifying content for simulation-based curricula in urology

DEFF Research Database (Denmark)

Nayahangan, Leizl Joy; Hansen, Rikke Bolling; Lindorff-Larsen, Karen Gilboe

2017-01-01

to identify technical procedures in urology that should be included in a simulation-based curriculum for residency training. MATERIALS AND METHODS: A national needs assessment was performed using the Delphi method involving 56 experts with significant roles in the education of urologists. Round 1 identified...
Rate of Clinical Complete Response for 1 Year or More in Bone-Metastatic Breast Cancer after Comprehensive Treatments including Autologous Formalin-Fixed Tumor Vaccine

Directory of Open Access Journals (Sweden)

Fumito Kuranishi

2018-01-01

Full Text Available Introduction. No effective treatment has been developed for bone-metastatic breast cancer. We found 3 cases with clinical complete response (cCR of the bone metastasis and longer overall survival of the retrospectively examined cohort treated comprehensively including autologous formalin-fixed tumor vaccine (AFTV. Patients and Methods. AFTV was prepared individually for each patient from their own formalin-fixed and paraffin-embedded breast cancer tissues. Results. Three patients maintained cCR status of the bone metastasis for 17 months or more. Rate of cCR for 1 year or more appeared to be 15% (3/20 after comprehensive treatments including AFTV. The median overall survival time (60.0 months and the 3- to 8-year survival rates after diagnosis of bone metastasis were greater than those of historical control cohorts in Japan (1988–2002 and in the nationwide population-based cohort study of Denmark (1999–2007. Conclusion. Bone-metastatic breast cancer may be curable after comprehensive treatments including AFTV, although larger scale clinical trial is required.
Exploration of the Influence of Factors Identified in the Literature on School-aged Children's Emotional Responses to Asthma.

Science.gov (United States)

Walker, Verónica García

Approximately 6.3 million US children suffer from asthma. The purpose of this study was to explore factors on school-aged children's emotional responses to asthma, N=85, ages 6-12. Correlations included Asthma related child emotional functioning QOL and (a) asthma severity, r=-0.30, pchild internalizing behaviors, r=-0.26, pchild externalizing behaviors r=-0.43, pasthma severity, r=-0.39, pchild internalizing behaviors, r=-0.22, pchild externalizing behaviors, r=-0.25; pasthma severity and child externalizing problems accounted for 26% of the variance in asthma related child emotional functioning QOL, F (4, 79)=7.051, pasthma severity, β=-0.31, pchild externalizing problem behaviors, β=-0.43, pasthma research should consider problem behaviors of school-aged children when addressing asthma related emotional functioning QOL. Copyright © 2016 Elsevier Inc. All rights reserved.
Validating the Modified Drug Adherence Work-Up (M-DRAW) Tool to Identify and Address Barriers to Medication Adherence.

Science.gov (United States)

Lee, Sun; Bae, Yuna H; Worley, Marcia; Law, Anandi

2017-09-08

Barriers to medication adherence stem from multiple factors. An effective and convenient tool is needed to identify these barriers so that clinicians can provide a tailored, patient-centered consultation with patients. The Modified Drug Adherence Work-up Tool (M-DRAW) was developed as a 13-item checklist questionnaire to identify barriers to medication adherence. The response scale was a 4-point Likert scale of frequency of occurrence (1 = never to 4 = often). The checklist was accompanied by a GUIDE that provided corresponding motivational interview-based intervention strategies for each identified barrier. The current pilot study examined the psychometric properties of the M-DRAW checklist (reliability, responsiveness and discriminant validity) in patients taking one or more prescription medication(s) for chronic conditions. A cross-sectional sample of 26 patients was recruited between December 2015 and March 2016 at an academic medical center pharmacy in Southern California. A priming question that assessed self-reported adherence was used to separate participants into the control group of 17 "adherers" (65.4%), and into the intervention group of nine "unintentional and intentional non-adherers" (34.6%). Comparable baseline characteristics were observed between the two groups. The M-DRAW checklist showed acceptable reliability (13 item; alpha = 0.74) for identifying factors and barriers leading to medication non-adherence. Discriminant validity of the tool and the priming question was established by the four-fold number of barriers to adherence identified within the self-selected intervention group compared to the control group (4.4 versus 1.2 barriers, p tool will include construct validation.
Assessing Sources of Stress to Aquatic Ecosystems: Using Biomarkers and Bioindicators to Characterize Exodure-Response Profiles of Anthropogenic Activities

Energy Technology Data Exchange (ETDEWEB)

Adams, S.M.

1999-03-29

Establishing causal relationships between sources of environmental stressors and aquatic ecosystem health if difficult because of the many biotic and abiotic factors which can influence or modify responses of biological systems to stress, the orders of magnitude involved in extrapolation over both spatial and temporal scales, and compensatory mechanisms such as density-dependent responses that operate in populations. To address the problem of establishing causality between stressors and effects on aquatic systems, a diagnostic approach, based on exposure-response profiles for various anthropogenic activities, was developed to help identify sources of stress responsible for effects on aquatic systems at ecological significant levels of biological organization (individual, population, community). To generate these exposure-effects profiles, biomarkers of exposure were plotted against bioindicators of corresponding effects for several major anthropogenic activities including petrochemical , pulp and paper, domestic sewage, mining operations, land-development activities, and agricultural activities. Biomarkers of exposure to environmental stressors varied depending on the type of anthropogenic activity involved. Bioindicator effects, however, including histopathological lesions, bioenergetic status, individual growth, reproductive impairment, and community-level responses were similar among many of the major anthropogenic activities. This approach is valuable to help identify and diagnose sources of stressors in environments impacted by multiple stressors. By identifying the types and sources of environmental stressors, aquatic ecosystems can be more effectively protected and managed to maintain acceptable levels of environmental quality and ecosystem fitness.
Applying Acoustical and Musicological Analysis to Detect Brain Responses to Realistic Music: A Case Study

Directory of Open Access Journals (Sweden)

Niels Trusbak Haumann

2018-05-01

Full Text Available Music information retrieval (MIR methods offer interesting possibilities for automatically identifying time points in music recordings that relate to specific brain responses. However, how the acoustical features and the novelty of the music structure affect the brain response is not yet clear. In the present study, we tested a new method for automatically identifying time points of brain responses based on MIR analysis. We utilized an existing database including brain recordings of 48 healthy listeners measured with electroencephalography (EEG and magnetoencephalography (MEG. While we succeeded in capturing brain responses related to acoustical changes in the modern tango piece Adios Nonino, we obtained less reliable brain responses with a metal rock piece and a modern symphony orchestra musical composition. However, brain responses might also relate to the novelty of the music structure. Hence, we added a manual musicological analysis of novelty in the musical structure to the computational acoustic analysis, obtaining strong brain responses even to the rock and modern pieces. Although no standardized method yet exists, these preliminary results suggest that analysis of novelty in music is an important aid to MIR analysis for investigating brain responses to realistic music.
Integrated RNA-Seq and sRNA-Seq Analysis Identifies Chilling and Freezing Responsive Key Molecular Players and Pathways in Tea Plant (Camellia sinensis)

Science.gov (United States)

Zheng, Chao; Zhao, Lei; Wang, Yu; Shen, Jiazhi; Zhang, Yinfei; Jia, Sisi; Li, Yusheng; Ding, Zhaotang

2015-01-01

Tea [Camellia sinensis (L) O. Kuntze, Theaceae] is one of the most popular non-alcoholic beverages worldwide. Cold stress is one of the most severe abiotic stresses that limit tea plants’ growth, survival and geographical distribution. However, the genetic regulatory network and signaling pathways involved in cold stress responses in tea plants remain unearthed. Using RNA-Seq, DGE and sRNA-Seq technologies, we performed an integrative analysis of miRNA and mRNA expression profiling and their regulatory network of tea plants under chilling (4℃) and freezing (-5℃) stress. Differentially expressed (DE) miRNA and mRNA profiles were obtained based on fold change analysis, miRNAs and target mRNAs were found to show both coherent and incoherent relationships in the regulatory network. Furthermore, we compared several key pathways (e.g., ‘Photosynthesis’), GO terms (e.g., ‘response to karrikin’) and transcriptional factors (TFs, e.g., DREB1b/CBF1) which were identified as involved in the early chilling and/or freezing response of tea plants. Intriguingly, we found that karrikins, a new group of plant growth regulators, and β-primeverosidase (BPR), a key enzyme functionally relevant with the formation of tea aroma might play an important role in both early chilling and freezing response of tea plants. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis further confirmed the results from RNA-Seq and sRNA-Seq analysis. This is the first study to simultaneously profile the expression patterns of both miRNAs and mRNAs on a genome-wide scale to elucidate the molecular mechanisms of early responses of tea plants to cold stress. In addition to gaining a deeper insight into the cold resistant characteristics of tea plants, we provide a good case study to analyse mRNA/miRNA expression and profiling of non-model plant species using next-generation sequencing technology. PMID:25901577
Bmp indicator mice reveal dynamic regulation of transcriptional response.

Directory of Open Access Journals (Sweden)

Anna L Javier

Full Text Available Cellular responses to Bmp ligands are regulated at multiple levels, both extracellularly and intracellularly. Therefore, the presence of these growth factors is not an accurate indicator of Bmp signaling activity. While a common approach to detect Bmp signaling activity is to determine the presence of phosphorylated forms of Smad1, 5 and 8 by immunostaining, this approach is time consuming and not quantitative. In order to provide a simpler readout system to examine the presence of Bmp signaling in developing animals, we developed BRE-gal mouse embryonic stem cells and a transgenic mouse line that specifically respond to Bmp ligand stimulation. Our reporter identifies specific transcriptional responses that are mediated by Smad1 and Smad4 with the Schnurri transcription factor complex binding to a conserved Bmp-Responsive Element (BRE, originally identified among Drosophila, Xenopus and human Bmp targets. Our BRE-gal mES cells specifically respond to Bmp ligands at concentrations as low as 5 ng/ml; and BRE-gal reporter mice, derived from the BRE-gal mES cells, show dynamic activity in many cellular sites, including extraembryonic structures and mammary glands, thereby making this a useful scientific tool.

FoxO and stress responses in the cnidarian Hydra vulgaris.

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Diane Bridge

2010-07-01

Full Text Available In the face of changing environmental conditions, the mechanisms underlying stress responses in diverse organisms are of increasing interest. In vertebrates, Drosophila, and Caenorhabditis elegans, FoxO transcription factors mediate cellular responses to stress, including oxidative stress and dietary restriction. Although FoxO genes have been identified in early-arising animal lineages including sponges and cnidarians, little is known about their roles in these organisms.We have examined the regulation of FoxO activity in members of the well-studied cnidarian genus Hydra. We find that Hydra FoxO is expressed at high levels in cells of the interstitial lineage, a cell lineage that includes multipotent stem cells that give rise to neurons, stinging cells, secretory cells and gametes. Using transgenic Hydra that express a FoxO-GFP fusion protein in cells of the interstitial lineage, we have determined that heat shock causes localization of the fusion protein to the nucleus. Our results also provide evidence that, as in bilaterian animals, Hydra FoxO activity is regulated by both Akt and JNK kinases.These findings imply that basic mechanisms of FoxO regulation arose before the evolution of bilaterians and raise the possibility that FoxO is involved in stress responses of other cnidarian species, including corals.
Development of a simple binary response questionnaire to identify airflow obstruction in a smoking population in Argentina.

Science.gov (United States)

Bergna, Miguel A; García, Gabriel R; Alchapar, Ramon; Altieri, Hector; Casas, Juan C Figueroa; Larrateguy, Luis; Nannini, Luis J; Pascansky, Daniel; Grabre, Pedro; Zabert, Gustavo; Miravitlles, Marc

2015-06-01

The CODE questionnaire (COPD detection questionnaire), a simple, binary response scale (yes/no), screening questionnaire, was developed for the identification of patients with chronic obstructive pulmonary disease (COPD). We conducted a survey of 468 subjects with a smoking history in 10 public hospitals in Argentina. Patients with a previous diagnosis of COPD, asthma and other respiratory illness were excluded. Items that measured conceptual domains in terms of characteristics of symptoms, smoking history and demographics data were considered. 96 (20.5%) subjects had a diagnosis of COPD according to the 2010 Global Initiative for Chronic Obstructive Lung Disease strategy document. The variables selected for the final questionnaire were based on univariate and multivariate analyses and clinical criteria. Finally, we selected the presence or absence of six variables (age ≥50 years, smoking history ≥30 pack-years, male sex, chronic cough, chronic phlegm and dyspnoea). Of patients without any of these six variables (0 points), none had COPD. The ability of the CODE questionnaire to discriminate between subjects with and without COPD was good (the area under the receiver operating characteristic curve was 0.75). Higher scores were associated with a greater probability of COPD. The CODE questionnaire is a brief, accurate questionnaire that can identify smoking individuals likely to have COPD. Copyright ©ERS 2015.
Development of a simple binary response questionnaire to identify airflow obstruction in a smoking population in Argentina

Directory of Open Access Journals (Sweden)

Miguel A. Bergna

2015-06-01

Full Text Available The CODE questionnaire (COPD detection questionnaire, a simple, binary response scale (yes/no, screening questionnaire, was developed for the identification of patients with chronic obstructive pulmonary disease (COPD. We conducted a survey of 468 subjects with a smoking history in 10 public hospitals in Argentina. Patients with a previous diagnosis of COPD, asthma and other respiratory illness were excluded. Items that measured conceptual domains in terms of characteristics of symptoms, smoking history and demographics data were considered. 96 (20.5% subjects had a diagnosis of COPD according to the 2010 Global Initiative for Chronic Obstructive Lung Disease strategy document. The variables selected for the final questionnaire were based on univariate and multivariate analyses and clinical criteria. Finally, we selected the presence or absence of six variables (age ≥50 years, smoking history ≥30 pack-years, male sex, chronic cough, chronic phlegm and dyspnoea. Of patients without any of these six variables (0 points, none had COPD. The ability of the CODE questionnaire to discriminate between subjects with and without COPD was good (the area under the receiver operating characteristic curve was 0.75. Higher scores were associated with a greater probability of COPD. The CODE questionnaire is a brief, accurate questionnaire that can identify smoking individuals likely to have COPD.
Global transcriptomic profiling of aspen trees under elevated [CO2] to identify potential molecular mechanisms responsible for enhanced radial growth.

Science.gov (United States)

Wei, Hairong; Gou, Jiqing; Yordanov, Yordan; Zhang, Huaxin; Thakur, Ramesh; Jones, Wendy; Burton, Andrew

2013-03-01

Aspen (Populus tremuloides) trees growing under elevated [CO(2)] at a free-air CO(2) enrichment (FACE) site produced significantly more biomass than control trees. We investigated the molecular mechanisms underlying the observed increase in biomass by producing transcriptomic profiles of the vascular cambium zone (VCZ) and leaves, and then performed a comparative study to identify significantly changed genes and pathways after 12 years exposure to elevated [CO(2)]. In leaves, elevated [CO(2)] enhanced expression of genes related to Calvin cycle activity and linked pathways. In the VCZ, the pathways involved in cell growth, cell division, hormone metabolism, and secondary cell wall formation were altered while auxin conjugation, ABA synthesis, and cytokinin glucosylation and degradation were inhibited. Similarly, the genes involved in hemicellulose and pectin biosynthesis were enhanced, but some genes that catalyze important steps in lignin biosynthesis pathway were inhibited. Evidence from systemic analysis supported the functioning of multiple molecular mechanisms that underpin the enhanced radial growth in response to elevated [CO(2)].
Transcriptome analysis reveals mucin 4 to be highly associated with periodontitis and identifies pleckstrin as a link to systemic diseases

Science.gov (United States)

Lundmark, Anna; Davanian, Haleh; Båge, Tove; Johannsen, Gunnar; Koro, Catalin; Lundeberg, Joakim; Yucel-Lindberg, Tülay

2015-01-01

The multifactorial chronic inflammatory disease periodontitis, which is characterized by destruction of tooth-supporting tissues, has also been implicated as a risk factor for various systemic diseases. Although periodontitis has been studied extensively, neither disease-specific biomarkers nor therapeutic targets have been identified, nor its link with systemic diseases. Here, we analyzed the global transcriptome of periodontitis and compared its gene expression profile with those of other inflammatory conditions, including cardiovascular disease (CVD), rheumatoid arthritis (RA), and ulcerative colitis (UC). Gingival biopsies from 62 patients with periodontitis and 62 healthy subjects were subjected to RNA sequencing. The up-regulated genes in periodontitis were related to inflammation, wounding and defense response, and apoptosis, whereas down-regulated genes were related to extracellular matrix organization and structural support. The most highly up-regulated gene was mucin 4 (MUC4), and its protein product was confirmed to be over-expressed in periodontitis. When comparing the expression profile of periodontitis with other inflammatory diseases, several gene ontology categories, including inflammatory response, cell death, cell motion, and homeostatic processes, were identified as common to all diseases. Only one gene, pleckstrin (PLEK), was significantly overexpressed in periodontitis, CVD, RA, and UC, implicating this gene as an important networking link between these chronic inflammatory diseases. PMID:26686060
The genome-wide early temporal response of Saccharomyces cerevisiae to oxidative stress induced by cumene hydroperoxide.

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Wei Sha

Full Text Available Oxidative stress is a well-known biological process that occurs in all respiring cells and is involved in pathophysiological processes such as aging and apoptosis. Oxidative stress agents include peroxides such as hydrogen peroxide, cumene hydroperoxide, and linoleic acid hydroperoxide, the thiol oxidant diamide, and menadione, a generator of superoxide, amongst others. The present study analyzed the early temporal genome-wide transcriptional response of Saccharomyces cerevisiae to oxidative stress induced by the aromatic peroxide cumene hydroperoxide. The accurate dataset obtained, supported by the use of temporal controls, biological replicates and well controlled growth conditions, provided a detailed picture of the early dynamics of the process. We identified a set of genes previously not implicated in the oxidative stress response, including several transcriptional regulators showing a fast transient response, suggesting a coordinated process in the transcriptional reprogramming. We discuss the role of the glutathione, thioredoxin and reactive oxygen species-removing systems, the proteasome and the pentose phosphate pathway. A data-driven clustering of the expression patterns identified one specific cluster that mostly consisted of genes known to be regulated by the Yap1p and Skn7p transcription factors, emphasizing their mediator role in the transcriptional response to oxidants. Comparison of our results with data reported for hydrogen peroxide identified 664 genes that specifically respond to cumene hydroperoxide, suggesting distinct transcriptional responses to these two peroxides. Genes up-regulated only by cumene hydroperoxide are mainly related to the cell membrane and cell wall, and proteolysis process, while those down-regulated only by this aromatic peroxide are involved in mitochondrial function.
Seabrook Station Level 2 PRA Update to Include Accident Management

International Nuclear Information System (INIS)

Lutz, Robert; Lucci, Melissa; Kiper, Kenneth; Henry, Robert

2006-01-01

A ground-breaking study was recently completed as part of the Seabrook Level 2 PRA update. This study updates the post-core damage phenomena to be consistent with the most recent information and includes accident management activities that should be modeled in the Level 2 PRA. Overall, the result is a Level 2 PRA that fully meets the requirements of the ASME PRA Standard with respect to modeling accident management in the LERF assessment and NRC requirements in Regulatory Guide 1.174 for considering late containment failures. This technical paper deals only with the incorporation of operator actions into the Level 2 PRA based on a comprehensive study of the Seabrook Station accident response procedures and guidance. The paper describes the process used to identify the key operator actions that can influence the Level 2 PRA results and the development of success criteria for these key operator actions. This addresses a key requirement of the ASME PRA Standard for considering SAMG. An important benefit of this assessment was the identification of Seabrook specific accident management insights that can be fed back into the Seabrook Station accident management procedures and guidance or the training provided to plant personnel for these procedures and guidance. (authors)
Optimal Responsible Investment

DEFF Research Database (Denmark)

Jessen, Pernille

Numerous institutions are now engaged in Socially Responsible Investment or have signed the "UN Principles for Responsible Investment". Retail investors, however, are still lacking behind. This is peculiar since the sector constitutes key stakeholders in environmental, social and governmental...... standards. This paper considers optimal responsible investment for a small retail investor. It extends conventional portfolio theory by allowing for a personal-value based investment decision. Preferences for responsibility are defined in the framework of mean-variance analysis and an optimal responsible...... investment model identified. Implications of the altered investment problem are investigated when the dynamics between portfolio risk, expected return and responsibility is considered. Relying on the definition of a responsible investor, it is shown how superior investment opportunities can emerge when...
Transcriptomic variation among six Arabidopsis thaliana accessions identified several novel genes controlling aluminium tolerance.

Science.gov (United States)

Kusunoki, Kazutaka; Nakano, Yuki; Tanaka, Keisuke; Sakata, Yoichi; Koyama, Hiroyuki; Kobayashi, Yuriko

2017-02-01

Differences in the expression levels of aluminium (Al) tolerance genes are a known determinant of Al tolerance among plant varieties. We combined transcriptomic analysis of six Arabidopsis thaliana accessions with contrasting Al tolerance and a reverse genetic approach to identify Al-tolerance genes responsible for differences in Al tolerance between accession groups. Gene expression variation increased in the signal transduction process under Al stress and in growth-related processes in the absence of stress. Co-expression analysis and promoter single nucleotide polymorphism searching suggested that both trans-acting polymorphisms of Al signal transduction pathway and cis-acting polymorphisms in the promoter sequences caused the variations in gene expression associated with Al tolerance. Compared with the wild type, Al sensitivity increased in T-DNA knockout (KO) lines for five genes, including TARGET OF AVRB OPERATION1 (TAO1) and an unannotated gene (At5g22530). These were identified from 53 Al-inducible genes showing significantly higher expression in tolerant accessions than in sensitive accessions. These results indicate that the difference in transcriptional signalling is partly associated with the natural variation in Al tolerance in Arabidopsis. Our study also demonstrates the feasibility of comparative transcriptome analysis by using natural genetic variation for the identification of genes responsible for Al stress tolerance. © 2016 John Wiley & Sons Ltd.
Fever in trauma patients: evaluation of risk factors, including traumatic brain injury.

Science.gov (United States)

Bengualid, Victoria; Talari, Goutham; Rubin, David; Albaeni, Aiham; Ciubotaru, Ronald L; Berger, Judith

2015-03-01

The role of fever in trauma patients remains unclear. Fever occurs as a response to release of cytokines and prostaglandins by white blood cells. Many factors, including trauma, can trigger release of these factors. To determine whether (1) fever in the first 48 hours is related to a favorable outcome in trauma patients and (2) fever is more common in patients with head trauma. Retrospective study of trauma patients admitted to the intensive care unit for at least 2 days. Data were analyzed by using multivariate analysis. Of 162 patients studied, 40% had fever during the first 48 hours. Febrile patients had higher mortality rates than did afebrile patients. When adjusted for severity of injuries, fever did not correlate with mortality. Neither the incidence of fever in the first 48 hours after admission to the intensive care unit nor the number of days febrile in the unit differed between patients with and patients without head trauma (traumatic brain injury). About 70% of febrile patients did not have a source found for their fever. Febrile patients without an identified source of infection had lower peak white blood cell counts, lower maximum body temperature, and higher minimum platelet counts than did febrile patients who had an infectious source identified. The most common infection was pneumonia. No relationship was found between the presence of fever during the first 48 hours and mortality. Patients with traumatic brain injury did not have a higher incidence of fever than did patients without traumatic brain injury. About 30% of febrile patients had an identifiable source of infection. Further studies are needed to understand the origin and role of fever in trauma patients. ©2015 American Association of Critical-Care Nurses.
Experiences of female partners of masculine-identifying trans persons.

Science.gov (United States)

Theron, Liesl; Collier, Kate L

2013-01-01

This paper explores the intimate relationship experiences of the cisgender (i.e., not transgender) female partners of masculine-identifying transgender persons, with a particular focus on these partners' self-understanding of their sexual orientation. Limited research about this topic has been conducted to date. Semi-structured interviews were conducted with eight South African women who are or have been cisgender female partners of masculine-identifying trans persons. Although the interviews showed that the relationship experiences of female partners of masculine-identifying trans persons are diverse, several common themes emerged in the narratives. The way that participants labelled their sexual orientation did not change from before to after their relationship with a transgender partner. The participants reported varied family and community responses to their relationships. Specific emotional and informational support needs for women with transgender partners were identified.
The response to September 11: a disaster case study.

Science.gov (United States)

Crane, Michael A; Levy-Carrick, Nomi C; Crowley, Laura; Barnhart, Stephanie; Dudas, Melissa; Onuoha, Uchechukwu; Globina, Yelena; Haile, Winta; Shukla, Gauri; Ozbay, Fatih

2014-01-01

The response to 9/11 continues into its 14th year. The World Trade Center Health Program (WTCHP), a long-term monitoring and treatment program now funded by the Zadroga Act of 2010, includes >60,000 World Trade Center (WTC) disaster responders and community members ("survivors"). The aim of this review is to identify several elements that have had a critical impact on the evolution of the WTC response and, directly or indirectly, the health of the WTC-exposed population. It further explores post-disaster monitoring efforts, recent scientific findings from the WTCHP, and some implications of this experience for ongoing and future environmental disaster response. Transparency and responsiveness, site safety and worker training, assessment of acute and chronic exposure, and development of clinical expertise are interconnected elements determining efficacy of disaster response. Even in a relatively well-resourced environment, challenges regarding allocation of appropriate attention to vulnerable populations and integration of treatment response to significant medical and mental health comorbidities remain areas of ongoing programmatic development. Copyright © 2014 Icahn School of Medicine at Mount Sinai. All rights reserved.
Method and apparatus for controlling a powertrain system including a multi-mode transmission

Science.gov (United States)

Hessell, Steven M.; Morris, Robert L.; McGrogan, Sean W.; Heap, Anthony H.; Mendoza, Gil J.

