WorldWideScience

Sample records for regulatory impact analysis

  1. Contribution of a fuzzy expert system to regulatory impact analysis

    Directory of Open Access Journals (Sweden)

    Marco Antônio da Cunha

    2015-09-01

    Full Text Available Regulatory Impact Analysis (RIA has been consolidating in Brazilian regulatory agencies throughout the last decades. The RIA methodology aims to examine the regulatory process, measure the costs and benefits generated, as well as other effects of social, political or economic nature caused by a new or an existing regulation. By analysing each regulatory option, the expert or regulator faces a myriad of variables, usually of qualitative nature, that are difficult to measure and with a high degree of uncertainty. This research complements the existing literature, given the scarcity of decision support models in RIA that – regardless of the problem treated – incorporate the tacit knowledge of the regulation expert. This paper proposes an exploratory approach using a Fuzzy Expert System, which therefore helps to enrich the decision process in the final stage of comparison of the regulatory options.

  2. Some aspects of implementing Regulatory Impact Analysis in Brazil

    Directory of Open Access Journals (Sweden)

    Camila Moreira de Castro

    2014-04-01

    Full Text Available In an increasingly complex society, regulatory polices emerge as an important tool in public management. Nevertheless, regulation per se is no longer enough, and the agenda for a regulatory reform is increasing. Following this context, Brazil has implemented Regulatory Impact Analysis (RIA in its regulatory agencies. Thus, Brazilian specificities have to be considered and, in this regard, a systematic approach provides a significant contribution. This article aims to address some critical reflections about which policy-makers should ask themselves before joining the implementation of a RIA system in the Brazilian context. Through a long-term perspective, the implementation of RIA must be seen as part of a permanent change in the administrative culture, understanding that RIA should be used as a further resource in the decision-making process, rather than a final solution.

  3. Regulatory Impact Analysis: Regulasi Pasar Modern di Kabuoaten Bantul

    Directory of Open Access Journals (Sweden)

    Hudiyanto Hudiyanto

    2012-05-01

    Full Text Available RIA or Regulatory Impact Analysis is an analysis tool that is used to develop the quality of rules or policy that is made by the Government. This article is analyzing the use of RIA that is currently being run by Bantul Government in managing he moern market that is threatening the very existence of local economy that is currently the backbone of bantul's people economical activities. Th analysis, it's found out that the most threatened business by modern market is grocery stores, but the Bupati Rules limits the definition of local economy to traditional markets, which means that this Bupati Rules isn't consistent in protecting local economy. The modern market has an oligopoly structure. This kinds of structure make benefit the consumer, but on the other side, it also impose the transaction fee to the supplier. Bupati Rules that only manages the existence of modern markets become inefficient in removing the negative impact of the modern market itself. In the structure of market with that strong network, policy that only obstruct would be ineffective, because once the permission is granted, the network will spread by any means necessary. The protection to local economy bargaining position to the consumer and seller.

  4. Regulatory Impact Analysis: a new tool for better regulation at ANVISA.

    Science.gov (United States)

    Alves, Flávia Neves Rocha; Peci, Alketa

    2011-08-01

    Regulatory Impact Analysis, which is recommended to regulatory departments, aims to improve regulatory quality by providing information about the costs and benefits of regulation as well as solutions to current issues to enhance the decision-making process. This article discusses the importance of Regulatory Impact Analysis in the context of the National Agency for Sanitary Surveillance performance as well as the agency's current phase of regulation improvement and strengthening. Also, the main definitions related to the regulatory field as well as some international case experiences are presented.

  5. Workshop: Improving the Assessment and Valuation of Climate Change Impacts for Policy and Regulatory Analysis: Research on Climate Change Impacts and Associated Economic Damages (part 2)

    Science.gov (United States)

    This is a workshop titled Improving the Assessment and Valuation of Climate Change Impacts for Policy and Regulatory Analysis: Research on Climate Change Impacts and Associated Economic Damages (part 2)

  6. Synthetic fuels and the environment: an environmental and regulatory impacts analysis

    Energy Technology Data Exchange (ETDEWEB)

    None

    1980-06-01

    Since July 1979 when DOE/EV-0044 report Environmental Analysis of Synthetic Liquid fuels was published the synthetic fuels program proposals of the Administration have undergone significant modifications. The program year for which the development goal of 1.5 million barrels per day is to be reached has been changed from 1990 to 1995. The program plan is now proposed to have two stages to ensure, among other things, better environmental protection: an initial stage emphasizing applied research and development (R and D), including environmental research, followed by a second stage that would accelerate deployment of those synthetic fuel technologies then judged most ready for rapid deployment and economic operation within the environmental protection requirements. These program changes have significantly expanded the scope of technologies to be considered in this environmental analysis and have increased the likelihood that accelerated environmental R and D efforts will be successful in solving principal environmental and worker safety concerns for most technologies prior to the initiation of the second stage of the accelerated deployment plan. Information is presented under the following section headings: summary; study description; the technologies and their environmental concerns (including, coal liquefaction and gasification, oil shale production, biomass and urban waste conversion); regulatory and institutional analyses; and environmental impacts analysis (including air and water quaility analyses, impacts of carbon dioxide and acid rain, water availability, solid and hazardous wastes, coal mining environmental impacts, transportation issues, community growth and change, and regional impacts). Additional information is presented in seventeen appendixes. (JGB)

  7. Technical support document: Energy conservation standards for consumer products: Dishwashers, clothes washers, and clothes dryers including: Environmental impacts; regulatory impact analysis

    Energy Technology Data Exchange (ETDEWEB)

    1990-12-01

    The Energy Policy and Conservation Act as amended (P.L. 94-163), establishes energy conservation standards for 12 of the 13 types of consumer products specifically covered by the Act. The legislation requires the Department of Energy (DOE) to consider new or amended standards for these and other types of products at specified times. This Technical Support Document presents the methodology, data and results from the analysis of the energy and economic impacts of standards on dishwashers, clothes washers, and clothes dryers. The economic impact analysis is performed in five major areas: An Engineering Analysis, which establishes technical feasibility and product attributes including costs of design options to improve appliance efficiency. A Consumer Analysis at two levels: national aggregate impacts, and impacts on individuals. The national aggregate impacts include forecasts of appliance sales, efficiencies, energy use, and consumer expenditures. The individual impacts are analyzed by Life-Cycle Cost (LCC), Payback Periods, and Cost of Conserved Energy (CCE), which evaluate the savings in operating expenses relative to increases in purchase price; A Manufacturer Analysis, which provides an estimate of manufacturers' response to the proposed standards. Their response is quantified by changes in several measures of financial performance for a firm. An Industry Impact Analysis shows financial and competitive impacts on the appliance industry. A Utility Analysis that measures the impacts of the altered energy-consumption patterns on electric utilities. A Environmental Effects analysis, which estimates changes in emissions of carbon dioxide, sulfur oxides, and nitrogen oxides, due to reduced energy consumption in the home and at the power plant. A Regulatory Impact Analysis collects the results of all the analyses into the net benefits and costs from a national perspective. 47 figs., 171 tabs. (JF)

  8. The impact of regulatory heterogeneity on agri-food trade

    NARCIS (Netherlands)

    Winchester, N.; Rau, M.L.; Goetz, C.; Larue, B.; Otsuki, T.; Shutes, K.; Wieck, C.; Burnquist, H.L.; Pinto de Souza, M.J.; Nunes de Faria, R.

    2012-01-01

    We estimate the impact of regulatory heterogeneity on agri-food trade using a gravity analysis that relies on detailed data on non-tariff measures (NTMs) collected by the NTM-Impact project. The data cover a broad range of import requirements for agricultural and food products for the EU and nine of

  9. Historical perspective, economic analysis, and regulatory analysis of the impacts of waste partitioning-transmutation on the disposal of radioactive wastes

    Energy Technology Data Exchange (ETDEWEB)

    Forsberg, C.W.; Croff, A.G.; Kocher, D.C.

    1990-10-01

    Partitioning-transmutation, sometimes called actinide burning, is an alternative approach to high-level radioactive waste management. It consists of removing long-lived radionuclides from wastes and destroying those radionuclides, thus reducing the long-term hazards of radioactive waste. It was studied in detail in the 1970's. New developments in technology and other factors are resulting in a reexamination of this waste management option. This report consists of three papers which summarize the historical work, update the analysis of the costs of waste disposal, and describe current regulatory requirements which might be impacted by P-T. The papers provide a starting point for future research on P-T. 152 refs., 2 figs., 19 tabs.

  10. The impact of regulatory obligations on fishers’ income

    DEFF Research Database (Denmark)

    Hadjimichael, Maria; J. Kaiser, Michel; Edwards-Jones, Gareth

    2013-01-01

    Profit is an important driver of fishers’ behaviour. Thus, identifying fishers’ regulatory preferences in economic terms can assist the creation of more acceptable, workable and sustainable policies. The Adaptive Conjoint Analysis (ACA) method was adapted from its original application as a market......Profit is an important driver of fishers’ behaviour. Thus, identifying fishers’ regulatory preferences in economic terms can assist the creation of more acceptable, workable and sustainable policies. The Adaptive Conjoint Analysis (ACA) method was adapted from its original application...... as a marketing tool to identify fishers’ most and least preferred regulatory obligations in terms of the impact these obligations have on their income. Significant differences were identified in fishers’ preferences that depended on the regulatory measures fishers operated under at the time of the study (which...... related to the fishery and the region in which the fishers belonged). All fishers agreed that access to resources, i.e. how much access they have within a certain sea area was most important for their income. However, there were differences in fishers’ preferences with regards to the majority...

  11. A feasibility study on regulatory analysis in the nuclear regulatory decision making process in Korea

    Energy Technology Data Exchange (ETDEWEB)

    Lee, K. J.; Lee, B. W.; Lee, D. K.; Lim, C. Y.; Choi, Y. S.; Kim, K. K. [Korea Advanced Institute of Science and Technology, Taejon (Korea, Republic of)

    1996-12-15

    Nuclear safety regulation has different implications from economic regulation. In recent survey, it was found that Korea people want more regulatory effort than current one. This indicates that scientific method is necessary to improve the efficiency of regulation with limited resources of regulators. The main reason to conduct the regulatory analysis like cost-benefit analysis is obtaining the rationality of regulation to be implemented and persuading the licensees to comply under the quantified condition. That is, the ultimate goal is to verify the necessity and justice of regulation and to achieve the safety goal with minimum impacts. Guidelines and procedures developed in this study should help regulators to reach that goal.

  12. A Framework for Integrating Environmental Justice in Regulatory Analysis

    Directory of Open Access Journals (Sweden)

    Onyemaechi C. Nweke

    2011-06-01

    Full Text Available With increased interest in integrating environmental justice into the process for developing environmental regulations in the United States, analysts and decision makers are confronted with the question of what methods and data can be used to assess disproportionate environmental health impacts. However, as a first step to identifying data and methods, it is important that analysts understand what information on equity impacts is needed for decision making. Such knowledge originates from clearly stated equity objectives and the reflection of those objectives throughout the analytical activities that characterize Regulatory Impact Analysis (RIA, a process that is traditionally used to inform decision making. The framework proposed in this paper advocates structuring analyses to explicitly provide pre-defined output on equity impacts. Specifically, the proposed framework emphasizes: (a defining equity objectives for the proposed regulatory action at the onset of the regulatory process, (b identifying specific and related sub-objectives for key analytical steps in the RIA process, and (c developing explicit analytical/research questions to assure that stated sub-objectives and objectives are met. In proposing this framework, it is envisioned that information on equity impacts informs decision-making in regulatory development, and that this is achieved through a systematic and consistent approach that assures linkages between stated equity objectives, regulatory analyses, selection of policy options, and the design of compliance and enforcement activities.

  13. Comparing Distributions of Environmental Outcomes for Regulatory Environmental Justice Analysis

    Directory of Open Access Journals (Sweden)

    Glenn Sheriff

    2011-05-01

    Full Text Available Economists have long been interested in measuring distributional impacts of policy interventions. As environmental justice (EJ emerged as an ethical issue in the 1970s, the academic literature has provided statistical analyses of the incidence and causes of various environmental outcomes as they relate to race, income, and other demographic variables. In the context of regulatory impacts, however, there is a lack of consensus regarding what information is relevant for EJ analysis, and how best to present it. This paper helps frame the discussion by suggesting a set of questions fundamental to regulatory EJ analysis, reviewing past approaches to quantifying distributional equity, and discussing the potential for adapting existing tools to the regulatory context.

  14. Regulatory analysis technical evaluation handbook. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-01-01

    The purpose of this Handbook is to provide guidance to the regulatory analyst to promote preparation of quality regulatory analysis documents and to implement the policies of the Regulatory Analysis Guidelines of the US Nuclear Regulatory Commission (NUREG/BR-0058 Rev. 2). This Handbook expands upon policy concepts included in the NRC Guidelines and translates the six steps in preparing regulatory analyses into implementable methodologies for the analyst. It provides standardized methods of preparation and presentation of regulatory analyses, with the inclusion of input that will satisfy all backfit requirements and requirements of NRC`s Committee to Review Generic Requirements. Information on the objectives of the safety goal evaluation process and potential data sources for preparing a safety goal evaluation is also included. Consistent application of the methods provided here will result in more directly comparable analyses, thus aiding decision-makers in evaluating and comparing various regulatory actions. The handbook is being issued in loose-leaf format to facilitate revisions. NRC intends to periodically revise the handbook as new and improved guidance, data, and methods become available.

  15. RSAT 2015: Regulatory Sequence Analysis Tools.

    Science.gov (United States)

    Medina-Rivera, Alejandra; Defrance, Matthieu; Sand, Olivier; Herrmann, Carl; Castro-Mondragon, Jaime A; Delerce, Jeremy; Jaeger, Sébastien; Blanchet, Christophe; Vincens, Pierre; Caron, Christophe; Staines, Daniel M; Contreras-Moreira, Bruno; Artufel, Marie; Charbonnier-Khamvongsa, Lucie; Hernandez, Céline; Thieffry, Denis; Thomas-Chollier, Morgane; van Helden, Jacques

    2015-07-01

    RSAT (Regulatory Sequence Analysis Tools) is a modular software suite for the analysis of cis-regulatory elements in genome sequences. Its main applications are (i) motif discovery, appropriate to genome-wide data sets like ChIP-seq, (ii) transcription factor binding motif analysis (quality assessment, comparisons and clustering), (iii) comparative genomics and (iv) analysis of regulatory variations. Nine new programs have been added to the 43 described in the 2011 NAR Web Software Issue, including a tool to extract sequences from a list of coordinates (fetch-sequences from UCSC), novel programs dedicated to the analysis of regulatory variants from GWAS or population genomics (retrieve-variation-seq and variation-scan), a program to cluster motifs and visualize the similarities as trees (matrix-clustering). To deal with the drastic increase of sequenced genomes, RSAT public sites have been reorganized into taxon-specific servers. The suite is well-documented with tutorials and published protocols. The software suite is available through Web sites, SOAP/WSDL Web services, virtual machines and stand-alone programs at http://www.rsat.eu/.

  16. 44 CFR 1.9 - Regulatory impact analyses.

    Science.gov (United States)

    2010-10-01

    ... HOMELAND SECURITY GENERAL RULEMAKING; POLICY AND PROCEDURES General § 1.9 Regulatory impact analyses. (a... monetary terms, and the identification of those likely to receive the benefits; (2) A description of the potential costs of the rule, including any adverse effects that cannot be quantified in monetary terms, and...

  17. Regulatory Impact Analysis Practice in New Zealand in the Light of Models of Evaluation Use – Inspiration for the Polish Government

    Directory of Open Access Journals (Sweden)

    Tomasz Kupiec

    2015-06-01

    Full Text Available Purpose: The paper describes the functioning of the RIA system in New Zealand using the analogy of RIA and the evaluation of public interventions. Presented solutions can provide nspiration for the Polish government in the process of improving the quality and extent of the use of RIA. Methodology: The analysis is based on a review of government documents and literature, as well as individual interviews and correspondence with representatives of the government of NZ. Conclusions: The RIA system in NZ is not error-free and its shortcomings include inter alia the lack of solutions with respect to ex-post analysis and insufficiently rigorous methodological approach. At the same time, a number of solutions can be regarded as good practice, e.g.: regular external quality reviews of RIS, obligation to supplement each RIS with ‘quality assessment’ and a ‘disclosure statement’ outlining their credibility and utility. Practical implications: The presented strengths of the RIA system in NZ may serve as an inspiration for modifying the RIA system in Poland. Originality: The RIA system is presented through the prism of the model of evaluation use, which is a related tool of collecting information about non-regulatory interventions.

  18. XcisClique: analysis of regulatory bicliques

    Directory of Open Access Journals (Sweden)

    Grene Ruth

    2006-04-01

    Full Text Available Abstract Background Modeling of cis-elements or regulatory motifs in promoter (upstream regions of genes is a challenging computational problem. In this work, set of regulatory motifs simultaneously present in the promoters of a set of genes is modeled as a biclique in a suitably defined bipartite graph. A biologically meaningful co-occurrence of multiple cis-elements in a gene promoter is assessed by the combined analysis of genomic and gene expression data. Greater statistical significance is associated with a set of genes that shares a common set of regulatory motifs, while simultaneously exhibiting highly correlated gene expression under given experimental conditions. Methods XcisClique, the system developed in this work, is a comprehensive infrastructure that associates annotated genome and gene expression data, models known cis-elements as regular expressions, identifies maximal bicliques in a bipartite gene-motif graph; and ranks bicliques based on their computed statistical significance. Significance is a function of the probability of occurrence of those motifs in a biclique (a hypergeometric distribution, and on the new sum of absolute values statistic (SAV that uses Spearman correlations of gene expression vectors. SAV is a statistic well-suited for this purpose as described in the discussion. Results XcisClique identifies new motif and gene combinations that might indicate as yet unidentified involvement of sets of genes in biological functions and processes. It currently supports Arabidopsis thaliana and can be adapted to other organisms, assuming the existence of annotated genomic sequences, suitable gene expression data, and identified regulatory motifs. A subset of Xcis Clique functionalities, including the motif visualization component MotifSee, source code, and supplementary material are available at https://bioinformatics.cs.vt.edu/xcisclique/.

  19. Proposed standby gasoline rationing plan. Economic and regulatory analysis draft

    Energy Technology Data Exchange (ETDEWEB)

    1978-06-01

    This economic and regulatory analysis meets the requirements of the Energy Policy and Conservation Act, which calls for an evaluation of the potential economic impacts of the gasoline rationing contingency plan. In addition, this analysis is intended to satisfy the requirements of the President's Executive Order No. 12044 of March 23, 1978, regarding government regulations, and provides an inflationary impact statement for the proposed rationing plan. To perform the analysis of rationing program impacts on the total national economy, three separate projections were required. First, a projection is made of the ''normal'' U.S. economy for a future period--the last quarter of 1980 through the third quarter of 1981 in this analysis. Second, a projection is made of the impacts which a petroleum supply interruption would have on the U.S. economy during this future period, assuming that DOE's standby allocation and price control regulations were implemented for crude oil and products. Third, and most significant, an estimate is made of the incremental impacts of the gasoline rationing program on this already-perturbed future U.S. economy.

  20. Technical support document: Energy efficiency standards for consumer products: Refrigerators, refrigerator-freezers, and freezers including draft environmental assessment, regulatory impact analysis

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-07-01

    The Energy Policy and Conservation Act (P.L. 94-163), as amended by the National Appliance Energy Conservation Act of 1987 (P.L. 100-12) and by the National Appliance Energy Conservation Amendments of 1988 (P.L. 100-357), and by the Energy Policy Act of 1992 (P.L. 102-486), provides energy conservation standards for 12 of the 13 types of consumer products` covered by the Act, and authorizes the Secretary of Energy to prescribe amended or new energy standards for each type (or class) of covered product. The assessment of the proposed standards for refrigerators, refrigerator-freezers, and freezers presented in this document is designed to evaluate their economic impacts according to the criteria in the Act. It includes an engineering analysis of the cost and performance of design options to improve the efficiency of the products; forecasts of the number and average efficiency of products sold, the amount of energy the products will consume, and their prices and operating expenses; a determination of change in investment, revenues, and costs to manufacturers of the products; a calculation of the costs and benefits to consumers, electric utilities, and the nation as a whole; and an assessment of the environmental impacts of the proposed standards.

  1. Global analysis of photosynthesis transcriptional regulatory networks.

    Science.gov (United States)

    Imam, Saheed; Noguera, Daniel R; Donohue, Timothy J

    2014-12-01

    Photosynthesis is a crucial biological process that depends on the interplay of many components. This work analyzed the gene targets for 4 transcription factors: FnrL, PrrA, CrpK and MppG (RSP_2888), which are known or predicted to control photosynthesis in Rhodobacter sphaeroides. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) identified 52 operons under direct control of FnrL, illustrating its regulatory role in photosynthesis, iron homeostasis, nitrogen metabolism and regulation of sRNA synthesis. Using global gene expression analysis combined with ChIP-seq, we mapped the regulons of PrrA, CrpK and MppG. PrrA regulates ∼34 operons encoding mainly photosynthesis and electron transport functions, while CrpK, a previously uncharacterized Crp-family protein, regulates genes involved in photosynthesis and maintenance of iron homeostasis. Furthermore, CrpK and FnrL share similar DNA binding determinants, possibly explaining our observation of the ability of CrpK to partially compensate for the growth defects of a ΔFnrL mutant. We show that the Rrf2 family protein, MppG, plays an important role in photopigment biosynthesis, as part of an incoherent feed-forward loop with PrrA. Our results reveal a previously unrealized, high degree of combinatorial regulation of photosynthetic genes and significant cross-talk between their transcriptional regulators, while illustrating previously unidentified links between photosynthesis and the maintenance of iron homeostasis.

  2. Transcription regulatory networks analysis using CAGE

    KAUST Repository

    Tegnér, Jesper N.

    2009-10-01

    Mapping out cellular networks in general and transcriptional networks in particular has proved to be a bottle-neck hampering our understanding of biological processes. Integrative approaches fusing computational and experimental technologies for decoding transcriptional networks at a high level of resolution is therefore of uttermost importance. Yet, this is challenging since the control of gene expression in eukaryotes is a complex multi-level process influenced by several epigenetic factors and the fine interplay between regulatory proteins and the promoter structure governing the combinatorial regulation of gene expression. In this chapter we review how the CAGE data can be integrated with other measurements such as expression, physical interactions and computational prediction of regulatory motifs, which together can provide a genome-wide picture of eukaryotic transcriptional regulatory networks at a new level of resolution. © 2010 by Pan Stanford Publishing Pte. Ltd. All rights reserved.

  3. Regulatory Impact Assessment (RIA and Rationality of Law – Legal Aspects

    Directory of Open Access Journals (Sweden)

    Jan Chmielewski

    2015-06-01

    Full Text Available Purpose: The fundamental aim of this article is to verify an assumption according to which the proper Regulatory Impact Assessment (RIA is a key factor in the rationality of law. Rational law is a law which is effective and able to realize and achieve social, economic and environmental aims determined and established by the lawmaker. Methodology: The scope of this paper – which determines its structure – encompasses the definition of RIA, including its specific (but non-legal forms such as benchmarking and evaluation. As far as we are concerned, these methods can provide – as a kind of Regulatory Impact Assessment a significant tool for measuring the rationality of regulations. Furthermore, the usefulness of benchmarking and evaluation has been recognised by representatives of jurisprudence. We will also explain the concept and the assumptions of the rationality of law on the grounds and in the light of the case law of the Polish Constitutional Tribunal and the Supreme Administrative Court. This should allow to countercheck the main thesis of this paper. The methodology encompasses primary legal methods such as literature, case law and legislation analysis. Findings: An indispensable condition of the rationality of law is actual elimination of irrational regulations which were not subjected to the Regulatory Impact Assessment. Practical implications: Although RIA is a problematic issue (in terms of its practical application,it is necessary to carry it out in order to assure the rationality of law. A good and desirable complement to Regulatory Impact Assessment are non-legal methods such as benchmarking and evaluation. Originality: Originality and value of this survey lies in taking into account the case law of the Polish Constitutional Tribunal and the Supreme Administrative Court. Additionally, this paper is original in that it considers non-legal methods in the examination of the rationality of law.