2015-09-08

A powertrain including an engine and torque machines is configured to transfer torque through a multi-mode transmission to an output member. A method for controlling the powertrain includes employing a closed-loop speed control system to control torque commands for the torque machines in response to a desired input speed. Upon approaching a power limit of a power storage device transferring power to the torque machines, power limited torque commands are determined for the torque machines in response to the power limit and the closed-loop speed control system is employed to determine an engine torque command in response to the desired input speed and the power limited torque commands for the torque machines.
Antibiotic Stimulation of a Bacillus subtilis Migratory Response

Science.gov (United States)

Liu, Yongjin; Kyle, Steven

2018-01-01

ABSTRACT Competitive interactions between bacteria reveal physiological adaptations that benefit fitness. Bacillus subtilis is a Gram-positive species with several adaptive mechanisms for competition and environmental stress. Biofilm formation, sporulation, and motility are the outcomes of widespread changes in a population of B. subtilis. These changes emerge from complex, regulated pathways for adapting to external stresses, including competition from other species. To identify competition-specific functions, we cultured B. subtilis with multiple species of Streptomyces and observed altered patterns of growth for each organism. In particular, when plated on agar medium near Streptomyces venezuelae, B. subtilis initiates a robust and reproducible mobile response. To investigate the mechanistic basis for the interaction, we determined the type of motility used by B. subtilis and isolated inducing metabolites produced by S. venezuelae. Bacillus subtilis has three defined forms of motility: swimming, swarming, and sliding. Streptomyces venezuelae induced sliding motility specifically in our experiments. The inducing agents produced by S. venezuelae were identified as chloramphenicol and a brominated derivative at subinhibitory concentrations. Upon further characterization of the mobile response, our results demonstrated that subinhibitory concentrations of chloramphenicol, erythromycin, tetracycline, and spectinomycin all activate a sliding motility response by B. subtilis. Our data are consistent with sliding motility initiating under conditions of protein translation stress. This report underscores the importance of hormesis as an early warning system for potential bacterial competitors and antibiotic exposure. IMPORTANCE Antibiotic resistance is a major challenge for the effective treatment of infectious diseases. Identifying adaptive mechanisms that bacteria use to survive low levels of antibiotic stress is important for understanding pathways to
Discovery of stimulation-responsive immune enhancers with CRISPR activation

Science.gov (United States)

Simeonov, Dimitre R.; Gowen, Benjamin G.; Boontanrart, Mandy; Roth, Theodore L.; Gagnon, John D.; Mumbach, Maxwell R.; Satpathy, Ansuman T.; Lee, Youjin; Bray, Nicolas L.; Chan, Alice Y.; Lituiev, Dmytro S.; Nguyen, Michelle L.; Gate, Rachel E.; Subramaniam, Meena; Li, Zhongmei; Woo, Jonathan M.; Mitros, Therese; Ray, Graham J.; Curie, Gemma L.; Naddaf, Nicki; Chu, Julia S.; Ma, Hong; Boyer, Eric; van Gool, Frederic; Huang, Hailiang; Liu, Ruize; Tobin, Victoria R.; Schumann, Kathrin; Daly, Mark J.; Farh, Kyle K.; Ansel, K. Mark; Ye, Chun J.; Greenleaf, William J.; Anderson, Mark S.; Bluestone, Jeffrey A.; Chang, Howard Y.; Corn, Jacob E.; Marson, Alexander

2017-09-01

The majority of genetic variants associated with common human diseases map to enhancers, non-coding elements that shape cell-type-specific transcriptional programs and responses to extracellular cues. Systematic mapping of functional enhancers and their biological contexts is required to understand the mechanisms by which variation in non-coding genetic sequences contributes to disease. Functional enhancers can be mapped by genomic sequence disruption, but this approach is limited to the subset of enhancers that are necessary in the particular cellular context being studied. We hypothesized that recruitment of a strong transcriptional activator to an enhancer would be sufficient to drive target gene expression, even if that enhancer was not currently active in the assayed cells. Here we describe a discovery platform that can identify stimulus-responsive enhancers for a target gene independent of stimulus exposure. We used tiled CRISPR activation (CRISPRa) to synthetically recruit a transcriptional activator to sites across large genomic regions (more than 100 kilobases) surrounding two key autoimmunity risk loci, CD69 and IL2RA. We identified several CRISPRa-responsive elements with chromatin features of stimulus-responsive enhancers, including an IL2RA enhancer that harbours an autoimmunity risk variant. Using engineered mouse models, we found that sequence perturbation of the disease-associated Il2ra enhancer did not entirely block Il2ra expression, but rather delayed the timing of gene activation in response to specific extracellular signals. Enhancer deletion skewed polarization of naive T cells towards a pro-inflammatory T helper (TH17) cell state and away from a regulatory T cell state. This integrated approach identifies functional enhancers and reveals how non-coding variation associated with human immune dysfunction alters context-specific gene programs.
Discovery of stimulation-responsive immune enhancers with CRISPR activation

Science.gov (United States)

Simeonov, Dimitre R.; Gowen, Benjamin G.; Boontanrart, Mandy; Roth, Theodore L.; Gagnon, John D.; Mumbach, Maxwell R.; Satpathy, Ansuman T.; Lee, Youjin; Bray, Nicolas L.; Chan, Alice Y.; Lituiev, Dmytro S.; Nguyen, Michelle L.; Gate, Rachel E.; Subramaniam, Meena; Li, Zhongmei; Woo, Jonathan M.; Mitros, Therese; Ray, Graham J.; Curie, Gemma L.; Naddaf, Nicki; Chu, Julia S.; Ma, Hong; Boyer, Eric; Van Gool, Frederic; Huang, Hailiang; Liu, Ruize; Tobin, Victoria R.; Schumann, Kathrin; Daly, Mark J.; Farh, Kyle K; Ansel, K. Mark; Ye, Chun J.; Greenleaf, William J.; Anderson, Mark S.; Bluestone, Jeffrey A.; Chang, Howard Y.; Corn, Jacob E.; Marson, Alexander

2017-01-01

The majority of genetic variants associated with common human diseases map to enhancers, non-coding elements that shape cell-type-specific transcriptional programs and responses to extracellular cues1–3. Systematic mapping of functional enhancers and their biological contexts is required to understand the mechanisms by which variation in non-coding genetic sequences contributes to disease. Functional enhancers can be mapped by genomic sequence disruption4–6, but this approach is limited to the subset of enhancers that are necessary in the particular cellular context being studied. We hypothesized that recruitment of a strong transcriptional activator to an enhancer would be sufficient to drive target gene expression, even if that enhancer was not currently active in the assayed cells. Here we describe a discovery platform that can identify stimulus-responsive enhancers for a target gene independent of stimulus exposure. We used tiled CRISPR activation (CRISPRa)7 to synthetically recruit a transcriptional activator to sites across large genomic regions (more than 100 kilobases) surrounding two key autoimmunity risk loci, CD69 and IL2RA. We identified several CRISPRa-responsive elements with chromatin features of stimulus-responsive enhancers, including an IL2RA enhancer that harbours an autoimmunity risk variant. Using engineered mouse models, we found that sequence perturbation of the disease-associated Il2ra enhancer did not entirely block Il2ra expression, but rather delayed the timing of gene activation in response to specific extracellular signals. Enhancer deletion skewed polarization of naive T cells towards a pro-inflammatory T helper (TH17) cell state and away from a regulatory T cell state. This integrated approach identifies functional enhancers and reveals how non-coding variation associated with human immune dysfunction alters context-specific gene programs. PMID:28854172
Processing negative valence of word pairs that include a positive word.

Science.gov (United States)

Itkes, Oksana; Mashal, Nira

2016-09-01

Previous research has suggested that cognitive performance is interrupted by negative relative to neutral or positive stimuli. We examined whether negative valence affects performance at the word or phrase level. Participants performed a semantic decision task on word pairs that included either a negative or a positive target word. In Experiment 1, the valence of the target word was congruent with the overall valence conveyed by the word pair (e.g., fat kid). As expected, response times were slower in the negative condition relative to the positive condition. Experiment 2 included target words that were incongruent with the overall valence of the word pair (e.g., fat salary). Response times were longer for word pairs whose overall valence was negative relative to positive, even though these word pairs included a positive word. Our findings support the Cognitive Primacy Hypothesis, according to which emotional valence is extracted after conceptual processing is complete.
Mechanisms of the placebo response in pain in osteoarthritis.

Science.gov (United States)

Abhishek, A; Doherty, M

2013-09-01

Administration of a placebo associates with symptomatic improvement in many conditions--the so-called placebo response. In this review we explain the concept of placebo response, examine the data that supports existence in osteoarthritis (OA), and discuss its possible mechanisms and determinants. A Pubmed literature search was carried out. Key articles were identified, and their findings discussed in a narrative review. Pain, stiffness, self-reported function and physician-global assessment in OA clearly improve in response to placebo. However, more objective measures such as quadriceps strength and radiographic progression appear less responsive. Although not directly studied in OA, contextual effects, patient expectation and conditioning are believed to be the main mechanisms. Neurotransmitter changes that mediate placebo-induced analgesia include increased endogenous opioid levels, increased dopamine levels, and reduced levels of cholecystokinin. Almost all parts of the brain involved in pain processing are influenced during placebo-induced analgesia. Determinants of the magnitude of placebo response include the patient-practitioner interaction, treatment response expectancy, knowledge of being treated, patient personality traits and placebo specific factors such as the route and frequency of administration, branding, and treatment costs. Clearer understanding of the neurobiology of placebo response validates its existence as a real phenomenon. Although routine administration of placebo for symptomatic improvement is difficult to justify, contextual factors that enhance treatment response should be employed in the management of chronic painful conditions such as OA where available treatments have only modest efficacy. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
Identifying the Key Weaknesses in Network Security at Colleges.

Science.gov (United States)

Olsen, Florence

2000-01-01

A new study identifies and ranks the 10 security gaps responsible for most outsider attacks on college computer networks. The list is intended to help campus system administrators establish priorities as they work to increase security. One network security expert urges that institutions utilize multiple security layers. (DB)
The host immune response to Clostridium difficile infection

Science.gov (United States)

2013-01-01

Clostridium difficile infection (CDI) is the most common infectious cause of healthcare-acquired diarrhoea. Outcomes of C. difficile colonization are varied, from asymptomatic carriage to fulminant colitis and death, due in part to the interplay between the pathogenic virulence factors of the bacterium and the counteractive immune responses of the host. Secreted toxins A and B are the major virulence factors of C. difficile and induce a profound inflammatory response by intoxicating intestinal epithelial cells causing proinflammatory cytokine release. Host cell necrosis, vascular permeability and neutrophil infiltration lead to an elevated white cell count, profuse diarrhoea and in severe cases, dehydration, hypoalbuminaemia and toxic megacolon. Other bacterial virulence factors, including surface layer proteins and flagella proteins, are detected by host cell surface signal molecules that trigger downstream cell-mediated immune pathways. Human studies have identified a role for serum and faecal immunoglobulin levels in protection from disease, but the recent development of a mouse model of CDI has enabled studies into the precise molecular interactions that trigger the immune response during infection. Key effector molecules have been identified that can drive towards a protective anti-inflammatory response or a damaging proinflammatory response. The limitations of current antimicrobial therapies for CDI have led to the development of both active and passive immunotherapies, none of which have, as yet been formally approved for CDI. However, recent advances in our understanding of the molecular basis of host immune protection against CDI may provide an exciting opportunity for novel therapeutic developments in the future. PMID:25165542

Key Response Planning Factors for the Aftermath of Nuclear Terrorism

Energy Technology Data Exchange (ETDEWEB)

Buddemeier, B R; Dillon, M B

2009-01-21

Despite hundreds of above-ground nuclear tests and data gathered from Hiroshima and Nagasaki, the effects of a ground-level, low-yield nuclear detonation in a modern urban environment are still the subject of considerable scientific debate. Extensive review of nuclear weapon effects studies and discussions with nuclear weapon effects experts from various federal agencies, national laboratories, and technical organizations have identified key issues and bounded some of the unknowns required to support response planning for a low-yield, ground-level nuclear detonation in a modern U.S. city. This study, which is focused primarily upon the hazards posed by radioactive fallout, used detailed fallout predictions from the advanced suite of three-dimensional (3-D) meteorology and plume/fallout models developed at Lawrence Livermore National Laboratory (LLNL), including extensive global Key Response Planning Factors for the Aftermath of Nuclear Terrorism geographical and real-time meteorological databases to support model calculations. This 3-D modeling system provides detailed simulations that account for complex meteorology and terrain effects. The results of initial modeling and analysis were presented to federal, state, and local working groups to obtain critical, broad-based review and feedback on strategy and messaging. This effort involved a diverse set of communities, including New York City, National Capitol Regions, Charlotte, Houston, Portland, and Los Angeles. The largest potential for reducing casualties during the post-detonation response phase comes from reducing exposure to fallout radiation. This can be accomplished through early, adequate sheltering followed by informed, delayed evacuation.B The response challenges to a nuclear detonation must be solved through multiple approaches of public education, planning, and rapid response actions. Because the successful response will require extensive coordination of a large number of organizations, supplemented by
Can quantitative sensory testing predict responses to analgesic treatment?

Science.gov (United States)

Grosen, K; Fischer, I W D; Olesen, A E; Drewes, A M

2013-10-01

The role of quantitative sensory testing (QST) in prediction of analgesic effect in humans is scarcely investigated. This updated review assesses the effectiveness in predicting analgesic effects in healthy volunteers, surgical patients and patients with chronic pain. A systematic review of English written, peer-reviewed articles was conducted using PubMed and Embase (1980-2013). Additional studies were identified by chain searching. Search terms included 'quantitative sensory testing', 'sensory testing' and 'analgesics'. Studies on the relationship between QST and response to analgesic treatment in human adults were included. Appraisal of the methodological quality of the included studies was based on evaluative criteria for prognostic studies. Fourteen studies (including 720 individuals) met the inclusion criteria. Significant correlations were observed between responses to analgesics and several QST parameters including (1) heat pain threshold in experimental human pain, (2) electrical and heat pain thresholds, pressure pain tolerance and suprathreshold heat pain in surgical patients, and (3) electrical and heat pain threshold and conditioned pain modulation in patients with chronic pain. Heterogeneity among studies was observed especially with regard to application of QST and type and use of analgesics. Although promising, the current evidence is not sufficiently robust to recommend the use of any specific QST parameter in predicting analgesic response. Future studies should focus on a range of different experimental pain modalities rather than a single static pain stimulation paradigm. © 2013 European Federation of International Association for the Study of Pain Chapters.
Identification of Reading Problems in First Grade within a Response-to-Intervention Framework

Science.gov (United States)

Speece, Deborah L.; Schatschneider, Christopher; Silverman, Rebecca; Case, Lisa Pericola; Cooper, David H.; Jacobs, Dawn M.

2011-01-01

Models of Response to Intervention (RTI) include parameters of assessment and instruction. This study focuses on assessment with the purpose of developing a screening battery that validly and efficiently identifies first-grade children at risk for reading problems. In an RTI model, these children would be candidates for early intervention. We…
The 1991 Department of the Army Service Response Force exercise: Procedural Guide SRFX-91

Energy Technology Data Exchange (ETDEWEB)

Madore, M.A.; Thomson, R.S.; Haffenden, R.A.; Baldwin, T.E.; Meleski, S.A.

1991-09-01

This procedural guide was written to assist the US Army in planning for a chemical emergency exercise at Tooele Army Depot in Utah. The roles of various members of the emergency response community are described for various accident scenarios, and the relationships between the various responders are identified. For the June 1991 exercise at Tooele, the emergency response community includes the command structure at Tooele Army Depot; the US Army Service Response Force and other Department of Defense agencies; emergency response personnel from Tooele, Salt Lake, and Utah counties and municipal governments; the Utah Comprehensive Emergency Management Agency and other state agencies; and various federal agencies.
Comparative transcriptome analysis of stylar canal cells identifies novel candidate genes implicated in the self-incompatibility response of Citrus clementina

Directory of Open Access Journals (Sweden)

Caruso Marco

2012-02-01

Full Text Available Abstract Background Reproductive biology in citrus is still poorly understood. Although in recent years several efforts have been made to study pollen-pistil interaction and self-incompatibility, little information is available about the molecular mechanisms regulating these processes. Here we report the identification of candidate genes involved in pollen-pistil interaction and self-incompatibility in clementine (Citrus clementina Hort. ex Tan.. These genes have been identified comparing the transcriptomes of laser-microdissected stylar canal cells (SCC isolated from two genotypes differing for self-incompatibility response ('Comune', a self-incompatible cultivar and 'Monreal', a self- compatible mutation of 'Comune'. Results The transcriptome profiling of SCC indicated that the differential regulation of few specific, mostly uncharacterized transcripts is associated with the breakdown of self-incompatibility in 'Monreal'. Among them, a novel F-box gene showed a drastic up-regulation both in laser microdissected stylar canal cells and in self-pollinated whole styles with stigmas of 'Comune' in concomitance with the arrest of pollen tube growth. Moreover, we identify a non-characterized gene family as closely associated to the self-incompatibility genetic program activated in 'Comune'. Three different aspartic-acid rich (Asp-rich protein genes, located in tandem in the clementine genome, were over-represented in the transcriptome of 'Comune'. These genes are tightly linked to a DELLA gene, previously found to be up-regulated in the self-incompatible genotype during pollen-pistil interaction. Conclusion The highly specific transcriptome survey of the stylar canal cells identified novel genes which have not been previously associated with self-pollen rejection in citrus and in other plant species. Bioinformatic and transcriptional analyses suggested that the mutation leading to self-compatibility in 'Monreal' affected the expression of non
Linking the salt transcriptome with physiological responses of a salt-resistant Populus species as a strategy to identify genes important for stress acclimation.

Science.gov (United States)

Brinker, Monika; Brosché, Mikael; Vinocur, Basia; Abo-Ogiala, Atef; Fayyaz, Payam; Janz, Dennis; Ottow, Eric A; Cullmann, Andreas D; Saborowski, Joachim; Kangasjärvi, Jaakko; Altman, Arie; Polle, Andrea

2010-12-01

To investigate early salt acclimation mechanisms in a salt-tolerant poplar species (Populus euphratica), the kinetics of molecular, metabolic, and physiological changes during a 24-h salt exposure were measured. Three distinct phases of salt stress were identified by analyses of the osmotic pressure and the shoot water potential: dehydration, salt accumulation, and osmotic restoration associated with ionic stress. The duration and intensity of these phases differed between leaves and roots. Transcriptome analysis using P. euphratica-specific microarrays revealed clusters of coexpressed genes in these phases, with only 3% overlapping salt-responsive genes in leaves and roots. Acclimation of cellular metabolism to high salt concentrations involved remodeling of amino acid and protein biosynthesis and increased expression of molecular chaperones (dehydrins, osmotin). Leaves suffered initially from dehydration, which resulted in changes in transcript levels of mitochondrial and photosynthetic genes, indicating adjustment of energy metabolism. Initially, decreases in stress-related genes were found, whereas increases occurred only when leaves had restored the osmotic balance by salt accumulation. Comparative in silico analysis of the poplar stress regulon with Arabidopsis (Arabidopsis thaliana) orthologs was used as a strategy to reduce the number of candidate genes for functional analysis. Analysis of Arabidopsis knockout lines identified a lipocalin-like gene (AtTIL) and a gene encoding a protein with previously unknown functions (AtSIS) to play roles in salt tolerance. In conclusion, by dissecting the stress transcriptome of tolerant species, novel genes important for salt endurance can be identified.
Characterization and evaluation of controls on post-fire streamflow response across western US watersheds

Directory of Open Access Journals (Sweden)

S. Saxe

2018-02-01

Full Text Available This research investigates the impact of wildfires on watershed flow regimes, specifically focusing on evaluation of fire events within specified hydroclimatic regions in the western United States, and evaluating the impact of climate and geophysical variables on response. Eighty-two watersheds were identified with at least 10 years of continuous pre-fire daily streamflow records and 5 years of continuous post-fire daily flow records. Percent change in annual runoff ratio, low flows, high flows, peak flows, number of zero flow days, baseflow index, and Richards–Baker flashiness index were calculated for each watershed using pre- and post-fire periods. Independent variables were identified for each watershed and fire event, including topographic, vegetation, climate, burn severity, percent area burned, and soils data. Results show that low flows, high flows, and peak flows increase in the first 2 years following a wildfire and decrease over time. Relative response was used to scale response variables with the respective percent area of watershed burned in order to compare regional differences in watershed response. To account for variability in precipitation events, runoff ratio was used to compare runoff directly to PRISM precipitation estimates. To account for regional differences in climate patterns, watersheds were divided into nine regions, or clusters, through k-means clustering using climate data, and regression models were produced for watersheds grouped by total area burned. Watersheds in Cluster 9 (eastern California, western Nevada, Oregon demonstrate a small negative response to observed flow regimes after fire. Cluster 8 watersheds (coastal California display the greatest flow responses, typically within the first year following wildfire. Most other watersheds show a positive mean relative response. In addition, simple regression models show low correlation between percent watershed burned and streamflow response, implying that
Biological significance of sperm whale responses to sonar: Comparison with anti-predator responses

NARCIS (Netherlands)

Curé, C.; Isojunno, S.; Visser, F.; Wensveen, P.J.; Sivle, L.D.; Kvadsheim, P.H.; Lam, F.A.; Miller, P.J.O.

2016-01-01

A key issue when investigating effects of anthropogenic noise on cetacean behavior is to identify the biological significance of the responses. Predator presence can be considered a natural high-level disturbance stimulus to which prey animals have evolved adaptive response strategies to reduce
Identifying the TeV gamma-ray source MGRO J2228+61, FINALLY!

Science.gov (United States)

Aliu, Ester

2012-09-01

New VERITAS observations of MGRO J2228+61 allow us to associate its TeV emission with the enigmatic radio supernova remnant SNR G106.3+2.7. This remnant is part of a large complex that includes the Boomerang pulsar and nebula. The reduced field suggests that the TeV emission is not powered by the Boomerang, but instead associated with a much larger remnant. A recent SUZAKU X-ray observation of the smaller gamma-ray error box reveals two possible pulsar candidates. We propose short ACIS exposures to identify these sources to determine if one or both can be responsible for the gamma-ray emission. This will allow us to address the long standing problem on the nature of both MGRO J2228+61 and SNR G106.3+2.7.
Adaptive and plastic responses of Quercus petraea populations to climate across Europe

DEFF Research Database (Denmark)

Sáenz-Romero, Cuauhtémoc; Lamy, Jean-Baptiste; Ducousso, Alexis

2017-01-01

geographically diverse populations. The tests were planted on 23 field sites in six European countries, in order to expose them to a wide range of climates, including sites reflecting future warmer and drier climates. By assessing tree height and survival, our objectives were twofold: (i) to identify the source......How temperate forests will respond to climate change is uncertain; projections range from severe decline to increased growth. We conducted field tests of sessile oak (Quercus petraea), a widespread keystone European forest tree species, including more than 150 000 trees sourced from 116...... of differential population responses to climate (genetic differentiation due to past divergent climatic selection vs. plastic responses to ongoing climate change) and (ii) to explore which climatic variables (temperature or precipitation) trigger the population responses. Tree growth and survival were modeled...
Discriminating talent-identified junior Australian football players using a video decision-making task.

Science.gov (United States)

Woods, Carl T; Raynor, Annette J; Bruce, Lyndell; McDonald, Zane

2016-01-01

This study examined if a video decision-making task could discriminate talent-identified junior Australian football players from their non-talent-identified counterparts. Participants were recruited from the 2013 under 18 (U18) West Australian Football League competition and classified into two groups: talent-identified (State U18 Academy representatives; n = 25; 17.8 ± 0.5 years) and non-talent-identified (non-State U18 Academy selection; n = 25; 17.3 ± 0.6 years). Participants completed a video decision-making task consisting of 26 clips sourced from the Australian Football League game-day footage, recording responses on a sheet provided. A score of "1" was given for correct and "0" for incorrect responses, with the participants total score used as the criterion value. One-way analysis of variance tested the main effect of "status" on the task criterion, whilst a bootstrapped receiver operating characteristic (ROC) curve assessed the discriminant ability of the task. An area under the curve (AUC) of 1 (100%) represented perfect discrimination. Between-group differences were evident (P talent-identified and non-talent-identified participants, respectively. Future research should investigate the mechanisms leading to the superior decision-making observed in the talent-identified group.
40 CFR 1502.14 - Alternatives including the proposed action.

Science.gov (United States)

2010-07-01

... impacts of the proposal and the alternatives in comparative form, thus sharply defining the issues and... action so that reviewers may evaluate their comparative merits. (c) Include reasonable alternatives not... identify such alternative in the final statement unless another law prohibits the expression of such a...
Transcriptome profiling identifies genes and pathways deregulated upon floxuridine treatment in colorectal cancer cells harboring GOF mutant p53

Directory of Open Access Journals (Sweden)

Arindam Datta

2016-06-01

Full Text Available Mutation in TP53 is a common genetic alteration in human cancers. Certain tumor associated p53 missense mutants acquire gain-of-function (GOF properties and confer oncogenic phenotypes including enhanced chemoresistance. The colorectal cancers (CRC harboring mutant p53 are generally aggressive in nature and difficult to treat. To identify a potential gene expression signature of GOF mutant p53-driven acquired chemoresistance in CRC, we performed transcriptome profiling of floxuridine (FUdR treated SW480 cells expressing mutant p53R273H (GEO#: GSE77533. We obtained several genes differentially regulated between FUdR treated and untreated cells. Further, functional characterization and pathway analysis revealed significant enrichment of crucial biological processes and pathways upon FUdR treatment in SW480 cells. Our data suggest that in response to chemotherapeutics treatment, cancer cells with GOF mutant p53 can modulate key cellular pathways to withstand the cytotoxic effect of the drugs. The genes and pathways identified in the present study can be further validated and targeted for better chemotherapy response in colorectal cancer patients harboring mutant p53.
Toward Understanding Tip Leakage Flows in Small Compressor Cores Including Stator Leakage Flow

Science.gov (United States)

Berdanier, Reid A.; Key, Nicole L.

2017-01-01

The focus of this work was to provide additional data to supplement the work reported in NASA/CR-2015-218868 (Berdanier and Key, 2015b). The aim of that project was to characterize the fundamental flow physics and the overall performance effects due to increased rotor tip clearance heights in axial compressors. Data have been collected in the three-stage axial research compressor at Purdue University with a specific focus on analyzing the multistage effects resulting from the tip leakage flow. Three separate rotor tip clearances were studied with nominal tip clearance gaps of 1.5 percent, 3.0 percent, and 4.0 percent based on a constant annulus height. Overall compressor performance was previously investigated at four corrected speedlines (100 percent, 90 percent, 80 percent, and 68 percent) for each of the three tip clearance configurations. This study extends the previously published results to include detailed steady and time-resolved pressure data at two loading conditions, nominal loading (NL) and high loading (HL), on the 100 percent corrected speedline for the intermediate clearance level (3.0 percent). Steady detailed radial traverses of total pressure at the exit of each stator row are supported by flow visualization techniques to identify regions of flow recirculation and separation. Furthermore, detailed radial traverses of time-resolved total pressures at the exit of each rotor row have been measured with a fast-response pressure probe. These data were combined with existing three-component velocity measurements to identify a novel technique for calculating blockage in a multistage compressor. Time-resolved static pressure measurements have been collected over the rotor tips for all rotors with each of the three tip clearance configurations for up to five loading conditions along the 100 percent corrected speedline using fast-response piezoresistive pressure sensors. These time-resolved static pressure measurements reveal new knowledge about the
Oil spill response planning on the Columbia river estuary

International Nuclear Information System (INIS)

Christopherson, S.K.; Slyman, P.M.

1993-01-01

The Columbia River Estuary lies along the Washington-Oregon state boundary on the west coast of the United States. The entire area is environmentally very sensitive with numerous large, shallow bays, exposed mud flats, wetland areas, and central channels having maximum currents of three to four knots. These features make the area very difficult to protect from an oil spill. Spill response is further complicated because of the many different state, federal, and local jurisdictions with mandated responsibilities in oil spill response and environmental protection. Under the leadership of the US Coast Guard Marine Safety Office in Portland, Oregon, a steering group was established to guide the development of a response plan for the Columbia River Estuary. A concerted effort was made to include representatives from response organizations, natural resource agencies, and resource users from federal, state, and local governments, and commercial sectors in the planning process. The first draft of an operational response plan was completed the summer of 1992 through a combination of technical workshops, field trips, and small working groups meeting with local communities. The Columbia River Estuary Response Plan prioritizes areas to protect; identifies specific response strategies for protecting these areas; and outlines the Iogistics needed to implement these strategies, including equipment needs, the location of staging areas, and the identification of pre-designed command posts. The local spill response cooperative and oil transportation industry are using the plan to coordinate the purchase of response equipment and the staging of this equipment at numerous locations along the river. The key to success is ensuring that all the groups responding to an event participate in the planning process together. This process has worked well and will serve as a model for response planning for other areas along the Columbia River and coastal areas of Washington and Oregon
Oil spill response planning under the Oil Pollution Act of 1990

International Nuclear Information System (INIS)

Lees, J.E.

1992-01-01

The oil spill in Alaska's Prince William Sound on March 24, 1989 illustrated the need for more resources, better planning, and better command and control to efficiently and effectively respond to, contain and cleanup catastrophic oil spills. In response to public concern and industry initiatives to resolve existing oil spill response problems. Congress enacted the comprehensive Oil Pollution Act of 1990 (OPA-90) on August 18, 1990. OPA-90 mandates comprehensive changes in vessel and facility response planning, envisioning a comprehensive and integrated oil spill response planning scheme, with revisions to reflect OPA-90's new requirements. Area Committees comprised of federal, state and local officials and others will prepare Area Contingency Plans for Coast Guard approval, which set forth the framework for responding to open-quotes worst case dischargesclose quotes. Owners and operators of tank vessels and onshore and offshore facilities must submit individual response plans for federal approval by February 18, 1993, identifying and ensuring availability of private personnel and equipment necessary to remove to the maximum extent practicable a open-quotes worst case discharge.close quotes The Coast Guard is considering rules to implement these requirements. Major challenges exist to meet the statutory requirements, including response times, skimming efficiencies, adverse weather and others that affect emergency response capability. This paper focuses on: (1) oil spill response problems identified and lessons learned from the Prince William Sound spill; (2) OPA-90's complex and technical oil spill response planning requirements and their effect on response planning for marine operations; (3) the federal regulatory program to implement OPA-90, defining spill response capability for a open-quotes worst case discharge,close quotes considering existing response resources and the new capabilities by the industry-supported Marine Spill Response Corporation
Comparative analysis of chrysanthemum transcriptome in response to three RNA viruses: Cucumber mosaic virus, Tomato spotted wilt virus and Potato virus X.