  4. Cost-benefit considerations in regulatory analysis

    Energy Technology Data Exchange (ETDEWEB)

    Mubayi, V.; Sailor, V.; Anandalingam, G.

    1995-10-01

    Justification for safety enhancements at nuclear facilities, e.g., a compulsory backfit to nuclear power plants, requires a value-impact analysis of the increase in overall public protection versus the cost of implementation. It has been customary to assess the benefits in terms of radiation dose to the public averted by the introduction of the safety enhancement. Comparison of such benefits with the costs of the enhancement then requires an estimate of the monetary value of averted dose (dollars/person rem). This report reviews available information on a variety of factors that affect this valuation and assesses the continuing validity of the figure of $1000/person-rem averted, which has been widely used as a guideline in performing value-impact analyses. Factors that bear on this valuation include the health risks of radiation doses, especially the higher risk estimates of the BEIR V committee, recent calculations of doses and offsite costs by consequence codes for hypothesized severe accidents at U.S. nuclear power plants under the NUREG-1150 program, and recent information on the economic consequences of the Chernobyl accident in the Soviet Union and estimates of risk avoidance based on the willingness-to-pay criterion. The report analyzes these factors and presents results on the dollars/person-rem ratio arising from different assumptions on the values of these factors.

  5. Impacts of Climate Policy on Regional Air Quality, Health, and Air Quality Regulatory Procedures

    Science.gov (United States)

    Thompson, T. M.; Selin, N. E.

    2011-12-01

    Both the changing climate, and the policy implemented to address climate change can impact regional air quality. We evaluate the impacts of potential selected climate policies on modeled regional air quality with respect to national pollution standards, human health and the sensitivity of health uncertainty ranges. To assess changes in air quality due to climate policy, we couple output from a regional computable general equilibrium economic model (the US Regional Energy Policy [USREP] model), with a regional air quality model (the Comprehensive Air Quality Model with Extensions [CAMx]). USREP uses economic variables to determine how potential future U.S. climate policy would change emissions of regional pollutants (CO, VOC, NOx, SO2, NH3, black carbon, and organic carbon) from ten emissions-heavy sectors of the economy (electricity, coal, gas, crude oil, refined oil, energy intensive industry, other industry, service, agriculture, and transportation [light duty and heavy duty]). Changes in emissions are then modeled using CAMx to determine the impact on air quality in several cities in the Northeast US. We first calculate the impact of climate policy by using regulatory procedures used to show attainment with National Ambient Air Quality Standards (NAAQS) for ozone and particulate matter. Building on previous work, we compare those results with the calculated results and uncertainties associated with human health impacts due to climate policy. This work addresses a potential disconnect between NAAQS regulatory procedures and the cost/benefit analysis required for and by the Clean Air Act.

  6. Differential Regulatory Analysis Based on Coexpression Network in Cancer Research

    Directory of Open Access Journals (Sweden)

    Junyi Li

    2016-01-01

    Full Text Available With rapid development of high-throughput techniques and accumulation of big transcriptomic data, plenty of computational methods and algorithms such as differential analysis and network analysis have been proposed to explore genome-wide gene expression characteristics. These efforts are aiming to transform underlying genomic information into valuable knowledges in biological and medical research fields. Recently, tremendous integrative research methods are dedicated to interpret the development and progress of neoplastic diseases, whereas differential regulatory analysis (DRA based on gene coexpression network (GCN increasingly plays a robust complement to regular differential expression analysis in revealing regulatory functions of cancer related genes such as evading growth suppressors and resisting cell death. Differential regulatory analysis based on GCN is prospective and shows its essential role in discovering the system properties of carcinogenesis features. Here we briefly review the paradigm of differential regulatory analysis based on GCN. We also focus on the applications of differential regulatory analysis based on GCN in cancer research and point out that DRA is necessary and extraordinary to reveal underlying molecular mechanism in large-scale carcinogenesis studies.

  7. Impact of regulatory science on global public health.

    Science.gov (United States)

    Patel, Meghal; Miller, Margaret Ann

    2012-07-01

    Regulatory science plays a vital role in protecting and promoting global public health by providing the scientific basis for ensuring that food and medical products are safe, properly labeled, and effective. Regulatory science research was first developed for the determination of product safety in the early part of the 20th Century, and continues to support innovation of the processes needed for regulatory policy decisions. Historically, public health laws and regulations were enacted following public health tragedies, and often the research tools and techniques required to execute these laws lagged behind the public health needs. Throughout history, similar public health problems relating to food and pharmaceutical products have occurred in countries around the world, and have usually led to the development of equivalent solutions. For example, most countries require a demonstration of pharmaceutical safety and efficacy prior to marketing these products using approaches that are similar to those initiated in the United States. The globalization of food and medical products has created a shift in regulatory compliance such that gaps in food and medical product safety can generate international problems. Improvements in regulatory research can advance the regulatory paradigm toward a more preventative, proactive framework. These improvements will advance at a greater pace with international collaboration by providing additional resources and new perspectives for approaching and anticipating public health problems. The following is a review of how past public health disasters have shaped the current regulatory landscape, and where innovation can facilitate the shift from reactive policies to proactive policies.

  8. NGNP Project Regulatory Gap Analysis for Modular HTGRs

    Energy Technology Data Exchange (ETDEWEB)

    Wayne Moe

    2011-09-01

    The Next Generation Nuclear Plant (NGNP) Project Regulatory Gap Analysis (RGA) for High Temperature Gas-Cooled Reactors (HTGR) was conducted to evaluate existing regulatory requirements and guidance against the design characteristics specific to a generic modular HTGR. This final report presents results and identifies regulatory gaps concerning current Nuclear Regulatory Commission (NRC) licensing requirements that apply to the modular HTGR design concept. This report contains appendices that highlight important HTGR licensing issues that were found during the RGA study. The information contained in this report will be used to further efforts in reconciling HTGR-related gaps in the NRC licensing structure, which has to date largely focused on light water reactor technology.

  9. Evidence-Based Policy Making and the Implementation of Regulatory Impact Assessment in Croatia

    Directory of Open Access Journals (Sweden)

    Zdravko Petak

    2015-06-01

    Full Text Available Purpose: This study is dealing with the application of evidence-based policy-making in Croatian public administration and the general role of applied policy analysis in the Croatian system of governance. Methodology: This development is illustrated by the peculiarities of introducing regulatory impact assessment (RIA tools in Croatian public administrative structures. Findings: The author is pointing out various limitations in the usage of policy analysis tools in formulating, implementing and evaluating public policies in Croatia. The crucial role of RIA for enhancing executive capacity of governance structures is particularly stressed in the study. The final part of the article is devoted to the prospects of further development of RIA as an applied policy analysis tool within the Croatian system of governance.

  10. Impact of energy and environmental legislation on industry: problems of regulatory cost assessment

    Energy Technology Data Exchange (ETDEWEB)

    Meier, P; Brown, S

    1980-01-01

    An examination is made of some of the problems of environmental impact assessment in the industrial sector, with particular attention to some important methodological problems frequently ignored. Some general problems of impact analysis are addressed in Section 2. This is followed in Section 3 by an overview of these major issues: the level of import substitutions, capital expenditures on pollution control, and a brief examination at how the industrial sector responded to post embargo energy price changes. Section 4 investigates marketplace responses to changes in manufacturing costs induced by regulatory requirements, from a general, theoretical microeconomics perspective. How industry responses can be estimated quantitatively for practical assessment purposes is taken up in Section 5, with a focus on the advantages and limitations of the two major modeling approaches (econometric and process models). These models allow investigations of the effects of different policies. (MCW)

  11. Sociotechnical systems as a framework for regulatory system design and evaluation: Using Work Domain Analysis to examine a new regulatory system.

    Science.gov (United States)

    Carden, Tony; Goode, Natassia; Read, Gemma J M; Salmon, Paul M

    2017-03-15

    Like most work systems, the domain of adventure activities has seen a series of serious incidents and subsequent calls to improve regulation. Safety regulation systems aim to promote safety and reduce accidents. However, there is scant evidence they have led to improved safety outcomes. In fact there is some evidence that the poor integration of regulatory system components has led to adverse safety outcomes in some contexts. Despite this, there is an absence of methods for evaluating regulatory and compliance systems. This article argues that sociotechnical systems theory and methods provide a suitable framework for evaluating regulatory systems. This is demonstrated through an analysis of a recently introduced set of adventure activity regulations. Work Domain Analysis (WDA) was used to describe the regulatory system in terms of its functional purposes, values and priority measures, purpose-related functions, object-related processes and cognitive objects. This allowed judgement to be made on the nature of the new regulatory system and on the constraints that may impact its efficacy following implementation. Importantly, the analysis suggests that the new system's functional purpose of ensuring safe activities is not fully supported in terms of the functions and objects available to fulfil them. Potential improvements to the design of the system are discussed along with the implications for regulatory system design and evaluation across the safety critical domains generally. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Inference of splicing regulatory activities by sequence neighborhood analysis.

    Directory of Open Access Journals (Sweden)

    Michael B Stadler

    2006-11-01

    Full Text Available Sequence-specific recognition of nucleic-acid motifs is critical to many cellular processes. We have developed a new and general method called Neighborhood Inference (NI that predicts sequences with activity in regulating a biochemical process based on the local density of known sites in sequence space. Applied to the problem of RNA splicing regulation, NI was used to predict hundreds of new exonic splicing enhancer (ESE and silencer (ESS hexanucleotides from known human ESEs and ESSs. These predictions were supported by cross-validation analysis, by analysis of published splicing regulatory activity data, by sequence-conservation analysis, and by measurement of the splicing regulatory activity of 24 novel predicted ESEs, ESSs, and neutral sequences using an in vivo splicing reporter assay. These results demonstrate the ability of NI to accurately predict splicing regulatory activity and show that the scope of exonic splicing regulatory elements is substantially larger than previously anticipated. Analysis of orthologous exons in four mammals showed that the NI score of ESEs, a measure of function, is much more highly conserved above background than ESE primary sequence. This observation indicates a high degree of selection for ESE activity in mammalian exons, with surprisingly frequent interchangeability between ESE sequences.

  13. Sensitivity analysis for missing data in regulatory submissions.

    Science.gov (United States)

    Permutt, Thomas

    2016-07-30

    The National Research Council Panel on Handling Missing Data in Clinical Trials recommended that sensitivity analyses have to be part of the primary reporting of findings from clinical trials. Their specific recommendations, however, seem not to have been taken up rapidly by sponsors of regulatory submissions. The NRC report's detailed suggestions are along rather different lines than what has been called sensitivity analysis in the regulatory setting up to now. Furthermore, the role of sensitivity analysis in regulatory decision-making, although discussed briefly in the NRC report, remains unclear. This paper will examine previous ideas of sensitivity analysis with a view to explaining how the NRC panel's recommendations are different and possibly better suited to coping with present problems of missing data in the regulatory setting. It will also discuss, in more detail than the NRC report, the relevance of sensitivity analysis to decision-making, both for applicants and for regulators. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  14. Regulatory activities of government: analysis of determinants

    Directory of Open Access Journals (Sweden)

    Primož Pevcin

    2006-12-01

    Full Text Available International comparisons show that large cross-country differences exist in the overall macro extent of regulation of the economy. In this context, the main purpose of the article is to investigate, why such differences exist by identifying and empirically verifying the effect of various factors that could potentially shape those differences. Empirical analysis based on the sample of 32 developed and democratic countries revealed that almost 70 % of variation in the macro extent of regulation could be explained with 7 statistically significant explanatory variables. The econometric analysis revealed that the macro extent of regulation decreases with income inequality in society, with the level of economic development, with the sizeof economy, with the share of transfer spending in GDP and with the share of government employment in labour force. On the other hand, the extent of regulation is positively related to government ownership of enterprises and to presidential political regime

  15. Regulatory environment and its impact on the market value of investor-owned electric utilities

    Science.gov (United States)

    Vishwanathan, Raman

    While other regulated industries have one by one been exposed to competitive reform, electric power, for over eighty years, has remained a great monopoly. For all those years, the vertically integrated suppliers of electricity in the United States have been assigned exclusive territorial (consumer) franchises and have been closely regulated. This environment is in the process change because the electric power industry is currently undergoing some dramatic adjustments. Since 1992, a number of states have initiated regulatory reform and are moving to allow retail customers to choose their energy supplier. There has also been a considerable federal government role in encouraging competition in the generation and transmission of electricity. The objective of this research is to investigate the reaction of investors to the prevailing regulatory environment in the electric utility industry by analyzing the market-to-book value for investor-owned electric utilities in the United States as a gauge of investor concern or support for change. In this study, the variable of interest is the market valuation of utilities, as it captures investor confidence to changes in the regulatory environment. Initially a classic regression model is analyzed on the full sample (of the 96 investor-owned utilities for the years 1992 through 1996), providing a total number of 480 (96 firms over 5 years) observations. Later fixed- and random-effects models are analyzed for the same full-sample model specified in the previous analysis. Also, the analysis is carried forward to examine the impact of the size of the utility and its degree of reliability on nuclear power generation on market values. In the period of this study, 1992--1996, the financial security markets downgraded utilities that were still operating in a regulated environment or had a substantial percentage of their power generation from nuclear power plants. It was also found that the financial market was sensitive to the size of

  16. Analysis of regulatory architectures in BST

    Institute of Scientific and Technical Information of China (English)

    BIAN Fuping; LIANG Min; ZHAO Xueming

    2003-01-01

    Based on the data envelopment analysis (DEA) theory, the optimal pathway of metabolic reaction networks in biochemical systems is studied. After calculating the mixed-integer linear programming (MILP) model given by Bailey et al. twice, the decision making units (DMU) and the prediction model of DEA are constructed, where the inputs are levels of manipulated parameters (enzyme) and outputs are concentrations of metabolites. When the metabolic networks are reconstructed, the data are obtained by calculating MILP framework twice and the optimal levels of the manipulated parameter at different regular loops are predicted, thus simplifying the calculations of Bailey's.

  17. Regulatory Cost Impacts for Selected Institutions of Higher Education in Texas.

    Science.gov (United States)

    Thornton, Nelson L., Jr.

    Regulatory cost impacts for 11 Texas colleges and universities for the 1977-78 academic year are presented as part of a continuing effort to assess the costs and impact of federally mandated social regulations. The 11 institutions are representative of each of the types previously reviewed as groups. For each institution, data are presented on the…

  18. A Research Paper On The Impact Of Regulatory Framework On IPO Under Pricing

    OpenAIRE

    Thakur, Preeti

    2015-01-01

    As we all know initial public offering (IPO) underpricing and regulatory framework is the hottest topic in the current industry, mainly because of India being a developing country and lot of growth in various sectors which leads a country to ultimate success. The purpose of this study is to study whether Underpricing exists in Indian IPOs or not and to study the impact of regulatory framework on IPO Underpricing. In this research project the data is analyzed by descriptive and comparative met...

  19. Regulatory Impact of RNA Secondary Structure across the Arabidopsis Transcriptome[W][OA

    Science.gov (United States)

    Li, Fan; Zheng, Qi; Vandivier, Lee E.; Willmann, Matthew R.; Chen, Ying; Gregory, Brian D.

    2012-01-01

    The secondary structure of an RNA molecule plays an integral role in its maturation, regulation, and function. However, the global influence of this feature on plant gene expression is still largely unclear. Here, we use a high-throughput, sequencing-based, structure-mapping approach in conjunction with transcriptome-wide sequencing of rRNA-depleted (RNA sequencing), small RNA, and ribosome-bound RNA populations to investigate the impact of RNA secondary structure on gene expression regulation in Arabidopsis thaliana. From this analysis, we find that highly unpaired and paired RNAs are strongly correlated with euchromatic and heterochromatic epigenetic histone modifications, respectively, providing evidence that secondary structure is necessary for these RNA-mediated posttranscriptional regulatory pathways. Additionally, we uncover key structural patterns across protein-coding transcripts that indicate RNA folding demarcates regions of protein translation and likely affects microRNA-mediated regulation of mRNAs in this model plant. We further reveal that RNA folding is significantly anticorrelated with overall transcript abundance, which is often due to the increased propensity of highly structured mRNAs to be degraded and/or processed into small RNAs. Finally, we find that secondary structure affects mRNA translation, suggesting that this feature regulates plant gene expression at multiple levels. These findings provide a global assessment of RNA folding and its significant regulatory effects in a plant transcriptome. PMID:23150631

  20. Accounting for Technological Change in Regulatory Impact Analyses: The Learning Curve Technique

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, Margaret [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Fujita, K. Sydny [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2013-04-30

    Regulatory impact assessment is formally required by the U.S. and many other nations in order to help governments weigh the costs and benefits of proposed regulations, particularly as they compare to those of alternative actions and other government priorities. 1 One of the “best practices” of regulatory impact assessments, as established by the OECD, is to use estimates of costs that are grounded in economic theory. Economic theory indicates that changes in compliance costs should be expected over time as a result of factors related to technological innovation. But many U.S. regulatory impact assessments have traditionally employed a practice that is in conflict with this expectation: they take current estimates of the costs of complying with a proposed regulation and project that those costs will remain unchanged over the full time period that the regulation would be in effect.

  1. Development of Regulatory Thermal-Hydraulic Analysis System (RETAS)

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Seung-Hoon; Kim, In-Goo; Kim, Hho-Jung; Cho, Yong Jin [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2007-10-15

    A review is provided of the reasons why the Korea Institute of Nuclear Safety needs improvement of the existing codes employed for a regulatory audit. The proposed new organization of the codes, developed or to be developed, is presented together with illustrative applications. Inspection of the quality assurance activities is planned to ensure the robustness of MARS (Multi-dimensional Analysis for Reactor Safety) code, served as a pivot of the organization.

  2. NASA's Agency-wide Strategy for Environmental Regulatory Risk Analysis and Communication

    Science.gov (United States)

    Duda, Kristen; Scroggins. Sharon

    2008-01-01

    NASA's mission is to pioneer the future in space exploration, scientific discovery, and aeronautics research. To help enable existing and future programs to pursue this mission, NASA has established the Principal Center for Regulatory Risk Analysis and Communication (RRAC PC) to proactively identify, analyze, and communicate environmental regulatory risks to the NASA community. The RRAC PC is chartered to evaluate the risks posed to NASA Programs and facilities by environmentally related drivers. The RRAC PC focuses on emerging environmental regulations, as well as risks related to operational changes that can trigger existing environmental requirements. Changing regulations have the potential to directly affect program activities. For example, regulatory changes can restrict certain activities or operations by mandating changes in how operations may be done or limiting where or how certain operations can take place. Regulatory changes also can directly affect the ability to use certain materials by mandating a production phase-out or restricting usage aPi'iications of certain materials. Such changes can result in NASA undertaking material replacement efforts. Even if a regulation does not directly affect NASA operations, U.S. and international regulations can pose program risks indirectly through requirements levied on manufacturers and vendors of components and materials. For example, manufacturers can change their formulations to comply with new regulatory requirements. Such changes can require time-consuming and costly requalification certification for use in human spaceflight programs. The RRAC PC has implemented several strategies for proactively managing regulatory change to minimize potential adverse impacts to NASA Programs and facilities. This presentation highlights the lessons learned through establishing the RRAC PC, the process by which the RRAC PC monitors and distributes information about emerging regulatory requirements, and the cross

  3. Are good ideas enough? The impact of socio-economic and regulatory factors on GMO commercialisation.

    Science.gov (United States)

    Vàzquez-Salat, Núria

    2013-01-01

    In recent years scientific literature has seen an increase in publications describing new transgenic applications. Although technically-sound, these promising developments might not necessarily translate into products available to the consumer. This article highlights the impact of external factors on the commercial viability of Genetically Modified (GM) animals in the pharmaceutical and food sectors. Through the division of the production chain into three Policy Domains -Science, Market and Public- I present an overview of the broad range of regulatory and socio-economic components that impacts on the path towards commercialisation of GM animals. To further illustrate the unique combination of forces that influence each application, I provide an in-depth analysis of two real cases: GM rabbits producing human polyclonal antibodies (pharmaceutical case study) and GM cows producing recombinant human lactoferrin (food case study). The inability to generalise over the commercial success of a given transgenic application should encourage researchers to perform these type of exercises early in the R & D process. Furthermore, through the analysis of these case studies we can observe a change in the biopolitics of Genetically Modified Organisms (GMOs). Contrary to the GM plant biopolitical landscape, developing states such as China and Argentina are placing themselves as global leaders in GM animals. The pro-GM attitude of these states is likely to cause a shift in the political evolution of global GMO governance.

  4. Regulatory Impact Assessment: Its Current Status and Development Prospects in Russia

    Directory of Open Access Journals (Sweden)

    A V Minaev

    2011-12-01

    Full Text Available The article examines the procedure of Regulatory Impact Assessment (RIA, which is widely used in developed countries for elaborating and making state-level decisions and is new to Russia. The paper analyzes the origins and essential features of the RIA model applied abroad, reviews major methodological approaches to the preparation of statements on regulatory impact assessment. The study focuses on the Russian RIA model, describing its differences from the foreign analogues; the paper also analyzes the shortcomings of this model. A forecast for the development of RIA in Russia is made by the author.

  5. Public Rules on Private Schools: Measuring the Regulatory Impact of State Statutes and School Choice Programs

    Science.gov (United States)

    Catt, Andrew D.

    2014-01-01

    This report provides a framework for understanding the impacts of state government statutes regulating private schools, regulations distinct to a given school choice program, and any regulatory growth over a program's lifespan. Examining school choice programs in operation for at least a few years provides important context and comparisons for…

  6. INSTITUTE OF REGULATORY IMPACT ASSESSMENT DEVELOPMENT OF EURASION UNION ENACTMENTS IN THE FIELD OF PUBLIC PROCUREMENT

    Directory of Open Access Journals (Sweden)

    Elena Agapova

    2016-02-01

    Full Text Available Transformation of normative regulation of the public procurement system in the conditions of formation of the Eurasian Union is a very important tool in formation of common markets of goods and services. However, its impact on the development of entrepreneurial activity is ambiguous, which requires the development of regulatory impact assessment instruments of projects normative acts in the field of development of competition policy and procurement system of Eurasian Economy Union.

  7. Dynamical modeling and analysis of large cellular regulatory networks

    Science.gov (United States)

    Bérenguier, D.; Chaouiya, C.; Monteiro, P. T.; Naldi, A.; Remy, E.; Thieffry, D.; Tichit, L.

    2013-06-01

    The dynamical analysis of large biological regulatory networks requires the development of scalable methods for mathematical modeling. Following the approach initially introduced by Thomas, we formalize the interactions between the components of a network in terms of discrete variables, functions, and parameters. Model simulations result in directed graphs, called state transition graphs. We are particularly interested in reachability properties and asymptotic behaviors, which correspond to terminal strongly connected components (or "attractors") in the state transition graph. A well-known problem is the exponential increase of the size of state transition graphs with the number of network components, in particular when using the biologically realistic asynchronous updating assumption. To address this problem, we have developed several complementary methods enabling the analysis of the behavior of large and complex logical models: (i) the definition of transition priority classes to simplify the dynamics; (ii) a model reduction method preserving essential dynamical properties, (iii) a novel algorithm to compact state transition graphs and directly generate compressed representations, emphasizing relevant transient and asymptotic dynamical properties. The power of an approach combining these different methods is demonstrated by applying them to a recent multilevel logical model for the network controlling CD4+ T helper cell response to antigen presentation and to a dozen cytokines. This model accounts for the differentiation of canonical Th1 and Th2 lymphocytes, as well as of inflammatory Th17 and regulatory T cells, along with many hybrid subtypes. All these methods have been implemented into the software GINsim, which enables the definition, the analysis, and the simulation of logical regulatory graphs.