Science.gov (United States)

Choi, Hoseong; Jo, Yeonhwa; Lian, Sen; Jo, Kyoung-Min; Chu, Hyosub; Yoon, Ju-Yeon; Choi, Seung-Kook; Kim, Kook-Hyung; Cho, Won Kyong

2015-06-01

The chrysanthemum is one of popular flowers in the world and a host for several viruses. So far, molecular interaction studies between the chrysanthemum and viruses are limited. In this study, we carried out a transcriptome analysis of chrysanthemum in response to three different viruses including Cucumber mosaic virus (CMV), Tomato spotted wilt virus (TSWV) and Potato virus X (PVX). A chrysanthemum 135K microarray derived from expressed sequence tags was successfully applied for the expression profiles of the chrysanthemum at early stage of virus infection. Finally, we identified a total of 125, 70 and 124 differentially expressed genes (DEGs) for CMV, TSWV and PVX, respectively. Many DEGs were virus specific; however, 33 DEGs were commonly regulated by three viruses. Gene ontology (GO) enrichment analysis identified a total of 132 GO terms, and of them, six GO terms related stress response and MCM complex were commonly identified for three viruses. Several genes functioning in stress response such as chitin response and ethylene mediated signaling pathway were up-regulated indicating their involvement in establishment of host immune system. In particular, TSWV infection significantly down-regulated genes related to DNA metabolic process including DNA replication, chromatin organization, histone modification and cytokinesis, and they are mostly targeted to nucleosome and MCM complex. Taken together, our comparative transcriptome analysis revealed several genes related to hormone mediated viral stress response and DNA modification. The identified chrysanthemums genes could be good candidates for further functional study associated with resistant to various plant viruses.
The global transcriptional response of fission yeast to hydrogen sulfide.

Directory of Open Access Journals (Sweden)

Xu Jia

Full Text Available BACKGROUND: Hydrogen sulfide (H(2S is a newly identified member of the small family of gasotransmitters that are endogenous gaseous signaling molecules that have a fundamental role in human biology and disease. Although it is a relatively recent discovery and the mechanism of H(2S activity is not completely understood, it is known to be involved in a number of cellular processes; H(2S can affect ion channels, transcription factors and protein kinases in mammals. METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we have used fission yeast as a model organism to study the global gene expression profile in response to H(2S by microarray. We initially measured the genome-wide transcriptional response of fission yeast to H(2S. Through the functional classification of genes whose expression profile changed in response to H(2S, we found that H(2S mainly influences genes that encode putative or known stress proteins, membrane transporters, cell cycle/meiotic proteins, transcription factors and respiration protein in the mitochondrion. Our analysis showed that there was a significant overlap between the genes affected by H(2S and the stress response. We identified that the target genes of the MAPK pathway respond to H(2S; we also identified that a number of transporters respond to H(2S, these include sugar/carbohydrate transporters, ion transporters, and amino acid transporters. We found many mitochondrial genes to be down regulated upon H(2S treatment and that H(2S can reduce mitochondrial oxygen consumption. CONCLUSION/SIGNIFICANCE: This study identifies potential molecular targets of the signaling molecule H(2S in fission yeast and provides clues about the identity of homologues human proteins and will further the understanding of the cellular role of H(2S in human diseases.
Magnetic Resonance Imaging Identifies Differential Response to Pro-Oxidant Chemotherapy in a Xenograft Model

Directory of Open Access Journals (Sweden)

Terry H. Landowski

2016-06-01

Full Text Available Induction of oxidative stress is a key component of cancer therapy. Pro-oxidant drugs have been demonstrated to enhance the efficacy of radiotherapy and chemotherapy. An emerging concept is that therapeutic outcomes are dictated by the differential redox buffering reserve in subpopulations of malignant cells, indicating the need for noninvasive biomarkers of tumor redox that can be used for dose identification and response assessment in a longitudinal setting. Magnetic resonance imaging (MRI enhanced with the thiol-binding contrast agent Gd-LC6-SH, and hemodynamic response imaging (HRI in combination with hypercapnia and hyperoxia were investigated as biomarkers of the pharmacodynamics of the small molecule pro-oxidant imexon (IMX. Human multiple myeloma cell lines 8226/S and an IMX-resistant variant, 8226/IM10, were established as contralateral tumors in SCID mice. T1slope, an MRI measure of the washout rate of Gd-LC6-SH, was significantly lower post-IMX therapy in 8226/S tumors compared with vehicle controls, indicating treatment-related oxidization of the tumor microenvironment, which was confirmed by analysis of tumor tissue for thiols. T1slope and ex vivo assays for thiols both indicated a more reduced microenvironment in 8226/IM10 tumors following IMX therapy. HRI with hypercapnia challenge revealed IMX inhibition of vascular dilation in 8226/S tumors but not 8226/IM10 tumors, consistent with decreased immunohistochemical staining for smooth muscle actin in treated 8226/S tumors. MRI enhanced with Gd-LC6-SH, and HRI coupled with a hypercapnic challenge provide noninvasive biomarkers of tumor response to the redox modulator imexon.
Effects of embedment including slip and separation on seismic SSI response of a nuclear reactor building

International Nuclear Information System (INIS)

Saxena, Navjeev; Paul, D.K.

2012-01-01

Highlights: ► Both the slip and separation of reactor base reduce with increase in embedment. ► The slip and separation become insignificant beyond 1/4 and 1/2 embedment respectively. ► The stresses in reactor reduce significantly upto 1/4 embedment. ► The stress reduction with embedment is more pronounced in case of tensile stresses. ► The modeling of interface is important beyond 1/8 embedment as stresses are underestimated otherwise. - Abstract: The seismic response of nuclear reactor containment building considering the effects of embedment, slip and separation at soil–structure interface requires modeling of the soil, structure and interface altogether. Slip and separation at the interface causes stress redistribution in the soil and the structure around the interface. The embedment changes the dynamic characteristics of the soil–structure system. Consideration of these aspects allows capturing the realistic response of the structure, which has been a research gap and presented here individually as well as taken together. Finite element analysis has been carried out in time domain to attempt the highly nonlinear problem. The study draws important conclusions useful for design of nuclear reactor containment building.

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

Science.gov (United States)

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

2013-11-01

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

Science.gov (United States)

McGinnis, Ellen W; McGinnis, Ryan S; Muzik, Maria; Hruschak, Jessica; Lopez-Duran, Nestor L; Perkins, Noel C; Fitzgerald, Kate; Rosenblum, Katherine L

2017-09-01

Temporal phases of threat response, including potential threat (anxiety), acute threat (startle, fear), and post-threat response modulation, have been identified as the underlying markers of anxiety disorders. Objective measures of response during these phases may help identify children at risk for anxiety; however, the complexity of current assessment techniques prevent their adoption in many research and clinical contexts. We propose an alternative technology, an inertial measurement unit (IMU), that enables noninvasive measurement of the movements associated with threat response, and test its ability to detect threat response phases in young children at a heightened risk for developing anxiety. We quantified the motion of 18 children (3-7 years old) during an anxiety-/fear-provoking behavioral task using an IMU. Specifically, measurements from a single IMU secured to the child's waist were used to extract root-mean-square acceleration and angular velocity in the horizontal and vertical directions, and tilt and yaw range of motion during each threat response phase. IMU measurements detected expected differences in child motion by threat phase. Additionally, potential threat motion was positively correlated to familial anxiety risk, startle range of motion was positively correlated with child internalizing symptoms, and response modulation motion was negatively correlated to familial anxiety risk. Results suggest differential theory-driven threat response phases and support previous literature connecting maternal child risk to anxiety with behavioral measures using more feasible objective methods. This is the first study demonstrating the utility of an IMU for characterizing the motion of young children to mark the phases of threat response modulation. The technique provides a novel and objective measure of threat response for mental health researchers.
Refining borders of genome-rearrangements including repetitions

Directory of Open Access Journals (Sweden)

JA Arjona-Medina

2016-10-01

Full Text Available Abstract Background DNA rearrangement events have been widely studied in comparative genomic for many years. The importance of these events resides not only in the study about relatedness among different species, but also to determine the mechanisms behind evolution. Although there are many methods to identify genome-rearrangements (GR, the refinement of their borders has become a huge challenge. Until now no accepted method exists to achieve accurate fine-tuning: i.e. the notion of breakpoint (BP is still an open issue, and despite repeated regions are vital to understand evolution they are not taken into account in most of the GR detection and refinement methods. Methods and results We propose a method to refine the borders of GR including repeated regions. Instead of removing these repetitions to facilitate computation, we take advantage of them using a consensus alignment sequence of the repeated region in between two blocks. Using the concept of identity vectors for Synteny Blocks (SB and repetitions, a Finite State Machine is designed to detect transition points in the difference between such vectors. The method does not force the BP to be a region or a point but depends on the alignment transitions within the SBs and repetitions. Conclusion The accurate definition of the borders of SB and repeated genomic regions and consequently the detection of BP might help to understand the evolutionary model of species. In this manuscript we present a new proposal for such a refinement. Features of the SBs borders and BPs are different and fit with what is expected. SBs with more diversity in annotations and BPs short and richer in DNA replication and stress response, which are strongly linked with rearrangements.
Integrated expression analysis of muscle hypertrophy identifies Asb2 as a negative regulator of muscle mass

Science.gov (United States)

Davey, Jonathan R.; Watt, Kevin I.; Parker, Benjamin L.; Chaudhuri, Rima; Ryall, James G.; Cunningham, Louise; Qian, Hongwei; Sartorelli, Vittorio; Chamberlain, Jeffrey; James, David E.

2016-01-01

The transforming growth factor-β (TGF-β) signaling network is a critical regulator of skeletal muscle mass and function and, thus, is an attractive therapeutic target for combating muscle disease, but the underlying mechanisms of action remain undetermined. We report that follistatin-based interventions (which modulate TGF-β network activity) can promote muscle hypertrophy that ameliorates aging-associated muscle wasting. However, the muscles of old sarcopenic mice demonstrate reduced response to follistatin compared with healthy young-adult musculature. Quantitative proteomic and transcriptomic analyses of young-adult muscles identified a transcription/translation signature elicited by follistatin exposure, which included repression of ankyrin repeat and SOCS box protein 2 (Asb2). Increasing expression of ASB2 reduced muscle mass, thereby demonstrating that Asb2 is a TGF-β network–responsive negative regulator of muscle mass. In contrast to young-adult muscles, sarcopenic muscles do not exhibit reduced ASB2 abundance with follistatin exposure. Moreover, preventing repression of ASB2 in young-adult muscles diminished follistatin-induced muscle hypertrophy. These findings provide insight into the program of transcription and translation events governing follistatin-mediated adaptation of skeletal muscle attributes and identify Asb2 as a regulator of muscle mass implicated in the potential mechanistic dysfunction between follistatin-mediated muscle growth in young and old muscles. PMID:27182554
Identification of immune response-related genes in the Chinese oak silkworm, Antheraea pernyi by suppression subtractive hybridization.

Science.gov (United States)

Liu, Qiu-Ning; Zhu, Bao-Jian; Wang, Lei; Wei, Guo-Qing; Dai, Li-Shang; Lin, Kun-Zhang; Sun, Yu; Qiu, Jian-Feng; Fu, Wei-Wei; Liu, Chao-Liang

2013-11-01

Insects possess an innate immune system that responds to invading microorganisms. In this study, a subtractive cDNA library was constructed to screen for immune response-related genes in the fat bodies of Antheraea pernyi (Lepidoptera: Saturniidae) pupa challenged with Escherichia coli. Four hundred putative EST clones were identified by suppression subtractive hybridization (SSH), including 50 immune response-related genes, three cytoskeleton genes, eight cell cycle and apoptosis genes, five respiration and energy metabolism genes, five transport genes, 40 metabolism genes, ten stress response genes, four transcription and translation regulation genes and 77 unknown genes. To verify the reliability of the SSH data, the transcription of a set of randomly selected immune response-related genes were confirmed by semi-quantitative reverse transcription-PCR (RT-PCR) and real-time quantitative reverse transcription-PCR (qRT-PCR). These identified immune response-related genes provide insight into understanding the innate immunity in A. pernyi. Copyright © 2013 Elsevier Inc. All rights reserved.
Ethical responsibilities of pharmacists when selling complementary medicines: a systematic review.

Science.gov (United States)

Salman Popattia, Amber; Winch, Sarah; La Caze, Adam

2018-04-01

The widespread sale of complementary medicines in community pharmacy raises important questions regarding the responsibilities of pharmacists when selling complementary medicines. This study reviews the academic literature that explores a pharmacist's responsibilities when selling complementary medicines. International Pharmaceutical Abstracts, Embase, PubMed, Cinahl, PsycINFO and Philosopher's index databases were searched for articles written in English and published between 1995 and 2017. Empirical studies discussing pharmacists' practices or perceptions, consumers' expectations and normative studies discussing ethical perspectives or proposing ethical frameworks related to pharmacists' responsibilities in selling complementary medicines were included in the review. Fifty-eight studies met the inclusion criteria. The majority of the studies discussing the responsibilities of pharmacists selling complementary medicines had an empirical focus. Pharmacists and consumers identified counselling and ensuring safe use of complementary medicines as the primary responsibilities of pharmacists. No formal ethical framework is explicitly employed to describe the responsibilities of pharmacists selling complementary medicines. To the degree any ethical framework is employed, a number of papers implicitly rely on principlism. The studies discussing the ethical perspectives of selling complementary medicines mainly describe the ethical conflict between a pharmacist's business and health professional role. No attempt is made to provide guidance on appropriate ways to resolve the conflict. There is a lack of explicit normative advice in the existing literature regarding the responsibilities of pharmacists selling complementary medicines. This review identifies the need to develop a detailed practice-specific ethical framework to guide pharmacists regarding their responsibilities when selling complementary medicines. © 2018 Royal Pharmaceutical Society.
"Identifying the hospitalised patient in crisis"--a consensus conference on the afferent limb of rapid response systems

DEFF Research Database (Denmark)

DeVita, Michael A; Smith, Gary B; Adam, Sheila K

2010-01-01

Most reports of Rapid Response Systems (RRS) focus on the efferent, response component of the system, although evidence suggests that improved vital sign monitoring and recognition of a clinical crisis may have outcome benefits. There is no consensus regarding how best to detect patient deteriora...
New land disposal restrictions on contaminated soil and debris, and newly identified toxicity characteristic organics

International Nuclear Information System (INIS)

Fortune, William B.; Schumann, Jean C.; Fallon, William E.; Badden, Janet W.; Smith, Edward H.

1992-01-01

The applicability of the Resource Conservation and Recovery Act (RCRA) Land Disposal Restrictions (LDR) program to radioactive mixed wastes (RMW) has been clarified through U.S. Environmental Protection Agency (EPA) and U.S. Department of Energy (DOE) rulemakings and notices. However, a number of waste management concerns involving RMW and RMW-contaminated soil and debris continue to exist with respect to achieving compliance with LDR provisions and treatment standards. Consequently, DOE has become increasingly proactive in its participation in the LDR rulemaking process and in the identification of LDR compliance issues associated with its RMW inventories. Both data and recommendations from across the DOE complex were collected and transmitted to EPA in response to proposed requirements that would implement LDR for contaminated soil and debris, and certain newly identified toxicity characteristic (TC) organics. Much of this information focused on concerns related to the application of proposed regulatory approaches to RMW streams. Highlights from the information included in these DOE responses are presented. (author)
Desired attributes of new graduate nurses as identified by the rural community.

Science.gov (United States)

Sivamalai, S

2008-01-01

Preparing nurse graduates for practice is challenging because of the diversity of skills expected of them. Increasingly consumers are more informed and expect quality care. To identify the attributes a rural community expect in new graduate nurses in order for them to provide quality care. A questionnaire was designed to assess the importance attached to a set of attributes of graduate nurses expected by a rural community. The community included a range of professionals working with government and hospitals, community volunteers and retired people. After pilot testing, the questionnaire was distributed using a cluster sampling technique. A total of 656 completed questionnaires were returned, giving a response rate of 69%. The respondents were asked to rate the importance of each item for the community on a five-point Likert scale (5 = extremely important, 4 = very important, 3 = moderately important, 2 = possibly importantly, and 1 = not important at all). Exploratory factor analysis was performed on the 38 items using SPSS (SPSS inc; Chicago, IL, USA). Principal Components Analysis was applied to identify the number of factors followed by Oblimin rotation. The sample of 656 respondents consisted of 68% females and 30% males (2% did not identify their gender). The majority of the respondents (75.6%) were born in Australia, while 3.2% were born in the UK Kingdom. Principal Components Analysis identified five factors with eigenvalues above one, explaining 47.4% of the total variance. Items that loaded greater than + or - 0.3, (approximately 10% of the common factor variance) was associated with the factor in question. Component 1 was labelled Sympathetic/ Patients' welfare with the item 'Nurses should be sensitive to the emotional needs of patients' showing the highest loading. Component 2 was called Contextual knowledge/ Interpersonal skills. It contained items indicating that nurses should have good personal skills and possess a broad contextual knowledge of issues
MOS modeling hierarchy including radiation effects

International Nuclear Information System (INIS)

Alexander, D.R.; Turfler, R.M.

1975-01-01

A hierarchy of modeling procedures has been developed for MOS transistors, circuit blocks, and integrated circuits which include the effects of total dose radiation and photocurrent response. The models were developed for use with the SCEPTRE circuit analysis program, but the techniques are suitable for other modern computer aided analysis programs. The modeling hierarchy permits the designer or analyst to select the level of modeling complexity consistent with circuit size, parametric information, and accuracy requirements. Improvements have been made in the implementation of important second order effects in the transistor MOS model, in the definition of MOS building block models, and in the development of composite terminal models for MOS integrated circuits
Numerical study of the mode selection in response spectrum analysis-condensed version

International Nuclear Information System (INIS)

Ng, D.S.

1986-01-01

For quality assurance of the dynamic response spectrum analysis, the Nuclear Regulatory Commission (NRC) recommends retaining all modes below the cutoff frequency at which the spectral acceleration (S/sub a/) returns to the peak zero period acceleration (ZPA). It also suggests that modes accounting for at least 90 percent of the structural masses be included in the analysis. A simple frame-type structure is generated as a baseline frame. Then groups of oscillators representing substructure are added onto the frame to study substructure behavior. A base case is established for each frame by including the specific number of modes used. The tests are conducted by incrementing the number of modes in the response spectrum analyses starting with one mode. The structural response of each modal increment is compared with the base case to identify the efficiency of mode selection method. All three methods are then applied to the MFTF-B Axicell Vacuum Vessel. The responses in critical components of the vessel, such as hangers and foundations, will be analyzed to confirm the accuracy of the selected method
Drug-related problems identified in medication reviews by Australian pharmacists

DEFF Research Database (Denmark)

Stafford, Andrew C; Tenni, Peter C; Peterson, Gregory M

2009-01-01

OBJECTIVE: In Australia, accredited pharmacists perform medication reviews for patients to identify and resolve drug-related problems. We analysed the drug-related problems identified in reviews for both home-dwelling and residential care-facility patients. The objective of this study was to exam......OBJECTIVE: In Australia, accredited pharmacists perform medication reviews for patients to identify and resolve drug-related problems. We analysed the drug-related problems identified in reviews for both home-dwelling and residential care-facility patients. The objective of this study....... These reviews had been self-selected by pharmacists and submitted as part of the reaccreditation process to the primary body responsible for accrediting Australian pharmacists to perform medication reviews. The drug-related problems identified in each review were classified by type and drugs involved. MAIN...... OUTCOME MEASURE: The number and nature of drug-related problems identified in pharmacist-conducted medication reviews. RESULTS: There were 1,038 drug-related problems identified in 234 medication reviews (mean 4.6 (+/-2.2) problems per review). The number of problems was higher (4.9 +/- 2.0 vs. 3.9 +/- 2...
10 CFR 851.20 - Management responsibilities and worker rights and responsibilities.

Science.gov (United States)

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Management responsibilities and worker rights and... Program Requirements § 851.20 Management responsibilities and worker rights and responsibilities. (a... workers of their rights and responsibility by appropriate means, including posting the DOE-designated...
Future arrangements for Great Britain's gas quality specifications. Government Response (including Summary of Responses) to consultation on future arrangements for Great Britain's gas quality specifications

International Nuclear Information System (INIS)

2007-01-01

Last year the Government consulted on GB's future gas quality specifications. The background is that some streams of imported gases have an energy content that exceeds the upper limit specified in GB's current gas quality regulations. The policy issue was whether to stick with the current regulated specifications, but at the cost of having to process imported gas to bring it within those specifications; or, at some time after 2020, to adjust those specifications, but at the cost of having to check (and potentially change) approximately 45m domestic gas appliances in 22m households, to ensure that they are capable of burning the high energy gas safely (and with a residual safety risk that some appliances are missed). The Consultation Document sought views on the proposal (backed up by the Partial Regulatory Impact Assessment) to adopt the 'no change' option. In the light of the responses, this is what the Government now proposes. The associated Impact Assessment estimates the total net benefit of the 'no change' option at UK Pounds 1.5bn - 14bn, with a best estimate of UK Pounds 8bn (NPV, 2005). The risks for gas prices and security of supply (included in the Impact Assessment) are judged to be small. The Government proposes a 'forward plan', consisting of support for Ofgem's work on maximising the commercial flexibilities for the GB gas market to handle gases of different specifications, whilst continuing to engage in EU discussions on the gas quality issue. (Author)
Single-cell-type quantitative proteomic and ionomic analysis of epidermal bladder cells from the halophyte model plant Mesembryanthemum crystallinum to identify salt-responsive proteins.

Science.gov (United States)

Barkla, Bronwyn J; Vera-Estrella, Rosario; Raymond, Carolyn

2016-05-10

Epidermal bladder cells (EBC) are large single-celled, specialized, and modified trichomes found on the aerial parts of the halophyte Mesembryanthemum crystallinum. Recent development of a simple but high throughput technique to extract the contents from these cells has provided an opportunity to conduct detailed single-cell-type analyses of their molecular characteristics at high resolution to gain insight into the role of these cells in the salt tolerance of the plant. In this study, we carry out large-scale complementary quantitative proteomic studies using both a label (DIGE) and label-free (GeLC-MS) approach to identify salt-responsive proteins in the EBC extract. Additionally we perform an ionomics analysis (ICP-MS) to follow changes in the amounts of 27 different elements. Using these methods, we were able to identify 54 proteins and nine elements that showed statistically significant changes in the EBC from salt-treated plants. GO enrichment analysis identified a large number of transport proteins but also proteins involved in photosynthesis, primary metabolism and Crassulacean acid metabolism (CAM). Validation of results by western blot, confocal microscopy and enzyme analysis helped to strengthen findings and further our understanding into the role of these specialized cells. As expected EBC accumulated large quantities of sodium, however, the most abundant element was chloride suggesting the sequestration of this ion into the EBC vacuole is just as important for salt tolerance. This single-cell type omics approach shows that epidermal bladder cells of M. crystallinum are metabolically active modified trichomes, with primary metabolism supporting cell growth, ion accumulation, compatible solute synthesis and CAM. Data are available via ProteomeXchange with identifier PXD004045.
Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits.

Science.gov (United States)

Justice, Anne E; Winkler, Thomas W; Feitosa, Mary F; Graff, Misa; Fisher, Virginia A; Young, Kristin; Barata, Llilda; Deng, Xuan; Czajkowski, Jacek; Hadley, David; Ngwa, Julius S; Ahluwalia, Tarunveer S; Chu, Audrey Y; Heard-Costa, Nancy L; Lim, Elise; Perez, Jeremiah; Eicher, John D; Kutalik, Zoltán; Xue, Luting; Mahajan, Anubha; Renström, Frida; Wu, Joseph; Qi, Qibin; Ahmad, Shafqat; Alfred, Tamuno; Amin, Najaf; Bielak, Lawrence F; Bonnefond, Amelie; Bragg, Jennifer; Cadby, Gemma; Chittani, Martina; Coggeshall, Scott; Corre, Tanguy; Direk, Nese; Eriksson, Joel; Fischer, Krista; Gorski, Mathias; Neergaard Harder, Marie; Horikoshi, Momoko; Huang, Tao; Huffman, Jennifer E; Jackson, Anne U; Justesen, Johanne Marie; Kanoni, Stavroula; Kinnunen, Leena; Kleber, Marcus E; Komulainen, Pirjo; Kumari, Meena; Lim, Unhee; Luan, Jian'an; Lyytikäinen, Leo-Pekka; Mangino, Massimo; Manichaikul, Ani; Marten, Jonathan; Middelberg, Rita P S; Müller-Nurasyid, Martina; Navarro, Pau; Pérusse, Louis; Pervjakova, Natalia; Sarti, Cinzia; Smith, Albert Vernon; Smith, Jennifer A; Stančáková, Alena; Strawbridge, Rona J; Stringham, Heather M; Sung, Yun Ju; Tanaka, Toshiko; Teumer, Alexander; Trompet, Stella; van der Laan, Sander W; van der Most, Peter J; Van Vliet-Ostaptchouk, Jana V; Vedantam, Sailaja L; Verweij, Niek; Vink, Jacqueline M; Vitart, Veronique; Wu, Ying; Yengo, Loic; Zhang, Weihua; Hua Zhao, Jing; Zimmermann, Martina E; Zubair, Niha; Abecasis, Gonçalo R; Adair, Linda S; Afaq, Saima; Afzal, Uzma; Bakker, Stephan J L; Bartz, Traci M; Beilby, John; Bergman, Richard N; Bergmann, Sven; Biffar, Reiner; Blangero, John; Boerwinkle, Eric; Bonnycastle, Lori L; Bottinger, Erwin; Braga, Daniele; Buckley, Brendan M; Buyske, Steve; Campbell, Harry; Chambers, John C; Collins, Francis S; Curran, Joanne E; de Borst, Gert J; de Craen, Anton J M; de Geus, Eco J C; Dedoussis, George; Delgado, Graciela E; den Ruijter, Hester M; Eiriksdottir, Gudny; Eriksson, Anna L; Esko, Tõnu; Faul, Jessica D; Ford, Ian; Forrester, Terrence; Gertow, Karl; Gigante, Bruna; Glorioso, Nicola; Gong, Jian; Grallert, Harald; Grammer, Tanja B; Grarup, Niels; Haitjema, Saskia; Hallmans, Göran; Hamsten, Anders; Hansen, Torben; Harris, Tamara B; Hartman, Catharina A; Hassinen, Maija; Hastie, Nicholas D; Heath, Andrew C; Hernandez, Dena; Hindorff, Lucia; Hocking, Lynne J; Hollensted, Mette; Holmen, Oddgeir L; Homuth, Georg; Jan Hottenga, Jouke; Huang, Jie; Hung, Joseph; Hutri-Kähönen, Nina; Ingelsson, Erik; James, Alan L; Jansson, John-Olov; Jarvelin, Marjo-Riitta; Jhun, Min A; Jørgensen, Marit E; Juonala, Markus; Kähönen, Mika; Karlsson, Magnus; Koistinen, Heikki A; Kolcic, Ivana; Kolovou, Genovefa; Kooperberg, Charles; Krämer, Bernhard K; Kuusisto, Johanna; Kvaløy, Kirsti; Lakka, Timo A; Langenberg, Claudia; Launer, Lenore J; Leander, Karin; Lee, Nanette R; Lind, Lars; Lindgren, Cecilia M; Linneberg, Allan; Lobbens, Stephane; Loh, Marie; Lorentzon, Mattias; Luben, Robert; Lubke, Gitta; Ludolph-Donislawski, Anja; Lupoli, Sara; Madden, Pamela A F; Männikkö, Reija; Marques-Vidal, Pedro; Martin, Nicholas G; McKenzie, Colin A; McKnight, Barbara; Mellström, Dan; Menni, Cristina; Montgomery, Grant W; Musk, Aw Bill; Narisu, Narisu; Nauck, Matthias; Nolte, Ilja M; Oldehinkel, Albertine J; Olden, Matthias; Ong, Ken K; Padmanabhan, Sandosh; Peyser, Patricia A; Pisinger, Charlotta; Porteous, David J; Raitakari, Olli T; Rankinen, Tuomo; Rao, D C; Rasmussen-Torvik, Laura J; Rawal, Rajesh; Rice, Treva; Ridker, Paul M; Rose, Lynda M; Bien, Stephanie A; Rudan, Igor; Sanna, Serena; Sarzynski, Mark A; Sattar, Naveed; Savonen, Kai; Schlessinger, David; Scholtens, Salome; Schurmann, Claudia; Scott, Robert A; Sennblad, Bengt; Siemelink, Marten A; Silbernagel, Günther; Slagboom, P Eline; Snieder, Harold; Staessen, Jan A; Stott, David J; Swertz, Morris A; Swift, Amy J; Taylor, Kent D; Tayo, Bamidele O; Thorand, Barbara; Thuillier, Dorothee; Tuomilehto, Jaakko; Uitterlinden, Andre G; Vandenput, Liesbeth; Vohl, Marie-Claude; Völzke, Henry; Vonk, Judith M; Waeber, Gérard; Waldenberger, Melanie; Westendorp, R G J; Wild, Sarah; Willemsen, Gonneke; Wolffenbuttel, Bruce H R; Wong, Andrew; Wright, Alan F; Zhao, Wei; Zillikens, M Carola; Baldassarre, Damiano; Balkau, Beverley; Bandinelli, Stefania; Böger, Carsten A; Boomsma, Dorret I; Bouchard, Claude; Bruinenberg, Marcel; Chasman, Daniel I; Chen, Yii-DerIda; Chines, Peter S; Cooper, Richard S; Cucca, Francesco; Cusi, Daniele; Faire, Ulf de; Ferrucci, Luigi; Franks, Paul W; Froguel, Philippe; Gordon-Larsen, Penny; Grabe, Hans-Jörgen; Gudnason, Vilmundur; Haiman, Christopher A; Hayward, Caroline; Hveem, Kristian; Johnson, Andrew D; Wouter Jukema, J; Kardia, Sharon L R; Kivimaki, Mika; Kooner, Jaspal S; Kuh, Diana; Laakso, Markku; Lehtimäki, Terho; Marchand, Loic Le; März, Winfried; McCarthy, Mark I; Metspalu, Andres; Morris, Andrew P; Ohlsson, Claes; Palmer, Lyle J; Pasterkamp, Gerard; Pedersen, Oluf; Peters, Annette; Peters, Ulrike; Polasek, Ozren; Psaty, Bruce M; Qi, Lu; Rauramaa, Rainer; Smith, Blair H; Sørensen, Thorkild I A; Strauch, Konstantin; Tiemeier, Henning; Tremoli, Elena; van der Harst, Pim; Vestergaard, Henrik; Vollenweider, Peter; Wareham, Nicholas J; Weir, David R; Whitfield, John B; Wilson, James F; Tyrrell, Jessica; Frayling, Timothy M; Barroso, Inês; Boehnke, Michael; Deloukas, Panagiotis; Fox, Caroline S; Hirschhorn, Joel N; Hunter, David J; Spector, Tim D; Strachan, David P; van Duijn, Cornelia M; Heid, Iris M; Mohlke, Karen L; Marchini, Jonathan; Loos, Ruth J F; Kilpeläinen, Tuomas O; Liu, Ching-Ti; Borecki, Ingrid B; North, Kari E; Cupples, L Adrienne

2017-04-26

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
The rate of high ovarian response in women identified at risk by a high serum AMH level is influenced by the type of gonadotropin.

Science.gov (United States)

Arce, Joan-Carles; Klein, Bjarke M; La Marca, Antonio

2014-06-01

The aim was to compare ovarian response and clinical outcome of potential high-responders after stimulation with highly purified menotropin (HP-hMG) or recombinant follicle-stimulating hormone (rFSH) for in vitro fertilisation/intracytoplasmic sperm injection. Retrospective analysis was performed on data collected in two randomized controlled trials, one conducted following a long GnRH agonist protocol and the other with an antagonist protocol. Potential high-responders (n = 155 and n = 188 in the agonist and antagonist protocol, respectively) were defined as having an initial anti-Müllerian hormone (AMH) value >75th percentile (5.2 ng/ml). In both protocols, HP-hMG stimulation in women in the high AMH category was associated with a significantly lower occurrence of high response (≥15 oocytes retrieved) than rFSH stimulation; 33% versus 51% (p = 0.025) and 31% versus 49% (p = 0.015) in the long agonist and antagonist protocol, respectively. In the potential high-responder women, trends for improved live birth rate were observed with HP-hMG compared with rFSH (long agonist protocol: 33% versus 20%, p = 0.074; antagonist protocol: 34% versus 23%, p = 0.075; overall population: 34% versus 22%, p = 0.012). In conclusion, the type of gonadotropin used for ovarian stimulation influences high-response rates and potentially clinical outcome in women identified as potential high-responders.
5 CFR 410.303 - Employee responsibilities.

Science.gov (United States)

2010-01-01

... Establishing and Implementing Training Programs § 410.303 Employee responsibilities. Employees are responsible... training needed to improve individual and organizational performance and identify methods to meet those... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Employee responsibilities. 410.303...
Science in support of the Deepwater Horizon response

Science.gov (United States)

Lubchenco, Jane; McNutt, Marcia K.; Dreyfus, Gabrielle; Murawski, Steven A.; Kennedy, David M.; Anastas, Paul T.; Chu, Steven; Hunter, Tom

2012-01-01

This introduction to the Special Feature presents the context for science during the Deepwater Horizon oil spill response, summarizes how scientific knowledge was integrated across disciplines and statutory responsibilities, identifies areas where scientific information was accurate and where it was not, and considers lessons learned and recommendations for future research and response. Scientific information was integrated within and across federal and state agencies, with input from nongovernmental scientists, across a diverse portfolio of needs—stopping the flow of oil, estimating the amount of oil, capturing and recovering the oil, tracking and forecasting surface oil, protecting coastal and oceanic wildlife and habitat, managing fisheries, and protecting the safety of seafood. Disciplines involved included atmospheric, oceanographic, biogeochemical, ecological, health, biological, and chemical sciences, physics, geology, and mechanical and chemical engineering. Platforms ranged from satellites and planes to ships, buoys, gliders, and remotely operated vehicles to laboratories and computer simulations. The unprecedented response effort depended directly on intense and extensive scientific and engineering data, information, and advice. Many valuable lessons were learned that should be applied to future events.
Identifying groups of nonparticipants in type 2 diabetes mellitus education.

Science.gov (United States)

Schäfer, Ingmar; Küver, Claudia; Wiese, Birgitt; Pawels, Marc; van den Bussche, Hendrik; Kaduszkiewicz, Hannah

2013-06-01

Patient education is a compulsory element of the nationwide disease management program (DMP) for type 2 diabetes mellitus in Germany. However, a considerable proportion of patients do not attend diabetes self-management education courses. Therefore, the purpose of this study was to describe patient-reported reasons for nonparticipation and to identify typical subgroups of nonparticipants in order to improve recruitment strategies. The authors performed a cross-sectional observational study on 165 participants and 132 nonparticipants in diabetes education using a postal survey and chart review. Participants and nonparticipants were compared using 2-sided t tests and χ2 tests. Nonparticipants were grouped by cluster analysis based on the reasons for nonparticipation. A total of 95% of participants and 36% of nonparticipants reported to have received a recommendation for diabetes education from their physician. The authors identified 4 typical subgroups of nonparticipants: the "informed and responsible," the "unconcerned without desire for more information," the "uninformed but responsible," and the "anxious and burdened with psychosocial problems and functional limitations." The physician's recommendation seems to influence participation in diabetes education and should be used intentionally to increase participation rates. Also, differentiating barriers of nonparticipants can be determined by the degree of feeling informed and responsible for diabetes management. Physicians should more clearly explore patients' perception of their knowledge of diabetes and their attribution of responsibility for diabetes management. Starting from this patient perspective might help physicians motivate patients to participate in diabetes education.

Identifiable Data Files - Health Outcomes Survey (HOS)

Data.gov (United States)

U.S. Department of Health & Human Services — The Medicare Health Outcomes Survey (HOS) identifiable data files are comprised of the entire national sample for a given 2-year cohort (including both respondents...
Identifying significant environmental features using feature recognition.

Science.gov (United States)

2015-10-01

The Department of Environmental Analysis at the Kentucky Transportation Cabinet has expressed an interest in feature-recognition capability because it may help analysts identify environmentally sensitive features in the landscape, : including those r...
Long noncoding RNAs responsive to Fusarium oxysporum infection in Arabidopsis thaliana.

Science.gov (United States)

Zhu, Qian-Hao; Stephen, Stuart; Taylor, Jennifer; Helliwell, Chris A; Wang, Ming-Bo

2014-01-01

Short noncoding RNAs have been demonstrated to play important roles in regulation of gene expression and stress responses, but the repertoire and functions of long noncoding RNAs (lncRNAs) remain largely unexplored, particularly in plants. To explore the role of lncRNAs in disease resistance, we used a strand-specific RNA-sequencing approach to identify lncRNAs responsive to Fusarium oxysporum infection in Arabidopsis thaliana. Antisense transcription was found in c. 20% of the annotated A. thaliana genes. Several noncoding natural antisense transcripts responsive to F. oxysporum infection were found in genes implicated in disease defense. While the majority of the novel transcriptionally active regions (TARs) were adjacent to annotated genes and could be an extension of the annotated transcripts, 159 novel intergenic TARs, including 20 F. oxysporum-responsive lncTARs, were identified. Ten F. oxysporum-induced lncTARs were functionally characterized using T-DNA insertion or RNA-interference knockdown lines, and five were demonstrated to be related to disease development. Promoter analysis suggests that some of the F. oxysporum-induced lncTARs are direct targets of transcription factor(s) responsive to pathogen attack. Our results demonstrated that strand-specific RNA sequencing is a powerful tool for uncovering hidden levels of transcriptome and that IncRNAs are important components of the antifungal networks in A. thaliana. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.
Pathway cross-talk network analysis identifies critical pathways in neonatal sepsis.

Science.gov (United States)

Meng, Yu-Xiu; Liu, Quan-Hong; Chen, Deng-Hong; Meng, Ying

2017-06-01

Despite advances in neonatal care, sepsis remains a major cause of morbidity and mortality in neonates worldwide. Pathway cross-talk analysis might contribute to the inference of the driving forces in bacterial sepsis and facilitate a better understanding of underlying pathogenesis of neonatal sepsis. This study aimed to explore the critical pathways associated with the progression of neonatal sepsis by the pathway cross-talk analysis. By integrating neonatal transcriptome data with known pathway data and protein-protein interaction data, we systematically uncovered the disease pathway cross-talks and constructed a disease pathway cross-talk network for neonatal sepsis. Then, attract method was employed to explore the dysregulated pathways associated with neonatal sepsis. To determine the critical pathways in neonatal sepsis, rank product (RP) algorithm, centrality analysis and impact factor (IF) were introduced sequentially, which synthetically considered the differential expression of genes and pathways, pathways cross-talks and pathway parameters in the network. The dysregulated pathways with the highest IF values as well as RPpathways in neonatal sepsis. By integrating three kinds of data, only 6919 common genes were included to perform the pathway cross-talk analysis. By statistic analysis, a total of 1249 significant pathway cross-talks were selected to construct the pathway cross-talk network. Moreover, 47 dys-regulated pathways were identified via attract method, 20 pathways were identified under RPpathways with the highest IF were also screened from the pathway cross-talk network. Among them, we selected 8 common pathways, i.e. critical pathways. In this study, we systematically tracked 8 critical pathways involved in neonatal sepsis by integrating attract method and pathway cross-talk network. These pathways might be responsible for the host response in infection, and of great value for advancing diagnosis and therapy of neonatal sepsis. Copyright © 2017
Identifying What Matters to Hysterectomy Patients: Postsurgery Perceptions, Beliefs, and Experiences

Directory of Open Access Journals (Sweden)

Andrew S. Bossick

2018-04-01

Full Text Available Purpose: Hysterectomy is the most common nonobstetrical surgery for women in the United States. Few investigations comparing hysterectomy surgical approaches include patient-centered outcomes. Methods: The study was performed at Henry Ford Health System (Detroit, MI between February 2015 and May 2015. A total of 1,038 eligible women — those 18 to 65 years of age and who had an electronic medical record-documented Current Procedural Terminology (CPT® code or an International Statistical Classification of Diseases, Ninth Edition (ICD-9 code of hysterectomy between December 2012 and December 2014 — were selected and recruited. A question guide was developed to investigate women’s experiences and feelings about the experience prior and subsequent to their hysterectomy. Analysis utilized the Framework Method. Study data were collected through structured focus groups with 24 posthysterectomy women in order to identify patient-centered outcomes to employ in a subsequent cohort study of hysterectomy surgical approaches. One pilot focus group and 5 additional focus groups were held. Qualitative data analysis, using data from coded transcripts of focus groups, was used to identify themes. Results: Focus groups with women who previously had a hysterectomy revealed their pre- and posthysterectomy perceptions. Responses were grouped into topics of pre- and postsurgical experiences, and information all women should know. Themes derived from responses: 1 decision-making; 2 the procedure (surgical experience; 3 recovery; 4 advice to past self; and 5 recommendations to other women. Conclusions: These analyzed data suggest a need for increased education and empowerment in the hysterectomy decision-making process, along with expanding information given for postoperative expectations and somatic changes that occur posthysterectomy. Findings about perceptions, beliefs, and attitudes of women having undergone hysterectomy could support health care providers
Global analysis of the yeast osmotic stress response by quantitative proteomics

DEFF Research Database (Denmark)

Soufi, Boumediene; Kelstrup, C.D.; Stoehr, G.

2009-01-01

a comprehensive, quantitative, and time-resolved analysis using high-resolution mass spectrometry of phospho-proteome and proteome changes in response to osmotic stress in yeast. We identified 5534 unique phosphopeptide variants and 3383 yeast proteins. More than 15% of the detected phosphorylation site status...... changed more than two-fold within 5 minutes of treatment. Many of the corresponding phosphoproteins are involved in the early response to environmental stress. Surprisingly, we find that 158 regulated phosphorylation sites are potential substrates of basophilic kinases as opposed to the classical proline......-directed MAP kinase network implicated in stress response mechanisms such as p38 and HOG pathways. Proteome changes reveal an increase in abundance of more than one hundred proteins after 20 min of salt stress. Many of these are involved in the cellular response to increased osmolarity, which include proteins...
Comparison of LMFBR piping response obtained using response spectrum and time history methods

International Nuclear Information System (INIS)

Hulbert, G.M.

1981-04-01

The dynamic response to a seismic event is calculated for a piping system using a response spectrum analysis method and two time history analysis methods. The results from the analytical methods are compared to identify causes for the differences between the sets of analytical results. Comparative methods are also presented which help to gain confidence in the accuracy of the analytical methods in predicting piping system structure response during seismic events
Genetic interactions of MAF1 identify a role for Med20 in transcriptional repression of ribosomal protein genes.

Directory of Open Access Journals (Sweden)

Ian M Willis

2008-07-01

Full Text Available Transcriptional repression of ribosomal components and tRNAs is coordinately regulated in response to a wide variety of environmental stresses. Part of this response involves the convergence of different nutritional and stress signaling pathways on Maf1, a protein that is essential for repressing transcription by RNA polymerase (pol III in Saccharomyces cerevisiae. Here we identify the functions buffering yeast cells that are unable to down-regulate transcription by RNA pol III. MAF1 genetic interactions identified in screens of non-essential gene-deletions and conditionally expressed essential genes reveal a highly interconnected network of 64 genes involved in ribosome biogenesis, RNA pol II transcription, tRNA modification, ubiquitin-dependent proteolysis and other processes. A survey of non-essential MAF1 synthetic sick/lethal (SSL genes identified six gene-deletions that are defective in transcriptional repression of ribosomal protein (RP genes following rapamycin treatment. This subset of MAF1 SSL genes included MED20 which encodes a head module subunit of the RNA pol II Mediator complex. Genetic interactions between MAF1 and subunits in each structural module of Mediator were investigated to examine the functional relationship between these transcriptional regulators. Gene expression profiling identified a prominent and highly selective role for Med20 in the repression of RP gene transcription under multiple conditions. In addition, attenuated repression of RP genes by rapamycin was observed in a strain deleted for the Mediator tail module subunit Med16. The data suggest that Mediator and Maf1 function in parallel pathways to negatively regulate RP mRNA and tRNA synthesis.
A novel nonsense mutation in the DMP1 gene identified by a genome-wide association study is responsible for inherited rickets in Corriedale sheep.

Directory of Open Access Journals (Sweden)

Xia Zhao

Full Text Available Inherited rickets of Corriedale sheep is characterized by decreased growth rate, thoracic lordosis and angular limb deformities. Previous outcross and backcross studies implicate inheritance as a simple autosomal recessive disorder. A genome wide association study was conducted using the Illumina OvineSNP50 BeadChip on 20 related sheep comprising 17 affected and 3 carriers. A homozygous region of 125 consecutive single-nucleotide polymorphism (SNP loci was identified in all affected sheep, covering a region of 6 Mb on ovine chromosome 6. Among 35 candidate genes in this region, the dentin matrix protein 1 gene (DMP1 was sequenced to reveal a nonsense mutation 250C/T on exon 6. This mutation introduced a stop codon (R145X and could truncate C-terminal amino acids. Genotyping by PCR-RFLP for this mutation showed all 17 affected sheep were "T T" genotypes; the 3 carriers were "C T"; 24 phenotypically normal related sheep were either "C T" or "C C"; and 46 unrelated normal control sheep from other breeds were all "C C". The other SNPs in DMP1 were not concordant with the disease and can all be ruled out as candidates. Previous research has shown that mutations in the DMP1 gene are responsible for autosomal recessive hypophosphatemic rickets in humans. Dmp1_knockout mice exhibit rickets phenotypes. We believe the R145X mutation to be responsible for the inherited rickets found in Corriedale sheep. A simple diagnostic test can be designed to identify carriers with the defective "T" allele. Affected sheep could be used as animal models for this form of human rickets, and for further investigation of the role of DMP1 in phosphate homeostasis.
A Novel Nonsense Mutation in the DMP1 Gene Identified by a Genome-Wide Association Study Is Responsible for Inherited Rickets in Corriedale Sheep

Science.gov (United States)

Blair, Hugh T.; Thompson, Keith G.; Rothschild, Max F.; Garrick, Dorian J.

2011-01-01

Inherited rickets of Corriedale sheep is characterized by decreased growth rate, thoracic lordosis and angular limb deformities. Previous outcross and backcross studies implicate inheritance as a simple autosomal recessive disorder. A genome wide association study was conducted using the Illumina OvineSNP50 BeadChip on 20 related sheep comprising 17 affected and 3 carriers. A homozygous region of 125 consecutive single-nucleotide polymorphism (SNP) loci was identified in all affected sheep, covering a region of 6 Mb on ovine chromosome 6. Among 35 candidate genes in this region, the dentin matrix protein 1 gene (DMP1) was sequenced to reveal a nonsense mutation 250C/T on exon 6. This mutation introduced a stop codon (R145X) and could truncate C-terminal amino acids. Genotyping by PCR-RFLP for this mutation showed all 17 affected sheep were “T T” genotypes; the 3 carriers were “C T”; 24 phenotypically normal related sheep were either “C T” or “C C”; and 46 unrelated normal control sheep from other breeds were all “C C”. The other SNPs in DMP1 were not concordant with the disease and can all be ruled out as candidates. Previous research has shown that mutations in the DMP1 gene are responsible for autosomal recessive hypophosphatemic rickets in humans. Dmp1_knockout mice exhibit rickets phenotypes. We believe the R145X mutation to be responsible for the inherited rickets found in Corriedale sheep. A simple diagnostic test can be designed to identify carriers with the defective “T” allele. Affected sheep could be used as animal models for this form of human rickets, and for further investigation of the role of DMP1 in phosphate homeostasis. PMID:21747952
Proteomics strategy for identifying candidate bioactive proteins in complex mixtures: application to the platelet releasate.

LENUS (Irish Health Repository)

O'Connor, Roisin

2010-01-01

Proteomic approaches have proven powerful at identifying large numbers of proteins, but there are fewer reports of functional characterization of proteins in biological tissues. Here, we describe an experimental approach that fractionates proteins released from human platelets, linking bioassay activity to identity. We used consecutive orthogonal separation platforms to ensure sensitive detection: (a) ion-exchange of intact proteins, (b) SDS-PAGE separation of ion-exchange fractions and (c) HPLC separation of tryptic digests coupled to electrospray tandem mass spectrometry. Migration of THP-1 monocytes in response to complete or fractionated platelet releasate was assessed and located to just one of the forty-nine ion-exchange fractions. Over 300 proteins were identified in the releasate, with a wide range of annotated biophysical and biochemical properties, in particular platelet activation, adhesion, and wound healing. The presence of PEDF and involucrin, two proteins not previously reported in platelet releasate, was confirmed by western blotting. Proteins identified within the fraction with monocyte promigratory activity and not in other inactive fractions included vimentin, PEDF, and TIMP-1. We conclude that this analytical platform is effective for the characterization of complex bioactive samples.
Differentially expressed genes of Tetrahymena thermophila in response to tributyltin (TBT) identified by suppression subtractive hybridization and real time quantitative PCR.

Science.gov (United States)

Feng, Lifang; Miao, Wei; Wu, Yuxuan

2007-02-15

Tributyltin (TBT) is widely used as antifouling paints, agriculture biocides, and plastic stabilizers around the world, resulting in great pollution problem in aquatic environments. However, it has been short of the biomonitor to detect TBT in freshwater. We constructed the suppression subtractive hybridization library of Tetrahymena thermophila exposed to TBT, and screened out 101 Expressed Sequence Tags whose expressions were significantly up- or down-regulated with TBT treatment. From this, a series of genes related to the TBT toxicity were discovered, such as glutathione-S-transferase gene (down-regulated), plasma membrane Ca2+ ATPase isoforms 3 gene (up-regulated) and NgoA (up-regulated). Furthermore, their expressions under different concentrations of TBT treatment (0.5-40 ppb) were detected by real time fluorescent quantitative PCR. The differentially expressed genes of T. thermophila in response to TBT were identified, which provide the basic to make Tetrahymena as a sensitive, rapid and convenient TBT biomonitor in freshwater based on rDNA inducible expression system.
Pulmonary response to surface‐coated nanotitanium dioxide particles includes induction of acute phase response genes, inflammatory cascades, and changes in microRNAs: A toxicogenomic study

DEFF Research Database (Denmark)

Halappanavar, Sabina; Jackson, Petra; Williams, Andrew

2011-01-01

with acute phase, inflammation and immune response 5 days post exposure with concomitant changes in several miRNAs. The role of these miRNAs in pulmonary response to inhaled particles is unknown and warrants further research. Environ. Mol. Mutagen., 2011. © 2011 Wiley‐Liss, Inc....... in increased levels of mRNA for acute phase markers serum amyloid A‐1 (Saa1) and serum amyloid A‐3 (Saa3), several C‐X‐C and C‐C motif chemokines, and cytokine tumor necrosis factor genes. Protein analysis of Saa1 and 3 showed selective upregulation of Saa3 in lung tissues. Sixteen miRNAs were induced by more...... than 1.2‐fold (adjusted P‐value changes in the expression of genes associated...
Gut Bacteria Affect Immunotherapy Response

Science.gov (United States)

Three new studies have identified intestinal bacteria that appear to influence the response to checkpoint inhibitors. This Cancer Currents blog post explains how the researchers think their findings could be used to improve patients’ responses to these immunotherapy drugs.
Adult Mouse DRG Explant and Dissociated Cell Models to Investigate Neuroplasticity and Responses to Environmental Insults Including Viral Infection.

Science.gov (United States)

Fornaro, Michele; Sharthiya, Harsh; Tiwari, Vaibhav

2018-03-09

This protocol describes an ex vivo model of mouse-derived dorsal root ganglia (DRG) explant and in vitro DRG-derived co-culture of dissociated sensory neurons and glial satellite cells. These are useful and versatile models to investigate a variety of biological responses associated with physiological and pathological conditions of the peripheral nervous system (PNS) ranging from neuron-glial interaction, neuroplasticity, neuroinflammation, and viral infection. The usage of DRG explant is scientifically advantageous compared to simplistic single cells models for multiple reasons. For instance, as an organotypic culture, the DRG explant allows ex vivo transfer of an entire neuronal network including the extracellular microenvironment that play a significant role in all the neuronal and glial functions. Further, DRG explants can also be maintained ex vivo for several days and the culture conditions can be perturbed as desired. In addition, the harvested DRG can be further dissociated into an in vitro co-culture of primary sensory neurons and satellite glial cells to investigate neuronal-glial interaction, neuritogenesis, axonal cone interaction with the extracellular microenvironment, and more general, any aspect associated with the neuronal metabolism. Therefore, the DRG-explant system offers a great deal of flexibility to study a wide array of events related to biological, physiological, and pathological conditions in a cost-effective manner.
Francisella tularensis subsp. tularensis induces a unique pulmonary inflammatory response: role of bacterial gene expression in temporal regulation of host defense responses.

Directory of Open Access Journals (Sweden)

Kathie-Anne Walters

Full Text Available Pulmonary exposure to Francisella tularensis is associated with severe lung pathology and a high mortality rate. The lack of induction of classical inflammatory mediators, including IL1-β and TNF-α, during early infection has led to the suggestion that F. tularensis evades detection by host innate immune surveillance and/or actively suppresses inflammation. To gain more insight into the host response to Francisella infection during the acute stage, transcriptomic analysis was performed on lung tissue from mice exposed to virulent (Francisella tularensis ssp tularensis SchuS4. Despite an extensive transcriptional response in the lungs of animals as early as 4 hrs post-exposure, Francisella tularensis was associated with an almost complete lack of induction of immune-related genes during the initial 24 hrs post-exposure. This broad subversion of innate immune responses was particularly evident when compared to the pulmonary inflammatory response induced by other lethal (Yersinia pestis and non-lethal (Legionella pneumophila, Pseudomonas aeruginosa pulmonary infections. However, the unique induction of a subset of inflammation-related genes suggests a role for dysregulation of lymphocyte function and anti-inflammatory pathways in the extreme virulence of Francisella. Subsequent activation of a classical inflammatory response 48 hrs post-exposure was associated with altered abundance of Francisella-specific transcripts, including those associated with bacterial surface components. In summary, virulent Francisella induces a unique pulmonary inflammatory response characterized by temporal regulation of innate immune pathways correlating with altered bacterial gene expression patterns. This study represents the first simultaneous measurement of both host and Francisella transcriptome changes that occur during in vivo infection and identifies potential bacterial virulence factors responsible for regulation of host inflammatory pathways.
Nine Loci for Ocular Axial Length Identified through Genome-wide Association Studies, Including Shared Loci with Refractive Error

Science.gov (United States)