  8. Impact of Self-Regulatory Influences on Writing Course Attainment.

    Science.gov (United States)

    Zimmerman, Barry J.; Bandura, Albert

    1994-01-01

    Using path analysis, studied the role of self-efficacy beliefs concerning academic attainment and regulation of writing, academic goals, and self-standards in writing-course attainment of 95 college freshmen. Different facets of perceived self-efficacy played a key role in writing-course attainment. (SLD)

  9. Analysis of deterministic cyclic gene regulatory network models with delays

    CERN Document Server

    Ahsen, Mehmet Eren; Niculescu, Silviu-Iulian

    2015-01-01

    This brief examines a deterministic, ODE-based model for gene regulatory networks (GRN) that incorporates nonlinearities and time-delayed feedback. An introductory chapter provides some insights into molecular biology and GRNs. The mathematical tools necessary for studying the GRN model are then reviewed, in particular Hill functions and Schwarzian derivatives. One chapter is devoted to the analysis of GRNs under negative feedback with time delays and a special case of a homogenous GRN is considered. Asymptotic stability analysis of GRNs under positive feedback is then considered in a separate chapter, in which conditions leading to bi-stability are derived. Graduate and advanced undergraduate students and researchers in control engineering, applied mathematics, systems biology and synthetic biology will find this brief to be a clear and concise introduction to the modeling and analysis of GRNs.

  10. Regulatory control analysis and design for sewer systems

    DEFF Research Database (Denmark)

    Mollerup, Ane Loft; Mikkelsen, Peter Steen; Thornberg, Dines

    2015-01-01

    . To this end, four distinct modes of operation are identified (dry weather, filling, saturation and emptying) and for each of these the process gain matrix is found. Based on the gain matrices a controllability analysis is performed, to screen for suitable pairings between measurements and actuators......A systematic methodology for regulatory control analysis and design is adapted for sewer system operation and evaluated. The main challenge with adapting the methodology is the handling of the stochastic and transient nature of the rainfall disturbances, inherent to sewer system operation...... in the case study area of Copenhagen. The analysis effectively reduces the number of potential controlled variables, by considering the sensitivity of the measurements towards changes in the manipulated variables. Several potential pairings are generated and the best alternative is chosen for closed...

  11. Use of multi-criteria decision analysis in regulatory alternatives analysis: a case study of lead free solder.

    Science.gov (United States)

    Malloy, Timothy F; Sinsheimer, Peter J; Blake, Ann; Linkov, Igor

    2013-10-01

    Regulators are implementing new programs that require manufacturers of products containing certain chemicals of concern to identify, evaluate, and adopt viable, safer alternatives. Such programs raise the difficult question for policymakers and regulated businesses of which alternatives are "viable" and "safer." To address that question, these programs use "alternatives analysis," an emerging methodology that integrates issues of human health and environmental effects with technical feasibility and economic impact. Despite the central role that alternatives analysis plays in these programs, the methodology itself is neither well-developed nor tailored to application in regulatory settings. This study uses the case of Pb-based bar solder and its non-Pb-based alternatives to examine the application of 2 multi-criteria decision analysis (MCDA) methods to alternatives analysis: multi-attribute utility analysis and outranking. The article develops and evaluates an alternatives analysis methodology and supporting decision-analysis software for use in a regulatory context, using weighting of the relevant decision criteria generated from a stakeholder elicitation process. The analysis produced complete rankings of the alternatives, including identification of the relative contribution to the ranking of each of the highest level decision criteria such as human health impacts, technical feasibility, and economic feasibility. It also examined the effect of variation in data conventions, weighting, and decision frameworks on the outcome. The results indicate that MCDA can play a critical role in emerging prevention-based regulatory programs. Multi-criteria decision analysis methods offer a means for transparent, objective, and rigorous analysis of products and processes, providing regulators and stakeholders with a common baseline understanding of the relative performance of alternatives and the trade-offs they present.

  12. Decisions, Science, and Values: Crafting Regulatory Alternatives Analysis.

    Science.gov (United States)

    Malloy, Timothy; Blake, Ann; Linkov, Igor; Sinsheimer, Peter

    2015-12-01

    Emerging "prevention-based" approaches to chemical regulation seek to minimize the use of toxic chemicals by mandating or directly incentivizing the adoption of viable safer alternative chemicals or processes. California and Maine are beginning to implement such programs, requiring manufacturers of consumer products containing certain chemicals of concern to identify and evaluate potential safer alternatives. In the European Union, the REACH program imposes similar obligations on manufacturers of certain substances of very high concern. Effective prevention-based regulation requires regulatory alternatives analysis (RAA), a methodology for comparing and evaluating the regulated chemical or process and its alternatives across a range of relevant criteria. RAA has both public and private dimensions. To a significant degree, alternatives analysis is an aspect of product design; that is, the process by which private industry designs the goods it sells. Accordingly, an RAA method should reflect the attributes of well-crafted product design tools used by businesses. But RAA adds health and environmental objectives to the mix of concerns taken into account by the product designer. Moreover, as part of a prevention-based regulatory regime, it implicates important public values such as legitimacy, equity, public engagement, and accountability. Thus, an RAA should reflect both private standards and public values, and be evaluated against them. This article adopts that perspective, identifying an integrated set of design principles for RAA, and illustrating the application of those principles.

  13. Impact of the Serbian Banking Regulatory Framework Development on the Economic Growth of Serbia

    Directory of Open Access Journals (Sweden)

    Nenad Milojević

    2013-04-01

    Full Text Available The dynamic relationship between the banking regulatory framework and Basel capital standards, on the one side and economic growth and other macroeconomic indicators on the other side, attracts international academic and business circles for many years. Perceived from the Serbian perspective, the impact of the banking regulation development, or the Basel standards application, on economic growth is one of the most actual issues, especially since Serbia starting from December 31st 2011, began the Basel II application. The fact that the National Bank of Serbia and the Serbian commercial banks, gradually directed attention to more actual Basel III standard, further increasing the importance of the topic that this paper will be addressed. Quantitative and qualitative analyzes that were performed during the research presented in this paper indicate a significant potential for further positive effects, including economic growth, due to the implementation of Basel standards in Serbia. Positive results of application largely depend on adequate preparation, analysis and actions of all relevant parties in Basel standards implementation.

  14. Risk Analysis as Regulatory Science: Toward The Establishment of Standards.

    Science.gov (United States)

    Murakami, Michio

    2016-09-01

    Understanding how to establish standards is essential for risk communication and also provides perspectives for further study. In this paper, the concept of risk analysis as regulatory science for the establishment of standards is demonstrated through examples of standards for evacuation and provisional regulation values in foods and drinking water. Moreover, academic needs for further studies related to standards are extracted. The concepts of the traditional 'Standard I', which has a paternalistic orientation, and 'Standard II', established through stakeholder consensus, are then systemized by introducing the current status of the new standards-related movement that developed after the Fukushima nuclear power plant accident, and the perspectives of the standards are discussed. Preparation of standards on the basis of stakeholder consensus through intensive risk dialogue before a potential nuclear power plant accident is suggested to be a promising approach to ensure a safe society and enhance subjective well-being.

  15. Identification of conserved regulatory elements by comparative genome analysis

    Directory of Open Access Journals (Sweden)

    Jareborg Niclas

    2003-05-01

    Full Text Available Abstract Background For genes that have been successfully delineated within the human genome sequence, most regulatory sequences remain to be elucidated. The annotation and interpretation process requires additional data resources and significant improvements in computational methods for the detection of regulatory regions. One approach of growing popularity is based on the preferential conservation of functional sequences over the course of evolution by selective pressure, termed 'phylogenetic footprinting'. Mutations are more likely to be disruptive if they appear in functional sites, resulting in a measurable difference in evolution rates between functional and non-functional genomic segments. Results We have devised a flexible suite of methods for the identification and visualization of conserved transcription-factor-binding sites. The system reports those putative transcription-factor-binding sites that are both situated in conserved regions and located as pairs of sites in equivalent positions in alignments between two orthologous sequences. An underlying collection of metazoan transcription-factor-binding profiles was assembled to facilitate the study. This approach results in a significant improvement in the detection of transcription-factor-binding sites because of an increased signal-to-noise ratio, as demonstrated with two sets of promoter sequences. The method is implemented as a graphical web application, ConSite, which is at the disposal of the scientific community at http://www.phylofoot.org/. Conclusions Phylogenetic footprinting dramatically improves the predictive selectivity of bioinformatic approaches to the analysis of promoter sequences. ConSite delivers unparalleled performance using a novel database of high-quality binding models for metazoan transcription factors. With a dynamic interface, this bioinformatics tool provides broad access to promoter analysis with phylogenetic footprinting.

  16. Differential network analysis reveals dysfunctional regulatory networks in gastric carcinogenesis.

    Science.gov (United States)

    Cao, Mu-Shui; Liu, Bing-Ya; Dai, Wen-Tao; Zhou, Wei-Xin; Li, Yi-Xue; Li, Yuan-Yuan

    2015-01-01

    Gastric Carcinoma is one of the most common cancers in the world. A large number of differentially expressed genes have been identified as being associated with gastric cancer progression, however, little is known about the underlying regulatory mechanisms. To address this problem, we developed a differential networking approach that is characterized by including a nascent methodology, differential coexpression analysis (DCEA), and two novel quantitative methods for differential regulation analysis. We first applied DCEA to a gene expression dataset of gastric normal mucosa, adenoma and carcinoma samples to identify gene interconnection changes during cancer progression, based on which we inferred normal, adenoma, and carcinoma-specific gene regulation networks by using linear regression model. It was observed that cancer genes and drug targets were enriched in each network. To investigate the dynamic changes of gene regulation during carcinogenesis, we then designed two quantitative methods to prioritize differentially regulated genes (DRGs) and gene pairs or links (DRLs) between adjacent stages. It was found that known cancer genes and drug targets are significantly higher ranked. The top 4% normal vs. adenoma DRGs (36 genes) and top 6% adenoma vs. carcinoma DRGs (56 genes) proved to be worthy of further investigation to explore their association with gastric cancer. Out of the 16 DRGs involved in two top-10 DRG lists of normal vs. adenoma and adenoma vs. carcinoma comparisons, 15 have been reported to be gastric cancer or cancer related. Based on our inferred differential networking information and known signaling pathways, we generated testable hypotheses on the roles of GATA6, ESRRG and their signaling pathways in gastric carcinogenesis. Compared with established approaches which build genome-scale GRNs, or sub-networks around differentially expressed genes, the present one proved to be better at enriching cancer genes and drug targets, and prioritizing

  17. An investigation on the impacts of regulatory interventions on wind power expansion in generation planning

    Energy Technology Data Exchange (ETDEWEB)

    Alishahi, Ehsan [Faculty of Electrical and Computer Engineering, Tarbiat Modares University, Tehran, P.O. Box 14115-143 (Iran, Islamic Republic of); Moghaddam, Mohsen P., E-mail: parsa@modares.ac.ir [Faculty of Electrical and Computer Engineering, Tarbiat Modares University, Tehran, P.O. Box 14115-143 (Iran, Islamic Republic of); Sheikh-El-Eslami, Mohammad K. [Faculty of Electrical and Computer Engineering, Tarbiat Modares University, Tehran, P.O. Box 14115-143 (Iran, Islamic Republic of)

    2011-08-15

    Large integration of intermittent wind generation in power system has necessitated the inclusion of more innovative and sophisticated approaches in power system investment planning. This paper presents a novel framework on the basis of a combination of stochastic dynamic programming (SDP) algorithm and game theory to study the impacts of different regulatory interventions to promote wind power investment in generation expansion planning. In this study, regulatory policies include Feed-in-Tariff (FIT) incentive, quota and tradable green certificate. The intermittent nature and uncertainties of wind power generation will cause the investors encounter risk in their investment decisions. To overcome this problem, a novel model has been derived to study the regulatory impacts on wind generation expansion planning. In our approach, the probabilistic nature of wind generation is modeled. The model can calculate optimal investment strategies, in which the wind power uncertainty is included. This framework is implemented on a test system to illustrate the working of the proposed approach. The result shows that FITs are the most effective policy to encourage the rapid and sustained deployment of wind power. FITs can significantly reduce the risks of investing in renewable energy technologies and thus create conditions conducive to rapid market growth. - Highlights: > The impacts of regulatory policies to promote wind power investment are investigated. > These policies include Feed-in-Tariff (FIT), quota and tradable green certificate. > Result shows that FIT is an effective policy to motivate the rapid growth of wind power. > In quota, customers are forced to provide the quota decided by regulators from wind.

  18. Regulatory Mutations Impacting Antibiotic Susceptibility in an Established Staphylococcus aureus Biofilm.

    Science.gov (United States)

    Atwood, Danielle N; Beenken, Karen E; Lantz, Tamara L; Meeker, Daniel G; Lynn, William B; Mills, Weston B; Spencer, Horace J; Smeltzer, Mark S

    2016-01-11

    We previously determined the extent to which mutations of different Staphylococcus aureus regulatory loci impact biofilm formation as assessed under in vitro conditions. Here we extend these studies to determine the extent to which those regulatory loci that had the greatest effect on biofilm formation also impact antibiotic susceptibility. The experiments were done under in vitro and in vivo conditions using two clinical isolates of S. aureus (LAC and UAMS-1) and two functionally diverse antibiotics (daptomycin and ceftaroline). Mutation of the staphylococcal accessory regulator (sarA) or sigB was found to significantly increase susceptibilities to both antibiotics and in both strains in a manner that could not be explained by changes in the MICs. The impact of a mutation in sarA was comparable to that of a mutation in sigB and greater than the impact observed with any other mutant. These results suggest that therapeutic strategies targeting sarA and/or sigB have the greatest potential to facilitate the ability to overcome the intrinsic antibiotic resistance that defines S. aureus biofilm-associated infections.

  19. Identification of High-Impact cis-Regulatory Mutations Using Transcription Factor Specific Random Forest Models.

    Directory of Open Access Journals (Sweden)

    Dmitry Svetlichnyy

    2015-11-01

    Full Text Available Cancer genomes contain vast amounts of somatic mutations, many of which are passenger mutations not involved in oncogenesis. Whereas driver mutations in protein-coding genes can be distinguished from passenger mutations based on their recurrence, non-coding mutations are usually not recurrent at the same position. Therefore, it is still unclear how to identify cis-regulatory driver mutations, particularly when chromatin data from the same patient is not available, thus relying only on sequence and expression information. Here we use machine-learning methods to predict functional regulatory regions using sequence information alone, and compare the predicted activity of the mutated region with the reference sequence. This way we define the Predicted Regulatory Impact of a Mutation in an Enhancer (PRIME. We find that the recently identified driver mutation in the TAL1 enhancer has a high PRIME score, representing a "gain-of-target" for MYB, whereas the highly recurrent TERT promoter mutation has a surprisingly low PRIME score. We trained Random Forest models for 45 cancer-related transcription factors, and used these to score variations in the HeLa genome and somatic mutations across more than five hundred cancer genomes. Each model predicts only a small fraction of non-coding mutations with a potential impact on the function of the encompassing regulatory region. Nevertheless, as these few candidate driver mutations are often linked to gains in chromatin activity and gene expression, they may contribute to the oncogenic program by altering the expression levels of specific oncogenes and tumor suppressor genes.

  20. NASA's Agency-Wide Strategy for Environmental Regulatory Risk Analysis and Communication

    Science.gov (United States)

    Scroggins, Sharon; Duda, Kristen

    2008-01-01

    This viewgraph presentation gives an overview of NASA's risk analysis communication programs associated with changing environmental policies. The topics include: 1) NASA Program Transition; 2) Principal Center for Regulatory Risk Analysis and Communication (RRAC PC); and 3) Regulatory Tracking and Communication Process.

  1. Regulatory pathway analysis by high-throughput in situ hybridization.

    Directory of Open Access Journals (Sweden)

    Axel Visel

    2007-10-01

    Full Text Available Automated in situ hybridization enables the construction of comprehensive atlases of gene expression patterns in mammals. Such atlases can become Web-searchable digital expression maps of individual genes and thus offer an entryway to elucidate genetic interactions and signaling pathways. Towards this end, an atlas housing approximately 1,000 spatial gene expression patterns of the midgestation mouse embryo was generated. Patterns were textually annotated using a controlled vocabulary comprising >90 anatomical features. Hierarchical clustering of annotations was carried out using distance scores calculated from the similarity between pairs of patterns across all anatomical structures. This process ordered hundreds of complex expression patterns into a matrix that reflects the embryonic architecture and the relatedness of patterns of expression. Clustering yielded 12 distinct groups of expression patterns. Because of the similarity of expression patterns within a group, members of each group may be components of regulatory cascades. We focused on the group containing Pax6, an evolutionary conserved transcriptional master mediator of development. Seventeen of the 82 genes in this group showed a change of expression in the developing neocortex of Pax6-deficient embryos. Electromobility shift assays were used to test for the presence of Pax6-paired domain binding sites. This led to the identification of 12 genes not previously known as potential targets of Pax6 regulation. These findings suggest that cluster analysis of annotated gene expression patterns obtained by automated in situ hybridization is a novel approach for identifying components of signaling cascades.

  2. Investigating regulatory signatures of human autophagy related gene 5 (ATG5 through functional in silico analysis

    Directory of Open Access Journals (Sweden)

    Avni Vij

    2016-09-01

    Full Text Available Autophagy is an essential, homeostatic process which removes damaged cellular proteins and organelles for cellular renewal. ATG5, a part of E3 ubiquitin ligase-like complex (Atg12-Atg5/Atg16L1, is a key regulator involved in autophagosome formation - a crucial phase of autophagy. In this study, we used different in silico methods for comprehensive analysis of ATG5 to investigate its less explored regulatory activity. We have predicted various physico-chemical parameters and two possible transmembrane models that helped in exposing its functional regions. Twenty four PTM sites and 44 TFBS were identified which could be targeted to modulate the autophagy pathway. Furthermore, LD analysis identified 3 blocks of genotyped SNPs and 2 deleterious nsSNPs that may have damaging impact on protein function and thus could be employed for carrying genome-wide association studies. In conclusion, the information obtained in this study could be helpful for better understanding of regulatory roles of ATG5 and provides a base for its implication in population-based studies.

  3. Impact of the regulatory loci agr, sarA and sae of Staphylococcus aureus on the induction of alpha-toxin during device-related infection resolved by direct quantitative transcript analysis.

    Science.gov (United States)

    Goerke, C; Fluckiger, U; Steinhuber, A; Zimmerli, W; Wolz, C

    2001-06-01

    The cytotoxic alpha-toxin (encoded by hla) of Staphylococcus aureus is regulated by three loci, agr, sarA and sae, in vitro. Here, we assess the regulation of hla in a guinea pig model of device-related infection by quantifying RNAIII (the effector molecule of agr) and hla directly in exudates accumulating in infected devices without subculturing of the bacteria. LightCycler reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify the transcripts. Strains RN6390 and Newman expressed considerably smaller amounts of RNAIII in the guinea pig than during in vitro growth. The residual RNAIII expression decreased during the course of infection and was negatively correlated with bacterial densities. As with RNAIII, the highest hla expression was detected in both strains early in infection. Even in strain Newman, a weak hla producer in vitro, a pronounced expression of hla was observed during infection. Likewise, four S. aureus isolates from cystic fibrosis (CF) patients expressed Q1hla despite an inactive agr during device-related infection as in the CF lung. Mutation of agr and sarA in strain Newman and RN6390 had no consequence for hla expression in vivo. In contrast, the mutation in sae resulted in severe downregulation of hla in vitro as well as in vivo. In conclusion, S. aureus seems to be provided with regulatory circuits different from those characterized in vitro to ensure alpha-toxin synthesis during infections.

  4. A Meta-Analysis of the Regulatory Focus Nomological Network: Work-Related Antecedents and Consequences

    Science.gov (United States)

    Gorman, C. Allen; Meriac, John P.; Overstreet, Benjamin L.; Apodaca, Steven; McIntyre, Ashley L.; Park, Paul; Godbey, Jennifer N.

    2012-01-01

    Regulatory focus theory (Higgins, 1997, 1998) has received a great deal of recent attention in the organizational behavior literature. Despite the amount of new evidence surrounding regulatory focus and its relationships with other variables, a quantitative summary of this literature is lacking. The authors used meta-analysis to summarize…

  5. Regulatory network analysis of microRNAs and genes in imatinib-resistant chronic myeloid leukemia.

    Science.gov (United States)

    Soltani, Ismael; Gharbi, Hanen; Hassine, Islem Ben; Bouguerra, Ghada; Douzi, Kais; Teber, Mouheb; Abbes, Salem; Menif, Samia

    2016-09-16

    Targeted therapy in the form of selective breakpoint cluster region-abelson (BCR/ABL) tyrosine kinase inhibitor (imatinib mesylate) has successfully been introduced in the treatment of the chronic myeloid leukemia (CML). However, acquired resistance against imatinib mesylate (IM) has been reported in nearly half of patients and has been recognized as major issue in clinical practice. Multiple resistance genes and microRNAs (miRNAs) are thought to be involved in the IM resistance process. These resistance genes and miRNAs tend to interact with each other through a regulatory network. Therefore, it is crucial to study the impact of these interactions in the IM resistance process. The present study focused on miRNA and gene network analysis in order to elucidate the role of interacting elements and to understand their functional contribution in therapeutic failure. Unlike previous studies which were centered only on genes or miRNAs, the prime focus of the present study was on relationships. To this end, three regulatory networks including differentially expressed, related, and global networks were constructed and analyzed in search of similarities and differences. Regulatory associations between miRNAs and their target genes, transcription factors and miRNAs, as well as miRNAs and their host genes were also macroscopically investigated. Certain key pathways in the three networks, especially in the differentially expressed network, were featured. The differentially expressed network emerged as a fault map of IM-resistant CML. Theoretically, the IM resistance process could be prevented by correcting the included errors. The present network-based approach to study resistance miRNAs and genes might help in understanding the molecular mechanisms of IM resistance in CML as well as in the improvement of CML therapy.

  6. Zooming in on regulatory intermediaries: The impact of non-state regulators on sustainable construction practice

    NARCIS (Netherlands)

    van der Heijden, J.

    2014-01-01

    Levi-Faur and Starobin (2013) have recently drawn our attention to the important role of regulatory intermediates in contemporary regulatory regimes. Among others they argue that regulatory intermediaries come in a wide variety of appearances, and that these can influence the outcomes of regulatory

  7. CONSTRUCTION AND ANALYSIS OF IPBR/XYLS HYBRID REGULATORY PROTEINS

    Science.gov (United States)

    IpbR and XylS are related regulatory proteins (having 56% identity). IpbR responds to isopropylbenzene as well as to a variety of hydrophobic chemicals to activate expression of the isopropylbenzene catabolic pathway operon of pRE4 from ipbOP. XylS responds to substituted benzoic...

  8. Genomic analysis of the hierarchical structure of regulatory networks

    Science.gov (United States)

    Yu, Haiyuan; Gerstein, Mark

    2006-01-01

    A fundamental question in biology is how the cell uses transcription factors (TFs) to coordinate the expression of thousands of genes in response to various stimuli. The relationships between TFs and their target genes can be modeled in terms of directed regulatory networks. These relationships, in turn, can be readily compared with commonplace “chain-of-command” structures in social networks, which have characteristic hierarchical layouts. Here, we develop algorithms for identifying generalized hierarchies (allowing for various loop structures) and use these approaches to illuminate extensive pyramid-shaped hierarchical structures existing in the regulatory networks of representative prokaryotes (Escherichia coli) and eukaryotes (Saccharomyces cerevisiae), with most TFs at the bottom levels and only a few master TFs on top. These masters are situated near the center of the protein–protein interaction network, a different type of network from the regulatory one, and they receive most of the input for the whole regulatory hierarchy through protein interactions. Moreover, they have maximal influence over other genes, in terms of affecting expression-level changes. Surprisingly, however, TFs at the bottom of the regulatory hierarchy are more essential to the viability of the cell. Finally, one might think master TFs achieve their wide influence through directly regulating many targets, but TFs with most direct targets are in the middle of the hierarchy. We find, in fact, that these midlevel TFs are “control bottlenecks” in the hierarchy, and this great degree of control for “middle managers” has parallels in efficient social structures in various corporate and governmental settings. PMID:17003135

  9. 78 FR 27235 - Technical Guidance for Assessing Environmental Justice in Regulatory Analysis

    Science.gov (United States)

    2013-05-09

    ..., Office of Policy, National Center for Environmental Economics, Mail code 1809T, Environmental Protection... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL PROTECTION AGENCY Technical Guidance for Assessing Environmental Justice in Regulatory Analysis...