Cheng, Ching-Yu; Schache, Maria; Ikram, M. Kamran; Young, Terri L.; Guggenheim, Jeremy A.; Vitart, Veronique; MacGregor, Stuart; Verhoeven, Virginie J.M.; Barathi, Veluchamy A.; Liao, Jiemin; Hysi, Pirro G.; Bailey-Wilson, Joan E.; St. Pourcain, Beate; Kemp, John P.; McMahon, George; Timpson, Nicholas J.; Evans, David M.; Montgomery, Grant W.; Mishra, Aniket; Wang, Ya Xing; Wang, Jie Jin; Rochtchina, Elena; Polasek, Ozren; Wright, Alan F.; Amin, Najaf; van Leeuwen, Elisabeth M.; Wilson, James F.; Pennell, Craig E.; van Duijn, Cornelia M.; de Jong, Paulus T.V.M.; Vingerling, Johannes R.; Zhou, Xin; Chen, Peng; Li, Ruoying; Tay, Wan-Ting; Zheng, Yingfeng; Chew, Merwyn; Rahi, Jugnoo S.; Hysi, Pirro G.; Yoshimura, Nagahisa; Yamashiro, Kenji; Miyake, Masahiro; Delcourt, Cécile; Maubaret, Cecilia; Williams, Cathy; Guggenheim, Jeremy A.; Northstone, Kate; Ring, Susan M.; Davey-Smith, George; Craig, Jamie E.; Burdon, Kathryn P.; Fogarty, Rhys D.; Iyengar, Sudha K.; Igo, Robert P.; Chew, Emily; Janmahasathian, Sarayut; Iyengar, Sudha K.; Igo, Robert P.; Chew, Emily; Janmahasathian, Sarayut; Stambolian, Dwight; Wilson, Joan E. Bailey; MacGregor, Stuart; Lu, Yi; Jonas, Jost B.; Xu, Liang; Saw, Seang-Mei; Baird, Paul N.; Rochtchina, Elena; Mitchell, Paul; Wang, Jie Jin; Jonas, Jost B.; Nangia, Vinay; Hayward, Caroline; Wright, Alan F.; Vitart, Veronique; Polasek, Ozren; Campbell, Harry; Vitart, Veronique; Rudan, Igor; Vatavuk, Zoran; Vitart, Veronique; Paterson, Andrew D.; Hosseini, S. Mohsen; Iyengar, Sudha K.; Igo, Robert P.; Fondran, Jeremy R.; Young, Terri L.; Feng, Sheng; Verhoeven, Virginie J.M.; Klaver, Caroline C.; van Duijn, Cornelia M.; Metspalu, Andres; Haller, Toomas; Mihailov, Evelin; Pärssinen, Olavi; Wedenoja, Juho; Wilson, Joan E. Bailey; Wojciechowski, Robert; Baird, Paul N.; Schache, Maria; Pfeiffer, Norbert; Höhn, René; Pang, Chi Pui; Chen, Peng; Meitinger, Thomas; Oexle, Konrad; Wegner, Aharon; Yoshimura, Nagahisa; Yamashiro, Kenji; Miyake, Masahiro; Pärssinen, Olavi; Yip, Shea Ping; Ho, Daniel W.H.; Pirastu, Mario; Murgia, Federico; Portas, Laura; Biino, Genevra; Wilson, James F.; Fleck, Brian; Vitart, Veronique; Stambolian, Dwight; Wilson, Joan E. Bailey; Hewitt, Alex W.; Ang, Wei; Verhoeven, Virginie J.M.; Klaver, Caroline C.; van Duijn, Cornelia M.; Saw, Seang-Mei; Wong, Tien-Yin; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Wong, Tien-Yin; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Wong, Tien-Yin; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Tai, E-Shyong; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Mackey, David A.; MacGregor, Stuart; Hammond, Christopher J.; Hysi, Pirro G.; Deangelis, Margaret M.; Morrison, Margaux; Zhou, Xiangtian; Chen, Wei; Paterson, Andrew D.; Hosseini, S. Mohsen; Mizuki, Nobuhisa; Meguro, Akira; Lehtimäki, Terho; Mäkelä, Kari-Matti; Raitakari, Olli; Kähönen, Mika; Burdon, Kathryn P.; Craig, Jamie E.; Iyengar, Sudha K.; Igo, Robert P.; Lass, Jonathan H.; Reinhart, William; Belin, Michael W.; Schultze, Robert L.; Morason, Todd; Sugar, Alan; Mian, Shahzad; Soong, Hunson Kaz; Colby, Kathryn; Jurkunas, Ula; Yee, Richard; Vital, Mark; Alfonso, Eduardo; Karp, Carol; Lee, Yunhee; Yoo, Sonia; Hammersmith, Kristin; Cohen, Elisabeth; Laibson, Peter; Rapuano, Christopher; Ayres, Brandon; Croasdale, Christopher; Caudill, James; Patel, Sanjay; Baratz, Keith; Bourne, William; Maguire, Leo; Sugar, Joel; Tu, Elmer; Djalilian, Ali; Mootha, Vinod; McCulley, James; Bowman, Wayne; Cavanaugh, H. Dwight; Verity, Steven; Verdier, David; Renucci, Ann; Oliva, Matt; Rotkis, Walter; Hardten, David R.; Fahmy, Ahmad; Brown, Marlene; Reeves, Sherman; Davis, Elizabeth A.; Lindstrom, Richard; Hauswirth, Scott; Hamilton, Stephen; Lee, W. Barry; Price, Francis; Price, Marianne; Kelly, Kathleen; Peters, Faye; Shaughnessy, Michael; Steinemann, Thomas; Dupps, B.J.; Meisler, David M.; Mifflin, Mark; Olson, Randal; Aldave, Anthony; Holland, Gary; Mondino, Bartly J.; Rosenwasser, George; Gorovoy, Mark; Dunn, Steven P.; Heidemann, David G.; Terry, Mark; Shamie, Neda; Rosenfeld, Steven I.; Suedekum, Brandon; Hwang, David; Stone, Donald; Chodosh, James; Galentine, Paul G.; Bardenstein, David; Goddard, Katrina; Chin, Hemin; Mannis, Mark; Varma, Rohit; Borecki, Ingrid; Chew, Emily Y.; Haller, Toomas; Mihailov, Evelin; Metspalu, Andres; Wedenoja, Juho; Simpson, Claire L.; Wojciechowski, Robert; Höhn, René; Mirshahi, Alireza; Zeller, Tanja; Pfeiffer, Norbert; Lackner, Karl J.; Donnelly, Peter; Barroso, Ines; Blackwell, Jenefer M.; Bramon, Elvira; Brown, Matthew A.; Casas, Juan P.; Corvin, Aiden; Deloukas, Panos; Duncanson, Audrey; Jankowski, Janusz; Markus, Hugh S.; Mathew, Christopher G.; Palmer, Colin N.A.; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J.; Trembath, Richard C.; Viswanathan, Ananth C.; Wood, Nicholas W.; Spencer, Chris C.A.; Band, Gavin; Bellenguez, Céline; Freeman, Colin; Hellenthal, Garrett; Giannoulatou, Eleni; Pirinen, Matti; Pearson, Richard; Strange, Amy; Su, Zhan; Vukcevic, Damjan; Donnelly, Peter; Langford, Cordelia; Hunt, Sarah E.; Edkins, Sarah; Gwilliam, Rhian; Blackburn, Hannah; Bumpstead, Suzannah J.; Dronov, Serge; Gillman, Matthew; Gray, Emma; Hammond, Naomi; Jayakumar, Alagurevathi; McCann, Owen T.; Liddle, Jennifer; Potter, Simon C.; Ravindrarajah, Radhi; Ricketts, Michelle; Waller, Matthew; Weston, Paul; Widaa, Sara; Whittaker, Pamela; Barroso, Ines; Deloukas, Panos; Mathew, Christopher G.; Blackwell, Jenefer M.; Brown, Matthew A.; Corvin, Aiden; Spencer, Chris C.A.; Bettecken, Thomas; Meitinger, Thomas; Oexle, Konrad; Pirastu, Mario; Portas, Laura; Nag, Abhishek; Williams, Katie M.; Yonova-Doing, Ekaterina; Klein, Ronald; Klein, Barbara E.; Hosseini, S. Mohsen; Paterson, Andrew D.; Genuth, S.; Nathan, D.M.; Zinman, B.; Crofford, O.; Crandall, J.; Reid, M.; Brown-Friday, J.; Engel, S.; Sheindlin, J.; Martinez, H.; Shamoon, H.; Engel, H.; Phillips, M.; Gubitosi-Klug, R.; Mayer, L.; Pendegast, S.; Zegarra, H.; Miller, D.; Singerman, L.; Smith-Brewer, S.; Novak, M.; Quin, J.; Dahms, W.; Genuth, Saul; Palmert, M.; Brillon, D.; Lackaye, M.E.; Kiss, S.; Chan, R.; Reppucci, V.; Lee, T.; Heinemann, M.; Whitehouse, F.; Kruger, D.; Jones, J.K.; McLellan, M.; Carey, J.D.; Angus, E.; Thomas, A.; Galprin, A.; Bergenstal, R.; Johnson, M.; Spencer, M.; Morgan, K.; Etzwiler, D.; Kendall, D.; Aiello, Lloyd Paul; Golden, E.; Jacobson, A.; Beaser, R.; Ganda, O.; Hamdy, O.; Wolpert, H.; Sharuk, G.; Arrigg, P.; Schlossman, D.; Rosenzwieg, J.; Rand, L.; Nathan, D.M.; Larkin, M.; Ong, M.; Godine, J.; Cagliero, E.; Lou, P.; Folino, K.; Fritz, S.; Crowell, S.; Hansen, K.; Gauthier-Kelly, C.; Service, J.; Ziegler, G.; Luttrell, L.; Caulder, S.; Lopes-Virella, M.; Colwell, J.; Soule, J.; Fernandes, J.; Hermayer, K.; Kwon, S.; Brabham, M.; Blevins, A.; Parker, J.; Lee, D.; Patel, N.; Pittman, C.; Lindsey, P.; Bracey, M.; Lee, K.; Nutaitis, M.; Farr, A.; Elsing, S.; Thompson, T.; Selby, J.; Lyons, T.; Yacoub-Wasef, S.; Szpiech, M.; Wood, D.; Mayfield, R.; Molitch, M.; Schaefer, B.; Jampol, L.; Lyon, A.; Gill, M.; Strugula, Z.; Kaminski, L.; Mirza, R.; Simjanoski, E.; Ryan, D.; Kolterman, O.; Lorenzi, G.; Goldbaum, M.; Sivitz, W.; Bayless, M.; Counts, D.; Johnsonbaugh, S.; Hebdon, M.; Salemi, P.; Liss, R.; Donner, T.; Gordon, J.; Hemady, R.; Kowarski, A.; Ostrowski, D.; Steidl, S.; Jones, B.; Herman, W.H.; Martin, C.L.; Pop-Busui, R.; Sarma, A.; Albers, J.; Feldman, E.; Kim, K.; Elner, S.; Comer, G.; Gardner, T.; Hackel, R.; Prusak, R.; Goings, L.; Smith, A.; Gothrup, J.; Titus, P.; Lee, J.; Brandle, M.; Prosser, L.; Greene, D.A.; Stevens, M.J.; Vine, A.K.; Bantle, J.; Wimmergren, N.; Cochrane, A.; Olsen, T.; Steuer, E.; Rath, P.; Rogness, B.; Hainsworth, D.; Goldstein, D.; Hitt, S.; Giangiacomo, J.; Schade, D.S.; Canady, J.L.; Chapin, J.E.; Ketai, L.H.; Braunstein, C.S.; Bourne, P.A.; Schwartz, S.; Brucker, A.; Maschak-Carey, B.J.; Baker, L.; Orchard, T.; Silvers, N.; Ryan, C.; Songer, T.; Doft, B.; Olson, S.; Bergren, R.L.; Lobes, L.; Rath, P. Paczan; Becker, D.; Rubinstein, D.; Conrad, P.W.; Yalamanchi, S.; Drash, A.; Morrison, A.; Bernal, M.L.; Vaccaro-Kish, J.; Malone, J.; Pavan, P.R.; Grove, N.; Iyer, M.N.; Burrows, A.F.; Tanaka, E.A.; Gstalder, R.; Dagogo-Jack, S.; Wigley, C.; Ricks, H.; Kitabchi, A.; Murphy, M.B.; Moser, S.; Meyer, D.; Iannacone, A.; Chaum, E.; Yoser, S.; Bryer-Ash, M.; Schussler, S.; Lambeth, H.; Raskin, P.; Strowig, S.; Zinman, B.; Barnie, A.; Devenyi, R.; Mandelcorn, M.; Brent, M.; Rogers, S.; Gordon, A.; Palmer, J.; Catton, S.; Brunzell, J.; Wessells, H.; de Boer, I.H.; Hokanson, J.; Purnell, J.; Ginsberg, J.; Kinyoun, J.; Deeb, S.; Weiss, M.; Meekins, G.; Distad, J.; Van Ottingham, L.; Dupre, J.; Harth, J.; Nicolle, D.; Driscoll, M.; Mahon, J.; Canny, C.; May, M.; Lipps, J.; Agarwal, A.; Adkins, T.; Survant, L.; Pate, R.L.; Munn, G.E.; Lorenz, R.; Feman, S.; White, N.; Levandoski, L.; Boniuk, I.; Grand, G.; Thomas, M.; Joseph, D.D.; Blinder, K.; Shah, G.; Boniuk; Burgess; Santiago, J.; Tamborlane, W.; Gatcomb, P.; Stoessel, K.; Taylor, K.; Goldstein, J.; Novella, S.; Mojibian, H.; Cornfeld, D.; Lima, J.; Bluemke, D.; Turkbey, E.; van der Geest, R.J.; Liu, C.; Malayeri, A.; Jain, A.; Miao, C.; Chahal, H.; Jarboe, R.; Maynard, J.; Gubitosi-Klug, R.; Quin, J.; Gaston, P.; Palmert, M.; Trail, R.; Dahms, W.; Lachin, J.; Cleary, P.; Backlund, J.; Sun, W.; Braffett, B.; Klumpp, K.; Chan, K.; Diminick, L.; Rosenberg, D.; Petty, B.; Determan, A.; Kenny, D.; Rutledge, B.; Younes, Naji; Dews, L.; Hawkins, M.; Cowie, C.; Fradkin, J.; Siebert, C.; Eastman, R.; Danis, R.; Gangaputra, S.; Neill, S.; Davis, M.; Hubbard, L.; Wabers, H.; Burger, M.; Dingledine, J.; Gama, V.; Sussman, R.; Steffes, M.; Bucksa, J.; Nowicki, M.; Chavers, B.; O’Leary, D.; Polak, J.; Harrington, A.; Funk, L.; Crow, R.; Gloeb, B.; Thomas, S.; O’Donnell, C.; Soliman, E.; Zhang, Z.M.; Prineas, R.; Campbell, C.; Ryan, C.; Sandstrom, D.; Williams, T.; Geckle, M.; Cupelli, E.; Thoma, F.; Burzuk, B.; Woodfill, T.; Low, P.; Sommer, C.; Nickander, K.; Budoff, M.; Detrano, R.; Wong, N.; Fox, M.; Kim, L.; Oudiz, R.; Weir, G.; Espeland, M.; Manolio, T.; Rand, L.; Singer, D.; Stern, M.; Boulton, A.E.; Clark, C.; D’Agostino, R.; Lopes-Virella, M.; Garvey, W.T.; Lyons, T.J.; Jenkins, A.; Virella, G.; Jaffa, A.; Carter, Rickey; Lackland, D.; Brabham, M.; McGee, D.; Zheng, D.; Mayfield, R.K.; Boright, A.; Bull, S.; Sun, L.; Scherer, S.; Zinman, B.; Natarajan, R.; Miao, F.; Zhang, L.; Chen;, Z.; Nathan, D.M.; Makela, Kari-Matti; Lehtimaki, Terho; Kahonen, Mika; Raitakari, Olli; Yoshimura, Nagahisa; Matsuda, Fumihiko; Chen, Li Jia; Pang, Chi Pui; Yip, Shea Ping; Yap, Maurice K.H.; Meguro, Akira; Mizuki, Nobuhisa; Inoko, Hidetoshi; Foster, Paul J.; Zhao, Jing Hua; Vithana, Eranga; Tai, E-Shyong; Fan, Qiao; Xu, Liang; Campbell, Harry; Fleck, Brian; Rudan, Igor; Aung, Tin; Hofman, Albert; Uitterlinden, André G.; Bencic, Goran; Khor, Chiea-Chuen; Forward, Hannah; Pärssinen, Olavi; Mitchell, Paul; Rivadeneira, Fernando; Hewitt, Alex W.; Williams, Cathy; Oostra, Ben A.; Teo, Yik-Ying; Hammond, Christopher J.; Stambolian, Dwight; Mackey, David A.; Klaver, Caroline C.W.; Wong, Tien-Yin; Saw, Seang-Mei; Baird, Paul N.

2013-01-01

Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways. PMID:24144296
Transparency in authors' contributions and responsibilities to promote integrity in scientific publication.

Science.gov (United States)

McNutt, Marcia K; Bradford, Monica; Drazen, Jeffrey M; Hanson, Brooks; Howard, Bob; Jamieson, Kathleen Hall; Kiermer, Véronique; Marcus, Emilie; Pope, Barbara Kline; Schekman, Randy; Swaminathan, Sowmya; Stang, Peter J; Verma, Inder M

2018-03-13

In keeping with the growing movement in scientific publishing toward transparency in data and methods, we propose changes to journal authorship policies and procedures to provide insight into which author is responsible for which contributions, better assurance that the list is complete, and clearly articulated standards to justify earning authorship credit. To accomplish these goals, we recommend that journals adopt common and transparent standards for authorship, outline responsibilities for corresponding authors, adopt the Contributor Roles Taxonomy (CRediT) (docs.casrai.org/CRediT) methodology for attributing contributions, include this information in article metadata, and require authors to use the ORCID persistent digital identifier (https://orcid.org). Additionally, we recommend that universities and research institutions articulate expectations about author roles and responsibilities to provide a point of common understanding for discussion of authorship across research teams. Furthermore, we propose that funding agencies adopt the ORCID identifier and accept the CRediT taxonomy. We encourage scientific societies to further authorship transparency by signing on to these recommendations and promoting them through their meetings and publications programs. Copyright © 2018 the Author(s). Published by PNAS.
Cell Wall Metabolism in Response to Abiotic Stress

Science.gov (United States)

Gall, Hyacinthe Le; Philippe, Florian; Domon, Jean-Marc; Gillet, Françoise; Pelloux, Jérôme; Rayon, Catherine

2015-01-01

This review focuses on the responses of the plant cell wall to several abiotic stresses including drought, flooding, heat, cold, salt, heavy metals, light, and air pollutants. The effects of stress on cell wall metabolism are discussed at the physiological (morphogenic), transcriptomic, proteomic and biochemical levels. The analysis of a large set of data shows that the plant response is highly complex. The overall effects of most abiotic stress are often dependent on the plant species, the genotype, the age of the plant, the timing of the stress application, and the intensity of this stress. This shows the difficulty of identifying a common pattern of stress response in cell wall architecture that could enable adaptation and/or resistance to abiotic stress. However, in most cases, two main mechanisms can be highlighted: (i) an increased level in xyloglucan endotransglucosylase/hydrolase (XTH) and expansin proteins, associated with an increase in the degree of rhamnogalacturonan I branching that maintains cell wall plasticity and (ii) an increased cell wall thickening by reinforcement of the secondary wall with hemicellulose and lignin deposition. Taken together, these results show the need to undertake large-scale analyses, using multidisciplinary approaches, to unravel the consequences of stress on the cell wall. This will help identify the key components that could be targeted to improve biomass production under stress conditions. PMID:27135320
Identifying Children in Middle Childhood Who Are at Risk for Reading Problems.

Science.gov (United States)

Speece, Deborah L; Ritchey, Kristen D; Silverman, Rebecca; Schatschneider, Christopher; Walker, Caroline Y; Andrusik, Katryna N

2010-06-01

The purpose of this study was to identify and evaluate a universal screening battery for reading that is appropriate for older elementary students in a response to intervention model. Multiple measures of reading and reading correlates were administered to 230 fourth-grade children. Teachers rated children's reading skills, academic competence, and attention. Children were classified as not-at-risk or at-risk readers based on a three-factor model reflecting reading comprehension, word recognition/decoding, and word fluency. Predictors of reading status included group-administered tests of reading comprehension, silent word reading fluency, and teacher ratings of reading problems. Inclusion of individually administered tests and growth estimates did not add substantial variance. The receiver-operator characteristic curve analysis yielded an area under the curve index of 0.90, suggesting this model may both accurately and efficiently screen older elementary students with reading problems.

Using module analysis for multiple choice responses

DEFF Research Database (Denmark)

Brewe, Eric; Bruun, Jesper; Bearden, Ian

2016-01-01

We describe a methodology for carrying out a network analysis of Force Concept Inventory (FCI) responses that aims to identify communities of incorrect responses. This method first treats FCI responses as a bipartite, student X response, network. We then use Locally Adaptive Network Sparsificatio...
Exploring the Rationales Expressed for Including a CSR Position to the Top Management Team

DEFF Research Database (Denmark)

Strand, Robert

Recently, a number of positions with corporate social responsibility (CSR) in the position title have been introduced to the top management teams (TMTs) of some of the world’s largest corporations. I explore this phenomenon. I revisit 10 such positions identified in a previous study to add...
Involvement of potato (Solanum tuberosum L.) MKK6 in response to potato virus Y.

Science.gov (United States)

Lazar, Ana; Coll, Anna; Dobnik, David; Baebler, Spela; Bedina-Zavec, Apolonija; Zel, Jana; Gruden, Kristina

2014-01-01

Mitogen-activated protein kinase (MAPK) cascades have crucial roles in the regulation of plant development and in plant responses to stress. Plant recognition of pathogen-associated molecular patterns or pathogen-derived effector proteins has been shown to trigger activation of several MAPKs. This then controls defence responses, including synthesis and/or signalling of defence hormones and activation of defence related genes. The MAPK cascade genes are highly complex and interconnected, and thus the precise signalling mechanisms in specific plant-pathogen interactions are still not known. Here we investigated the MAPK signalling network involved in immune responses of potato (Solanum tuberosum L.) to Potato virus Y, an important potato pathogen worldwide. Sequence analysis was performed to identify the complete MAPK kinase (MKK) family in potato, and to identify those regulated in the hypersensitive resistance response to Potato virus Y infection. Arabidopsis has 10 MKK family members, of which we identified five in potato and tomato (Solanum lycopersicum L.), and eight in Nicotiana benthamiana. Among these, StMKK6 is the most strongly regulated gene in response to Potato virus Y. The salicylic acid treatment revealed that StMKK6 is regulated by the hormone that is in agreement with the salicylic acid-regulated domains found in the StMKK6 promoter. The involvement of StMKK6 in potato defence response was confirmed by localisation studies, where StMKK6 accumulated strongly only in Potato-virus-Y-infected plants, and predominantly in the cell nucleus. Using a yeast two-hybrid method, we identified three StMKK6 targets downstream in the MAPK cascade: StMAPK4_2, StMAPK6 and StMAPK13. These data together provide further insight into the StMKK6 signalling module and its involvement in plant defence.
Identifying parasitic current pathways in CIGS solar cells by modelling dark J-V response

NARCIS (Netherlands)

Williams, B.L.; Smit, S.; Kniknie, B.J.; Bakker, K.; Keuning, W.; Schropp, R.E.I.; Creatore, M.; Kessels, W.M.M.

2015-01-01

The non-uniform presence of shunting defects is a significant cause of poor reproducibility across large-area solar cells, or from batch-to-batch for small area cells, but the most commonly used value for shunt parameterisation (the shunt resistance) fails to identify the cause for shunting. Here,
Non-response to (statin) therapy

DEFF Research Database (Denmark)

Trompet, S; Postmus, I; Slagboom, P E

2016-01-01

PURPOSE: In pharmacogenetic research, genetic variation in non-responders and high responders is compared with the aim to identify the genetic loci responsible for this variation in response. However, an important question is whether the non-responders are truly biologically non-responsive......-responders from the analysis. RESULTS: Non-responders to statin therapy were younger (p = 0.001), more often smoked (p levels (p ... that non-adherence is investigated instead of non-responsiveness....
MRI features of the complete histopathological response of locally advanced rectal cancer to neoadjuvant chemoradiotherapy

Energy Technology Data Exchange (ETDEWEB)

Franklin, J.M., E-mail: jamiemfranklin@hotmail.com [Churchill Hospital, Headington, Oxford (United Kingdom); Anderson, E.M.; Gleeson, F.V. [Churchill Hospital, Headington, Oxford (United Kingdom)

2012-06-15

Aim: To describe the post-chemoradiotherapy magnetic resonance imaging (MRI) features of locally advanced rectal carcinoma (LARC) in which there has been a complete histopathological response to neoadjuvant chemoradiotherapy (CRT). Materials and methods: This retrospective cohort study was performed between January 2005 and November 2009 at a regional cancer centre. Consecutive patients with LARC and a histopathological complete response to long-course CRT were identified. Pre- and post-treatment MRI images were reviewed using a proforma for predefined features and response criteria. ymrT0 was defined as the absence of residual abnormality on MRI. Results: Twenty patients were included in the study. Seven (35%) ypT0 tumours were ymrT0. All 13 ypT0 tumours not achieving ymrT0 appearances had a good radiological response, with at least 65% tumour reduction. The appearances were heterogeneous: in 11/13 patients the tumour was replaced by a region of at least 50% low signal on MRI, with 8/13 having {>=}80% low signal, and 3/13 with 100% low signal. Conclusion: MRI may be useful in identifying a complete histopathological response. However, the MRI appearances of ypT0 tumours are heterogeneous and conventional MRI complete response criteria will not detect the majority of patients with a complete histopathological response.
MRI features of the complete histopathological response of locally advanced rectal cancer to neoadjuvant chemoradiotherapy

International Nuclear Information System (INIS)

Franklin, J.M.; Anderson, E.M.; Gleeson, F.V.

2012-01-01

Aim: To describe the post-chemoradiotherapy magnetic resonance imaging (MRI) features of locally advanced rectal carcinoma (LARC) in which there has been a complete histopathological response to neoadjuvant chemoradiotherapy (CRT). Materials and methods: This retrospective cohort study was performed between January 2005 and November 2009 at a regional cancer centre. Consecutive patients with LARC and a histopathological complete response to long-course CRT were identified. Pre- and post-treatment MRI images were reviewed using a proforma for predefined features and response criteria. ymrT0 was defined as the absence of residual abnormality on MRI. Results: Twenty patients were included in the study. Seven (35%) ypT0 tumours were ymrT0. All 13 ypT0 tumours not achieving ymrT0 appearances had a good radiological response, with at least 65% tumour reduction. The appearances were heterogeneous: in 11/13 patients the tumour was replaced by a region of at least 50% low signal on MRI, with 8/13 having ≥80% low signal, and 3/13 with 100% low signal. Conclusion: MRI may be useful in identifying a complete histopathological response. However, the MRI appearances of ypT0 tumours are heterogeneous and conventional MRI complete response criteria will not detect the majority of patients with a complete histopathological response.
Quantitative trait loci identified for blood chemistry components of an advanced intercross line of chickens under heat stress.

Science.gov (United States)

Van Goor, Angelica; Ashwell, Christopher M; Persia, Michael E; Rothschild, Max F; Schmidt, Carl J; Lamont, Susan J

2016-04-14

Heat stress in poultry results in considerable economic losses and is a concern for both animal health and welfare. Physiological changes occur during periods of heat stress, including changes in blood chemistry components. A highly advanced intercross line, created from a broiler (heat susceptible) by Fayoumi (heat resistant) cross, was exposed to daily heat cycles for seven days starting at 22 days of age. Blood components measured pre-heat treatment and on the seventh day of heat treatment included pH, pCO2, pO2, base excess, HCO3, TCO2, K, Na, ionized Ca, hematocrit, hemoglobin, sO2, and glucose. A genome-wide association study (GWAS) for these traits and their calculated changes was conducted to identify quantitative trait loci (QTL) using a 600 K SNP panel. There were significant increases in pH, base excess, HCO3, TCO2, ionized Ca, hematocrit, hemoglobin, and sO2, and significant decreases in pCO2 and glucose after 7 days of heat treatment. Heritabilities ranged from 0.01-0.21 for pre-heat measurements, 0.01-0.23 for measurements taken during heat, and 0.00-0.10 for the calculated change due to heat treatment. All blood components were highly correlated within measurement days, but not correlated between measurement days. The GWAS revealed 61 QTL for all traits, located on GGA (Gallus gallus chromosome) 1, 3, 6, 9, 10, 12-14, 17, 18, 21-28, and Z. A functional analysis of the genes in these QTL regions identified the Angiopoietin pathway as significant. The QTL that co-localized for three or more traits were on GGA10, 22, 26, 28, and Z and revealed candidate genes for birds' response to heat stress. The results of this study contribute to our knowledge of levels and heritabilities of several blood components of chickens under thermoneutral and heat stress conditions. Most components responded to heat treatment. Mapped QTL may serve as markers for genomic selection to enhance heat tolerance in poultry. The Angiopoietin pathway is likely involved in the
Three newly identified galectin homologues from triangle sail mussel (Hyriopsis cumingii) function as potential pattern-recognition receptors.

Science.gov (United States)

Zhao, Ling-Ling; Hui, Kaimin; Wang, Yu-Qing; Wang, Yue; Ren, Qian; Li, Xin-Cang

2018-05-01

Galactoside-binding lectins, also known as galectins, play crucial roles in innate immune response in invertebrates. In this study, three cDNA sequences from Hyriopsis cumingii were identified and collectively called HcGalec genes. Each of the three deduced HcGalec proteins contained a galactose-binding lectin domain or a GLECT domain. All the three HcGalec genes are mainly present in the hepatopancreas and gills, and their expression is induced at 24 h after bacterial challenge. Three recombinant HcGalec proteins can bind and agglutinate (Ca 2+ -dependent) various microorganisms, including Gram-positive and Gram-negative bacteria. These proteins can attach to mannan and peptidoglycan. Meanwhile, the expression of the three HcGalec genes in the gills were significantly down-regulated after dsRNA interference (HcGalec1-RNAi, HcGalec2-RNAi, and HcGalec3-RNAi) and Vibrio parahaemolyticus injection. The expression levels of some antimicrobial peptides, including lysozyme 1 and lysozyme 2, were also markedly decreased after dsRNA interference. Overall, these results suggested that these three HcGalec proteins may function as potential receptors participating in the innate immune responses of H. cumingii against bacterial infection. Copyright © 2018 Elsevier Ltd. All rights reserved.
Systems analysis of apoptotic priming in ovarian cancer identifies vulnerabilities and predictors of drug response.

Science.gov (United States)

Zervantonakis, Ioannis K; Iavarone, Claudia; Chen, Hsing-Yu; Selfors, Laura M; Palakurthi, Sangeetha; Liu, Joyce F; Drapkin, Ronny; Matulonis, Ursula; Leverson, Joel D; Sampath, Deepak; Mills, Gordon B; Brugge, Joan S

2017-08-28

The lack of effective chemotherapies for high-grade serous ovarian cancers (HGS-OvCa) has motivated a search for alternative treatment strategies. Here, we present an unbiased systems-approach to interrogate a panel of 14 well-annotated HGS-OvCa patient-derived xenografts for sensitivity to PI3K and PI3K/mTOR inhibitors and uncover cell death vulnerabilities. Proteomic analysis reveals that PI3K/mTOR inhibition in HGS-OvCa patient-derived xenografts induces both pro-apoptotic and anti-apoptotic signaling responses that limit cell killing, but also primes cells for inhibitors of anti-apoptotic proteins. In-depth quantitative analysis of BCL-2 family proteins and other apoptotic regulators, together with computational modeling and selective anti-apoptotic protein inhibitors, uncovers new mechanistic details about apoptotic regulators that are predictive of drug sensitivity (BIM, caspase-3, BCL-X L ) and resistance (MCL-1, XIAP). Our systems-approach presents a strategy for systematic analysis of the mechanisms that limit effective tumor cell killing and the identification of apoptotic vulnerabilities to overcome drug resistance in ovarian and other cancers.High-grade serous ovarian cancers (HGS-OvCa) frequently develop chemotherapy resistance. Here, the authors through a systematic analysis of proteomic and drug response data of 14 HGS-OvCa PDXs demonstrate that targeting apoptosis regulators can improve response of these tumors to inhibitors of the PI3K/mTOR pathway.
The Immune Response against Acinetobacter baumannii, an Emerging Pathogen in Nosocomial Infections

Science.gov (United States)

García-Patiño, María Guadalupe; García-Contreras, Rodolfo; Licona-Limón, Paula

2017-01-01

Acinetobacter baumannii is the etiologic agent of a wide range of nosocomial infections, including pneumonia, bacteremia, and skin infections. Over the last 45 years, an alarming increase in the antibiotic resistance of this opportunistic microorganism has been reported, a situation that hinders effective treatments. In order to develop effective therapies against A. baumannii it is crucial to understand the basis of host–bacterium interactions, especially those concerning the immune response of the host. Different innate immune cells such as monocytes, macrophages, dendritic cells, and natural killer cells have been identified as important effectors in the defense against A. baumannii; among them, neutrophils represent a key immune cell indispensable for the control of the infection. Several immune strategies to combat A. baumannii have been identified such as recognition of the bacteria by immune cells through pattern recognition receptors, specifically toll-like receptors, which trigger bactericidal mechanisms including oxidative burst and cytokine and chemokine production to amplify the immune response against the pathogen. However, a complete picture of the protective immune strategies activated by this bacteria and its potential therapeutic use remains to be determined and explored. PMID:28446911
Structural-Vibration-Response Data Analysis

Science.gov (United States)

Smith, W. R.; Hechenlaible, R. N.; Perez, R. C.

1983-01-01

Computer program developed as structural-vibration-response data analysis tool for use in dynamic testing of Space Shuttle. Program provides fast and efficient time-domain least-squares curve-fitting procedure for reducing transient response data to obtain structural model frequencies and dampings from free-decay records. Procedure simultaneously identifies frequencies, damping values, and participation factors for noisy multiple-response records.
A Drosophila immune response against Ras-induced overgrowth

Directory of Open Access Journals (Sweden)

Thomas Hauling

2014-03-01

Full Text Available Our goal is to characterize the innate immune response against the early stage of tumor development. For this, animal models where genetic changes in specific cells and tissues can be performed in a controlled way have become increasingly important, including the fruitfly Drosophila melanogaster. Many tumor mutants in Drosophila affect the germline and, as a consequence, also the immune system itself, making it difficult to ascribe their phenotype to a specific tissue. Only during the past decade, mutations have been induced systematically in somatic cells to study the control of tumorous growth by neighboring cells and by immune cells. Here we show that upon ectopic expression of a dominant-active form of the Ras oncogene (RasV12, both imaginal discs and salivary glands are affected. Particularly, the glands increase in size, express metalloproteinases and display apoptotic markers. This leads to a strong cellular response, which has many hallmarks of the granuloma-like encapsulation reaction, usually mounted by the insect against larger foreign objects. RNA sequencing of the fat body reveals a characteristic humoral immune response. In addition we also identify genes that are specifically induced upon expression of RasV12. As a proof-of-principle, we show that one of the induced genes (santa-maria, which encodes a scavenger receptor, modulates damage to the salivary glands. The list of genes we have identified provides a rich source for further functional characterization. Our hope is that this will lead to a better understanding of the earliest stage of innate immune responses against tumors with implications for mammalian immunity.
Applying an Evidence-Based Assessment Model to Identify Students at Risk for Perceived Academic Problems following Concussion.

Science.gov (United States)

Ransom, Danielle M; Burns, Alison R; Youngstrom, Eric A; Vaughan, Christopher G; Sady, Maegan D; Gioia, Gerard A

2016-11-01

The aim of this study was to demonstrate the utility of an evidence-based assessment (EBA) model to establish a multimodal set of tools for identifying students at risk for perceived post-injury academic problems. Participants included 142 students diagnosed with concussion (age: M=14.95; SD=1.80; 59% male), evaluated within 4 weeks of injury (median=16 days). Demographics, pre-injury history, self- and parent-report measures assessing symptom severity and executive functions, and cognitive test performance were examined as predictors of self-reported post-injury academic problems. Latent class analysis categorized participants into "high" (44%) and "low" (56%) levels of self-reported academic problems. Receiver operating characteristic analyses revealed significant discriminative validity for self- and parent-reported symptom severity and executive dysfunction and self-reported exertional response for identifying students reporting low versus high academic problems. Parent-reported symptom ratings [area under the receiver operating characteristic curve (AUC)=.79] and executive dysfunction (AUC=.74), and self-reported ratings of executive dysfunction (AUC=.84), symptoms (AUC=.80), and exertional response (AUC=.70) each classified students significantly better than chance (psperspective in the management of concussion by applying traditional strengths of neuropsychological assessment to clinical decision making. (JINS, 2016, 22, 1038-1049).
Excessive biologic response to IFNβ is associated with poor treatment response in patients with multiple sclerosis.

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Richard A Rudick

Full Text Available BACKGROUND: Interferon-beta (IFNβ is used to inhibit disease activity in multiple sclerosis (MS, but its mechanisms of action are incompletely understood, individual treatment response varies, and biological markers predicting response to treatment have yet to be identified. METHODS: The relationship between the molecular response to IFNβ and treatment response was determined in 85 patients using a longitudinal design in which treatment effect was categorized by brain magnetic resonance imaging as good (n = 70 or poor response (n = 15. Molecular response was quantified using a customized cDNA macroarray assay for 166 IFN-regulated genes (IRGs. RESULTS: The molecular response to IFNβ differed significantly between patients in the pattern and number of regulated genes. The molecular response was strikingly stable for individuals for as long as 24 months, however, suggesting an individual 'IFN response fingerprint'. Unexpectedly, patients with poor response showed an exaggerated molecular response. IRG induction ratios demonstrated an exaggerated molecular response at both the first and 6-month IFNβ injections. CONCLUSION: MS patients exhibit individually unique but temporally stable biological responses to IFNβ. Poor treatment response is not explained by the duration of biological effects or the specific genes induced. Rather, individuals with poor treatment response have a generally exaggerated biological response to type 1 IFN injections. We hypothesize that the molecular response to type I IFN identifies a pathogenetically distinct subset of MS patients whose disease is driven in part by innate immunity. The findings suggest a strategy for biologically based, rational use of IFNβ for individual MS patients.
An overview of the Environmental Response Team's air surveillance procedures at emergency response activities

Energy Technology Data Exchange (ETDEWEB)

Turpin, R.D.; Campagna, P.R. (U.S. Environmental Protection Agency, Edison, NJ (USA))

The Safety and Air Surveillance Section of the United States Environmental Protection Agency's Environmental Response Team responds to emergency air releases such as tire fires and explosions. The air surveillance equipment and procedures used by the organization are described, and case studies demonstrating the various emergency response activities are presented. Air response activities include emergency air responses, occupational and human health air responses and remedial air responses. Monitoring and sampling equipment includes photoionization detectors, combustible gas meters, real-time aerosol monitors, personal sampling pumps, and high flow pumps. Case histories presented include disposal of dioxane from a cotton plant, response to oil well fires in Kuwait, disposal of high pressure cylinders in American Samoa, and response to hurricane Hugo. 3 refs., 1 tab.
Anti-schistosomal intervention targets identified by lifecycle transcriptomic analyses.

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Jennifer M Fitzpatrick

2009-11-01

Full Text Available Novel methods to identify anthelmintic drug and vaccine targets are urgently needed, especially for those parasite species currently being controlled by singular, often limited strategies. A clearer understanding of the transcriptional components underpinning helminth development will enable identification of exploitable molecules essential for successful parasite/host interactions. Towards this end, we present a combinatorial, bioinformatics-led approach, employing both statistical and network analyses of transcriptomic data, for identifying new immunoprophylactic and therapeutic lead targets to combat schistosomiasis.Utilisation of a Schistosoma mansoni oligonucleotide DNA microarray consisting of 37,632 elements enabled gene expression profiling from 15 distinct parasite lifecycle stages, spanning three unique ecological niches. Statistical approaches of data analysis revealed differential expression of 973 gene products that minimally describe the three major characteristics of schistosome development: asexual processes within intermediate snail hosts, sexual maturation within definitive vertebrate hosts and sexual dimorphism amongst adult male and female worms. Furthermore, we identified a group of 338 constitutively expressed schistosome gene products (including 41 transcripts sharing no sequence similarity outside the Platyhelminthes, which are likely to be essential for schistosome lifecycle progression. While highly informative, statistics-led bioinformatics mining of the transcriptional dataset has limitations, including the inability to identify higher order relationships between differentially expressed transcripts and lifecycle stages. Network analysis, coupled to Gene Ontology enrichment investigations, facilitated a re-examination of the dataset and identified 387 clusters (containing 12,132 gene products displaying novel examples of developmentally regulated classes (including 294 schistosomula and/or adult transcripts with no
Genetic and pharmacological screens converge in identifying FLIP, BCL2 and IAP proteins as key regulators of sensitivity to the TRAIL-inducing anti-cancer agent ONC201/TIC10

OpenAIRE

Allen, Joshua E.; Prabhu, Varun V.; Talekar, Mala; van den Heuvel, AP; Lim, Bora; Dicker, David T.; Fritz, Jennifer L.; Beck, Adam; El-Deiry, Wafik S.

2015-01-01

ONC201/TIC10 is a small molecule inducer of the TRAIL gene under current investigation as a novel anticancer agent. In this study, we identify critical molecular determinants of ONC201 sensitivity offering potential utility as pharmacodynamic or predictive response markers. By screening a library of kinase siRNAs in combination with a subcytotoxic dose of ONC201, we identified several kinases that ablated tumor cell sensitivity, including the MAPK pathway inducer KSR1. Unexpectedly, KSR1 sile...
Response to bio-terrorism directed against animals.

Science.gov (United States)

Williams, J L; Sheesley, D

2000-01-01

The Animal and Plant Health Inspection Service (APHIS) has a long history of rapid direction, control, and eradication of devastating diseases. Our immediate response mechanisms to diseases such as avian influenza, Venezuelan equine encephalomyelitis, and Newcastle disease, have long been recognized by the global emergency response community as models of control and eradication. APHIS and the U.S. livestock industries, in partnership with the Animal Agriculture Coalition, re-evaluated the Nation's animal health emergency preparedness and response systems. The group identified areas that negatively impact, biologically and/or economically, the Nation's animal and food production industries. To counter the increased risks including bioterrorism, APHIS plans to establish a world-class "Center of Excellence for Animal Health Emergency Management." APHIS, Intelligence agencies, other Federal departments, State governments, and industries are working together to provide accurate information on the foreign and domestic threats posed to the U.S. agricultural sector by biological weapons. Additionally, the same agencies and organizations are evaluating, updating, and improving the coordination and training mechanisms necessary to respond in the even of a widespread pest or disease outbreak.
Topic A. Have all the relevant issues been identified

International Nuclear Information System (INIS)

Bernero, R.M.

1994-01-01

This work is an answer to the question : have all the relevant issues been identified? The author tries to answer more particularly to the following three points : 1) can risk or responsibility for action be imposed on future generations. 2) Are current safety norms suitable for the future? 3) what controls are appropriate for inter generational cost/benefit evaluations. (O.L.)

Tiered High-Throughput Screening Approach to Identify ...

Science.gov (United States)

High-throughput screening (HTS) for potential thyroid–disrupting chemicals requires a system of assays to capture multiple molecular-initiating events (MIEs) that converge on perturbed thyroid hormone (TH) homeostasis. Screening for MIEs specific to TH-disrupting pathways is limited in the US EPA ToxCast screening assay portfolio. To fill one critical screening gap, the Amplex UltraRed-thyroperoxidase (AUR-TPO) assay was developed to identify chemicals that inhibit TPO, as decreased TPO activity reduces TH synthesis. The ToxCast Phase I and II chemical libraries, comprised of 1,074 unique chemicals, were initially screened using a single, high concentration to identify potential TPO inhibitors. Chemicals positive in the single concentration screen were retested in concentration-response. Due to high false positive rates typically observed with loss-of-signal assays such as AUR-TPO, we also employed two additional assays in parallel to identify possible sources of nonspecific assay signal loss, enabling stratification of roughly 300 putative TPO inhibitors based upon selective AUR-TPO activity. A cell-free luciferase inhibition assay was used to identify nonspecific enzyme inhibition among the putative TPO inhibitors, and a cytotoxicity assay using a human cell line was used to estimate the cellular tolerance limit. Additionally, the TPO inhibition activities of 150 chemicals were compared between the AUR-TPO and an orthogonal peroxidase oxidation assay using
Validating the Modified Drug Adherence Work-Up (M-DRAW Tool to Identify and Address Barriers to Medication Adherence

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Sun Lee

2017-09-01

Full Text Available Barriers to medication adherence stem from multiple factors. An effective and convenient tool is needed to identify these barriers so that clinicians can provide a tailored, patient-centered consultation with patients. The Modified Drug Adherence Work-up Tool (M-DRAW was developed as a 13-item checklist questionnaire to identify barriers to medication adherence. The response scale was a 4-point Likert scale of frequency of occurrence (1 = never to 4 = often. The checklist was accompanied by a GUIDE that provided corresponding motivational interview-based intervention strategies for each identified barrier. The current pilot study examined the psychometric properties of the M-DRAW checklist (reliability, responsiveness and discriminant validity in patients taking one or more prescription medication(s for chronic conditions. A cross-sectional sample of 26 patients was recruited between December 2015 and March 2016 at an academic medical center pharmacy in Southern California. A priming question that assessed self-reported adherence was used to separate participants into the control group of 17 “adherers” (65.4%, and into the intervention group of nine “unintentional and intentional non-adherers” (34.6%. Comparable baseline characteristics were observed between the two groups. The M-DRAW checklist showed acceptable reliability (13 item; alpha = 0.74 for identifying factors and barriers leading to medication non-adherence. Discriminant validity of the tool and the priming question was established by the four-fold number of barriers to adherence identified within the self-selected intervention group compared to the control group (4.4 versus 1.2 barriers, p < 0.05. The current study did not investigate construct validity due to small sample size and challenges on follow-up with patients. Future testing of the tool will include construct validation.
An Xpert screen to identify carbapenemases

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Mubin Kazi

2016-01-01

Full Text Available To prevent the spread of carbapenemases-producing Enterobacteriaceae (CPE active surveillance, contact isolation and cohorting infected patients should be practiced. Rectal swabs for the Xpert MDRO-assay of 32 patients were included. 71.85% were positive for targets incorporated into the MDRO-assay; whereas 28% were phenotypically not CRE and Xpert negative (9.37% had different mechanism [bla OXA]. The assay identified 59.3%, 9.37% and 3.1% as bla NDM, bla NDM+VIM and bla VIM, respectively. The assay is a screening test that identifies CPE harbouring organism within an hour and can be installed at tertiary-care facilities to screen colonized patients.
Transcriptomic Analysis of Responses to Imbalanced Carbon: Nitrogen Availabilities in Rice Seedlings.

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Aobo Huang

Full Text Available The internal C:N balance must be tightly controlled for the normal growth and development of plants. However, the underlying mechanisms, by which plants sense and balance the intracellular C:N status correspondingly to exogenous C:N availabilities remain elusive. In this study, we use comparative gene expression analysis to identify genes that are responsive to imbalanced C:N treatments in the aerial parts of rice seedlings. Transcripts of rice seedlings treated with four C:N availabilities (1:1, 1:60, 60:1 and 60:60 were compared and two groups of genes were classified: high C:low N responsive genes and low C:high N responsive genes. Our analysis identified several functional correlated genes including chalcone synthase (CHS, chlorophyll a-b binding protein (CAB and other genes that are implicated in C:N balancing mechanism, such as alternative oxidase 1B (OsAOX1B, malate dehydrogenase (OsMDH and lysine and histidine specific transporter 1 (OsLHT1. Additionally, six jasmonate synthetic genes and key regulatory genes involved in abiotic and biotic stresses, such as OsMYB4, autoinhibited calcium ATPase 3 (OsACA3 and pleiotropic drug resistance 9 (OsPDR9, were differentially expressed under high C:low N treatment. Gene ontology analysis showed that high C:low N up-regulated genes were primarily enriched in fatty acid biosynthesis and defense responses. Coexpression network analysis of these genes identified eight jasmonate ZIM domain protein (OsJAZ genes and several defense response related regulators, suggesting that high C:low N status may act as a stress condition, which induces defense responses mediated by jasmonate signaling pathway. Our transcriptome analysis shed new light on the C:N balancing mechanisms and revealed several important regulators of C:N status in rice seedlings.
The chemokine receptor CCR1 is identified in mast cell-derived exosomes.

Science.gov (United States)

Liang, Yuting; Qiao, Longwei; Peng, Xia; Cui, Zelin; Yin, Yue; Liao, Huanjin; Jiang, Min; Li, Li

2018-01-01

Mast cells are important effector cells of the immune system, and mast cell-derived exosomes carrying RNAs play a role in immune regulation. However, the molecular function of mast cell-derived exosomes is currently unknown, and here, we identify differentially expressed genes (DEGs) in mast cells and exosomes. We isolated mast cells derived exosomes through differential centrifugation and screened the DEGs from mast cell-derived exosomes, using the GSE25330 array dataset downloaded from the Gene Expression Omnibus database. Biochemical pathways were analyzed by Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway on the online tool DAVID. DEGs-associated protein-protein interaction networks (PPIs) were constructed using the STRING database and Cytoscape software. The genes identified from these bioinformatics analyses were verified by qRT-PCR and Western blot in mast cells and exosomes. We identified 2121 DEGs (843 up and 1278 down-regulated genes) in HMC-1 cell-derived exosomes and HMC-1 cells. The up-regulated DEGs were classified into two significant modules. The chemokine receptor CCR1 was screened as a hub gene and enriched in cytokine-mediated signaling pathway in module one. Seven genes, including CCR1, CD9, KIT, TGFBR1, TLR9, TPSAB1 and TPSB2 were screened and validated through qRT-PCR analysis. We have achieved a comprehensive view of the pivotal genes and pathways in mast cells and exosomes and identified CCR1 as a hub gene in mast cell-derived exosomes. Our results provide novel clues with respect to the biological processes through which mast cell-derived exosomes modulate immune responses.
Cell response to surgery.

LENUS (Irish Health Repository)

Ni Choileain, Niamh

2012-02-03

OBJECTIVES: To describe the profound alterations in host immunity that are produced by major surgery as demonstrated by experimental and clinical studies, and to evaluate the benefits of therapeutic strategies aimed at attenuating perioperative immune dysfunction. DATA SOURCES: A review of the English-language literature was conducted, incorporating searches of the MEDLINE, EMBASE, and Cochrane collaboration databases to identify laboratory and clinical studies investigating the cellular response to surgery. STUDY SELECTION: Original articles and case reports describing immune dysfunction secondary to surgical trauma were included. DATA EXTRACTION: The results were compiled to show outcomes of different studies and were compared. DATA SYNTHESIS: Current evidence indicates that the early systemic inflammatory response syndrome observed after major surgery that is characterized by proinflammatory cytokine release, microcirculatory disturbance, and cell-mediated immune dysfunction is followed by a compensatory anti-inflammatory response syndrome, which predisposes the patient to opportunistic infection, multiple organ dysfunction syndrome, and death. Because there are currently no effective treatment options for multiple organ dysfunction syndrome, measures to prevent its onset should be initiated at an early stage. Accumulating experimental evidence suggests that targeted therapeutic strategies involving immunomodulatory agents such as interferon gamma, granulocyte colony-stimulating factor, the prostaglandin E(2) antagonist, indomethacin, and pentoxifylline may be used for the treatment of systemic inflammatory response syndrome to prevent the onset of multiple organ dysfunction syndrome. CONCLUSIONS: Surgical trauma produces profound immunological dysfunction. Therapeutic strategies directed at restoring immune homeostasis should aim to redress the physiological proinflammatory-anti-inflammatory cell imbalance associated with major surgery.
Analysis of the SOS response of Vibrio and other bacteria with multiple chromosomes

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Sanchez-Alberola Neus

2012-02-01

Full Text Available Abstract Background The SOS response is a well-known regulatory network present in most bacteria and aimed at addressing DNA damage. It has also been linked extensively to stress-induced mutagenesis, virulence and the emergence and dissemination of antibiotic resistance determinants. Recently, the SOS response has been shown to regulate the activity of integrases in the chromosomal superintegrons of the Vibrionaceae, which encompasses a wide range of pathogenic species harboring multiple chromosomes. Here we combine in silico and in vitro techniques to perform a comparative genomics analysis of the SOS regulon in the Vibrionaceae, and we extend the methodology to map this transcriptional network in other bacterial species harboring multiple chromosomes. Results Our analysis provides the first comprehensive description of the SOS response in a family (Vibrionaceae that includes major human pathogens. It also identifies several previously unreported members of the SOS transcriptional network, including two proteins of unknown function. The analysis of the SOS response in other bacterial species with multiple chromosomes uncovers additional regulon members and reveals that there is a conserved core of SOS genes, and that specialized additions to this basic network take place in different phylogenetic groups. Our results also indicate that across all groups the main elements of the SOS response are always found in the large chromosome, whereas specialized additions are found in the smaller chromosomes and plasmids. Conclusions Our findings confirm that the SOS response of the Vibrionaceae is strongly linked with pathogenicity and dissemination of antibiotic resistance, and suggest that the characterization of the newly identified members of this regulon could provide key insights into the pathogenesis of Vibrio. The persistent location of key SOS genes in the large chromosome across several bacterial groups confirms that the SOS response plays an
Analysis of the SOS response of Vibrio and other bacteria with multiple chromosomes.

Science.gov (United States)

Sanchez-Alberola, Neus; Campoy, Susana; Barbé, Jordi; Erill, Ivan

2012-02-03

The SOS response is a well-known regulatory network present in most bacteria and aimed at addressing DNA damage. It has also been linked extensively to stress-induced mutagenesis, virulence and the emergence and dissemination of antibiotic resistance determinants. Recently, the SOS response has been shown to regulate the activity of integrases in the chromosomal superintegrons of the Vibrionaceae, which encompasses a wide range of pathogenic species harboring multiple chromosomes. Here we combine in silico and in vitro techniques to perform a comparative genomics analysis of the SOS regulon in the Vibrionaceae, and we extend the methodology to map this transcriptional network in other bacterial species harboring multiple chromosomes. Our analysis provides the first comprehensive description of the SOS response in a family (Vibrionaceae) that includes major human pathogens. It also identifies several previously unreported members of the SOS transcriptional network, including two proteins of unknown function. The analysis of the SOS response in other bacterial species with multiple chromosomes uncovers additional regulon members and reveals that there is a conserved core of SOS genes, and that specialized additions to this basic network take place in different phylogenetic groups. Our results also indicate that across all groups the main elements of the SOS response are always found in the large chromosome, whereas specialized additions are found in the smaller chromosomes and plasmids. Our findings confirm that the SOS response of the Vibrionaceae is strongly linked with pathogenicity and dissemination of antibiotic resistance, and suggest that the characterization of the newly identified members of this regulon could provide key insights into the pathogenesis of Vibrio. The persistent location of key SOS genes in the large chromosome across several bacterial groups confirms that the SOS response plays an essential role in these organisms and sheds light into the
How physicians identify with predetermined personalities and links to perceived performance and wellness outcomes: a cross-sectional study.

Science.gov (United States)

Lemaire, Jane B; Wallace, Jean E

2014-11-29

Certain personalities are ascribed to physicians. This research aims to measure the extent to which physicians identify with three predetermined personalities (workaholic, Type A and control freak) and to explore links to perceptions of professional performance, and wellness outcomes. This is a cross-sectional study using a mail-out questionnaire sent to all practicing physicians (2957 eligible, 1178 responses, 40% response rate) in a geographical health region within a western Canadian province. Survey items were used to assess the extent to which participants felt they are somewhat of a workaholic, Type A and/or control freak, and if they believed that having these personalities makes one a better doctor. Participants' wellness outcomes were also measured. Zero-order correlations were used to determine the relationships between physicians identifying with a personality and feeling it makes one a better doctor. T-tests were used to compare measures of physician wellness for those who identified with the personality versus those who did not. 53% of participants identified with the workaholic personality, 62% with the Type A, and 36% with the control freak. Identifying with any one of the personalities was correlated with feeling it makes one a better physician. There were statistically significant differences in several wellness outcomes comparing participants who identified with the personalities versus those who did not. These included higher levels of emotional exhaustion (workaholic, Type A and control freak), higher levels of anxiety (Type A and control freak) and higher levels of depression, poorer mental health and lower levels of job satisfaction (control freak). Participants who identified with the workaholic personality versus those who did not reported higher levels of job satisfaction, rewarding patient experiences and career commitment. Most participants identified with at least one of the three personalities. The beliefs of some participants that
Stressor-induced proteome alterations in zebrafish: A meta-analysis of response patterns

Energy Technology Data Exchange (ETDEWEB)

Groh, Ksenia J., E-mail: ksenia.groh@eawag.ch [Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Dübendorf (Switzerland); ETH Zürich, Swiss Federal Institute of Technology, Department of Chemistry and Applied Biosciences, 8093 Zürich (Switzerland); Suter, Marc J.-F. [Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Dübendorf (Switzerland); ETH Zürich, Swiss Federal Institute of Technology, Department of Environmental Systems Science, 8092 Zürich (Switzerland)

2015-02-15

Highlights: • We compared reported proteome changes induced by various stressors in zebrafish. • Several proteins groups frequently responding to diverse stressors were identified. • These included energy metabolism enzymes, heat shock and cytoskeletal proteins. • Insufficient proteome coverage impedes identification of more specific responses. • Further research needs for proteomics in ecotoxicology are discussed. - Abstract: Proteomics approaches are being increasingly applied in ecotoxicology on the premise that the identification of specific protein expression changes in response to a particular chemical would allow elucidation of the underlying molecular pathways leading to an adverse effect. This in turn is expected to promote the development of focused testing strategies for specific groups of toxicants. Although both gel-based and gel-free global characterization techniques provide limited proteome coverage, the conclusions regarding the cellular processes affected are still being drawn based on the few changes detected. To investigate how specific the detected responses are, we analyzed a set of studies that characterized proteome alterations induced by various physiological, chemical and biological stressors in zebrafish, a popular model organism. Our analysis highlights several proteins and protein groups, including heat shock and oxidative stress defense proteins, energy metabolism enzymes and cytoskeletal proteins, to be most frequently identified as responding to diverse stressors. In contrast, other potentially more specifically responding protein groups are detected much less frequently. Thus, zebrafish proteome responses to stress reported by different studies appear to depend mostly on the level of stress rather than on the specific stressor itself. This suggests that the most broadly used current proteomics technologies do not provide sufficient proteome coverage to allow in-depth investigation of specific mechanisms of toxicant action
Stressor-induced proteome alterations in zebrafish: A meta-analysis of response patterns

International Nuclear Information System (INIS)

Groh, Ksenia J.; Suter, Marc J.-F.