  10. Impact of Regulatory Interventions to Reduce Intake of Artificial Trans–Fatty Acids: A Systematic Review

    Science.gov (United States)

    Almíron-Roig, Eva; Monsivais, Pablo; Jebb, Susan A.; Benjamin Neelon, Sara E.; Griffin, Simon J.; Ogilvie, David B.

    2015-01-01

    We examined the impact of regulatory action to reduce levels of artificial trans–fatty acids (TFAs) in food. We searched Medline, Embase, ISI Web of Knowledge, and EconLit (January 1980 to December 2012) for studies related to government regulation of food- or diet-related health behaviors from which we extracted the subsample of legislative initiatives to reduce artificial TFAs in food. We screened 38 162 articles and identified 14 studies that examined artificial TFA controls limiting permitted levels or mandating labeling. These measures achieved good compliance, with evidence of appropriate reformulation. Regulations grounded on maximum limits and mandated labeling can lead to reductions in actual and reported TFAs in food and appear to encourage food producers to reformulate their products. PMID:25602897

  11. Impact of regulatory interventions to reduce intake of artificial trans-fatty acids: a systematic review.

    Science.gov (United States)

    Hendry, Vivien L; Almíron-Roig, Eva; Monsivais, Pablo; Jebb, Susan A; Neelon, Sara E Benjamin; Griffin, Simon J; Ogilvie, David B

    2015-03-01

    We examined the impact of regulatory action to reduce levels of artificial trans-fatty acids (TFAs) in food. We searched Medline, Embase, ISI Web of Knowledge, and EconLit (January 1980 to December 2012) for studies related to government regulation of food- or diet-related health behaviors from which we extracted the subsample of legislative initiatives to reduce artificial TFAs in food. We screened 38 162 articles and identified 14 studies that examined artificial TFA controls limiting permitted levels or mandating labeling. These measures achieved good compliance, with evidence of appropriate reformulation. Regulations grounded on maximum limits and mandated labeling can lead to reductions in actual and reported TFAs in food and appear to encourage food producers to reformulate their products.

  12. Analysis of regulatory structure for a potential fusion reactor industry

    Energy Technology Data Exchange (ETDEWEB)

    1981-03-01

    The report is divided into eight sections. The preface describes the authors of the report, the methodology used in its preparation, and some basic legal terms. The summary describes the principal features of the proposed regulatory system and also includes two flow charts comparing our model with present NRC practices and a summary table briefly outlining the reasoning behind our recommendations. The main body of the report is divided into six sections. This part of the report discusses the existing federal and state programs for regulating electric energy, describes NRC operations and the criticisms of that agency, discusses the features of our proposed regulatory model, recommends certain steps for implementing the proposed model, and states the conclusions of the report.

  13. Dynamical Analysis of Protein Regulatory Network in Budding Yeast Nucleus

    Institute of Scientific and Technical Information of China (English)

    LI Fang-Ting; JIA Xun

    2006-01-01

    @@ Recent progresses in the protein regulatory network of budding yeast Saccharomyces cerevisiae have provided a global picture of its protein network for further dynamical research. We simplify and modularize the protein regulatory networks in yeast nucleus, and study the dynamical properties of the core 37-node network by a Boolean network model, especially the evolution steps and final fixed points. Our simulation results show that the number of fixed points N(k) for a given size of the attraction basin k obeys a power-law distribution N(k)∝k-2.024. The yeast network is more similar to a scale-free network than a random network in the above dynamical properties.

  14. Analysis of regulatory-ethical framework of clinical trials

    OpenAIRE

    Milošević-Georgiev Andrijana; Krajnović Dušanka; Milovanović Srđan; Ignjatović Svetlana; Đurić Dušan; Marinković Valentina

    2013-01-01

    Introduction. Every clinical trial has to meet all ethical criteria in addition to the scientific ones. The basic ethical principles in the clinical trials are the following: nonmaleficence, beneficence, respect for autonomy and the principle of justice. Objective. The aim of the study was to analyze clinical cases with the outcomes leading to the changes in regulatory­ethical framework related to the clinical trials, as well as the outcomes of key clinical trials that influenced the in...

  15. Regulatory focus and work-related outcomes: a review and meta-analysis.

    Science.gov (United States)

    Lanaj, Klodiana; Chang, Chu-Hsiang Daisy; Johnson, Russell E

    2012-09-01

    Regulatory focus theory (Higgins, 1997) has received growing attention in organizational psychology, necessitating a quantitative review that synthesizes its effects on important criteria. In addition, there is need for theoretical integration of regulatory focus theory with personality research. Theoretical integration is particularly relevant, since personality traits and dispositions are distal factors that are unlikely to have direct effects on work behaviors, yet they may have indirect effects via regulatory focus. The current meta-analysis introduces an integrative framework in which the effects of personality on work behaviors are best understood when considered in conjunction with more proximal motivational processes such as regulatory focus. Using a distal-proximal approach, we identify personality antecedents and work-related consequences of regulatory foci in a framework that considers both general and work-specific regulatory foci as proximal motivational processes. We present meta-analytic results for relations of regulatory focus with its antecedents (approach and avoid temperaments, conscientiousness, openness to experience, agreeableness, self-esteem, and self-efficacy) and its consequences (work behaviors and attitudes). In addition to estimates of bivariate relationships, we support a meta-analytic path model in which distal personality traits relate to work behaviors via the mediating effects of general and work-specific regulatory focus. Results from tests of incremental and relative validity indicated that regulatory foci predict unique variance in work behaviors after controlling for established personality, motivation, and attitudinal predictors. Consistent with regulatory focus theory and our integrative theoretical framework, regulatory focus has meaningful relations with work outcomes and is not redundant with other individual difference variables.

  16. Side Impact Regulatory Trends, Crash Environment and Injury Risk in the USA.

    Science.gov (United States)

    Prasad, Priya; Dalmotas, Dainius; Chouinard, Aline

    2015-11-01

    Light duty vehicles in the US are designed to meet and exceed regulatory standards, self-imposed industry agreements and safety rating tests conducted by NHTSA and IIHS. The evolution of side impact regulation in the US from 1973 to 2015 is discussed in the paper along with two key industry agreements in 2003 affecting design of restraint systems and structures for side impact protection. A combination of all the above influences shows that vehicles in the US are being designed to more demanding and comprehensive requirements than in any other region of the world. The crash environment in the US related to side impacts was defined based on data in the nationally representative crash database NASS. Crash environment factors, including the distribution of cars, light trucks and vans (LTV's), and medium-to-heavy vehicles (MHV's) in the fleet, and the frequency of their interactions with one another in side impacts, were considered. Other factors like, crash severity in terms of closing velocity between two vehicles involved in crash, gender and age of involved drivers in two-vehicle and single vehicle crashes, were also examined. Injury risks in side impacts to drivers and passengers were determined in various circumstances such as near-side, far-side, and single vehicle crashes as a function of crash severity, in terms of estimated closing speed or lateral delta-V. Also injury risks in different pairs of striking and struck cars and LTV's, were estimated. A logistic regression model for studying injury risks in two vehicle crashes was developed. The risk factors included in the model include case and striking vehicles, consisting of cars, SUV's, vans, and pickup trucks, delta-V, damage extent, occupant proximity to the impact side, age and gender of the occupant, and belt use. Results show that car occupants make up the vast majority of serious-to-fatally injured occupants. Injury rates of car occupants in two-vehicle collision are highest when the car is struck by a

  17. Porcine tissue-specific regulatory networks derived from meta-analysis of the transcriptome.

    Science.gov (United States)

    Pérez-Montarelo, Dafne; Hudson, Nicholas J; Fernández, Ana I; Ramayo-Caldas, Yuliaxis; Dalrymple, Brian P; Reverter, Antonio

    2012-01-01

    The processes that drive tissue identity and differentiation remain unclear for most tissue types. So are the gene networks and transcription factors (TF) responsible for the differential structure and function of each particular tissue, and this is particularly true for non model species with incomplete genomic resources. To better understand the regulation of genes responsible for tissue identity in pigs, we have inferred regulatory networks from a meta-analysis of 20 gene expression studies spanning 480 Porcine Affymetrix chips for 134 experimental conditions on 27 distinct tissues. We developed a mixed-model normalization approach with a covariance structure that accommodated the disparity in the origin of the individual studies, and obtained the normalized expression of 12,320 genes across the 27 tissues. Using this resource, we constructed a network, based on the co-expression patterns of 1,072 TF and 1,232 tissue specific genes. The resulting network is consistent with the known biology of tissue development. Within the network, genes clustered by tissue and tissues clustered by site of embryonic origin. These clusters were significantly enriched for genes annotated in key relevant biological processes and confirm gene functions and interactions from the literature. We implemented a Regulatory Impact Factor (RIF) metric to identify the key regulators in skeletal muscle and tissues from the central nervous systems. The normalization of the meta-analysis, the inference of the gene co-expression network and the RIF metric, operated synergistically towards a successful search for tissue-specific regulators. Novel among these findings are evidence suggesting a novel key role of ERCC3 as a muscle regulator. Together, our results recapitulate the known biology behind tissue specificity and provide new valuable insights in a less studied but valuable model species.

  18. Porcine tissue-specific regulatory networks derived from meta-analysis of the transcriptome.

    Directory of Open Access Journals (Sweden)

    Dafne Pérez-Montarelo

    Full Text Available The processes that drive tissue identity and differentiation remain unclear for most tissue types. So are the gene networks and transcription factors (TF responsible for the differential structure and function of each particular tissue, and this is particularly true for non model species with incomplete genomic resources. To better understand the regulation of genes responsible for tissue identity in pigs, we have inferred regulatory networks from a meta-analysis of 20 gene expression studies spanning 480 Porcine Affymetrix chips for 134 experimental conditions on 27 distinct tissues. We developed a mixed-model normalization approach with a covariance structure that accommodated the disparity in the origin of the individual studies, and obtained the normalized expression of 12,320 genes across the 27 tissues. Using this resource, we constructed a network, based on the co-expression patterns of 1,072 TF and 1,232 tissue specific genes. The resulting network is consistent with the known biology of tissue development. Within the network, genes clustered by tissue and tissues clustered by site of embryonic origin. These clusters were significantly enriched for genes annotated in key relevant biological processes and confirm gene functions and interactions from the literature. We implemented a Regulatory Impact Factor (RIF metric to identify the key regulators in skeletal muscle and tissues from the central nervous systems. The normalization of the meta-analysis, the inference of the gene co-expression network and the RIF metric, operated synergistically towards a successful search for tissue-specific regulators. Novel among these findings are evidence suggesting a novel key role of ERCC3 as a muscle regulator. Together, our results recapitulate the known biology behind tissue specificity and provide new valuable insights in a less studied but valuable model species.

  19. The Pro-Cyclical Impact of Basel III Regulatory Capital on Bank Capital Risk

    OpenAIRE

    Song, Guoxiang

    2014-01-01

    To raise the quality of regulatory capital, Basel III capital rules recognize unrealized gains and losses on all available-for-sale (AFS) securities in Common Equity Tier 1 Capital (CET1). However, by examining the correlations between U.S. GDP growth rate, interest rates and regulatory capital ratios computed using Basel III regulatory capital definition for six U.S. global systemically important banks (G-SIBs) since 2007, this chapter finds that Basel III regulatory capital will enhance the...

  20. Discovery and analysis of evolutionarily conserved intronic splicing regulatory elements.

    Directory of Open Access Journals (Sweden)

    Gene W Yeo

    2007-05-01

    Full Text Available Knowledge of the functional cis-regulatory elements that regulate constitutive and alternative pre-mRNA splicing is fundamental for biology and medicine. Here we undertook a genome-wide comparative genomics approach using available mammalian genomes to identify conserved intronic splicing regulatory elements (ISREs. Our approach yielded 314 ISREs, and insertions of ~70 ISREs between competing splice sites demonstrated that 84% of ISREs altered 5' and 94% altered 3' splice site choice in human cells. Consistent with our experiments, comparisons of ISREs to known splicing regulatory elements revealed that 40%-45% of ISREs might have dual roles as exonic splicing silencers. Supporting a role for ISREs in alternative splicing, we found that 30%-50% of ISREs were enriched near alternatively spliced (AS exons, and included almost all known binding sites of tissue-specific alternative splicing factors. Further, we observed that genes harboring ISRE-proximal exons have biases for tissue expression and molecular functions that are ISRE-specific. Finally, we discovered that for Nova1, neuronal PTB, hnRNP C, and FOX1, the most frequently occurring ISRE proximal to an alternative conserved exon in the splicing factor strongly resembled its own known RNA binding site, suggesting a novel application of ISRE density and the propensity for splicing factors to auto-regulate to associate RNA binding sites to splicing factors. Our results demonstrate that ISREs are crucial building blocks in understanding general and tissue-specific AS regulation and the biological pathways and functions regulated by these AS events.

  1. Engineering assessment and feasibility study of Chattanooga Shale as a future source of uranium. [Environmental, socioeconomic, regulatory impacts

    Energy Technology Data Exchange (ETDEWEB)

    1978-06-01

    This volume characterizes the major baseline environmental features of the Chattanooga Shale study and projects the effects which may accrue from implementation of a large scale development to recover uranium from the shale. Environmental, socioeconomic, and regulatory impacts are covered. The prototype project is located in Dekalb County in Tennessee. (DLC)

  2. Structural Analysis of the Global Multimedia Scenario: Technological, Market, Environmental, and Regulatory Issues.

    Science.gov (United States)

    Nicolo, Enrico; Sapio, Bartolomeo

    1996-01-01

    Presents a strategic evaluation of the global multimedia scenario, considering both stand-alone workstations and distributed multimedia in the worldwide interactive network, including educational databases on the Internet. Discusses 50 technological, market, environmental, and regulatory factors and estimates their impacts on each other using WISE…

  3. Association analysis identifies ZNF750 regulatory variants in psoriasis

    Directory of Open Access Journals (Sweden)

    Birnbaum Ramon Y

    2011-12-01

    Full Text Available Abstract Background Mutations in the ZNF750 promoter and coding regions have been previously associated with Mendelian forms of psoriasis and psoriasiform dermatitis. ZNF750 encodes a putative zinc finger transcription factor that is highly expressed in keratinocytes and represents a candidate psoriasis gene. Methods We examined whether ZNF750 variants were associated with psoriasis in a large case-control population. We sequenced the promoter and exon regions of ZNF750 in 716 Caucasian psoriasis cases and 397 Caucasian controls. Results We identified a total of 47 variants, including 38 rare variants of which 35 were novel. Association testing identified two ZNF750 haplotypes associated with psoriasis (p ZNF750 promoter and 5' UTR variants displayed a 35-55% reduction of ZNF750 promoter activity, consistent with the promoter activity reduction seen in a Mendelian psoriasis family with a ZNF750 promoter variant. However, the rare promoter and 5' UTR variants identified in this study did not strictly segregate with the psoriasis phenotype within families. Conclusions Two haplotypes of ZNF750 and rare 5' regulatory variants of ZNF750 were found to be associated with psoriasis. These rare 5' regulatory variants, though not causal, might serve as a genetic modifier of psoriasis.

  4. Trypanosoma cruzi Experimental Infection Impacts on the Thymic Regulatory T Cell Compartment

    Science.gov (United States)

    González, Florencia Belén; Calmon-Hamaty, Flavia; Nô Seara Cordeiro, Synara; Fernández Bussy, Rodrigo; Spinelli, Silvana Virginia; D'Attilio, Luciano; Bottasso, Oscar; Savino, Wilson; Cotta-de-Almeida, Vinícius; Villar, Silvina Raquel; Pérez, Ana Rosa

    2016-01-01

    The dynamics of regulatory T cells in the course of Trypanosoma cruzi infection is still debated. We previously demonstrated that acute murine T. cruzi infection results in an impaired peripheral CD4+Foxp3+ T cell differentiation due to the acquisition of an abnormal Th1-like phenotype and altered functional features, negatively impacting on the course of infection. Moreover, T. cruzi infection induces an intense thymic atrophy. As known, the thymus is the primary lymphoid organ in which thymic-derived regulatory T cells, known as tTregs, differentiate. Considering the lack of available data about the effect of T. cruzi infection upon tTregs, we examined tTreg dynamics during the course of disease. We confirmed that T. cruzi infection induces a marked loss of tTreg cell number associated to cell precursor exhaustion, partially avoided by glucocorticoid ablation- and IL-2 survival factor depletion. At the same time, tTregs accumulate within the CD4 single-positive compartment, exhibiting an increased Ki-67/Annexin V ratio compared to controls. Moreover, tTregs enhance after the infection the expression of signature markers (CD25, CD62L and GITR) and they also display alterations in the expression of migration-associated molecules (α chains of VLAs and chemokine receptors) such as functional fibronectin-driven migratory disturbance. Taken together, we provide data demonstrating profound alterations in tTreg compartment during acute murine T. cruzi infection, denoting that their homeostasis is significantly affected. The evident loss of tTreg cell number may compromise the composition of tTreg peripheral pool, and such sustained alteration over time may be partially related to the immune dysregulation observed in the chronic phase of the disease. PMID:26745276

  5. Upstream petroleum licensing: a comparative approach on regulatory frameworks and economic impacts

    Energy Technology Data Exchange (ETDEWEB)

    Cunha, Amanda L. [Felsberg e Associados, Sao Paulo, SP (Brazil)

    2008-07-01

    The recent discoveries hit in the pre-salt area, such as Tupi, Jupiter, Bem-te-vi and Carioca may place Brazil amongst the largest oil producers in the world. As a result, the Brazilian regulatory framework, which was originally envisaged in a scenario of higher exploration risk, has been under heavy public scrutiny. The Brazilian Government has already taken the first steps towards substantial changes in the country's contracting model for upstream activities. By means of Resolution No. 6/2007, the National Council for Energy Policy ('CNPE') not only determined the removal of 41 blocks with sub-salt geology from the ANP 9 Th Bid Round, but also stressed the need for a different regime for E and P activities in the country's continental shelf. At this moment, there is a great deal of controversy on the contracting model to be adopted, mainly whether the concession model should be maintained, but subject to higher levels of government take, or a production sharing model should apply. This paper goes through the evolution of international oil agreements, from early concessions to modern agreements. A special emphasis is placed on concession/license regimes as well as on production sharing agreements (PSAs). Besides drawing a comparative line between such models, this article assesses their economic impacts and whether the regulatory framework currently in force in Brazil is suitable for a scenario of lower risk, showing that any desired level of regulation may be achieved in the context of a PSA as easily as in a exclusive concession. (author)

  6. Development of default uncertainties for the value/benefit attributes in the regulatory analysis technical evaluation handbook

    Energy Technology Data Exchange (ETDEWEB)

    Gallucci, Raymond H.V., E-mail: Ray.Gallucci@nrc.gov

    2016-08-15

    Highlights: • Uncertainties for values/benefits. • Upper bound four times higher than mean. • Distributional histograms. - Abstract: NUREG/BR-0184, Regulatory Analysis Technical Evaluation (RATE) Handbook, was produced in 1997 as an update to the original NUREG/CR-3568, A Handbook for Value-Impact Assessment (1983). Both documents, especially the later RATE Handbook, have been used extensively by the USNRC and its contractors not only for regulatory analyses to support backfit considerations but also for similar applications, such as Severe Accident Management Alternative (SAMA) analyses as part of license renewals. While both provided high-level guidance on the performance of uncertainty analyses for the various value/benefit attributes, detailed quantification was not of prime interest at the times of the Handbooks’ development, defaulting only to best estimates with low and high bounds on these attributes. As the USNRC examines the possibility of updating the RATE Handbook, renewed interest in a more quantitative approach to uncertainty analyses for the attributes has surfaced. As the result of an effort to enhance the RATE Handbook to permit at least default uncertainty analyses for the value/benefit attributes, it has proven feasible to assign default uncertainties in terms of 95th %ile upper bounds (and absolute lower bounds) on the five dominant value/benefit attributes, and their sum, when performing a regulatory analysis via the RATE Handbook. Appropriate default lower bounds of zero (no value/benefit) and an upper bound (95th %ile) that is four times higher than the mean (for individual value/benefit attributes) or three times higher (for their summation) can be recommended. Distributions in the form of histograms on the summed value/benefit attributes are also provided which could be combined, after appropriate scaling and most likely via simulation, with their counterpart(s) from the impact/cost analysis to yield a final distribution on the net

  7. Economic Analysis of the Radio Spectrum for Regulatory Purposes

    DEFF Research Database (Denmark)

    Falch, Morten; Tadayoni, Reza

    will be necessary to ensure efficient and harmonised patterns of usage across countries. In this respect an assessment of the economic value of various applications is an important input. This paper measures the economic value in terms of contribution to GDP. We use this approach, as it is very difficult to assess...... not a purely technical matter. Economic considerations must be taken into account as well. A free market approach may be suitable for assigning frequency bands between operators within the same application, but is less suitable for allocation between various applications. Here regulatory intervention...... the user value as long as there is no market for trade in frequency licenses. The economic value of the radio spectrum has been calculated for six different service applications (fixed links, Maritime and aeronautic applications, broadcasting services, mobile services, private mobile radio network services...

  8. A regulatory perspective on the radiological impact of NORM industries: the case of the Spanish phosphate industry

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Talavera, M., E-mail: mgtm@csn.e [Consejo de Seguridad Nuclear (CSN), Justo Dorado, 11, E-28040 Madrid (Spain); Matarranz, J.L.M.; Salas, R.; Ramos, L. [Consejo de Seguridad Nuclear (CSN), Justo Dorado, 11, E-28040 Madrid (Spain)

    2011-01-15

    Radioactive and chemical risks coexist in NORM industries although they are usually addressed separately by regulations. The European Union (EU) has developed extensive legislation concerning both matters, which has been diversely reflected in national policies. We consider the case of the Spanish phosphate industry and analyse to which extent regulatory mandates have reduced the historical and ongoing radiological impact on the environment of phosphate facilities. Although no specific radiological constraints on effluent monitoring and release or on waste disposal have yet been imposed on NORM industries in Spain, other environmental regulations have achieved a substantial reduction on the phosphate industry impact. Nevertheless, a more efficient control could be established by eliminating the current conceptual and practical separation of chemical and radioactive risks in NORM industries. We highlight research needs to accomplish so and propose shorter-term measures that require active cooperation among the regulatory bodies involved. - Research highlights: {yields} The radiological impact of the Spanish phosphate industry has substantially decreased as a side result of environmental regulations on chemical pollution.{yields} A more efficient control of NORM industries could be established by eliminating the current conceptual and practical separation of chemical and radioactive risks.{yields} Further research is needed on how interactions between radiation and chemicals might affect regulatory limits and on a systematic way to input stakeholder preferences in MCDA.{yields} On shorter-term, administrative measures that require active cooperation among the regulatory bodies involved can be taken.

  9. Impact of Transcription Units rearrangement on the evolution of the regulatory network of gamma-proteobacteria

    Directory of Open Access Journals (Sweden)

    Vasconcelos Ana

    2008-03-01

    Full Text Available Abstract Background In the past years, several studies begun to unravel the structure, dynamical properties, and evolution of transcriptional regulatory networks. However, even those comparative studies that focus on a group of closely related organisms are limited by the rather scarce knowledge on regulatory interactions outside a few model organisms, such as E. coli among the prokaryotes. Results In this paper we used the information annotated in Tractor_DB (a database of regulatory networks in gamma-proteobacteria to calculate a normalized Site Orthology Score (SOS that quantifies the conservation of a regulatory link across thirty genomes of this subclass. Then we used this SOS to assess how regulatory connections have evolved in this group, and how the variation of basic regulatory connection is reflected on the structure of the chromosome. We found that individual regulatory interactions shift between different organisms, a process that may be described as rewiring the network. At this evolutionary scale (the gamma-proteobacteria subclass this rewiring process may be an important source of variation of regulatory incoming interactions for individual networks. We also noticed that the regulatory links that form feed forward motifs are conserved in a better correlated manner than triads of random regulatory interactions or pairs of co-regulated genes. Furthermore, the rewiring process that takes place at the most basic level of the regulatory network may be linked to rearrangements of genetic material within bacterial chromosomes, which change the structure of Transcription Units and therefore the regulatory connections between Transcription Factors and structural genes. Conclusion The rearrangements that occur in bacterial chromosomes-mostly inversion or horizontal gene transfer events – are important sources of variation of gene regulation at this evolutionary scale.

  10. Nicotine exposure and transgenerational impact: a prospective study on small regulatory microRNAs.

    Science.gov (United States)

    Taki, Faten A; Pan, Xiaoping; Lee, Myon-Hee; Zhang, Baohong

    2014-12-17

    Early developmental stages are highly sensitive to stress and it has been reported that pre-conditioning with tobacco smoking during adolescence predisposes those youngsters to become smokers as adults. However, the molecular mechanisms of nicotine-induced transgenerational consequences are unknown. In this study, we genome-widely investigated the impact of nicotine exposure on small regulatory microRNAs (miRNAs) and its implication on health disorders at a transgenerational aspect. Our results demonstrate that nicotine exposure, even at the low dose, affected the global expression profiles of miRNAs not only in the treated worms (F0 parent generation) but also in two subsequent generations (F1 and F2, children and grandchildren). Some miRNAs were commonly affected by nicotine across two or more generations while others were specific to one. The general miRNA patterns followed a "two-hit" model as a function of nicotine exposure and abstinence. Target prediction and pathway enrichment analyses showed daf-4, daf-1, fos-1, cmk-1, and unc-30 to be potential effectors of nicotine addiction. These genes are involved in physiological states and phenotypes that paralleled previously published nicotine induced behavior. Our study offered new insights and further awareness on the transgenerational effects of nicotine exposed during the vulnerable post-embryonic stages, and identified new biomarkers for nicotine addiction.

  11. IDO expression in brain tumors increases the recruitment of regulatory T cells and negatively impacts survival.

    Science.gov (United States)

    Wainwright, Derek A; Balyasnikova, Irina V; Chang, Alan L; Ahmed, Atique U; Moon, Kyung-Sub; Auffinger, Brenda; Tobias, Alex L; Han, Yu; Lesniak, Maciej S

    2012-11-15

    Glioblastoma multiforme (GBM) is an aggressive adult brain tumor with a poor prognosis. One hallmark of GBM is the accumulation of immunosuppressive and tumor-promoting CD4(+)FoxP3(+)GITR(+) regulatory T cells (Tregs). Here, we investigated the role of indoleamine 2,3 dioxygenase (IDO) in brain tumors and the impact on Treg recruitment. To determine the clinical relevance of IDO expression in brain tumors, we first correlated patient survival to the level of IDO expression from resected glioma specimens. We also used novel orthotopic and transgenic models of glioma to study how IDO affects Tregs. The impact of tumor-derived and peripheral IDO expression on Treg recruitment, GITR expression, and long-term survival was determined. Downregulated IDO expression in glioma predicted a significantly better prognosis in patients. Coincidently, both IDO-competent and deficient mice showed a survival advantage bearing IDO-deficient brain tumors, when compared with IDO-competent brain tumors. Moreover, IDO deficiency was associated with a significant decrease in brain-resident Tregs, both in orthotopic and transgenic mouse glioma models. IDO deficiency was also associated with lower GITR expression levels on Tregs. Interestingly, the long-term survival advantage conferred by IDO deficiency was lost in T-cell-deficient mice. These clinical and preclinical data confirm that IDO expression increases the recruitment of immunosuppressive Tregs that lead to tumor outgrowth. In contrast, IDO deficiency decreases Treg recruitment and enhances T-cell-mediated tumor rejection. Thus, the data suggest a critical role for IDO-mediated immunosuppression in glioma and support the continued investigation of IDO-Treg interactions in the context of brain tumors. ©2012 AACR.

  12. Impact of Safety-Related Regulatory Action on Clinical Practice A Systematic Review

    NARCIS (Netherlands)

    Piening, Sigrid; Haaijer-Ruskamp, Flora M.; de Vries, Jonie T. N.; van der Elst, Menno E.; de Graeff, Pieter A.; Straus, Sabine M. J. M.; Mol, Peter G. M.

    2012-01-01

    Background: After market approval, new serious safety issues are regularly identified for drugs that lead to regulatory action to inform healthcare professionals. However, the effectiveness of these safety-related regulatory actions is under question. We currently lack a comprehensive overview of th

  13. The impact of regulatory fit on performance in an inattentional blindness paradigm.

    Science.gov (United States)

    Memmert, Daniel; Unkelbach, Christian; Ganns, Steffen

    2010-01-01

    When people's self-regulatory focus (e.g., focus on gains vs. focus on avoiding losses) matches environmental demands (e.g., search gains vs. avoid losses), Regulatory Focus Theory predicts performance improvements because of "regulatory fit" (Higgins, 1997). In this article, the authors investigate attentional differences due to regulatory fit as a possible cause for changes in performance, using an inattentional blindness paradigm. Participants counted passes in a basketball game, during which an unexpected object appears (in the present study, a gorilla). We measured participants' chronic self-regulatory focus with a standardized questionnaire and experimentally manipulated their situational focus. If experimental focus fitted chronic focus, more participants detected the unexpected object compared to the nonfit conditions, suggesting that fit led to a broader scope of attention. The data are discussed in relation to other cognitive consequences of regulatory fit, and how these might explain performance differences in a wide range of tasks that do not directly follow from Regulatory Focus Theory.

  14. Impact of regulatory measures on antipsychotics drug consumption in Castilla y León, Spain.

    Science.gov (United States)

    Martín Arias, L H; Treceño Lobato, C; Pérez García, S; García Ortega, P; Sáinz Gil, M; Sanz Fadrique, R; Carvajal García-Pando, A

    2016-12-01

    Antipsychotics are currently used to treat different diseases; even some off-labelled conditions are treated with this medication. Consumption and cost of antipsychotic drugs sharply increased in Spain after second-generation drugs were marketed; several regulatory measures were adopted to curb this trend. The aim of this study was to examine the impact of these measures upon the use and cost of antipsychotics. Study of drug use (SDU) from 1995 to 2012. Consumption and cost data were obtained from the CONCYLIA database; this database contains the retail community pharmacies sales of medicinal products reimbursed by the National Health System in Castilla y León (Spain). Data are presented as defined daily doses per 1000 inhabitants per day (DID) and day treatment cost (DTC). First-generation antipsychotics prescriptions gradually decreased from 3.0 to 1.8 DID; meanwhile, prescriptions for second-generation antipsychotics considerably increased from 0.3 to 9.9 DID. The use of risperidone dropped after the marketing of its structural derivative paliperidone with a similar efficacy but with a substantially higher cost per day. In 2011 and thereafter, patients in Spain began to pay a part of the medications cost, but this did not decrease antipsychotics consumption. Global cost of antipsychotics only began to fall after measures were adopted to lower the price of medicines because of the economic collapse in Spain after May 2010. Several health policy measures have tried to reduce antipsychotics consumption in Spain, special ways of dispensing, marketing of generic drugs and special economic measures for patients. These measures eventually failed to avoid the increase in antipsychotics use. The cost only dropped when lowering prescription drug prices took place. Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  15. MicroRNA and transcription factor mediated regulatory network analysis reveals critical regulators and regulatory modules in myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Guangde Zhang

    Full Text Available Myocardial infarction (MI is a severe coronary artery disease and a leading cause of mortality and morbidity worldwide. However, the molecular mechanisms of MI have yet to be fully elucidated. In this study, we compiled MI-related genes, MI-related microRNAs (miRNAs and known human transcription factors (TFs, and we then identified 1,232 feed-forward loops (FFLs among these miRNAs, TFs and their co-regulated target genes through integrating target prediction. By merging these FFLs, the first miRNA and TF mediated regulatory network for MI was constructed, from which four regulators (SP1, ESR1, miR-21-5p and miR-155-5p and three regulatory modules that might play crucial roles in MI were then identified. Furthermore, based on the miRNA and TF mediated regulatory network and literature survey, we proposed a pathway model for miR-21-5p, the miR-29 family and SP1 to demonstrate their potential co-regulatory mechanisms in cardiac fibrosis, apoptosis and angiogenesis. The majority of the regulatory relations in the model were confirmed by previous studies, which demonstrated the reliability and validity of this miRNA and TF mediated regulatory network. Our study will aid in deciphering the complex regulatory mechanisms involved in MI and provide putative therapeutic targets for MI.

  16. Standardization of SOPs to Evaluations: Impacts on Regulatory Decisions using Learning and Memory as Case Studies

    Science.gov (United States)

    In an era of global trade and regulatory cooperation, consistent and scientifically based interpretation of developmental neurotoxicity (DNT) studies is essential, particularly for non­ standard assays and variable endpoints. Because there is flexibility in the selection of ...

  17. Standardization of SOPs to Evaluations: Impacts on Regulatory Decisions using Learning and Memory as Case Studies

    Science.gov (United States)

    In an era of global trade and regulatory cooperation, consistent and scientifically based interpretation of developmental neurotoxicity (DNT) studies is essential, particularly for non­ standard assays and variable endpoints. Because there is flexibility in the selection of ...

  18. Cloning and bioinformatic analysis of lovastatin biosynthesis regulatory gene lovE

    Institute of Scientific and Technical Information of China (English)

    HUANG Xin; LI Hao-ming

    2009-01-01

    Background Lovastatin is an effective drug for treatment of hyperlipidemia.This study aimed to clone Iovastatin biosynthesis regulatory gene lovE and analyze the structure and function of its encoding protein.Methods According to the Iovastatin synthase gene sequence from genebank,primers were designed to amplify and clone the Iovastatin biosynthesis regulatory gene lovE from Aspergillus terms genomic DNA.Bioinformatic analysis of lovE and its encoding animo acid sequence was performed through intemet resources and software like DNAMAN.Results Target fragment lovE,almost 1500 bp in length,was amplified from Aspergillus terms genomic DNA and the secondary and three-dimensional structures of LovE protein were predicted.Conclusion In the Iovastatin biosynthesis process lovE is a regulatory gene and LovE protein is a GAL4-1ike transcriptional factor.

  19. Comparative Analysis of Regulatory Motif Discovery Tools for Transcription Factor Binding Sites

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In the post-genomic era, identification of specific regulatory motifs or transcription factor binding sites (TFBSs) in non-coding DNA sequences, which is essential to elucidate transcriptional regulatory networks, has emerged as an obstacle that frustrates many researchers. Consequently, numerous motif discovery tools and correlated databases have been applied to solving this problem. However, these existing methods, based on different computational algorithms, show diverse motif prediction efficiency in non-coding DNA sequences. Therefore, understanding the similarities and differences of computational algorithms and enriching the motif discovery literatures are important for users to choose the most appropriate one among the online available tools. Moreover, there still lacks credible criterion to assess motif discovery tools and instructions for researchers to choose the best according to their own projects. Thus integration of the related resources might be a good approach to improve accuracy of the application. Recent studies integrate regulatory motif discovery tools with experimental methods to offer a complementary approach for researchers, and also provide a much-needed model for current researches on transcriptional regulatory networks. Here we present a comparative analysis of regulatory motif discovery tools for TFBSs.

  20. Results of regulatory impact survey of industrial and medical materials licensees of the Office of Nuclear Material Safety and Safeguards

    Energy Technology Data Exchange (ETDEWEB)

    Lach, D.; Melber, B.; Brichoux, J. [Battelle Human Affairs Research Center, Seattle, WA (United States); Hattrup, M.; Conger, R.; Hughes, K. [Pacific Northwest Lab., Richland, WA (United States)

    1995-06-01

    This report presents the findings of a regulatory impact survey of nuclear materials licensees of the United States Nuclear Regulatory Commission (NRC). Commissioners of the NRC directed staff to provide the Commission with first hand information from licensees that could be used to improve the overall regulatory program. A self-administered, mail-out survey questionnaire was used to collect data from a sample of licensees who had interaction with the NRC during the previous 12 months. A total of 371 respondents of the 589 who were sent questionnaires returned completed surveys, for a response rate of 63%. The body of the report presents the findings of the survey including a brief introduction to the approach used, followed by survey findings regarding regulations, policies and regulatory guidance; experience with licensing applications, renewals and amendments; inspections; reporting requirements; and enforcement actions. The appendices of the report include a copy of the survey as administered to licensees, a fuller description of the survey design and data collection methods, and detailed graphic material describing survey responses.

  1. Regulatory focus and generalized trust: the impact of prevention-focused self-regulation on trusting others.

    Science.gov (United States)

    Keller, Johannes; Mayo, Ruth; Greifeneder, Rainer; Pfattheicher, Stefan

    2015-01-01

    The current research suggests that taking self-regulatory mechanisms into account provides insights regarding individuals' responses to threats in social interactions. In general, based on the notion that a prevention-focused orientation of self-regulation is associated with a need for security and a vigilant tendency to avoid losses and other types of negative events we advocate that a prevention-focused orientation, both as a disposition as well as a situationally induced state, lowers generalized trust, thus hindering cooperation within social interactions that entail threats. Specifically, we found that the more individuals' habitual self-regulatory orientation is dominated by a prevention focus, the less likely they are to score high on a self-report measure of generalized trust (Study 1), and to express trust in a trust game paradigm as manifested in lower sums of transferred money (Studies 2 and 3). Similar findings were found when prevention focus was situationally manipulated (Study 4). Finally, one possible factor underlying the impact of prevention-focused self-regulation on generalized trust was demonstrated as individuals with a special sensitivity to negative information were significantly affected by a subtle prevention focus manipulation (versus control condition) in that they reacted with reduced trust in the trust game (Study 5). In sum, the current findings document the crucial relevance of self-regulatory orientations as conceptualized in regulatory focus theory regarding generalized trust and responses to threats within a social interaction. The theoretical and applied implications of the findings are discussed.

  2. The impact of measurement errors in the identification of regulatory networks

    Directory of Open Access Journals (Sweden)

    Sato João R

    2009-12-01

    Full Text Available Abstract Background There are several studies in the literature depicting measurement error in gene expression data and also, several others about regulatory network models. However, only a little fraction describes a combination of measurement error in mathematical regulatory networks and shows how to identify these networks under different rates of noise. Results This article investigates the effects of measurement error on the estimation of the parameters in regulatory networks. Simulation studies indicate that, in both time series (dependent and non-time series (independent data, the measurement error strongly affects the estimated parameters of the regulatory network models, biasing them as predicted by the theory. Moreover, when testing the parameters of the regulatory network models, p-values computed by ignoring the measurement error are not reliable, since the rate of false positives are not controlled under the null hypothesis. In order to overcome these problems, we present an improved version of the Ordinary Least Square estimator in independent (regression models and dependent (autoregressive models data when the variables are subject to noises. Moreover, measurement error estimation procedures for microarrays are also described. Simulation results also show that both corrected methods perform better than the standard ones (i.e., ignoring measurement error. The proposed methodologies are illustrated using microarray data from lung cancer patients and mouse liver time series data. Conclusions Measurement error dangerously affects the identification of regulatory network models, thus, they must be reduced or taken into account in order to avoid erroneous conclusions. This could be one of the reasons for high biological false positive rates identified in actual regulatory network models.

  3. iRegNet3D: three-dimensional integrated regulatory network for the genomic analysis of coding and non-coding disease mutations.

    Science.gov (United States)

    Liang, Siqi; Tippens, Nathaniel D; Zhou, Yaoda; Mort, Matthew; Stenson, Peter D; Cooper, David N; Yu, Haiyuan

    2017-01-18

    The mechanistic details of most disease-causing mutations remain poorly explored within the context of regulatory networks. We present a high-resolution three-dimensional integrated regulatory network (iRegNet3D) in the form of a web tool, where we resolve the interfaces of all known transcription factor (TF)-TF, TF-DNA and chromatin-chromatin interactions for the analysis of both coding and non-coding disease-associated mutations to obtain mechanistic insights into their functional impact. Using iRegNet3D, we find that disease-associated mutations may perturb the regulatory network through diverse mechanisms including chromatin looping. iRegNet3D promises to be an indispensable tool in large-scale sequencing and disease association studies.

  4. Quantitative analysis of regulatory flexibility under changing environmental conditions

    Science.gov (United States)

    Edwards, Kieron D; Akman, Ozgur E; Knox, Kirsten; Lumsden, Peter J; Thomson, Adrian W; Brown, Paul E; Pokhilko, Alexandra; Kozma-Bognar, Laszlo; Nagy, Ferenc; Rand, David A; Millar, Andrew J

    2010-01-01

    The circadian clock controls 24-h rhythms in many biological processes, allowing appropriate timing of biological rhythms relative to dawn and dusk. Known clock circuits include multiple, interlocked feedback loops. Theory suggested that multiple loops contribute the flexibility for molecular rhythms to track multiple phases of the external cycle. Clear dawn- and dusk-tracking rhythms illustrate the flexibility of timing in Ipomoea nil. Molecular clock components in Arabidopsis thaliana showed complex, photoperiod-dependent regulation, which was analysed by comparison with three contrasting models. A simple, quantitative measure, Dusk Sensitivity, was introduced to compare the behaviour of clock models with varying loop complexity. Evening-expressed clock genes showed photoperiod-dependent dusk sensitivity, as predicted by the three-loop model, whereas the one- and two-loop models tracked dawn and dusk, respectively. Output genes for starch degradation achieved dusk-tracking expression through light regulation, rather than a dusk-tracking rhythm. Model analysis predicted which biochemical processes could be manipulated to extend dusk tracking. Our results reveal how an operating principle of biological regulators applies specifically to the plant circadian clock. PMID:21045818

  5. Comparative analysis of chromatin landscape in regulatory regions of human housekeeping and tissue specific genes

    Directory of Open Access Journals (Sweden)

    Dasgupta Dipayan

    2005-05-01

    Full Text Available Abstract Background Global regulatory mechanisms involving chromatin assembly and remodelling in the promoter regions of genes is implicated in eukaryotic transcription control especially for genes subjected to spatial and temporal regulation. The potential to utilise global regulatory mechanisms for controlling gene expression might depend upon the architecture of the chromatin in and around the gene. In-silico analysis can yield important insights into this aspect, facilitating comparison of two or more classes of genes comprising of a large number of genes within each group. Results In the present study, we carried out a comparative analysis of chromatin characteristics in terms of the scaffold/matrix attachment regions, nucleosome formation potential and the occurrence of repetitive sequences, in the upstream regulatory regions of housekeeping and tissue specific genes. Our data show that putative scaffold/matrix attachment regions are more abundant and nucleosome formation potential is higher in the 5' regions of tissue specific genes as compared to the housekeeping genes. Conclusion The differences in the chromatin features between the two groups of genes indicate the involvement of chromatin organisation in the control of gene expression. The presence of global regulatory mechanisms mediated through chromatin organisation can decrease the burden of invoking gene specific regulators for maintenance of the active/silenced state of gene expression. This could partially explain the lower number of genes estimated in the human genome.

  6. 78 FR 36113 - Snapper-Grouper Fishery Off the Southern Atlantic States; Regulatory Amendment 13

    Science.gov (United States)

    2013-06-17

    ... unnecessary negative socio-economic impacts to participants in the snapper-grouper fishery and fishing... environmental assessment, regulatory impact review, Regulatory Flexibility Act analysis, and fishery impact... would not have a significant economic impact on a substantial number of small entities. The...

  7. Impact of regulatory requirements on medicine registration in African countries - perceptions and experiences of pharmaceutical companies in South Africa.

    Science.gov (United States)

    Narsai, Kirti; Williams, Abeda; Mantel-Teeuwisse, Aukje Kaija

    2012-07-01

    Access to medicines has long been and remains a challenge in African countries. The impact of medicines registration policies in these countries poses a challenge for pharmaceutical companies wanting to register medicines in these countries. The recent AMRHI (African Medicines Registration Harmonisation Initiative) has increased the focus on the need for harmonisation. Medicines registration regulations differ across African countries. Anecdotal evidence, based on the experience of pharmaceutical companies on progress towards harmonisation is somewhat different, i.e. that country specific requirements were a barrier to the registration of medicines. The objective of this study was therefore to determine the nature and extent of regulatory hurdles experienced by pharmaceutical companies who wish to register and supply medicines to African countries. This cross-sectional descriptive pilot study was conducted across pharmaceutical companies, both local and multinational. These companies were based in South Africa and were also members of Pharmaceutical Industry Association of South Africa (PIASA). The pharmaceutical companies supply both the private and public sectors. An online survey was developed using Survey Monkey. Survey questions focused on the following strands: nature and level of current supply of medicines to African countries by companies, general regulatory requirements, region specific questions and country specific questions across four regional economic communities in Africa, namely; Southern African Development Community (SADC), East African Community (EAC), Economic Community of the West African States (ECOWAS) and Economic Community of Central African States (ECCAS). A total of 33 responses were received to the questionnaire of which 26 respondents were from the PIASA Regulatory working group and 7 were from the PIASA Export working group.It was noted that since most of the regulatory authorities in Africa are resource-constrained, harmonisation of

  8. Impact of regulatory requirements on medicine registration in African countries – perceptions and experiences of pharmaceutical companies in South Africa

    Science.gov (United States)

    Narsai, Kirti; Williams, Abeda; Mantel-Teeuwisse, Aukje Kaija

    2012-01-01

    Objective: Access to medicines has long been and remains a challenge in African countries. The impact of medicines registration policies in these countries poses a challenge for pharmaceutical companies wanting to register medicines in these countries. The recent AMRHI (African Medicines Registration Harmonisation Initiative) has increased the focus on the need for harmonisation. Medicines registration regulations differ across African countries. Anecdotal evidence, based on the experience of pharmaceutical companies on progress towards harmonisation is somewhat different, i.e. that country specific requirements were a barrier to the registration of medicines. The objective of this study was therefore to determine the nature and extent of regulatory hurdles experienced by pharmaceutical companies who wish to register and supply medicines to African countries. Methods: This cross-sectional descriptive pilot study was conducted across pharmaceutical companies, both local and multinational. These companies were based in South Africa and were also members of Pharmaceutical Industry Association of South Africa (PIASA). The pharmaceutical companies supply both the private and public sectors. An online survey was developed using Survey Monkey. Survey questions focused on the following strands: nature and level of current supply of medicines to African countries by companies, general regulatory requirements, region specific questions and country specific questions across four regional economic communities in Africa, namely; Southern African Development Community (SADC), East African Community (EAC), Economic Community of the West African States (ECOWAS) and Economic Community of Central African States (ECCAS). Results: A total of 33 responses were received to the questionnaire of which 26 respondents were from the PIASA Regulatory working group and 7 were from the PIASA Export working group.It was noted that since most of the regulatory authorities in Africa are resource

  9. Genome-wide analysis of the salmonella Fis regulon and its regulatory mechanism on pathogenicity islands.

    Directory of Open Access Journals (Sweden)

    Hui Wang

    Full Text Available Fis, one of the most important nucleoid-associated proteins, functions as a global regulator of transcription in bacteria that has been comprehensively studied in Escherichia coli K12. Fis also influences the virulence of Salmonella enterica and pathogenic E. coli by regulating their virulence genes, however, the relevant mechanism is unclear. In this report, using combined RNA-seq and chromatin immunoprecipitation (ChIP-seq technologies, we first identified 1646 Fis-regulated genes and 885 Fis-binding targets in the S. enterica serovar Typhimurium, and found a Fis regulon different from that in E. coli. Fis has been reported to contribute to the invasion ability of S. enterica. By using cell infection assays, we found it also enhances the intracellular replication ability of S. enterica within macrophage cell, which is of central importance for the pathogenesis of infections. Salmonella pathogenicity islands (SPI-1 and SPI-2 are crucial for the invasion and survival of S. enterica in host cells. Using mutation and overexpression experiments, real-time PCR analysis, and electrophoretic mobility shift assays, we demonstrated that Fis regulates 63 of the 94 Salmonella pathogenicity island (SPI-1 and SPI-2 genes, by three regulatory modes: i binds to SPI regulators in the gene body or in upstream regions; ii binds to SPI genes directly to mediate transcriptional activation of themselves and downstream genes; iii binds to gene encoding OmpR which affects SPI gene expression by controlling SPI regulators SsrA and HilD. Our results provide new insights into the impact of Fis on SPI genes and the pathogenicity of S. enterica.