2015-01-01

Highlights: • We compared reported proteome changes induced by various stressors in zebrafish. • Several proteins groups frequently responding to diverse stressors were identified. • These included energy metabolism enzymes, heat shock and cytoskeletal proteins. • Insufficient proteome coverage impedes identification of more specific responses. • Further research needs for proteomics in ecotoxicology are discussed. - Abstract: Proteomics approaches are being increasingly applied in ecotoxicology on the premise that the identification of specific protein expression changes in response to a particular chemical would allow elucidation of the underlying molecular pathways leading to an adverse effect. This in turn is expected to promote the development of focused testing strategies for specific groups of toxicants. Although both gel-based and gel-free global characterization techniques provide limited proteome coverage, the conclusions regarding the cellular processes affected are still being drawn based on the few changes detected. To investigate how specific the detected responses are, we analyzed a set of studies that characterized proteome alterations induced by various physiological, chemical and biological stressors in zebrafish, a popular model organism. Our analysis highlights several proteins and protein groups, including heat shock and oxidative stress defense proteins, energy metabolism enzymes and cytoskeletal proteins, to be most frequently identified as responding to diverse stressors. In contrast, other potentially more specifically responding protein groups are detected much less frequently. Thus, zebrafish proteome responses to stress reported by different studies appear to depend mostly on the level of stress rather than on the specific stressor itself. This suggests that the most broadly used current proteomics technologies do not provide sufficient proteome coverage to allow in-depth investigation of specific mechanisms of toxicant action
Regulation of Cancer Cell Responsiveness to Ionizing Radiation Treatment by Cyclic AMP Response Element Binding Nuclear Transcription Factor

Directory of Open Access Journals (Sweden)

Francesca D’Auria

2017-05-01

Full Text Available Cyclic AMP response element binding (CREB protein is a member of the CREB/activating transcription factor (ATF family of transcription factors that play an important role in the cell response to different environmental stimuli leading to proliferation, differentiation, apoptosis, and survival. A number of studies highlight the involvement of CREB in the resistance to ionizing radiation (IR therapy, demonstrating a relationship between IR-induced CREB family members’ activation and cell survival. Consistent with these observations, we have recently demonstrated that CREB and ATF-1 are expressed in leukemia cell lines and that low-dose radiation treatment can trigger CREB activation, leading to survival of erythro-leukemia cells (K562. On the other hand, a number of evidences highlight a proapoptotic role of CREB following IR treatment of cancer cells. Since the development of multiple mechanisms of resistance is one key problem of most malignancies, including those of hematological origin, it is highly desirable to identify biological markers of responsiveness/unresponsiveness useful to follow-up the individual response and to adjust anticancer treatments. Taking into account all these considerations, this mini-review will be focused on the involvement of CREB/ATF family members in response to IR therapy, to deepen our knowledge of this topic, and to pave the way to translation into a therapeutic context.
Identifying protein phosphorylation sites with kinase substrate specificity on human viruses.

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Neil Arvin Bretaña

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

Science.gov (United States)

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

2012-01-01

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

Institute of Scientific and Technical Information of China (English)

沈志渔; 刘兴国; 周小虎

2009-01-01

SOE social responsibility has undergone three stages of evolution.In essence,corporate social responsibility includes social obligations and social expectations.Public attention to SOE social responsibility issues has affected the thinking surrounding SOE restructuring,including the promulgating of objectives and methods.Based on corporate social responsibility,SOE managers must set up a perfect SOE social responsibility system and strengthen supervisory mechanisms;in respect to corporate governance models,SOEs should undertake reform for the corporate citizen governance model.
Molecular characterization of the submergence response of Arabidopsis thaliana ecotype Columbia

DEFF Research Database (Denmark)

Lee, S.C.; Mustroph, A.; Sasidaharan, R.

2011-01-01

partial pressure of the petiole and root had stabilized at c. 6 and 0.1 kPa, respectively. As controls, plants were untreated or exposed to darkness. Following quantitative profiling of cellular mRNAs with the Affymetrix ATH1 platform, changes in the transcriptome in response to submergence, early...... darkness, and O2-deprivation were evaluated by fuzzy k-means clustering. This identified genes co-regulated at the conditional, developmental or organ-specific level. Mutants for 10 differentially expressed HYPOXIA-RESPONSIVE UNKNOWN PROTEIN (HUP) genes were screened for altered submergence tolerance....... • The analysis identified 34 genes that were ubiquitously co-regulated by submergence and O2 deprivation. The biological functions of these include signaling, transcription, and anaerobic energy metabolism. HUPs comprised 40% of the co-regulated transcripts and mutants of seven of these genes were significantly...
Modifiers of notch transcriptional activity identified by genome-wide RNAi

Directory of Open Access Journals (Sweden)

Firnhaber Christopher B

2010-10-01

Full Text Available Abstract Background The Notch signaling pathway regulates a diverse array of developmental processes, and aberrant Notch signaling can lead to diseases, including cancer. To obtain a more comprehensive understanding of the genetic network that integrates into Notch signaling, we performed a genome-wide RNAi screen in Drosophila cell culture to identify genes that modify Notch-dependent transcription. Results Employing complementary data analyses, we found 399 putative modifiers: 189 promoting and 210 antagonizing Notch activated transcription. These modifiers included several known Notch interactors, validating the robustness of the assay. Many novel modifiers were also identified, covering a range of cellular localizations from the extracellular matrix to the nucleus, as well as a large number of proteins with unknown function. Chromatin-modifying proteins represent a major class of genes identified, including histone deacetylase and demethylase complex components and other chromatin modifying, remodeling and replacement factors. A protein-protein interaction map of the Notch-dependent transcription modifiers revealed that a large number of the identified proteins interact physically with these core chromatin components. Conclusions The genome-wide RNAi screen identified many genes that can modulate Notch transcriptional output. A protein interaction map of the identified genes highlighted a network of chromatin-modifying enzymes and remodelers that regulate Notch transcription. Our results open new avenues to explore the mechanisms of Notch signal regulation and the integration of this pathway into diverse cellular processes.
Identifying Barriers and Enablers in the Dietary Management of Type 2 Diabetes in M'Bour, Senegal.

Science.gov (United States)

Foley, Evan; BeLue, Rhonda

2017-07-01

The purpose of this study was to identify cultural enablers and barriers to dietary management of type 2 diabetes in M'Bour, Senegal. This qualitative study used the PEN-3 cultural model to explore diabetes dietary management within a cultural framework. Content analysis identified emergent themes based on the PEN-3 model. Forty-one individuals completed interviews. Themes reflecting ways that culture affects adherence to the diabetic diet included (a) having a different diet or eating separately from the communal family plate creates feelings of social isolation; (b) forgoing the diabetic diet sometimes occurs so that family members have enough food; (c) reducing servings of traditional foods feels like abandoning culture; and (d) women being responsible for preparing food, while men typically manage money for purchasing food yet do not provide input on what food is purchased. Results suggest that educating family units on the dietary management of diabetes may be more effective than individual education.
Identification and Expression Profiling of the Auxin Response Factors in Dendrobium officinale under Abiotic Stresses.

Science.gov (United States)

Chen, Zhehao; Yuan, Ye; Fu, Di; Shen, Chenjia; Yang, Yanjun

2017-05-04

Auxin response factor (ARF) proteins play roles in plant responses to diverse environmental stresses by binding specifically to the auxin response element in the promoters of target genes. Using our latest public Dendrobium transcriptomes, a comprehensive characterization and analysis of 14 DnARF genes were performed. Three selected DnARFs , including DnARF1 , DnARF4 , and DnARF6 , were confirmed to be nuclear proteins according to their transient expression in epidermal cells of Nicotiana benthamiana leaves. Furthermore, the transcription activation abilities of DnARF1 , DnARF4 , and DnARF6 were tested in a yeast system. Our data showed that DnARF6 is a transcriptional activator in Dendrobium officinale . To uncover the basic information of DnARF gene responses to abiotic stresses, we analyzed their expression patterns under various hormones and abiotic treatments. Based on our data, several hormones and significant stress responsive DnARF genes have been identified. Since auxin and ARF genes have been identified in many plant species, our data is imperative to reveal the function of ARF mediated auxin signaling in the adaptation to the challenging Dendrobium environment.
Almost-sure identifiability of multidimensional harmonic retrieval

NARCIS (Netherlands)

Jiang, T; Sidiropoulos, ND; ten Berge, JMF

Two-dimensional (2-D) and, more generally, multidimensional harmonic retrieval is of interest in a variety of applications, including transmitter localization and joint time and frequency offset estimation in wireless communications. The associated identifiability problem is key in understanding the

Apple F-box Protein MdMAX2 Regulates Plant Photomorphogenesis and Stress Response

Directory of Open Access Journals (Sweden)

Jian-Ping An

2016-11-01

Full Text Available MAX2 (MORE AXILLARY GROWTH2 is involved in diverse physiological processes, including photomorphogenesis, the abiotic stress response, as well as karrikin and strigolactone signaling-mediated shoot branching. In this study, MdMAX2, an F-box protein that is a homolog of Arabidopsis MAX2, was identified and characterized. Overexpression of MdMAX2 in apple calli enhanced the accumulation of anthocyanin. Ectopic expression of MdMAX2 in Arabidopsis exhibited photomorphogenesis phenotypes, including increased anthocyanin content and decreased hypocotyl length. Further study indicated that MdMAX2 might promote plant photomorphogenesis by affecting the auxin signaling as well as other plant hormones. Transcripts of MdMAX2 were noticeably up-regulated in response to NaCl and Mannitol treatments. Moreover, compared with the wild type, the MdMAX2-overexpressing apple calli and Arabidopsis exhibited increased tolerance to salt and drought stresses. Taken together, these results suggest that MdMAX2 plays a positive regulatory role in plant photomorphogenesis and stress response.
Elements of person knowledge: Episodic recollection helps us to identify people but not to recognize their faces.

Science.gov (United States)

MacKenzie, Graham; Donaldson, David I

2016-12-01

Faces automatically draw attention, allowing rapid assessments of personality and likely behaviour. How we respond to people is, however, highly dependent on whether we know who they are. According to face processing models person knowledge comes from an extended neural system that includes structures linked to episodic memory. Here we use scalp recorded brain signals to demonstrate the specific role of episodic memory processes during face processing. In two experiments we recorded Event-Related Potentials (ERPs) while participants made identify, familiar or unknown responses to famous faces. ERPs revealed neural signals previously associated with episodic recollection for identify but not familiar faces. These findings provide novel evidence suggesting that recollection is central to face processing, providing one source of person knowledge that can be used to moderate the initial impressions gleaned from the core neural system that supports face recognition. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.
Race, Genetic Ancestry and Response to Antidepressant Treatment for Major Depression

Science.gov (United States)

Murphy, Eleanor; Hou, Liping; Maher, Brion S; Woldehawariat, Girma; Kassem, Layla; Akula, Nirmala; Laje, Gonzalo; McMahon, Francis J

2013-01-01

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study revealed poorer antidepressant treatment response among black compared with white participants. This racial disparity persisted even after socioeconomic and baseline clinical factors were taken into account. Some studies have suggested genetic contributions to this disparity, but none have attempted to disentangle race and genetic ancestry. Here we used genome-wide single-nucleotide polymorphism (SNP) data to examine independent contributions of race and genetic ancestry to citalopram response. Secondary data analyses included 1877 STAR*D participants who completed an average of 10 weeks of citalopram treatment and provided DNA samples. Participants reported their race as White (n=1464), black (n=299) or other/mixed (n=114). Genetic ancestry was estimated by multidimensional scaling (MDS) analyses of about 500 000 SNPs. Ancestry proportions were estimated by STRUCTURE. Structural equation modeling was used to examine the direct and indirect effects of observed and latent predictors of response, defined as change in the Quick Inventory of Depressive Symptomatology (QIDS) score from baseline to exit. Socioeconomic and baseline clinical factors, race, and anxiety significantly predicted response, as previously reported. However, direct effects of race disappeared in all models that included genetic ancestry. Genetic African ancestry predicted lower treatment response in all models. Although socioeconomic and baseline clinical factors drive racial differences in antidepressant response, genetic ancestry, rather than self-reported race, explains a significant fraction of the residual differences. Larger samples would be needed to identify the specific genetic mechanisms that may be involved, but these findings underscore the importance of including more African-American patients in drug trials. PMID:23827886
NRC Information No. 90-01: Importance of proper response to self-identified violations by licensees

International Nuclear Information System (INIS)

Cunningham, R.E.

1992-01-01

NRC expects a high standard of compliance by its licensees and requires that licensees provide NRC accurate and complete information and that required records will also be complete and accurate in all material respects. Licensees should be aware of the importance placed by NRC on licensee programs for self detection, correction and reporting of violations or errors related to regulatory requirements. The General Statement of Policy and Procedures for NRC Enforcement Actions in Appendix C to 10 CFR Part 2 underscores the importance of licensees responding promptly and properly to self-identified violations in two ways. It is suggested that when a licensee identifies a violation involving an NRC-required record, the licensee should make a dated notation indicating identification, either on the record itself or other appropriate documentation retrievable for NRC review. The record with the self-identified violation noted should not be altered in any way to mask the correction. The licensee should determine the cause of the violation, correct the root cause of the violation, and document such findings in an appropriate manner. Licensees should also assure that if a report of the violation is required, the report is submitted to NRC in a timely manner. These actions will be considered by NRC in making any enforcement decision, and generally lead to lesser or no civil penalty
Exome Sequencing and Linkage Analysis Identified Novel Candidate Genes in Recessive Intellectual Disability Associated with Ataxia.

Science.gov (United States)

Jazayeri, Roshanak; Hu, Hao; Fattahi, Zohreh; Musante, Luciana; Abedini, Seyedeh Sedigheh; Hosseini, Masoumeh; Wienker, Thomas F; Ropers, Hans Hilger; Najmabadi, Hossein; Kahrizi, Kimia

2015-10-01

Intellectual disability (ID) is a neuro-developmental disorder which causes considerable socio-economic problems. Some ID individuals are also affected by ataxia, and the condition includes different mutations affecting several genes. We used whole exome sequencing (WES) in combination with homozygosity mapping (HM) to identify the genetic defects in five consanguineous families among our cohort study, with two affected children with ID and ataxia as major clinical symptoms. We identified three novel candidate genes, RIPPLY1, MRPL10, SNX14, and a new mutation in known gene SURF1. All are autosomal genes, except RIPPLY1, which is located on the X chromosome. Two are housekeeping genes, implicated in transcription and translation regulation and intracellular trafficking, and two encode mitochondrial proteins. The pathogenesis of these variants was evaluated by mutation classification, bioinformatic methods, review of medical and biological relevance, co-segregation studies in the particular family, and a normal population study. Linkage analysis and exome sequencing of a small number of affected family members is a powerful new technique which can be used to decrease the number of candidate genes in heterogenic disorders such as ID, and may even identify the responsible gene(s).
Familial factors responsible for persistent crying-induced asthma: a case report.

Science.gov (United States)

Weinstein, A G

1987-10-01

Crying behavior of the asthmatic child may induce wheezing symptoms. This may be a clinical problem for families with asthmatic children who exhibit frequent and persistent crying behavior. This case report identifies behaviors by the child and parents that may be responsible for continual crying. Child factors include (1) "spoiled" personality, (2) poor self-image, (3) biologic sensitivity to foods, medication, and environmental allergens producing irritability. Parental factors include poor disciplinary practices secondary to (1) disrupted home life, (2) guilt, and (3) overprotective behavior. Identification of these factors may be helpful in establishing clinical management strategies to reduce crying-induced asthma.
In Response

Science.gov (United States)

Egeland, Janice A.; Shaw, Jon A.; Endicott, Jean; Allen, Cleona R.; Hostetter, Abram M.

2005-01-01

This article features the response to the important commentary by Dr. Carlson. The Amish Study represents, as she notes, a special research population for investigation of "classic" bipolar disorder viewed against a homogeneous cultural landscape where emerging biological and behavioral prodromal features can be identified. Dr. Carlson questions…
A RAD-Based Genetic Map for Anchoring Scaffold Sequences and Identifying QTLs in Bitter Gourd (Momordica charantia)

Science.gov (United States)

Cui, Junjie; Luo, Shaobo; Niu, Yu; Huang, Rukui; Wen, Qingfang; Su, Jianwen; Miao, Nansheng; He, Weiming; Dong, Zhensheng; Cheng, Jiaowen; Hu, Kailin

2018-01-01

Genetic mapping is a basic tool necessary for anchoring assembled scaffold sequences and for identifying QTLs controlling important traits. Though bitter gourd (Momordica charantia) is both consumed and used as a medicinal, research on its genomics and genetic mapping is severely limited. Here, we report the construction of a restriction site associated DNA (RAD)-based genetic map for bitter gourd using an F2 mapping population comprising 423 individuals derived from two cultivated inbred lines, the gynoecious line ‘K44’ and the monoecious line ‘Dali-11.’ This map comprised 1,009 SNP markers and spanned a total genetic distance of 2,203.95 cM across the 11 linkage groups. It anchored a total of 113 assembled scaffolds that covered about 251.32 Mb (85.48%) of the 294.01 Mb assembled genome. In addition, three horticulturally important traits including sex expression, fruit epidermal structure, and immature fruit color were evaluated using a combination of qualitative and quantitative data. As a result, we identified three QTL/gene loci responsible for these traits in three environments. The QTL/gene gy/fffn/ffn, controlling sex expression involved in gynoecy, first female flower node, and female flower number was detected in the reported region. Particularly, two QTLs/genes, Fwa/Wr and w, were found to be responsible for fruit epidermal structure and white immature fruit color, respectively. This RAD-based genetic map promotes the assembly of the bitter gourd genome and the identified genetic loci will accelerate the cloning of relevant genes in the future. PMID:29706980
A RAD-Based Genetic Map for Anchoring Scaffold Sequences and Identifying QTLs in Bitter Gourd (Momordica charantia

Directory of Open Access Journals (Sweden)

Junjie Cui

2018-04-01

Full Text Available Genetic mapping is a basic tool necessary for anchoring assembled scaffold sequences and for identifying QTLs controlling important traits. Though bitter gourd (Momordica charantia is both consumed and used as a medicinal, research on its genomics and genetic mapping is severely limited. Here, we report the construction of a restriction site associated DNA (RAD-based genetic map for bitter gourd using an F2 mapping population comprising 423 individuals derived from two cultivated inbred lines, the gynoecious line ‘K44’ and the monoecious line ‘Dali-11.’ This map comprised 1,009 SNP markers and spanned a total genetic distance of 2,203.95 cM across the 11 linkage groups. It anchored a total of 113 assembled scaffolds that covered about 251.32 Mb (85.48% of the 294.01 Mb assembled genome. In addition, three horticulturally important traits including sex expression, fruit epidermal structure, and immature fruit color were evaluated using a combination of qualitative and quantitative data. As a result, we identified three QTL/gene loci responsible for these traits in three environments. The QTL/gene gy/fffn/ffn, controlling sex expression involved in gynoecy, first female flower node, and female flower number was detected in the reported region. Particularly, two QTLs/genes, Fwa/Wr and w, were found to be responsible for fruit epidermal structure and white immature fruit color, respectively. This RAD-based genetic map promotes the assembly of the bitter gourd genome and the identified genetic loci will accelerate the cloning of relevant genes in the future.
Corporate Social Responsibility and Sustainability in Danish Public Procurement

DEFF Research Database (Denmark)

Andrecka, Marta

2017-01-01

understand the continuously developing concepts of SPP, as well as to identify the drivers and barriers that promote or hinder its further implementation. This article firstly deals with the relationship between the concepts of sustainability, Corporate Social Responsibility (CSR) and public procurement....... Secondly, as Denmark has been known as a pioneer in sustainable development, including implementation of it in public purchasing this article focuses on recent developments in the areas of CSR and sustainable public procurement in Denmark, and analyses relevant Danish Public Procurement Complaints Board...
Microarray and growth analyses identify differences and similarities of early corn response to weeds, shade, and nitrogen stress

Science.gov (United States)

Weed interference with crop growth is often attributed to water, nutrient, or light competition; however, specific physiological responses to these stresses are not well described. This study’s objective was to compare growth, yield, and gene expression responses of corn to nitrogen (N), low light (...
The next step for stress research in primates: To identify relationships between glucocorticoid secretion and fitness.

Science.gov (United States)

Beehner, Jacinta C; Bergman, Thore J

2017-05-01

Glucocorticoids are hormones that mediate the energetic demands that accompany environmental challenges. It is therefore not surprising that these metabolic hormones have come to dominate endocrine research on the health and fitness of wild populations. Yet, several problems have been identified in the vertebrate research that also apply to the non-human primate research. First, glucocorticoids should not be used as a proxy for fitness (unless a link has previously been established between glucocorticoids and fitness for a particular population). Second, stress research in behavioral ecology has been overly focused on "chronic stress" despite little evidence that chronic stress hampers fitness in wild animals. Third, research effort has been disproportionately focused on the causes of glucocorticoid variation rather than the fitness consequences. With these problems in mind, we have three objectives for this review. We describe the conceptual framework behind the "stress concept", emphasizing that high glucocorticoids do not necessarily indicate a stress response, and that a stress response does not necessarily indicate an animal is in poor health. Then, we conduct a comprehensive review of all studies on "stress" in wild primates, including any study that examined environmental factors, the stress response, and/or fitness (or proxies for fitness). Remarkably, not a single primate study establishes a connection between all three. Finally, we provide several recommendations for future research in the field of primate behavioral endocrinology, primarily the need to move beyond identifying the factors that cause glucocorticoid secretion to additionally focus on the relationship between glucocorticoids and fitness. We believe that this is an important next step for research on stress physiology in primates. Copyright © 2017 Elsevier Inc. All rights reserved.
Membrane-associated proteomics of chickpea identifies Sad1/UNC-84 protein (CaSUN1), a novel component of dehydration signaling

Science.gov (United States)

Jaiswal, Dinesh Kumar; Mishra, Poonam; Subba, Pratigya; Rathi, Divya; Chakraborty, Subhra; Chakraborty, Niranjan

2014-02-01

Dehydration affects almost all the physiological processes including those that result in the accumulation of misfolded proteins in the endoplasmic reticulum (ER), which in turn elicits a highly conserved signaling, the unfolded protein response (UPR). We investigated the dehydration-responsive membrane-associated proteome of a legume, chickpea, by 2-DE coupled with mass spectrometry. A total of 184 protein spots were significantly altered over a dehydration treatment of 120 h. Among the differentially expressed proteins, a non-canonical SUN domain protein, designated CaSUN1 (Cicer arietinum Sad1/UNC-84), was identified. CaSUN1 localized to the nuclear membrane and ER, besides small vacuolar vesicles. The transcripts were downregulated by both abiotic and biotic stresses, but not by abscisic acid treatment. Overexpression of CaSUN1 conferred stress tolerance in transgenic Arabidopsis. Furthermore, functional complementation of the yeast mutant, slp1, could rescue its growth defects. We propose that the function of CaSUN1 in stress response might be regulated via UPR signaling.
Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework

International Nuclear Information System (INIS)

Calabrese, Edward J.; Bachmann, Kenneth A.; Bailer, A. John; Bolger, P. Michael; Borak, Jonathan; Cai, Lu; Cedergreen, Nina; Cherian, M. George; Chiueh, Chuang C.; Clarkson, Thomas W.; Cook, Ralph R.; Diamond, David M.; Doolittle, David J.; Dorato, Michael A.; Duke, Stephen O.; Feinendegen, Ludwig; Gardner, Donald E.; Hart, Ronald W.; Hastings, Kenneth L.; Hayes, A. Wallace; Hoffmann, George R.; Ives, John A.; Jaworowski, Zbigniew; Johnson, Thomas E.; Jonas, Wayne B.; Kaminski, Norbert E.; Keller, John G.; Klaunig, James E.; Knudsen, Thomas B.; Kozumbo, Walter J.; Lettieri, Teresa; Liu, Shu-Zheng; Maisseu, Andre; Maynard, Kenneth I.; Masoro, Edward J.; McClellan, Roger O.; Mehendale, Harihara M.; Mothersill, Carmel; Newlin, David B.; Nigg, Herbert N.; Oehme, Frederick W.; Phalen, Robert F.; Philbert, Martin A.; Rattan, Suresh I.S.; Riviere, Jim E.; Rodricks, Joseph; Sapolsky, Robert M.; Scott, Bobby R.; Seymour, Colin; Sinclair, David A.; Smith-Sonneborn, Joan; Snow, Elizabeth T.; Spear, Linda; Stevenson, Donald E.; Thomas, Yolene; Tubiana, Maurice; Williams, Gary M.; Mattson, Mark P.

2007-01-01

Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose-response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose-response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines
Metabolic responses of Eisenia fetida after sub-lethal exposure to organic contaminants with different toxic modes of action

Energy Technology Data Exchange (ETDEWEB)

McKelvie, Jennifer R.; Wolfe, David M.; Celejewski, Magda A. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada); Alaee, Mehran [Environment Canada, 867 Lakeshore Rd., P.O. Box 5050, Burlington, ON L7R 4A6 (Canada); Simpson, Andre J. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada); Simpson, Myrna J., E-mail: myrna.simpson@utoronto.ca [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada)

2011-12-15

Nuclear magnetic resonance (NMR) - based metabolomics has the potential to identify toxic responses of contaminants within a mixture in contaminated soil. This study evaluated the metabolic response of Eisenia fetida after exposure to an array of organic compounds to determine whether contaminant-specific responses could be identified. The compounds investigated in contact tests included: two pesticides (carbaryl and chlorpyrifos), three pharmaceuticals (carbamazephine, estrone and caffeine), two persistent organohalogens (Aroclor 1254 and PBDE 209) and two industrial compounds (nonylphenol and dimethyl phthalate). Control and contaminant-exposed metabolic profiles were distinguished using principal component analysis and potential contaminant-specific biomarkers of exposure were found for several contaminants. These results suggest that NMR-based metabolomics offers considerable promise for differentiating between the different toxic modes of action (MOA) associated with sub-lethal toxicity to earthworms. - Highlights: > NMR-based earthworm metabolomic analysis of the toxic mode of action of various environmental contaminants. > Organic chemicals with different toxic modes of action resulted in varied metabolomic responses for E. fetida. > NMR-based metabolomics differentiates between the different modes of action associated with sub-lethal toxicity. - {sup 1}H NMR metabolomics was used to identify potential biomarkers of organic contaminant exposure in Eisenia fetida earthworms.
Integrated outage management: Leveraging utility system assets including GIS and AMR for optimum outage response

Energy Technology Data Exchange (ETDEWEB)

Finamore, E. P.

2004-02-01

The control of electrical system outages is discussed. The principal argument advanced is that traditional stand-alone methods of outage response will no longer get the job done without utility companies integrating their outage management systems with other system assets such as GIS (geographic information system) and AMR (advanced metering systems). Many meter reading systems, while primarily supporting customer billing, can also provide outage alarm and some are also capable of service restoration notification, which is an invaluable benefit to service operators since it obviates the need for verifying system restoration by labour-intensive on-site visits or customer call-backs. If successfully leveraged, optimization of all utility assets and improvements in labour productivity can results in improved outage management performance gains without affecting performance in other areas.
Study of the integrated immune response induced by an inactivated EV71 vaccine.

Directory of Open Access Journals (Sweden)

Longding Liu

Full Text Available Enterovirus 71 (EV71, a major causative agent of hand-foot-and-mouth disease (HFMD, causes outbreaks among children in the Asia-Pacific region. A vaccine is urgently needed. Based on successful pre-clinical work, phase I and II clinical trials of an inactivated EV71 vaccine, which included the participants of 288 and 660 respectively, have been conducted. In the present study, the immune response and the correlated modulation of gene expression in the peripheral blood mononuclear cells (PBMCs of 30 infants (6 to 11 months immunized with this vaccine or placebo and consented to join this study in the phase II clinical trial were analyzed. The results showed significantly greater neutralizing antibody and specific T cell responses in vaccine group after two inoculations on days 0 and 28. Additionally, more than 600 functional genes that were up- or down-regulated in PBMCs were identified by the microarray assay, and these genes included 68 genes associated with the immune response in vaccine group. These results emphasize the gene expression profile of the immune system in response to an inactivated EV71 vaccine in humans and confirmed that such an immune response was generated as the result of the positive mobilization of the immune system. Furthermore, the immune response was not accompanied by the development of a remarkable inflammatory response.NCT01391494 and NCT01512706.
Labeling surface epitopes to identify Cryptosporidium life stages using a scanning electron microscopy-based immunogold approach.