  10. Bioinformatics analysis of two-component regulatory systems in Staphylococcus epidermidis

    Institute of Scientific and Technical Information of China (English)

    QIN Zhiqiang; ZHONG Yang; ZHANG Jian; HE Youyu; WU Yang; JIANG Juan; CHEN Jiemin; LUO Xiaomin; QU Di

    2004-01-01

    Sixteen pairs of two-component regulatory systems are identified in the genome of Staphylococcus epidermidis ATCC12228 strain, which is newly sequenced by our laboratory for Medical Molecular Virology and Chinese National Human Genome Center at Shanghai, by using bioinformatics analysis. Comparative analysis of the twocomponent regulatory systems in S. epidermidis and that of S.aureus and Bacillus subtilis shows that these systems may regulate some important biological functions, e.g. growth,biofilm formation, and expression of virulence factors in S.epidermidis. Two conserved domains, i.e. HATPase_c and REC domains, are found in all 16 pairs of two-component proteins.Homologous modelling analysis indicates that there are 4similar HATPase_c domain structures of histidine kinases and 13 similar REC domain structures of response regulators,and there is one AMP-PNP binding pocket in the HATPase_c domain and three active aspartate residues in the REC domain. Preliminary experiment reveals that the bioinformatics analysis of the conserved domain structures in the two-component regulatory systems in S. epidermidis may provide useful information for discovery of potential drug target.

  11. The impact of regulatory approaches targeting collaborative economy in the tourism accommodation sector:

    DEFF Research Database (Denmark)

    Dredge, Dianne; Gyimóthy, Szilvia; Birkbak, Andreas

    stimulated a range of ancillary services offered by small and micro-entrepreneurs. However, incumbent industry actors (such as hotels, apartment hotels, bed and breakfasts, hostels and vacation rentals) are concerned about the uneven regulatory landscape and the unfair competition this may create. Municipal...

  12. INCLUSive: A web portal and service registry for microarray and regulatory sequence analysis.

    Science.gov (United States)

    Coessens, Bert; Thijs, Gert; Aerts, Stein; Marchal, Kathleen; De Smet, Frank; Engelen, Kristof; Glenisson, Patrick; Moreau, Yves; Mathys, Janick; De Moor, Bart

    2003-07-01

    INCLUSive is a suite of algorithms and tools for the analysis of gene expression data and the discovery of cis-regulatory sequence elements. The tools allow normalization, filtering and clustering of microarray data, functional scoring of gene clusters, sequence retrieval, and detection of known and unknown regulatory elements using probabilistic sequence models and Gibbs sampling. All tools are available via different web pages and as web services. The web pages are connected and integrated to reflect a methodology and facilitate complex analysis using different tools. The web services can be invoked using standard SOAP messaging. Example clients are available for download to invoke the services from a remote computer or to be integrated with other applications. All services are catalogued and described in a web service registry. The INCLUSive web portal is available for academic purposes at http://www.esat.kuleuven.ac.be/inclusive.

  13. CyTargetLinker: a cytoscape app to integrate regulatory interactions in network analysis.

    Directory of Open Access Journals (Sweden)

    Martina Kutmon

    Full Text Available INTRODUCTION: The high complexity and dynamic nature of the regulation of gene expression, protein synthesis, and protein activity pose a challenge to fully understand the cellular machinery. By deciphering the role of important players, including transcription factors, microRNAs, or small molecules, a better understanding of key regulatory processes can be obtained. Various databases contain information on the interactions of regulators with their targets for different organisms, data recently being extended with the results of the ENCODE (Encyclopedia of DNA Elements project. A systems biology approach integrating our understanding on different regulators is essential in interpreting the regulation of molecular biological processes. IMPLEMENTATION: We developed CyTargetLinker (http://projects.bigcat.unimaas.nl/cytargetlinker, a Cytoscape app, for integrating regulatory interactions in network analysis. Recently we released CyTargetLinker as one of the first apps for Cytoscape 3. It provides a user-friendly and flexible interface to extend biological networks with regulatory interactions, such as microRNA-target, transcription factor-target and/or drug-target. Importantly, CyTargetLinker employs identifier mapping to combine various interaction data resources that use different types of identifiers. RESULTS: Three case studies demonstrate the strength and broad applicability of CyTargetLinker, (i extending a mouse molecular interaction network, containing genes linked to diabetes mellitus, with validated and predicted microRNAs, (ii enriching a molecular interaction network, containing DNA repair genes, with ENCODE transcription factor and (iii building a regulatory meta-network in which a biological process is extended with information on transcription factor, microRNA and drug regulation. CONCLUSIONS: CyTargetLinker provides a simple and extensible framework for biologists and bioinformaticians to integrate different regulatory interactions

  14. Data Quality Objectives for Regulatory Requirements for Hazardous and Radioactive Air Emissions Sampling and Analysis

    Energy Technology Data Exchange (ETDEWEB)

    MULKEY, C.H.

    1999-07-06

    This document describes the results of the data quality objective (DQO) process undertaken to define data needs for state and federal requirements associated with toxic, hazardous, and/or radiological air emissions under the jurisdiction of the River Protection Project (RPP). Hereafter, this document is referred to as the Air DQO. The primary drivers for characterization under this DQO are the regulatory requirements pursuant to Washington State regulations, that may require sampling and analysis. The federal regulations concerning air emissions are incorporated into the Washington State regulations. Data needs exist for nonradioactive and radioactive waste constituents and characteristics as identified through the DQO process described in this document. The purpose is to identify current data needs for complying with regulatory drivers for the measurement of air emissions from RPP facilities in support of air permitting. These drivers include best management practices; similar analyses may have more than one regulatory driver. This document should not be used for determining overall compliance with regulations because the regulations are in constant change, and this document may not reflect the latest regulatory requirements. Regulatory requirements are also expected to change as various permits are issued. Data needs require samples for both radionuclides and nonradionuclide analytes of air emissions from tanks and stored waste containers. The collection of data is to support environmental permitting and compliance, not for health and safety issues. This document does not address health or safety regulations or requirements (those of the Occupational Safety and Health Administration or the National Institute of Occupational Safety and Health) or continuous emission monitoring systems. This DQO is applicable to all equipment, facilities, and operations under the jurisdiction of RPP that emit or have the potential to emit regulated air pollutants.

  15. Analysis of regulatory protease sequences identified through bioinformatic data mining of the Schistosoma mansoni genome

    Directory of Open Access Journals (Sweden)

    Minchella Dennis J

    2009-10-01

    Full Text Available Abstract Background New chemotherapeutic agents against Schistosoma mansoni, an etiological agent of human schistosomiasis, are a priority due to the emerging drug resistance and the inability of current drug treatments to prevent reinfection. Proteases have been under scrutiny as targets of immunological or chemotherapeutic anti-Schistosoma agents because of their vital role in many stages of the parasitic life cycle. Function has been established for only a handful of identified S. mansoni proteases, and the vast majority of these are the digestive proteases; very few of the conserved classes of regulatory proteases have been identified from Schistosoma species, despite their vital role in numerous cellular processes. To that end, we identified protease protein coding genes from the S. mansoni genome project and EST library. Results We identified 255 protease sequences from five catalytic classes using predicted proteins of the S. mansoni genome. The vast majority of these show significant similarity to proteins in KEGG and the Conserved Domain Database. Proteases include calpains, caspases, cytosolic and mitochondrial signal peptidases, proteases that interact with ubiquitin and ubiquitin-like molecules, and proteases that perform regulated intramembrane proteolysis. Comparative analysis of classes of important regulatory proteases find conserved active site domains, and where appropriate, signal peptides and transmembrane helices. Phylogenetic analysis provides support for inferring functional divergence among regulatory aspartic, cysteine, and serine proteases. Conclusion Numerous proteases are identified for the first time in S. mansoni. We characterized important regulatory proteases and focus analysis on these proteases to complement the growing knowledge base of digestive proteases. This work provides a foundation for expanding knowledge of proteases in Schistosoma species and examining their diverse function and potential as targets

  16. Manager's Discretionary Power and Comparability of Financial Reports: An Analysis of the Regulatory Transition Process in Brazilian Accounting

    Directory of Open Access Journals (Sweden)

    Alex Mussoi Ribeiro

    2016-04-01

    Full Text Available This research aimed to directly evaluate the impact of the accounting regulatory flexibility movement on the comparability of financial reports. The country chosen for the analysis was Brazil, because it was one of the few countries in the world where a process of regulatory change from a completely rule-based standard with a strong link to tax accounting (Lopes, 2011 to a principle-based standard with greater need for decision by managers who prepare the financial reports took place. To measure comparability, the accounting function similarity model developed by DeFranco, Kothari and Verdi (2011 was used. The companies analyzed were all listed ones with full data for the period concerned having, at least, a pair company within the same economic activity sector. To obtain the research results, we adopted a panel data model where the years 2005 to 2012 were compared to the year 2004. The results obtained prove that, on average, there was no significant decrease in the comparability level within country during the regulatory transition period in Brazil. On the contrary, there was an increase in genuine comparability in the year 2012 when compared to 2004. In the model adjusted by stepwise, the years 2011 and 2012 had a significantly higher average comparability when compared to 2004. The results found corroborate other researches addressing the quality of accounting information (Collins, Pasewark, & Riley, 2012; Psaros & Trotman, 2004; Agoglia, Doupnik, & Tsakumis, 2011 and prove the superiority of the principle-based standard also over the comparability of financial reports. The main conclusion of this research is that increasing manager's discretionary power through flexibility of accounting standards does not decrease the comparability of financial reports.

  17. Cross-impacts analysis development and energy policy analysis applications

    Energy Technology Data Exchange (ETDEWEB)

    Roop, J.M.; Scheer, R.M.; Stacey, G.S.

    1986-12-01

    Purpose of this report is to describe the cross-impact analysis process and microcomputer software developed for the Office of Policy, Planning, and Analysis (PPA) of DOE. First introduced in 1968, cross-impact analysis is a technique that produces scenarios of future conditions and possibilities. Cross-impact analysis has several unique attributes that make it a tool worth examining, especially in the current climate when the outlook for the economy and several of the key energy markets is uncertain. Cross-impact analysis complements the econometric, engineering, systems dynamics, or trend approaches already in use at DOE. Cross-impact analysis produces self-consistent scenarios in the broadest sense and can include interaction between the economy, technology, society and the environment. Energy policy analyses that couple broad scenarios of the future with detailed forecasting can produce more powerful results than scenario analysis or forecasts can produce alone.

  18. Impact of alemtuzumab treatment on the survival and function of human regulatory T cells in vitro.

    Science.gov (United States)

    Havari, Evis; Turner, Michael J; Campos-Rivera, Juanita; Shankara, Srinivas; Nguyen, Tri-Hung; Roberts, Bruce; Siders, William; Kaplan, Johanne M

    2014-01-01

    Alemtuzumab is a humanized monoclonal antibody specific for the CD52 protein present at high levels on the surface of B and T lymphocytes. In clinical trials, alemtuzumab has shown a clinical benefit superior to that of interferon-β in relapsing-remitting multiple sclerosis patients. Treatment with alemtuzumab leads to the depletion of circulating lymphocytes followed by a repopulation process characterized by alterations in the number, proportions and properties of lymphocyte subsets. Of particular interest, an increase in the percentage of T cells with a regulatory phenotype (Treg cells) has been observed in multiple sclerosis patients after alemtuzumab. Since Treg cells play an important role in the control of autoimmune responses, the effect of alemtuzumab on Treg cells was further studied in vitro. Alemtuzumab effectively mediated complement-dependent cytolysis of human T lymphocytes and the remaining population was enriched in T cells with a regulatory phenotype. The alemtuzumab-exposed T cells displayed functional regulatory characteristics including anergy to stimulation with allogeneic dendritic cells and ability to suppress the allogeneic response of autologous T cells. Consistent with the observed increase in Treg cell frequency, the CD25(hi) T-cell population was necessary for the suppressive activity of alemtuzumab-exposed T cells. The mechanism of this suppression was found to be dependent on both cell-cell contact and interleukin-2 consumption. These findings suggest that an alemtuzumab-mediated increase in the proportion of Treg cells may play a role in promoting the long-term efficacy of alemtuzumab in patients with multiple sclerosis.

  19. South Fork Tolt River Hydroelectric Project : Adopted Portions of a 1987 Federal Energy Regulatory Commission`s Final Environmental Impact Statement.

    Energy Technology Data Exchange (ETDEWEB)

    United States. Bonneville Power Administration.

    1992-07-01

    The South Fork Tolt River Hydroelectric Project that world produce 6.55 average megawatts of firm energy per year and would be sited in the Snohomish River Basin, Washington, was evaluated by the Federal Energy Regulatory commission (FERC) along with six other proposed projects for environmental effects and economic feasibility Based on its economic analysis and environmental evaluation of the project, the FERC staff found that the South Fork Tolt River Project would be economically feasible and would result in insignificant Impacts if sedimentation issues could be resolved. Upon review, the BPA is adopting portions of the 1987 FERC FEIS that concern the South Fork Tolt River Hydroelectric Project and updating specific sections in an Attachment.

  20. A Framework for the Evaluation of Biosecurity, Commercial, Regulatory, and Scientific Impacts of Plant Viruses and Viroids Identified by NGS Technologies

    Science.gov (United States)

    Massart, Sebastien; Candresse, Thierry; Gil, José; Lacomme, Christophe; Predajna, Lukas; Ravnikar, Maja; Reynard, Jean-Sébastien; Rumbou, Artemis; Saldarelli, Pasquale; Škorić, Dijana; Vainio, Eeva J.; Valkonen, Jari P. T.; Vanderschuren, Hervé; Varveri, Christina; Wetzel, Thierry

    2017-01-01

    Recent advances in high-throughput sequencing technologies and bioinformatics have generated huge new opportunities for discovering and diagnosing plant viruses and viroids. Plant virology has undoubtedly benefited from these new methodologies, but at the same time, faces now substantial bottlenecks, namely the biological characterization of the newly discovered viruses and the analysis of their impact at the biosecurity, commercial, regulatory, and scientific levels. This paper proposes a scaled and progressive scientific framework for efficient biological characterization and risk assessment when a previously known or a new plant virus is detected by next generation sequencing (NGS) technologies. Four case studies are also presented to illustrate the need for such a framework, and to discuss the scenarios. PMID:28174561

  1. Dynamic Wireless Power Transfer - Grid Impacts Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Markel, Tony; Meintz, Andrew; Gonder, Jeff

    2015-12-04

    This presentation discusses the current status of analysis of the electricity grid impacts of a dynamic wireless power transfer system deployed to the Atlanta region on select high traffic roadway segments.

  2. Mendeley Impact on Scientific Writing: Thematic Analysis

    National Research Council Canada - National Science Library

    Salija, Kisman; Hidayat, Rahmat; Patak, Andi Anto

    2016-01-01

    .... This study aims at exposing the Mendeley impact on scientific writing. The thematic analysis was applied in this study to transcribe the recordings and translate as well as analyze the transcripts through NVivo 8 software...

  3. Analytic stability analysis of three-component self-regulatory genetic circuit

    CERN Document Server

    Lee, Julian

    2014-01-01

    A self-regulatory genetic circuit, where a protein acts as a positive regulator of its own production, is known to be a simplest form of biological network with a positive feedback loop. Although at least three components, DNA, RNA, and the protein, are required to form such a circuit, the stability analysis of fixed points of the self-regulatory circuit has been performed only after reducing the system into to a two-component system consisting of RNA and protein only, assuming a fast equilibration of the DNA component. Here, the stability of fixed points of the three-component positive feedback loop is analyzed by obtaining eigenvalues of full three dimensional Hessian matrix. In addition to rigorously identifying the stable fixed points and the saddle points, detailed information can be obtained, such as the number of positive eigenvalues near a saddle point. In particular, complex eigenvalues is shown to exist for sufficiently slow binding and unbinding of the auto-regulatory transcription factor to DNA, l...

  4. Analysis of mammalian cis-regulatory DNA elements by homologous recombination.

    Science.gov (United States)

    Fiering, S; Bender, M A; Groudine, M

    1999-01-01

    The use of homologous recombination to modify and thereby functionally analyze cis-regulatory DNA elements in mammalian cells has become an important approach in mammalian gene expression research. We have emphasized the necessity of designing a system that allows the removal of selectable markers used in targeting and facilitates the further modification of the region under study. To perform these tasks, we presently favor making an initial HR-mediated replacement of the entire element under study with an active positive selectable marker in combination with either an inactive second positive selectable marker or an active negative selectable marker. The plug and socket system, in which an inactive selectable marker is complemented by HR, is the most dependable and well-characterized option for making secondary modifications. However, the double-replacement system has certain advantages, and the recently developed RMCE approach, which allows replacement of a negative selectable marker by site-specific recombinase-mediated insertion without using a positive selectable marker, will likely prove very valuable in future experiments. Each of the systems, or combinations thereof, should be considered in light of the specifics of any given experiment to select the most appropriate option. Although the emphasis of this article has been the analysis of cis-acting regulatory elements involved in transcription, these same approaches can be used to analyze other regulatory elements (e.g., origins of replication) and to make multiple subtle mutations in polypeptides.

  5. The pairwise disconnectivity index as a new metric for the topological analysis of regulatory networks

    Directory of Open Access Journals (Sweden)

    Wingender Edgar

    2008-05-01

    Full Text Available Abstract Background Currently, there is a gap between purely theoretical studies of the topology of large bioregulatory networks and the practical traditions and interests of experimentalists. While the theoretical approaches emphasize the global characterization of regulatory systems, the practical approaches focus on the role of distinct molecules and genes in regulation. To bridge the gap between these opposite approaches, one needs to combine 'general' with 'particular' properties and translate abstract topological features of large systems into testable functional characteristics of individual components. Here, we propose a new topological parameter – the pairwise disconnectivity index of a network's element – that is capable of such bridging. Results The pairwise disconnectivity index quantifies how crucial an individual element is for sustaining the communication ability between connected pairs of vertices in a network that is displayed as a directed graph. Such an element might be a vertex (i.e., molecules, genes, an edge (i.e., reactions, interactions, as well as a group of vertices and/or edges. The index can be viewed as a measure of topological redundancy of regulatory paths which connect different parts of a given network and as a measure of sensitivity (robustness of this network to the presence (absence of each individual element. Accordingly, we introduce the notion of a path-degree of a vertex in terms of its corresponding incoming, outgoing and mediated paths, respectively. The pairwise disconnectivity index has been applied to the analysis of several regulatory networks from various organisms. The importance of an individual vertex or edge for the coherence of the network is determined by the particular position of the given element in the whole network. Conclusion Our approach enables to evaluate the effect of removing each element (i.e., vertex, edge, or their combinations from a network. The greatest potential value of

  6. Comparative analysis of module-based versus direct methods for reverse-engineering transcriptional regulatory networks

    Directory of Open Access Journals (Sweden)

    Joshi Anagha

    2009-05-01

    Full Text Available Abstract Background A myriad of methods to reverse-engineer transcriptional regulatory networks have been developed in recent years. Direct methods directly reconstruct a network of pairwise regulatory interactions while module-based methods predict a set of regulators for modules of coexpressed genes treated as a single unit. To date, there has been no systematic comparison of the relative strengths and weaknesses of both types of methods. Results We have compared a recently developed module-based algorithm, LeMoNe (Learning Module Networks, to a mutual information based direct algorithm, CLR (Context Likelihood of Relatedness, using benchmark expression data and databases of known transcriptional regulatory interactions for Escherichia coli and Saccharomyces cerevisiae. A global comparison using recall versus precision curves hides the topologically distinct nature of the inferred networks and is not informative about the specific subtasks for which each method is most suited. Analysis of the degree distributions and a regulator specific comparison show that CLR is 'regulator-centric', making true predictions for a higher number of regulators, while LeMoNe is 'target-centric', recovering a higher number of known targets for fewer regulators, with limited overlap in the predicted interactions between both methods. Detailed biological examples in E. coli and S. cerevisiae are used to illustrate these differences and to prove that each method is able to infer parts of the network where the other fails. Biological validation of the inferred networks cautions against over-interpreting recall and precision values computed using incomplete reference networks. Conclusion Our results indicate that module-based and direct methods retrieve largely distinct parts of the underlying transcriptional regulatory networks. The choice of algorithm should therefore be based on the particular biological problem of interest and not on global metrics which cannot be

  7. Systematic Discovery of Archaeal Transcription Factor Functions in Regulatory Networks through Quantitative Phenotyping Analysis.

    Science.gov (United States)

    Darnell, Cynthia L; Tonner, Peter D; Gulli, Jordan G; Schmidler, Scott C; Schmid, Amy K

    2017-01-01

    Gene regulatory networks (GRNs) are critical for dynamic transcriptional responses to environmental stress. However, the mechanisms by which GRN regulation adjusts physiology to enable stress survival remain unclear. Here we investigate the functions of transcription factors (TFs) within the global GRN of the stress-tolerant archaeal microorganism Halobacterium salinarum. We measured growth phenotypes of a panel of TF deletion mutants in high temporal resolution under heat shock, oxidative stress, and low-salinity conditions. To quantitate the noncanonical functional forms of the growth trajectories observed for these mutants, we developed a novel modeling framework based on Gaussian process regression and functional analysis of variance (FANOVA). We employ unique statistical tests to determine the significance of differential growth relative to the growth of the control strain. This analysis recapitulated known TF functions, revealed novel functions, and identified surprising secondary functions for characterized TFs. Strikingly, we observed that the majority of the TFs studied were required for growth under multiple stress conditions, pinpointing regulatory connections between the conditions tested. Correlations between quantitative phenotype trajectories of mutants are predictive of TF-TF connections within the GRN. These phenotypes are strongly concordant with predictions from statistical GRN models inferred from gene expression data alone. With genome-wide and targeted data sets, we provide detailed functional validation of novel TFs required for extreme oxidative stress and heat shock survival. Together, results presented in this study suggest that many TFs function under multiple conditions, thereby revealing high interconnectivity within the GRN and identifying the specific TFs required for communication between networks responding to disparate stressors. IMPORTANCE To ensure survival in the face of stress, microorganisms employ inducible damage repair

  8. Analysis of regulatory networks constructed based on gene coexpression in pituitary adenoma.

    Science.gov (United States)

    Gong, Jie; Diao, Bo; Yao, Guo Jie; Liu, Ying; Xu, Guo Zheng

    2013-12-01

    Gene coexpression patterns can reveal gene collections with functional consistency. This study systematically constructs regulatory networks for pituitary tumours by integrating gene coexpression, transcriptional and posttranscriptional regulation. Through network analysis, we elaborate the incidence mechanism of pituitary adenoma. The Pearson's correlation coefficient was utilized to calculate the level of gene coexpression. By comparing pituitary adenoma samples with normal samples, pituitary adenoma-specific gene coexpression patterns were identified. For pituitary adenoma-specific coexpressed genes, we integrated transcription factor (TF) and microRNA (miRNA) regulation to construct a complex regulatory network from the transcriptional and posttranscriptional perspectives. Network module analysis identified the synergistic regulation of genes by miRNAs and TFs in pituitary adenoma. We identified 142 pituitary adenoma-specific active genes, including 43 TFs and 99 target genes of TFs. Functional enrichment of these 142 genes revealed that the occurrence of pituitary adenoma induced abnormalities in intracellular metabolism and angiogenesis process. These 142 genes were also significantly enriched in adenoma pathway. Module analysis of the systematic regulatory network found that three modules contained elements that were closely related to pituitary adenoma, such as FGF2 and SP1, as well as transcription factors and miRNAs involved in the tumourigenesis. These results show that in the occurrence of pituitary adenoma, miRNA, TF and genes interact with each other. Based on gene expression, the proposed method integrates interaction information from different levels and systematically explains the occurrence of pituitary tumours. It facilitates the tracing of the origin of the disease and can provide basis for early diagnosis of complex diseases or cancer without obvious symptoms.

  9. Analysis of regulatory networks constructed based on gene coexpression in pituitary adenoma

    Indian Academy of Sciences (India)

    Jie Gong; Bo Diao; Guo Jie Yao; Ying Liu; Guo Zheng Xu

    2013-12-01

    Gene coexpression patterns can reveal gene collections with functional consistency. This study systematically constructs regulatory networks for pituitary tumours by integrating gene coexpression, transcriptional and posttranscriptional regulation. Through network analysis, we elaborate the incidence mechanism of pituitary adenoma. The Pearson’s correlation coefficient was utilized to calculate the level of gene coexpression. By comparing pituitary adenoma samples with normal samples, pituitary adenoma-specific gene coexpression patterns were identified. For pituitary adenoma-specific coexpressed genes, we integrated transcription factor (TF) and microRNA (miRNA) regulation to construct a complex regulatory network from the transcriptional and posttranscriptional perspectives. Network module analysis identified the synergistic regulation of genes by miRNAs and TFs in pituitary adenoma. We identified 142 pituitary adenoma-specific active genes, including 43 TFs and 99 target genes of TFs. Functional enrichment of these 142 genes revealed that the occurrence of pituitary adenoma induced abnormalities in intracellular metabolism and angiogenesis process. These 142 genes were also significantly enriched in adenoma pathway. Module analysis of the systematic regulatory network found that three modules contained elements that were closely related to pituitary adenoma, such as FGF2 and SP1, as well as transcription factors and miRNAs involved in the tumourigenesis. These results show that in the occurrence of pituitary adenoma, miRNA, TF and genes interact with each other. Based on gene expression, the proposed method integrates interaction information from different levels and systematically explains the occurrence of pituitary tumours. It facilitates the tracing of the origin of the disease and can provide basis for early diagnosis of complex diseases or cancer without obvious symptoms.

  10. Genome-wide prediction of transcriptional regulatory elements of human promoters using gene expression and promoter analysis data

    Directory of Open Access Journals (Sweden)

    Kim Seon-Young

    2006-07-01

    Full Text Available Abstract Background A complete understanding of the regulatory mechanisms of gene expression is the next important issue of genomics. Many bioinformaticians have developed methods and algorithms for predicting transcriptional regulatory mechanisms from sequence, gene expression, and binding data. However, most of these studies involved the use of yeast which has much simpler regulatory networks than human and has many genome wide binding data and gene expression data under diverse conditions. Studies of genome wide transcriptional networks of human genomes currently lag behind those of yeast. Results We report herein a new method that combines gene expression data analysis with promoter analysis to infer transcriptional regulatory elements of human genes. The Z scores from the application of gene set analysis with gene sets of transcription factor binding sites (TFBSs were successfully used to represent the activity of TFBSs in a given microarray data set. A significant correlation between the Z scores of gene sets of TFBSs and individual genes across multiple conditions permitted successful identification of many known human transcriptional regulatory elements of genes as well as the prediction of numerous putative TFBSs of many genes which will constitute a good starting point for further experiments. Using Z scores of gene sets of TFBSs produced better predictions than the use of mRNA levels of a transcription factor itself, suggesting that the Z scores of gene sets of TFBSs better represent diverse mechanisms for changing the activity of transcription factors in the cell. In addition, cis-regulatory modules, combinations of co-acting TFBSs, were readily identified by our analysis. Conclusion By a strategic combination of gene set level analysis of gene expression data sets and promoter analysis, we were able to identify and predict many transcriptional regulatory elements of human genes. We conclude that this approach will aid in decoding

  11. Identification of a cis-regulatory element by transient analysis of co-ordinately regulated genes

    Directory of Open Access Journals (Sweden)

    Allan Andrew C

    2008-07-01

    Full Text Available Abstract Background Transcription factors (TFs co-ordinately regulate target genes that are dispersed throughout the genome. This co-ordinate regulation is achieved, in part, through the interaction of transcription factors with conserved cis-regulatory motifs that are in close proximity to the target genes. While much is known about the families of transcription factors that regulate gene expression in plants, there are few well characterised cis-regulatory motifs. In Arabidopsis, over-expression of the MYB transcription factor PAP1 (PRODUCTION OF ANTHOCYANIN PIGMENT 1 leads to transgenic plants with elevated anthocyanin levels due to the co-ordinated up-regulation of genes in the anthocyanin biosynthetic pathway. In addition to the anthocyanin biosynthetic genes, there are a number of un-associated genes that also change in expression level. This may be a direct or indirect consequence of the over-expression of PAP1. Results Oligo array analysis of PAP1 over-expression Arabidopsis plants identified genes co-ordinately up-regulated in response to the elevated expression of this transcription factor. Transient assays on the promoter regions of 33 of these up-regulated genes identified eight promoter fragments that were transactivated by PAP1. Bioinformatic analysis on these promoters revealed a common cis-regulatory motif that we showed is required for PAP1 dependent transactivation. Conclusion Co-ordinated gene regulation by individual transcription factors is a complex collection of both direct and indirect effects. Transient transactivation assays provide a rapid method to identify direct target genes from indirect target genes. Bioinformatic analysis of the promoters of these direct target genes is able to locate motifs that are common to this sub-set of promoters, which is impossible to identify with the larger set of direct and indirect target genes. While this type of analysis does not prove a direct interaction between protein and DNA

  12. Clinical Impact of Regulatory T cells (Treg) in Cancer and HIV.

    Science.gov (United States)

    Whiteside, Theresa L

    2015-12-01

    The role of regulatory T cells, (Treg) in human cancer and HIV-1 infections has been under intense scrutiny. While the lack of a marker specific for human Treg has made it challenging to phenotype these cells, combinations of several markers and functional attributes of Treg have made it possible to assess their contributions to immune homeostasis in health and disease. Treg diversity and their plasticity create a challenge in deciding whether they are beneficial to the host by down-regulating excessive immune activation or are responsible for adverse effects such as suppression of anti-tumor immune responses resulting in promotion of tumor growth. Treg are emerging as active participants in several biochemical pathways involved in immune regulation. This review attempts to integrate current information about human Treg in respect to their activities in cancer and HIV-1. The goal is to evaluate the potential of Treg as targets for future immune or pharmacologic therapies for cancer or HIV-1 infections.

  13. 集成调节匹配对广告态度的影响%Impact of Integral Regulatory Fit on Attitudes toward Advertisement

    Institute of Scientific and Technical Information of China (English)

    王丹萍; 庄贵军; 周茵

    2013-01-01

    This study investigates how integral regulatory fit between regulatory focus and information framing influences recipients' attitudes toward an advertisement and identifies boundary conditions of the impacts.The study develops hypotheses based on regulatory fit effect and information processing theories,collect data from two experiments with college students as research objects,and then test hypotheses with analysis of variance.The results show that recipients' attitudes toward advertisement is more positive when they read an advertisement with integral regulatory fit compared with integral regulatory unfit.Particularly,for advertisements focusing on problem description,loss framing is more persuasive than gain framing.For advertisements focusing on problem-solving description,gain framing is more persuasive than loss framing.Furthermore,the two experiments demonstrate boundary conditions of the impact of integral regulatory fit on attitudes toward an advertisement are high issue involvement and high cognitive demand (i.e.high information processing motivation) by measuring the situational (study 1) and idiosyncratic (study 2) information processing motivation.%探讨受众的调节定向与信息框架的集成调节匹配对受众广告态度的影响以及集成调节匹配影响广告态度的边界条件.基于调节匹配效应和信息处理理论建立假设,通过两项以学生为被试的实验收集数据,采用方差分析方法进行假设检验.实验结果表明,集成调节匹配的广告较不匹配的广告更能塑造受众积极的广告态度,当广告侧重描述问题时,广告采用亏损框架宣传更能塑造受众积极的广告态度;当广告侧重描述问题解决时,广告采用得益框架宣传更能塑造受众积极的广告态度.实验1和实验2分别从受众情境性信息处理动机和特质性信息处理动机两方面发现,集成调节匹配对广告态度的影响作用产生的边界条件分别为受众高话

  14. Ancestral regulatory circuits governing ectoderm patterning downstream of Nodal and BMP2/4 revealed by gene regulatory network analysis in an echinoderm.

    Directory of Open Access Journals (Sweden)

    Alexandra Saudemont

    Full Text Available Echinoderms, which are phylogenetically related to vertebrates and produce large numbers of transparent embryos that can be experimentally manipulated, offer many advantages for the analysis of the gene regulatory networks (GRN regulating germ layer formation. During development of the sea urchin embryo, the ectoderm is the source of signals that pattern all three germ layers along the dorsal-ventral axis. How this signaling center controls patterning and morphogenesis of the embryo is not understood. Here, we report a large-scale analysis of the GRN deployed in response to the activity of this signaling center in the embryos of the Mediterranean sea urchin Paracentrotus lividus, in which studies with high spatial resolution are possible. By using a combination of in situ hybridization screening, overexpression of mRNA, recombinant ligand treatments, and morpholino-based loss-of-function studies, we identified a cohort of transcription factors and signaling molecules expressed in the ventral ectoderm, dorsal ectoderm, and interposed neurogenic ("ciliary band" region in response to the known key signaling molecules Nodal and BMP2/4 and defined the epistatic relationships between the most important genes. The resultant GRN showed a number of striking features. First, Nodal was found to be essential for the expression of all ventral and dorsal marker genes, and BMP2/4 for all dorsal genes. Second, goosecoid was identified as a central player in a regulatory sub-circuit controlling mouth formation, while tbx2/3 emerged as a critical factor for differentiation of the dorsal ectoderm. Finally, and unexpectedly, a neurogenic ectoderm regulatory circuit characterized by expression of "ciliary band" genes was triggered in the absence of TGF beta signaling. We propose a novel model for ectoderm regionalization, in which neural ectoderm is the default fate in the absence of TGF beta signaling, and suggest that the stomodeal and neural subcircuits that we

  15. Gene and metabolite regulatory network analysis of early developing fruit tissues highlights new candidate genes for the control of tomato fruit composition and development.

    Science.gov (United States)

    Mounet, Fabien; Moing, Annick; Garcia, Virginie; Petit, Johann; Maucourt, Michael; Deborde, Catherine; Bernillon, Stéphane; Le Gall, Gwénaëlle; Colquhoun, Ian; Defernez, Marianne; Giraudel, Jean-Luc; Rolin, Dominique; Rothan, Christophe; Lemaire-Chamley, Martine

    2009-03-01

    Variations in early fruit development and composition may have major impacts on the taste and the overall quality of ripe tomato (Solanum lycopersicum) fruit. To get insights into the networks involved in these coordinated processes and to identify key regulatory genes, we explored the transcriptional and metabolic changes in expanding tomato fruit tissues using multivariate analysis and gene-metabolite correlation networks. To this end, we demonstrated and took advantage of the existence of clear structural and compositional differences between expanding mesocarp and locular tissue during fruit development (12-35 d postanthesis). Transcriptome and metabolome analyses were carried out with tomato microarrays and analytical methods including proton nuclear magnetic resonance and liquid chromatography-mass spectrometry, respectively. Pairwise comparisons of metabolite contents and gene expression profiles detected up to 37 direct gene-metabolite correlations involving regulatory genes (e.g. the correlations between glutamine, bZIP, and MYB transcription factors). Correlation network analyses revealed the existence of major hub genes correlated with 10 or more regulatory transcripts and embedded in a large regulatory network. This approach proved to be a valuable strategy for identifying specific subsets of genes implicated in key processes of fruit development and metabolism, which are therefore potential targets for genetic improvement of tomato fruit quality.

  16. The Food and Drug Administration Office of Women's Health: Impact of Science on Regulatory Policy: An Update.

    Science.gov (United States)

    Elahi, Merina; Eshera, Noha; Bambata, Nkosazana; Barr, Helen; Lyn-Cook, Beverly; Beitz, Julie; Rios, Maria; Taylor, Deborah R; Lightfoote, Marilyn; Hanafi, Nada; DeJager, Lowri; Wiesenfeld, Paddy; Scott, Pamela E; Fadiran, Emmanuel O; Henderson, Marsha B

    2016-03-01

    The U.S. Food and Drug Administration Office of Women's Health (FDA OWH) has supported women's health research for ∼20 years, funding more than 300 studies on women's health issues, including research on diseases/conditions that disproportionately affect women in addition to the evaluation of sex differences in the performance of and response to medical products. These important women's health issues are studied from a regulatory perspective, with a focus on improving and optimizing medical product development and the evaluation of product safety and efficacy in women. These findings have influenced industry direction, labeling, product discontinuation, safety notices, and clinical practice. In addition, OWH-funded research has addressed gaps in the knowledge about diseases and medical conditions that impact women across the life span such as cardiovascular disease, pregnancy, menopause, osteoporosis, and the safe use of numerous medical products.

  17. Gene Regulatory Network Analysis Reveals Differences in Site-specific Cell Fate Determination in Mammalian Brain

    Directory of Open Access Journals (Sweden)

    Gokhan eErtaylan

    2014-12-01

    Full Text Available Neurogenesis - the generation of new neurons - is an ongoing process that persists in the adult mammalian brain of several species, including humans. In this work we analyze two discrete brain regions: the subventricular zone (SVZ lining the walls of the lateral ventricles; and the subgranular zone (SGZ of the dentate gyrus of the hippocampus in mice and shed light on the SVZ and SGZ specific neurogenesis. We propose a computational model that relies on the construction and analysis of region specific gene regulatory networks from the publicly available data on these two regions. Using this model a number of putative factors involved in neuronal stem cell (NSC identity and maintenance were identified. We also demonstrate potential gender and niche-derived differences based on cell surface and nuclear receptors via Ar, Hif1a and Nr3c1.We have also conducted cell fate determinant analysis for SVZ NSC populations to Olfactory Bulb interneurons and SGZ NSC populations to the granule cells of the Granular Cell Layer. We report thirty-one candidate cell fate determinant gene pairs, ready to be validated. We focus on Ar - Pax6 in SVZ and Sox2 - Ncor1 in SGZ. Both pairs are expressed and localized in the suggested anatomical structures as shown by in situ hybridization and found to physically interact.Finally, we conclude that there are fundamental differences between SGZ and SVZ neurogenesis. We argue that these regulatory mechanisms are linked to the observed differential neurogenic potential of these regions. The presence of nuclear and cell surface receptors in the region specific regulatory circuits indicate the significance of niche derived extracellular factors, hormones and region specific factors such as the oxygen sensitivity, dictating SGZ and SVZ specific neurogenesis.

  18. Safety assessment technology on the free drop impact and puncture analysis of the cask for radioactive material transport

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dew Hey [Korea Institute of Nuclear Safety, Taejon (Korea, Republic of); Lee, Young Shin; Ryu, Chung Hyun; Kim, Hyun Su; Lee, Ho Chul; Hong, Song Jin; Choi, Young Jin; Lee, Jae Hyung; Na, Jae Yun [Chungnam National Univ., Taejon (Korea, Republic of)

    2001-03-15

    In this study, the regulatory condition and analysis condition is analyzed for the free drop and puncture impact analysis to develop the safety assessment technology. Impact analysis is performed with finite element method which is one of the many analysis methods of the shipping cask. LS-DYNA3D and ABAQUS is suitable for the free drop and the puncture impact analysis of the shipping cask. For the analysis model, the KSC-4 that is the shipping cask to transport spent nuclear fuel is investigated. The results of both LS-DYNA3D and ABAQUS is completely corresponded. And The integrity of the shipping cask is verified. Using this study, the reliable safety assessment technology is supplied to the staff. The efficient and reliable regulatory tasks is performed using the standard safety assessment technology.

  19. Regulatory T cell number in multiple sclerosis patients: A meta-analysis.

    Science.gov (United States)

    Noori-Zadeh, Ali; Mesbah-Namin, Seyed Alireza; Bistoon-Beigloo, Sara; Bakhtiyari, Salar; Abbaszadeh, Hojjat-Allah; Darabi, Shahram; Rajabibazl, Masoumeh; Abdanipour, Alireza

    2016-01-01

    Regulatory T cells (Treg cells), defined as CD4(+) CD25(+) FoxP3(+) T cells by expression of CD4, high-affinity IL-2 receptor and the transcription factor, forkhead box P3 (FoxP3). They play a pivotal role in protecting individuals from autoimmunity and a growing body of evidence suggests their role in the prevention of multiple sclerosis development. However, there are discrepancies about the type of defect in the Treg cells of multiple sclerosis patients and especially whether the Treg number alteration could be contributed to multiple sclerosis pathogenesis. Indeed, whether low number of Treg cells can be a risk factor contributing to multiple sclerosis pathogenesis is the matter of debate and there is not any comprehensive agreement on it. Thus, the objective of this systematic review and meta-analysis was to precisely quantify the nature and magnitude of the association between Treg cell number and the risk ratio/odds ratio (OR) of multiple sclerosis in the case-control studies. Hence, medical databases of Embase, PubMed/Medline, PubMed, PubMed Central and SCOPUS were searched for empirical papers using "Regulatory T cell frequency", "Treg frequency" in combination with "multiple sclerosis". In the case-control studies, papers were reviewed for inclusion/exclusion criteria and 8 publications were included. Under random-effect model meta-analysis the data showed that the frequency of Treg cells was not a risk factor in multiple sclerosis using current laboratory methods.

  20. A study on the regulatory network with promoter analysis for Arabidopsis DREB-genes

    Science.gov (United States)

    Sazegari, Sima; Niazi, Ali; Ahmadi, Farajolah Shahriary

    2015-01-01

    Dehydration response element binding factors (DREBs) are one of the principal plant transcription factor subfamilies that regulate the expression of many abiotic stress-inducible genes. This sub-family belongs to AP2 transcription factor family and plays a considerable role in improving abiotic stresses tolerance in plants. Therefore, it is of interest to identify critical cis-acting elements involved in abiotic stress responses. In this study, we survey promoter cis-elements for ATDREBs genes (Arabidopsis thaliana DREBs). Regulatory networks based on ATDREB candidate genes were also generated to find other genes that are functionally similar to DREBs. The study was conducted on all 20 Arabidopsis thaliana non redundant DREB genes stored in RefSeq database. Promoter analysis and regulatory network prediction was accomplished by use of Plant CARE program and GeneMANIA web tool, respectively. The results indicated that among all genes, DREB1A, DREB1C, DREB2C, DREB2G and DEAR3 have the most type of diverse motifs involved in abiotic stress responses. It is implied that co-operation of abscisic acid, ethylene, salicylic acid and methyl jasmonate signaling is crucial for the regulation of the expression of drought and cold responses through DREB transcription factors. Gene network analysis showed different co-expressed but functionally similar genes that had physical and functional interactions with candidate DREB genes. PMID:25848171

  1. Impact of Safety-Related Regulatory Action on Drug Use in Ambulatory Care in the Netherlands

    NARCIS (Netherlands)

    Piening, S.; Reber, K. C.; Wieringa, J. E.; Straus, S. M. J. M.; de Graeff, P. A.; Haaijer-Ruskamp, F. M.; Mol, P. G. M.

    2012-01-01

    The effect of Direct Healthcare Professional Communications (DHPCs) informing health-care providers of serious drug safety issues has been questioned. The aim of this study was to evaluate the impact of DHPCs on drug use. Nationwide dispensing data for the period 2000-2008 for new users of 46 drugs

  2. Impact of Safety-Related Regulatory Action on Drug Use in Ambulatory Care in the Netherlands

    NARCIS (Netherlands)

    Piening, S.; Reber, K. C.; Wieringa, J. E.; Straus, S. M. J. M.; de Graeff, P. A.; Haaijer-Ruskamp, F. M.; Mol, P. G. M.

    The effect of Direct Healthcare Professional Communications (DHPCs) informing health-care providers of serious drug safety issues has been questioned. The aim of this study was to evaluate the impact of DHPCs on drug use. Nationwide dispensing data for the period 2000-2008 for new users of 46 drugs

  3. A genome-wide analysis of small regulatory RNAs in the human pathogen group A Streptococcus.

    Directory of Open Access Journals (Sweden)

    Nataly Perez

    Full Text Available The coordinated regulation of gene expression is essential for pathogens to infect and cause disease. A recently appreciated mechanism of regulation is that afforded by small regulatory RNA (sRNA molecules. Here, we set out to assess the prevalence of sRNAs in the human bacterial pathogen group A Streptococcus (GAS. Genome-wide identification of candidate GAS sRNAs was performed through a tiling Affymetrix microarray approach and identified 40 candidate sRNAs within the M1T1 GAS strain MGAS2221. Together with a previous bioinformatic approach this brings the number of novel candidate sRNAs in GAS to 75, a number that approximates the number of GAS transcription factors. Transcripts were confirmed by Northern blot analysis for 16 of 32 candidate sRNAs tested, and the abundance of several of these sRNAs were shown to be temporally regulated. Six sRNAs were selected for further study and the promoter, transcriptional start site, and Rho-independent terminator identified for each. Significant variation was observed between the six sRNAs with respect to their stability during growth, and with respect to their inter- and/or intra-serotype-specific levels of abundance. To start to assess the contribution of sRNAs to gene regulation in M1T1 GAS we deleted the previously described sRNA PEL from four clinical isolates. Data from genome-wide expression microarray, quantitative RT-PCR, and Western blot analyses are consistent with PEL having no regulatory function in M1T1 GAS. The finding that candidate sRNA molecules are prevalent throughout the GAS genome provides significant impetus to the study of this fundamental gene-regulatory mechanism in an important human pathogen.

  4. Report to the US Nuclear Regulatory Commission on Analysis and Evaluation of Operational Data, 1986

    Energy Technology Data Exchange (ETDEWEB)

    None

    1987-05-01

    This annual report of the US Nuclear Regulatory Commission's Office for Analysis and Evaluation of Operational Data (AEOD) is devoted to the activities performed during calendar year 1986. Comments and observations are provided on operating experience at nuclear power plants and other NRC licensees, including results from selected AEOD studies; summaries of abnormal occurrences involving US nuclear plants; reviews of licensee event reports and their quality, reactor scram experience from 1984 to 1986, engineered safety features actuations, and the trends and patterns analysis program; and assessments of nonreactor and medical misadministration events. In addition, the report provides the year-end status of all recommendations included in AEOD studies, and listings of all AEOD reports issued from 1980 through 1986.

  5. Impact of a Fragmented Regulatory Environment on Sustainable Urban Development Design Management

    Directory of Open Access Journals (Sweden)

    Kerry Anne London

    2009-12-01

    Full Text Available The building project development approval process is increasingly complex and fraught with conflict due to the rise of the sustainable urban development movement and inclusive decision making. Coupled with this, government decision-making decentralization has resulted in a fragmented and over-regulated compliance system. Problems arising from the process include wasted resources, excessive time delays, increased holding and litigation costs, inadequate planning coordination, high levels of advocacy costs and a divisive politicized approval process. In Australia, despite attempts by government and industry associations, numerous problems are still unresolved. Design managers increasingly assume a liaison role during the approval phase. There is a long tradition of planning theory literature which provides context for understanding the knowledge-power-participation relationship for this paper. This study investigated the policy, process and practice conflicts during the approval stage in achieving sustainable urban developments. Three regional local government areas within one state jurisdiction and observations from detailed structured focus group interviews involving 23 stakeholders, proposers and assessors were analysed to explore this conflictual environment. As a result of regulatory fragmentation and excessive consultation, various persuasion tactics have been developed by all stakeholders of which `reciprocity' and `authority' were identified as the most common. Two challenges for design managers were thus identified: first, the emergence of the role of a by default central informal arbitrator across conflicting planning instruments; and, second, as a navigator through a set of persuasion tactics. An inclusive knowledge-based design management framework for sustainable urban development is proposed considering Habermas' communicative planning theory, Foucaltian governance and discursive powers thesis and Cialdini's persuasion theory, as

  6. On the Path to SunShot - Utility Regulatory Business Model Reforms forAddressing the Financial Impacts of Distributed Solar on Utilities

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2016-05-01

    Net-energy metering (NEM) with volumetric retail electricity pricing has enabled rapid proliferation of distributed photovoltaics (DPV) in the United States. However, this transformation is raising concerns about the potential for higher electricity rates and cost-shifting to non-solar customers, reduced utility shareholder profitability, reduced utility earnings opportunities, and inefficient resource allocation. Although DPV deployment in most utility territories remains too low to produce significant impacts, these concerns have motivated real and proposed reforms to utility regulatory and business models, with profound implications for future DPV deployment. This report explores the challenges and opportunities associated with such reforms in the context of the U.S. Department of Energy’s SunShot Initiative. As such, the report focuses on a subset of a broader range of reforms underway in the electric utility sector. Drawing on original analysis and existing literature, we analyze the significance of DPV’s financial impacts on utilities and non-solar ratepayers under current NEM rules and rate designs, the projected effects of proposed NEM and rate reforms on DPV deployment, and alternative reforms that could address utility and ratepayer concerns while supporting continued DPV growth. We categorize reforms into one or more of four conceptual strategies. Understanding how specific reforms map onto these general strategies can help decision makers identify and prioritize options for addressing specific DPV concerns that balance stakeholder interests.