Science.gov (United States)

Edwards, Hanna; Thompson, R C Andrew; Koh, Wan H; Clode, Peta L

2012-02-01

The Apicomplexan parasite Cryptosporidium parvum is responsible for the widespread disease cryptosporidiosis, in both humans and livestock. The nature of C. parvum infection is far from understood and many questions remain in regard to host-parasite interactions, limiting successful treatment of the disease. To definitively identify a range of C. parvum stages in cell culture and to begin to investigate host cell interactions in some of the lesser known life stages, we have utilized a combined scanning electron microscopy and immunolabeling approach, correlating high resolution microstructural information with definitive immunogold labeling of Cryptosporidium stages. Several life cycle stages, including oocysts, merozoites I, trophozoites, gamonts and microgametocytes, were successfully immunolabeled in an in vitro model system. Developing oocysts were clearly immunolabeled, but this did not persist once excystation had occurred. Immunolabeling visualized on the host cell surface adjacent to invasive merozoites is likely to be indicative of receptor shedding, with merozoites also initiating host responses that manifested as abnormal microvilli on the host cell surface. Small sub-micron stages such as microgametocytes, which were impossible to identify as single entities without immunolabeling, were readily visualized and observed to attach to host cells via novel membranous projections. Epicellular parasites also expressed Cryptosporidium-derived epitopes within their encapsulating membrane. These data have allowed us to confidently identify a variety of C. parvum stages in cell culture at high resolution. With this, we provide new insight into C. parvum - host cell interactions and highlight future opportunities for investigating and targeting receptor-mediated interactions between Cryptosporidium life cycle stages and host cells. Copyright © 2011 Elsevier Ltd. All rights reserved.
BRIC-21: Global Transcriptome Profiling to Identify Cellular Stress Mechanisms Responsible for Spaceflight-Induced Antibiotic Resistance

Science.gov (United States)

Nicholson, Wayne L.; Fajardo-Cavazos, Patricia

2015-01-01

Comparisons of spaceflight stress responses in Bacillus subtilis spores and Staphylococcus epidermidis cells to ground-based controls will be conducted to uncover alterations in their antibiotic susceptibility.
CATALISE: A Multinational and Multidisciplinary Delphi Consensus Study. Identifying Language Impairments in Children.

Directory of Open Access Journals (Sweden)

D V M Bishop

Full Text Available Delayed or impaired language development is a common developmental concern, yet there is little agreement about the criteria used to identify and classify language impairments in children. Children's language difficulties are at the interface between education, medicine and the allied professions, who may all adopt different approaches to conceptualising them. Our goal in this study was to use an online Delphi technique to see whether it was possible to achieve consensus among professionals on appropriate criteria for identifying children who might benefit from specialist services. We recruited a panel of 59 experts representing ten disciplines (including education, psychology, speech-language therapy/pathology, paediatrics and child psychiatry from English-speaking countries (Australia, Canada, Ireland, New Zealand, United Kingdom and USA. The starting point for round 1 was a set of 46 statements based on articles and commentaries in a special issue of a journal focusing on this topic. Panel members rated each statement for both relevance and validity on a seven-point scale, and added free text comments. These responses were synthesised by the first two authors, who then removed, combined or modified items with a view to improving consensus. The resulting set of statements was returned to the panel for a second evaluation (round 2. Consensus (percentage reporting 'agree' or 'strongly agree' was at least 80 percent for 24 of 27 round 2 statements, though many respondents qualified their response with written comments. These were again synthesised by the first two authors. The resulting consensus statement is reported here, with additional summary of relevant evidence, and a concluding commentary on residual disagreements and gaps in the evidence base.

CATALISE: A Multinational and Multidisciplinary Delphi Consensus Study. Identifying Language Impairments in Children.

Science.gov (United States)

Bishop, D V M; Snowling, Margaret J; Thompson, Paul A; Greenhalgh, Trisha

2016-01-01

Delayed or impaired language development is a common developmental concern, yet there is little agreement about the criteria used to identify and classify language impairments in children. Children's language difficulties are at the interface between education, medicine and the allied professions, who may all adopt different approaches to conceptualising them. Our goal in this study was to use an online Delphi technique to see whether it was possible to achieve consensus among professionals on appropriate criteria for identifying children who might benefit from specialist services. We recruited a panel of 59 experts representing ten disciplines (including education, psychology, speech-language therapy/pathology, paediatrics and child psychiatry) from English-speaking countries (Australia, Canada, Ireland, New Zealand, United Kingdom and USA). The starting point for round 1 was a set of 46 statements based on articles and commentaries in a special issue of a journal focusing on this topic. Panel members rated each statement for both relevance and validity on a seven-point scale, and added free text comments. These responses were synthesised by the first two authors, who then removed, combined or modified items with a view to improving consensus. The resulting set of statements was returned to the panel for a second evaluation (round 2). Consensus (percentage reporting 'agree' or 'strongly agree') was at least 80 percent for 24 of 27 round 2 statements, though many respondents qualified their response with written comments. These were again synthesised by the first two authors. The resulting consensus statement is reported here, with additional summary of relevant evidence, and a concluding commentary on residual disagreements and gaps in the evidence base.
[Materiality Analysis of Health Plans Based on Stakeholder Engagement and the Issues Included at ISO 26000:2010].

Science.gov (United States)

Moyano Santiago, Miguel Angel; Rivera Lirio, Juana María

2017-01-18

Health plans of the Spanish autonomous communities can incorporate sustainable development criteria in its development. There have been no analysis or proposals about development and indicators. The goal is to add a contribution to help build better health plans aimed at sustainable development and help to manage economic, social and environmental impacts of health systems criteria. We used a variation of the RAND/UCLA or modified Delphi technique method. The process consisted of a bibliographical and context matters and issues related to health and social responsibility analysis based on ISO 26000: 2010. A survey by deliberately to a selection of 70 expert members of the identified stakeholders was carried out and a discussion group was held to determine the consensus on the issues addressed in the survey sample. The research was conducted in 2015. From the literature review 33 health issues included in ISO 26000:2010 were obtained. 7 survey proved relevant high consensus, 8 relevance and average consensus and 18 with less relevance and high level of dissent. The expert group excluded 4 of the 18 subjects with less consensus. 29 issues included 33 at work, divided into 7 subjects contained in the guide ISO 26000 of social responsibility, were relevant stakeholders regarding possible inclusion in health plans. Considering the direct relationship published by ISO (International Organization for Standardization) among the issues ISO 26000 and the economic, social and environmental indicators in GRI (Global Reporting Initiative) in its G4 version, a panel with monitoring indicators related to relevant issues were elaborated.
Predictors of excellent response to lithium

DEFF Research Database (Denmark)

Kessing, Lars Vedel; Hellmund, Gunnar; Andersen, Per Kragh

2011-01-01

The aim of this study was to identify sociodemographic and clinical predictors of excellent response, that is, 'cure' of future affective episodes, to lithium in monotherapy. We used nationwide registers to identify all patients with a diagnosis of bipolar disorder in psychiatric hospital settings...... who were prescribed lithium from 1995 to 2006 in Denmark (N=3762). Excellent lithium responders were defined as patients who after a stabilization lithium start-up period of 6 months, continued lithium in monotherapy without getting hospitalized. The rate of excellent response to lithium...... with somatic comorbidity had increased rates of non-response to lithium compared with patients without somatic comorbidity (HR=1.23, 95% CI: 1.00-1.52).It is concluded that the prevalence of excellent response to lithium monotherapy is low and such patients are characterized by few earlier psychiatric...
Certification prerequisites for activities related to the trading of demand response resources

International Nuclear Information System (INIS)

Alcázar-Ortega, Manuel; Calpe, Carmen; Theisen, Thomas; Rodríguez-García, Javier

2015-01-01

Certification according to international standards brings many benefits to the society, including technical, economic and environmental aspects. In this context, this paper highlights the benefits of certification of Demand Response, including the additional credibility which provides to the trading of flexibility and higher confidence between different players. The consequence is a dynamic environment which facilitates the market acceptance of Demand Response services and products, providing significant benefits to providers and users of such services. A methodology for the systematic certification of different activities related to the transaction of Demand Response resources has been developed and it is presented here. In particular, three types of certificate have been specified, considering the certification of the entity providing the resource (Demand Response Provider), the contractual framework between the provider and the requester (Demand Response Product) and the physical platform to enable and guarantee such transaction (Demand Response Energy Service Trader). The results of this paper may help regulators and standardization bodies in the design and specification of a future norm to allow the certification of the above-mentioned activities, or a further development of existing regulation for certification of energy efficiency systems (like ISO (International Standard Organization) 50001), where certification of Demand Response activities could be complementary. - Highlights: • Inexistence of a standard on Demand Response limits the application of demand flexibility. • Demand flexibility is essential for the cost-effective integration of renewable generation technologies. • Benefits of certification of activities in the trading of Demand Response are highlighted. • Necessary activities for a standard interchange of Demand Response are identified. • The specifications of a new standard for Demand Response certification are given.
Climate Change Effects on Agriculture: Economic Responses to Biophysical Shocks

Science.gov (United States)

Nelson, Gerald C.; Valin, Hugo; Sands, Ronald D.; Havlik, Petr; Ahammad, Helal; Deryng, Delphine; Elliott, Joshua; Fujimori, Shinichiro; Hasegawa, Tomoko; Heyhoe, Edwina

2014-01-01

Agricultural production is sensitive to weather and thus directly affected by climate change. Plausible estimates of these climate change impacts require combined use of climate, crop, and economic models. Results from previous studies vary substantially due to differences in models, scenarios, and data. This paper is part of a collective effort to systematically integrate these three types of models. We focus on the economic component of the assessment, investigating how nine global economic models of agriculture represent endogenous responses to seven standardized climate change scenarios produced by two climate and five crop models. These responses include adjustments in yields, area, consumption, and international trade. We apply biophysical shocks derived from the Intergovernmental Panel on Climate Change's representative concentration pathway with end-of-century radiative forcing of 8.5 W/m(sup 2). The mean biophysical yield effect with no incremental CO2 fertilization is a 17% reduction globally by 2050 relative to a scenario with unchanging climate. Endogenous economic responses reduce yield loss to 11%, increase area of major crops by 11%, and reduce consumption by 3%. Agricultural production, cropland area, trade, and prices show the greatest degree of variability in response to climate change, and consumption the lowest. The sources of these differences include model structure and specification; in particular, model assumptions about ease of land use conversion, intensification, and trade. This study identifies where models disagree on the relative responses to climate shocks and highlights research activities needed to improve the representation of agricultural adaptation responses to climate change.
Genome-wide analysis of the CCCH zinc finger family identifies tissue specific and stress responsive candidates in chickpea (Cicer arietinum L.).

Science.gov (United States)

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

2017-01-01

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

Science.gov (United States)

Kholikov, I V; Sazonova, K L

2015-08-01

The present article deals with international legal issues that arise in case when various mass diseases go beyond any national jurisdiction. The emphasis is made on the problem of international responsibility, which different actors have to bear in such cases. The authors also examine the implementation of responsibility mechanism, including the indentication of the relevant international court, authorized to establish such liability and identify the specific forms of its realization.
Ball Screw Actuator Including a Compliant Ball Screw Stop

Science.gov (United States)

Wingett, Paul T. (Inventor); Hanlon, Casey (Inventor)

2017-01-01

An actuator includes a ball nut, a ball screw, and a ball screw stop. The ball nut is adapted to receive an input torque and in response rotates and supplies a drive force. The ball screw extends through the ball nut and has a first end and a second end. The ball screw receives the drive force from the ball nut and in response selectively translates between a retract position and a extend position. The ball screw stop is mounted on the ball screw proximate the first end to translate therewith. The ball screw stop engages the ball nut when the ball screw is in the extend position, translates, with compliance, a predetermined distance toward the first end upon engaging the ball nut, and prevents further rotation of the ball screw upon translating the predetermined distance.
Dynamic Analysis of Wind Turbines Including Soil-Structure Interaction

DEFF Research Database (Denmark)

Harte, M.; Basu, B.; Nielsen, Søren R.K.

2012-01-01

This paper investigates the along-wind forced vibration response of an onshore wind turbine. The study includes the dynamic interaction effects between the foundation and the underlying soil, as softer soils can influence the dynamic response of wind turbines. A Multi-Degree-of-Freedom (MDOF......) horizontal axes onshore wind turbine model is developed for dynamic analysis using an Euler–Lagrangian approach. The model is comprised of a rotor blade system, a nacelle and a flexible tower connected to a foundation system using a substructuring approach. The rotor blade system consists of three rotating...... for displacement of the turbine system are obtained and the modal frequencies of the combined turbine-foundation system are estimated. Simulations are presented for the MDOF turbine structure subjected to wind loading for different soil stiffness conditions. Steady state and turbulent wind loading, developed using...
Global business, global responsibilities: Corporate social responsibility orientations within a multinational bank

OpenAIRE

van den Heuvel, G.G.A.; Soeters, J.M.M.L.; Goessling, T.

2014-01-01

This study examines the effects of culture, gender, and function on orientation toward corporate social responsibility (CSR) among 416 employees of an international financial service organization. The main objective of the study is to investigate the variation of corporate social responsibility orientation (CSRO) across national cultures. The authors draw on a theory of cultural value orientations to identify three culturally distinct transnational clusters: West Europe, the English speaking ...
Lignin, mitochondrial family and photorespiratory transporter classification as case studies in using co-expression, co-response and protein locations to aid in identifying transport functions

Directory of Open Access Journals (Sweden)

Takayuki eTohge

2014-03-01

Full Text Available Whole genome sequencing and the relative ease of transcript profiling have facilitated the collection and data warehousing of immense quantities of expression data. However, a substantial proportion of genes are not yet functionally annotated a problem which is particularly acute for transport proteins. In Arabidopsis, for example, only a minor fraction of the estimated 700 intracellular transporters have been identified at the molecular genetic level. Furthermore it is only within the last couple of years that critical genes such as those encoding the final transport step required for the long distance transport of sucrose and the first transporter of the core photorespiratory pathway have been identified. Here we will describe how transcriptional coordination between genes of known function and non-annotated genes allows the identification of putative transporters on the premise that such co-expressed genes tend to be functionally related. We will additionally extend this to include the expansion of this approach to include phenotypic information from other levels of cellular organization such as proteomic and metabolomic data and provide case studies wherein this approach has successfully been used to fill knowledge gaps in important metabolic pathways and physiological processes.
Forward genetics screen coupled with whole-genome resequencing identifies novel gene targets for improving heterologous enzyme production in Aspergillus niger.

Science.gov (United States)

Reilly, Morgann C; Kim, Joonhoon; Lynn, Jed; Simmons, Blake A; Gladden, John M; Magnuson, Jon K; Baker, Scott E

2018-02-01

Plant biomass, once reduced to its composite sugars, can be converted to fuel substitutes. One means of overcoming the recalcitrance of lignocellulose is pretreatment followed by enzymatic hydrolysis. However, currently available commercial enzyme cocktails are inhibited in the presence of residual pretreatment chemicals. Recent studies have identified a number of cellulolytic enzymes from bacteria that are tolerant to pretreatment chemicals such as ionic liquids. The challenge now is generation of these enzymes in copious amounts, an arena where fungal organisms such as Aspergillus niger have proven efficient. Fungal host strains still need to be engineered to increase production titers of heterologous protein over native enzymes, which has been a difficult task. Here, we developed a forward genetics screen coupled with whole-genome resequencing to identify specific lesions responsible for a protein hyper-production phenotype in A. niger. This strategy successfully identified novel targets, including a low-affinity glucose transporter, MstC, whose deletion significantly improved secretion of recombinant proteins driven by a glucoamylase promoter.
Forward genetics screen coupled with whole-genome resequencing identifies novel gene targets for improving heterologous enzyme production in Aspergillus niger

Energy Technology Data Exchange (ETDEWEB)

Reilly, Morgann C. [Joint BioEnergy Institute, Emeryville, CA (United States); Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Kim, Joonhoon [Joint BioEnergy Institute, Emeryville, CA (United States); Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Lynn, Jed [Joint BioEnergy Institute, Emeryville, CA (United States); Wright-Patterson Air Force Base, Dayton, OH (United States); Simmons, Blake A. [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Gladden, John M. [Joint BioEnergy Institute, Emeryville, CA (United States); Sandia National Lab. (SNL-CA), Livermore, CA (United States); Magnuson, Jon K. [Joint BioEnergy Institute, Emeryville, CA (United States); Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Baker, Scott E. [Joint BioEnergy Institute, Emeryville, CA (United States); Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

2018-01-06

Plant biomass, once reduced to its composite sugars, can be converted to fuel substitutes. One means of overcoming the recalcitrance of lignocellulose is pretreatment followed by enzymatic hydrolysis. However, currently available commercial enzyme cocktails are inhibited in the presence of residual pretreatment chemicals. Recent studies have identified a number of cellulolytic enzymes from bacteria that are tolerant to pretreatment chemicals such as ionic liquids. The challenge now is generation of these enzymes in copious amounts, an arena where fungal organisms such as Aspergillus niger have proven efficient. Fungal host strains still need to be engineered to increase production titers of heterologous protein over native enzymes, which has been a difficult task. Here, we developed a forward genetics screen coupled with whole-genome resequencing to identify specific lesions responsible for a protein hyper-production phenotype in A. niger. This strategy successfully identified novel targets, including a low-affinity glucose transporter, MstC, whose deletion significantly improved secretion of recombinant proteins driven by a glucoamylase promoter.
The Response of Tigriopus californicusto Chlorophytic Macroalgae, Including Cladophora trichotomaKützing

Science.gov (United States)

Powlik, J. J.; Lewis, A. G.; Verma, N.

1997-03-01

The harpacticoid copepod Tigriopus californicusis not observed to maintain populations in supralittoral pools containing the alga Cladophora trichotoma. Laboratory microcosms and field treatments in Barkley Sound, British Columbia, Canada were inoculated with T. californicusand monitored seasonally (winter, spring, summer). After 5 days, C. trichotomamicrocosms held fewer survivors (18·6±7·3%) compared to treatments without vegetation (95·6±0·1%) or those containing the alga Enteromorpha compressa(93·8±5·4%), mean±SE. Though more difficult to determine in situ, results from inoculated field sites were similar. Copepodite and adult T. californicuswere the most adversely affected, while the survival of nauplii was generally maintained over 5-day intervals of observation. Other invertebrates, including littorines, barnacles and mussels were more abundant in C. trichotomapools at lower tidal elevations. Although several factors (exposure, nutrient supply, predation) are likely to contribute to the observed ' exclusion ' of T. californicusfrom pools containing C. trichotoma, the present results additionally suggest the deleterious influence of an unidentified chemical exudate from C. trichotoma. The particular susceptibility of mature T. californicusto this exudate precludes the establishment of viable copepod populations in these pools. 1997 Academic Press Limited
Systematically extracting metal- and solvent-related occupational information from free-text responses to lifetime occupational history questionnaires.

Science.gov (United States)

Friesen, Melissa C; Locke, Sarah J; Tornow, Carina; Chen, Yu-Cheng; Koh, Dong-Hee; Stewart, Patricia A; Purdue, Mark; Colt, Joanne S

2014-06-01

Lifetime occupational history (OH) questionnaires often use open-ended questions to capture detailed information about study participants' jobs. Exposure assessors use this information, along with responses to job- and industry-specific questionnaires, to assign exposure estimates on a job-by-job basis. An alternative approach is to use information from the OH responses and the job- and industry-specific questionnaires to develop programmable decision rules for assigning exposures. As a first step in this process, we developed a systematic approach to extract the free-text OH responses and convert them into standardized variables that represented exposure scenarios. Our study population comprised 2408 subjects, reporting 11991 jobs, from a case-control study of renal cell carcinoma. Each subject completed a lifetime OH questionnaire that included verbatim responses, for each job, to open-ended questions including job title, main tasks and activities (task), tools and equipment used (tools), and chemicals and materials handled (chemicals). Based on a review of the literature, we identified exposure scenarios (occupations, industries, tasks/tools/chemicals) expected to involve possible exposure to chlorinated solvents, trichloroethylene (TCE) in particular, lead, and cadmium. We then used a SAS macro to review the information reported by study participants to identify jobs associated with each exposure scenario; this was done using previously coded standardized occupation and industry classification codes, and a priori lists of associated key words and phrases related to possibly exposed tasks, tools, and chemicals. Exposure variables representing the occupation, industry, and task/tool/chemicals exposure scenarios were added to the work history records of the study respondents. Our identification of possibly TCE-exposed scenarios in the OH responses was compared to an expert's independently assigned probability ratings to evaluate whether we missed identifying
Genotype-phenotype associations in French patients with phenylketonuria and importance of genotype for full assessment of tetrahydrobiopterin responsiveness.

Science.gov (United States)

Jeannesson-Thivisol, Elise; Feillet, François; Chéry, Céline; Perrin, Pascal; Battaglia-Hsu, Shyue-Fang; Herbeth, Bernard; Cano, Aline; Barth, Magalie; Fouilhoux, Alain; Mention, Karine; Labarthe, François; Arnoux, Jean-Baptiste; Maillot, François; Lenaerts, Catherine; Dumesnil, Cécile; Wagner, Kathy; Terral, Daniel; Broué, Pierre; de Parscau, Loïc; Gay, Claire; Kuster, Alice; Bédu, Antoine; Besson, Gérard; Lamireau, Delphine; Odent, Sylvie; Masurel, Alice; Guéant, Jean-Louis; Namour, Fares

2015-12-15

Mutations in Phenylalanine Hydroxylase (PAH) gene cause phenylketonuria. Sapropterin (BH4), the enzyme cofactor, is an important therapeutical strategy in phenylketonuria. However, PAH is a highly polymorphic gene and it is difficult to identify BH4-responsive genotypes. We seek here to improve prediction of BH4-responsiveness through comparison of genotypes, BH4-loading test, predictions of responsiveness according to the literature and types and locations of mutations. A total of 364 French patients among which, 9 % had mild hyperphenylalaninemia, 17.7 % mild phenylketonuria and 73.1 % classical phenylketonuria, benefited from a 24-hour BH4-loading test and had the PAH gene sequenced and analyzed by Multiplex Ligation Probe Amplification. Overall, 31.6 % of patients were BH4-responsive. The number of different mutations found was 127, including 26 new mutations. The mutations c.434A > T, c.500A > T, c.529G > C, c.1045 T > G and c.1196 T > C were newly classified as being BH4-responsive. We identified 261 genotypes, among which 46 were newly recognized as being BH4-responsive. Even though patients carry 2 responsive alleles, BH4-responsiveness cannot be predicted with certainty unless they present mild hyperphenylalaninemia. BH4-responsiveness cannot be predicted in patients carrying one responsive mutation only. In general, the milder the phenotype is, the stronger the BH4-response is. Almost exclusively missense mutations, particularly in exons 12, 11 and 8, are associated with BH4-responsiveness and any other type of mutation predicts a negative response. This study is the first of its kind, in a French population, to identify the phenotype associated with several combinations of PAH mutations. As others, it highlights the necessity of performing simultaneously BH4 loading test and molecular analysis in monitoring phenylketonuria patients.
Targeted next generation sequencing identifies functionally deleterious germline mutations in novel genes in early-onset/familial prostate cancer.

Directory of Open Access Journals (Sweden)

Paula Paulo

2018-04-01

Full Text Available Considering that mutations in known prostate cancer (PrCa predisposition genes, including those responsible for hereditary breast/ovarian cancer and Lynch syndromes, explain less than 5% of early-onset/familial PrCa, we have sequenced 94 genes associated with cancer predisposition using next generation sequencing (NGS in a series of 121 PrCa patients. We found monoallelic truncating/functionally deleterious mutations in seven genes, including ATM and CHEK2, which have previously been associated with PrCa predisposition, and five new candidate PrCa associated genes involved in cancer predisposing recessive disorders, namely RAD51C, FANCD2, FANCI, CEP57 and RECQL4. Furthermore, using in silico pathogenicity prediction of missense variants among 18 genes associated with breast/ovarian cancer and/or Lynch syndrome, followed by KASP genotyping in 710 healthy controls, we identified "likely pathogenic" missense variants in ATM, BRIP1, CHEK2 and TP53. In conclusion, this study has identified putative PrCa predisposing germline mutations in 14.9% of early-onset/familial PrCa patients. Further data will be necessary to confirm the genetic heterogeneity of inherited PrCa predisposition hinted in this study.
Opportunities for Automated Demand Response in California Wastewater Treatment Facilities

Energy Technology Data Exchange (ETDEWEB)

Aghajanzadeh, Arian [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Wray, Craig [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); McKane, Aimee [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

2015-08-30

Previous research over a period of six years has identified wastewater treatment facilities as good candidates for demand response (DR), automated demand response (Auto-DR), and Energy Efficiency (EE) measures. This report summarizes that work, including the characteristics of wastewater treatment facilities, the nature of the wastewater stream, energy used and demand, as well as details of the wastewater treatment process. It also discusses control systems and automated demand response opportunities. Furthermore, this report summarizes the DR potential of three wastewater treatment facilities. In particular, Lawrence Berkeley National Laboratory (LBNL) has collected data at these facilities from control systems, submetered process equipment, utility electricity demand records, and governmental weather stations. The collected data were then used to generate a summary of wastewater power demand, factors affecting that demand, and demand response capabilities. These case studies show that facilities that have implemented energy efficiency measures and that have centralized control systems are well suited to shed or shift electrical loads in response to financial incentives, utility bill savings, and/or opportunities to enhance reliability of service. In summary, municipal wastewater treatment energy demand in California is large, and energy-intensive equipment offers significant potential for automated demand response. In particular, large load reductions were achieved by targeting effluent pumps and centrifuges. One of the limiting factors to implementing demand response is the reaction of effluent turbidity to reduced aeration at an earlier stage of the process. Another limiting factor is that cogeneration capabilities of municipal facilities, including existing power purchase agreements and utility receptiveness to purchasing electricity from cogeneration facilities, limit a facility’s potential to participate in other DR activities.
Proteomic identification of Drosophila melanogaster male accessory gland proteins, including a pro-cathepsin and a soluble γ-glutamyl transpeptidase

Directory of Open Access Journals (Sweden)

Sajid Mohammed

2006-05-01

Full Text Available Background In Drosophila melanogaster, the male seminal fluid contains proteins that are important for reproductive success. Many of these proteins are synthesised by the male accessory glands and are secreted into the accessory gland lumen, where they are stored until required. Previous studies on the identification of Drosophila accessory gland products have largely focused on characterisation of male-specific accessory gland cDNAs from D. melanogaster and, more recently, Drosophila simulans. In the present study, we have used a proteomics approach without any sex bias to identify proteins in D. melanogaster accessory gland secretions. Results Thirteen secreted accessory gland proteins, including seven new accessory gland proteins, were identified by 2D-gel electrophoresis combined with mass spectrometry of tryptic fragments. They included protein-folding and stress-response proteins, a hormone, a lipase, a serpin, a cysteine-rich protein and two peptidases, a pro-enzyme form of a cathepsin K-like cysteine peptidase and a γ-glutamyl transpeptidase. Enzymatic studies established that accessory gland secretions contain a cysteine peptidase zymogen that can be activated at low pH. This peptidase may have a role in the processing of female and other male-derived proteins, but is unlikely to be involved in the processing of the sex peptide. γ-Glutamyl transpeptidases are type II integral membrane proteins; however, the identified AG γ-glutamyl transpeptidase (GGT-1 is unusual in that it is predicted to be a soluble secreted protein, a prediction that is supported by biochemical evidence. GGT-1 is possibly involved in maintaining a protective redox environment for sperm. The strong γ-glutamyl transpeptidase activity found in the secretions provides an explanation for the observation that glutamic acid is the most abundant free amino acid in accessory gland secretions of D. melanogaster. Conclusion We have applied biochemical approaches, not used
Proteomic identification of Drosophila melanogaster male accessory gland proteins, including a pro-cathepsin and a soluble gamma-glutamyl transpeptidase.

Science.gov (United States)

Walker, Michael J; Rylett, Caroline M; Keen, Jeff N; Audsley, Neil; Sajid, Mohammed; Shirras, Alan D; Isaac, R Elwyn

2006-05-02

In Drosophila melanogaster, the male seminal fluid contains proteins that are important for reproductive success. Many of these proteins are synthesised by the male accessory glands and are secreted into the accessory gland lumen, where they are stored until required. Previous studies on the identification of Drosophila accessory gland products have largely focused on characterisation of male-specific accessory gland cDNAs from D. melanogaster and, more recently, Drosophila simulans. In the present study, we have used a proteomics approach without any sex bias to identify proteins in D. melanogaster accessory gland secretions. Thirteen secreted accessory gland proteins, including seven new accessory gland proteins, were identified by 2D-gel electrophoresis combined with mass spectrometry of tryptic fragments. They included protein-folding and stress-response proteins, a hormone, a lipase, a serpin, a cysteine-rich protein and two peptidases, a pro-enzyme form of a cathepsin K-like cysteine peptidase and a gamma-glutamyl transpeptidase. Enzymatic studies established that accessory gland secretions contain a cysteine peptidase zymogen that can be activated at low pH. This peptidase may have a role in the processing of female and other male-derived proteins, but is unlikely to be involved in the processing of the sex peptide. gamma-Glutamyl transpeptidases are type II integral membrane proteins; however, the identified AG gamma-glutamyl transpeptidase (GGT-1) is unusual in that it is predicted to be a soluble secreted protein, a prediction that is supported by biochemical evidence. GGT-1 is possibly involved in maintaining a protective redox environment for sperm. The strong gamma-glutamyl transpeptidase activity found in the secretions provides an explanation for the observation that glutamic acid is the most abundant free amino acid in accessory gland secretions of D. melanogaster. We have applied biochemical approaches, not used previously, to characterise

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