  7. Impact Analysis on an Attributed Goal Graph

    Science.gov (United States)

    Hayashi, Shinpei; Tanabe, Daisuke; Kaiya, Haruhiko; Saeki, Motoshi

    Requirements changes frequently occur at any time of a software development process, and their management is a crucial issue to develop software of high quality. Meanwhile, goal-oriented analysis techniques are being put into practice to elicit requirements. In this situation, the change management of goal graphs and its support are necessary. This paper presents a technique related to the change management of goal graphs, realizing impact analysis on a goal graph when its modifications occur. Our impact analysis detects conflicts that arise when a new goal is added, and investigates the achievability of the other goals when an existing goal is deleted. We have implemented a supporting tool for automating the analysis. Two case studies suggested the efficiency of the proposed approach.

  8. Techniques for analyzing the impacts of certain electric-utility ratemaking and regulatory-policy concepts. Regulatory laws and policies. [State by state

    Energy Technology Data Exchange (ETDEWEB)

    None

    1980-08-01

    This report is a legal study prepared to provide a review of the substantive and procedural laws of each regulatory jurisdiction that may affect implementation of the PURPA standards, and to summarize the current state of consideration and implementation of policies and rate designs similar or identical to the PURPA standards by state regulatory agencies and nonregulated utilities. This report is divided into three sections. The first section, the Introduction, summarizes the standards promulgated by PURPA and the results of the legal study. The second section, State Regulatory Law and Procedure, summarizes for each state or other ratemaking jurisdiction: (1) general constitutional and statutory provisions affecting utility rates and conditions of service; (2) specific laws or decisions affecting policy or rate design issues covered by PURPA standards; and (3) statutes and decisions governing administrative procedures, including judicial review. A chart showing actions taken on the policy and rate design issues addressed by PURPA is also included for each jurisdiction, and citations to relevant authorities are presented for each standard. State statutes or decisions that specifically define a state standard similar or identical to a PURPA standard, or that refer to one of the three PURPA objectives, are noted. The third section, Nonregulated Electric Utilities, summarizes information available on nonregulated utilities, i.e., publicly or cooperatively owned utilities which are specifically exempted from state regulation by state law.

  9. Basin-Scale Hydrologic Impacts of CO2 Storage: Regulatory and Capacity Implications

    Energy Technology Data Exchange (ETDEWEB)

    Birkholzer, J.T.; Zhou, Q.

    2009-04-02

    Industrial-scale injection of CO{sub 2} into saline sedimentary basins will cause large-scale fluid pressurization and migration of native brines, which may affect valuable groundwater resources overlying the deep sequestration reservoirs. In this paper, we discuss how such basin-scale hydrologic impacts can (1) affect regulation of CO{sub 2} storage projects and (2) may reduce current storage capacity estimates. Our assessment arises from a hypothetical future carbon sequestration scenario in the Illinois Basin, which involves twenty individual CO{sub 2} storage projects in a core injection area suitable for long-term storage. Each project is assumed to inject five million tonnes of CO{sub 2} per year for 50 years. A regional-scale three-dimensional simulation model was developed for the Illinois Basin that captures both the local-scale CO{sub 2}-brine flow processes and the large-scale groundwater flow patterns in response to CO{sub 2} storage. The far-field pressure buildup predicted for this selected sequestration scenario suggests that (1) the area that needs to be characterized in a permitting process may comprise a very large region within the basin if reservoir pressurization is considered, and (2) permits cannot be granted on a single-site basis alone because the near- and far-field hydrologic response may be affected by interference between individual sites. Our results also support recent studies in that environmental concerns related to near-field and far-field pressure buildup may be a limiting factor on CO{sub 2} storage capacity. In other words, estimates of storage capacity, if solely based on the effective pore volume available for safe trapping of CO{sub 2}, may have to be revised based on assessments of pressure perturbations and their potential impact on caprock integrity and groundwater resources, respectively. We finally discuss some of the challenges in making reliable predictions of large-scale hydrologic impacts related to CO{sub 2

  10. Impact of Global Patent and Regulatory Reform on Patent Strategies for Biotechnology

    Directory of Open Access Journals (Sweden)

    Vincent J. Napoleon

    2009-04-01

    Full Text Available  I come to you this morning not as an intellectual property lawyer but as a former general counsel of biotechnology and pharmaceutical related companies, as an attorney with significant exposure to intellectual property issues and as one who has seen first-hand the importance of intellectual property in shaping commercial strategies in biotechnology. With that as a backdrop, I would like to thank you for allowing me the opportunity to share with you today thoughts that I have regarding patents and the impact of patent reform on biotechnology. It has been said that the best way to predict the future is to invent it. However, I believe that the best way to control the future is to patent it.

  11. Constructing a Knowledge Base for Gene Regulatory Dynamics by Formal Concept Analysis Methods

    CERN Document Server

    Wollbold, Johannes; Ganter, Bernhard

    2008-01-01

    Our aim is to build a set of rules, such that reasoning over temporal dependencies within gene regulatory networks is possible. The underlying transitions may be obtained by discretizing observed time series, or they are generated based on existing knowledge, e.g. by Boolean networks or their nondeterministic generalization. We use the mathematical discipline of formal concept analysis (FCA), which has been applied successfully in domains as knowledge representation, data mining or software engineering. By the attribute exploration algorithm, an expert or a supporting computer program is enabled to decide about the validity of a minimal set of implications and thus to construct a sound and complete knowledge base. From this all valid implications are derivable that relate to the selected properties of a set of genes. We present results of our method for the initiation of sporulation in Bacillus subtilis. However the formal structures are exhibited in a most general manner. Therefore the approach may be adapte...

  12. Regulatory Analysis on the Safety Assessment of NPPs against Aircraft Crash

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Yun; Park, Jong Seuk; Chung, Yun Suk; Jung, Rae Young [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2011-10-15

    Following the 9/11 terror, a new regulation (10CFR 50.150) was enacted in June 2009 in the United States mandating the assessment of new nuclear power plants (NPPs) against intentional aircraft crashes, along with a regulation (10CFR 50.54 (h)(h)) in March 2009 that requires the establishment of accident mitigation measures for NPPs in operation. The UAE requested that the Korean NPP (APR 1400) design meet the U.S.'s new requirements related to the intentional aircraft crash. During the UAE NPP contract bidding process, France claimed that the Korean NPP is vulnerable to aircraft crashes comparing with the French NPP (EPR). Under these international and domestic environments, the necessity to establish a domestic regulation concerning the intentional aircraft crash was raised. This paper proposes a draft regulatory position on this issue through a comprehensive analysis of various influencing factors

  13. Comparative analysis of RNA regulatory elements of amino acid metabolism genes in Actinobacteria

    Directory of Open Access Journals (Sweden)

    Gelfand Mikhail S

    2005-10-01

    Full Text Available Abstract Background Formation of alternative structures in mRNA in response to external stimuli, either direct or mediated by proteins or other RNAs, is a major mechanism of regulation of gene expression in bacteria. This mechanism has been studied in detail using experimental and computational approaches in proteobacteria and Firmicutes, but not in other groups of bacteria. Results Comparative analysis of amino acid biosynthesis operons in Actinobacteria resulted in identification of conserved regions upstream of several operons. Classical attenuators were predicted upstream of trp operons in Corynebacterium spp. and Streptomyces spp., and trpS and leuS genes in some Streptomyces spp. Candidate leader peptides with terminators were observed upstream of ilvB genes in Corynebacterium spp., Mycobacterium spp. and Streptomyces spp. Candidate leader peptides without obvious terminators were found upstream of cys operons in Mycobacterium spp. and several other species. A conserved pseudoknot (named LEU element was identified upstream of leuA operons in most Actinobacteria. Finally, T-boxes likely involved in the regulation of translation initiation were observed upstream of ileS genes from several Actinobacteria. Conclusion The metabolism of tryptophan, cysteine and leucine in Actinobacteria seems to be regulated on the RNA level. In some cases the mechanism is classical attenuation, but in many cases some components of attenuators are missing. The most interesting case seems to be the leuA operon preceded by the LEU element that may fold into a conserved pseudoknot or an alternative structure. A LEU element has been observed in a transposase gene from Bifidobacterium longum, but it is not conserved in genes encoding closely related transposases despite a very high level of protein similarity. One possibility is that the regulatory region of the leuA has been co-opted from some element involved in transposition. Analysis of phylogenetic patterns

  14. Massively parallel cis-regulatory analysis in the mammalian central nervous system.

    Science.gov (United States)

    Shen, Susan Q; Myers, Connie A; Hughes, Andrew E O; Byrne, Leah C; Flannery, John G; Corbo, Joseph C

    2016-02-01

    Cis-regulatory elements (CREs, e.g., promoters and enhancers) regulate gene expression, and variants within CREs can modulate disease risk. Next-generation sequencing has enabled the rapid generation of genomic data that predict the locations of CREs, but a bottleneck lies in functionally interpreting these data. To address this issue, massively parallel reporter assays (MPRAs) have emerged, in which barcoded reporter libraries are introduced into cells, and the resulting barcoded transcripts are quantified by next-generation sequencing. Thus far, MPRAs have been largely restricted to assaying short CREs in a limited repertoire of cultured cell types. Here, we present two advances that extend the biological relevance and applicability of MPRAs. First, we adapt exome capture technology to instead capture candidate CREs, thereby tiling across the targeted regions and markedly increasing the length of CREs that can be readily assayed. Second, we package the library into adeno-associated virus (AAV), thereby allowing delivery to target organs in vivo. As a proof of concept, we introduce a capture library of about 46,000 constructs, corresponding to roughly 3500 DNase I hypersensitive (DHS) sites, into the mouse retina by ex vivo plasmid electroporation and into the mouse cerebral cortex by in vivo AAV injection. We demonstrate tissue-specific cis-regulatory activity of DHSs and provide examples of high-resolution truncation mutation analysis for multiplex parsing of CREs. Our approach should enable massively parallel functional analysis of a wide range of CREs in any organ or species that can be infected by AAV, such as nonhuman primates and human stem cell-derived organoids.

  15. Assessment of the impact of scheduled postmarketing safety summary analyses on regulatory actions.

    Science.gov (United States)

    Sekine, S; Pinnow, E E; Wu, E; Kurtzig, R; Hall, M; Dal Pan, G J

    2016-07-01

    In addition to standard postmarketing drug safety monitoring, Section 915 of the Food and Drug Administration Amendments Act of 2007 (FDAAA) requires the US Food and Drug Administration (FDA) to conduct a summary analysis of adverse event reports to identify risks of a drug or biologic product 18 months after product approval, or after 10,000 patients have used the product, whichever is later. We assessed the extent to which these analyses identified new safety signals and resultant safety-related label changes. Among 458 newly approved products, 300 were the subjects of a scheduled analysis; a new safety signal that resulted in a safety-related label change was found for 11 of these products. Less than 2% of 713 safety-related label changes were based on the scheduled analyses. Our study suggests that the safety summary analyses provide only marginal value over other pharmacovigilance activities.

  16. Kindness in the blood: A randomized controlled trial of the gene regulatory impact of prosocial behavior.

    Science.gov (United States)

    Nelson-Coffey, S Katherine; Fritz, Megan M; Lyubomirsky, Sonja; Cole, Steve W

    2017-07-01

    Prosocial behavior is linked to longevity, but few studies have experimentally manipulated prosocial behavior to identify the causal mechanisms underlying this association. One possible mediating pathway involves changes in gene expression that may subsequently influence disease development or resistance. In the current study, we examined changes in a leukocyte gene expression profile known as the Conserved Transcriptional Response to Adversity (CTRA) in 159 adults who were randomly assigned for 4 weeks to engage in prosocial behavior directed towards specific others, prosocial behavior directed towards the world in general, self-focused kindness, or a neutral control task. Those randomized to prosocial behavior towards specific others demonstrated improvements (i.e., reductions) in leukocyte expression of CTRA indicator genes. No significant changes in CTRA gene expression were observed in the other 3 conditions. These findings suggest that prosocial behavior can causally impact leukocyte gene expression profiles in ways that might potentially help explain the previously observed health advantages associated with social ties. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Psychological resilience and the gene regulatory impact of posttraumatic stress in Nepali child soldiers.

    Science.gov (United States)

    Kohrt, Brandon A; Worthman, Carol M; Adhikari, Ramesh P; Luitel, Nagendra P; Arevalo, Jesusa M G; Ma, Jeffrey; McCreath, Heather; Seeman, Teresa E; Crimmins, Eileen M; Cole, Steven W

    2016-07-19

    Adverse social conditions in early life have been linked to increased expression of proinflammatory genes and reduced expression of antiviral genes in circulating immune cells-the conserved transcriptional response to adversity (CTRA). However, it remains unclear whether such effects are specific to the Western, educated, industrialized, rich, and democratic (WEIRD) cultural environments in which previous research has been conducted. To assess the roles of early adversity and individual psychological resilience in immune system gene regulation within a non-WEIRD population, we evaluated CTRA gene-expression profiles in 254 former child soldiers and matched noncombatant civilians 5 y after the People's War in Nepal. CTRA gene expression was up-regulated in former child soldiers. These effects were linked to the degree of experienced trauma and associated distress-that is, posttraumatic stress disorder (PTSD) severity-more than to child soldier status per se. Self-perceived psychological resilience was associated with marked buffering of CTRA activation such that PTSD-affected former child soldiers with high levels of personal resilience showed molecular profiles comparable to those of PTSD-free civilians. These results suggest that CTRA responses to early life adversity are not restricted to WEIRD cultural contexts and they underscore the key role of resilience in determining the molecular impact of adverse environments.

  18. Mitigating regulatory impact: the case of partial price controls on metformin in India.

    Science.gov (United States)

    Bhaskarabhatla, Ajay; Chatterjee, Chirantan; Anurag, Priyatam; Pennings, Enrico

    2017-03-01

    The use of drug price controls is a contentious issue globally. Low- and middle-income countries use direct price controls to improve access to essential drugs. But such price controls have little meaning if they are not designed and implemented well, and the extent to which firms coordinate in these countries to weaken price controls has been largely overlooked. In mid-2013, India adopted partial price-cap regulation for some, but not all, formulations of several essential medicines. Using data on sales and prices of the out-of-patent oral antidiabetic drug Metformin—considered essential by WHO since 1998—and employing the differences-in-differences methodology, we examine the impact of the regulation on curbing prices. We find that firms coordinated to increase the price of the regulated formulation in the period before regulation, which led to a higher ceiling price. We also find, using triple-differences analyses, that the coordination is stronger among larger firms and for time-release formulations. We present anecdotal evidence to suggest that pharmaceutical trade associations facilitated coordination among firms, and we conclude that partial price control of Metformin in India is, at best, a modest improvement over no regulation.

  19. A methodology for the structural and functional analysis of signaling and regulatory networks

    Directory of Open Access Journals (Sweden)

    Simeoni Luca

    2006-02-01

    Full Text Available Abstract Background Structural analysis of cellular interaction networks contributes to a deeper understanding of network-wide interdependencies, causal relationships, and basic functional capabilities. While the structural analysis of metabolic networks is a well-established field, similar methodologies have been scarcely developed and applied to signaling and regulatory networks. Results We propose formalisms and methods, relying on adapted and partially newly introduced approaches, which facilitate a structural analysis of signaling and regulatory networks with focus on functional aspects. We use two different formalisms to represent and analyze interaction networks: interaction graphs and (logical interaction hypergraphs. We show that, in interaction graphs, the determination of feedback cycles and of all the signaling paths between any pair of species is equivalent to the computation of elementary modes known from metabolic networks. Knowledge on the set of signaling paths and feedback loops facilitates the computation of intervention strategies and the classification of compounds into activators, inhibitors, ambivalent factors, and non-affecting factors with respect to a certain species. In some cases, qualitative effects induced by perturbations can be unambiguously predicted from the network scheme. Interaction graphs however, are not able to capture AND relationships which do frequently occur in interaction networks. The consequent logical concatenation of all the arcs pointing into a species leads to Boolean networks. For a Boolean representation of cellular interaction networks we propose a formalism based on logical (or signed interaction hypergraphs, which facilitates in particular a logical steady state analysis (LSSA. LSSA enables studies on the logical processing of signals and the identification of optimal intervention points (targets in cellular networks. LSSA also reveals network regions whose parametrization and initial

  20. The Impacts of Human Visitation on Mussel Bed Communities Along the California Coast: Are Regulatory Marine Reserves Effective in Protecting These Communities?

    Science.gov (United States)

    Smith, Jayson R.; Fong, Peggy; Ambrose, Richard F.

    2008-04-01

    Rocky intertidal habitats frequently are used by humans for recreational, educational, and subsistence-harvesting purposes, with intertidal populations damaged by visitation activities such as extraction, trampling, and handling. California Marine Managed Areas, particularly regulatory marine reserves (MRs), were established to provide legal protection and enhancement of coastal resources and include prohibitions on harvesting intertidal populations. However, the effectiveness of MRs is unclear as enforcement of no-take laws is weak and no regulations protect intertidal species from other detrimental visitor impacts such as trampling. The goal of this study was two-fold: (1) to determine impacts from human visitation on California mussel populations ( Mytilus californianus) and mussel bed community diversity; and (2) to investigate the effectiveness of regulatory MRs in reducing visitor impacts on these populations. Surveys of mussel populations and bed-associated diversity were compared: (1) at sites subjected to either high or low levels of human use, and (2) at sites either unprotected or with regulatory protection banning collecting. At sites subjected to higher levels of human visitation, mussel populations were significantly lower than low-use sites. Comparisons of mussel populations inside and outside of regulatory MRs revealed no consistent pattern suggesting that California no-take regulatory reserves may have limited effectiveness in protecting mussel communities. In areas where many people visit intertidal habitats for purposes other than collecting, many organisms will be affected by trampling, turning of rocks, and handling. In these cases, effective protection of rocky intertidal communities requires an approach that goes beyond the singular focus on collecting to reduce the full suite of impacts.

  1. Frogs and ponds: a multilevel analysis of the regulatory mode complementarity hypothesis.

    Science.gov (United States)

    Pierro, Antonio; Presaghi, Fabio; Higgins, E Tory; Klein, Kristen M; Kruglanski, Arie W

    2012-02-01

    Regulatory mode is a psychological construct pertaining to the self-regulatory orientation of individuals or teams engaged in goal pursuit. Locomotion, the desire for continuous progress or movement in goal pursuit, and assessment, the desire to critically evaluate and compare goals and means, are orthogonal regulatory modes. However, they are also complementary, in that both locomotion and assessment are necessary for effectual goal pursuit. In the present research, the authors sought to demonstrate that multilevel regulatory mode complementarity can positively affect individual-level performance on goal-relevant tasks. The authors recruited 289 employees (177 men, 112 women) from preexisting work teams in workplace organizations in Italy and obtained (a) employees' individual-level scores on the Regulatory Mode Scale and (b) supervisor ratings of each employee's work performance. The results supported the multilevel complementarity hypothesis for regulatory mode. Limitations and recommendations for future research are discussed.

  2. Biosimilars: impact of biologic product life cycle and European experience on the regulatory trajectory in the United States.

    Science.gov (United States)

    Ahmed, Islah; Kaspar, Ben; Sharma, Uma

    2012-02-01

    Biosimilars are defined as biologic products that are highly similar to reference products, notwithstanding minor differences in clinically inactive components, with no clinically meaningful differences between the biologic product and the reference product in terms of safety profile, purity, and potency. Due to the high cost of innovator biologics, as well as an increase in the number of these products reaching patent expiry, the development of a process for approving biosimilar products has become a crucial regulatory issue in the United States. This commentary explores the relationship between structural/biophysical variation and the risk/benefit profile of biosimilars and reference biologics that have undergone process changes in the context of the most recent biophysical, nonclinical, and clinical data available. The search strategy used PubMed, EMBASE, and MEDLINE for the retrieval of documents pertaining to biologic manufacturing, comparative analysis of biosimilars and originator biologics, and relevant review articles on biosimilars. For regulatory documents pertaining to the processes of the approval of biosimilars, biologics, and generics, a search for legislative decisions, briefing summaries, concept papers, guidance, and evaluations of approved and rejected applications for biosimilars published by the World Health Organization, US Food and Drug Administration, European Medicines Agency (EMA), and other national regulatory authorities was conducted. Selected articles from key opinion leaders and manufacturers were also reviewed. These searches were conducted to provide a review of historical and contemporary issues in the consideration of the current status of worldwide biosimilar use and regulation. A total of 18 marketing applications covering 9 development programs were surveyed. Of these, 14 applications were approved and 4 were rejected by the EMA. None of the biosimilars were reported to have evidence of significant clinical variation relative

  3. Genomic analysis reveals major determinants of cis-regulatory variation in Capsella grandiflora.

    Science.gov (United States)

    Steige, Kim A; Laenen, Benjamin; Reimegård, Johan; Scofield, Douglas G; Slotte, Tanja

    2017-01-31

    Understanding the causes of cis-regulatory variation is a long-standing aim in evolutionary biology. Although cis-regulatory variation has long been considered important for adaptation, we still have a limited understanding of the selective importance and genomic determinants of standing cis-regulatory variation. To address these questions, we studied the prevalence, genomic determinants, and selective forces shaping cis-regulatory variation in the outcrossing plant Capsella grandiflora We first identified a set of 1,010 genes with common cis-regulatory variation using analyses of allele-specific expression (ASE). Population genomic analyses of whole-genome sequences from 32 individuals showed that genes with common cis-regulatory variation (i) are under weaker purifying selection and (ii) undergo less frequent positive selection than other genes. We further identified genomic determinants of cis-regulatory variation. Gene body methylation (gbM) was a major factor constraining cis-regulatory variation, whereas presence of nearby transposable elements (TEs) and tissue specificity of expression increased the odds of ASE. Our results suggest that most common cis-regulatory variation in C. grandiflora is under weak purifying selection, and that gene-specific functional constraints are more important for the maintenance of cis-regulatory variation than genome-scale variation in the intensity of selection. Our results agree with previous findings that suggest TE silencing affects nearby gene expression, and provide evidence for a link between gbM and cis-regulatory constraint, possibly reflecting greater dosage sensitivity of body-methylated genes. Given the extensive conservation of gbM in flowering plants, this suggests that gbM could be an important predictor of cis-regulatory variation in a wide range of plant species.

  4. Proteome analysis of the rice etioplast: metabolic and regulatory networks and novel protein functions.

    Science.gov (United States)

    von Zychlinski, Anne; Kleffmann, Torsten; Krishnamurthy, Nandini; Sjölander, Kimmen; Baginsky, Sacha; Gruissem, Wilhelm

    2005-08-01

    We report an extensive proteome analysis of rice etioplasts, which were highly purified from dark-grown leaves by a novel protocol using Nycodenz density gradient centrifugation. Comparative protein profiling of different cell compartments from leaf tissue demonstrated the purity of the etioplast preparation by the absence of diagnostic marker proteins of other cell compartments. Systematic analysis of the etioplast proteome identified 240 unique proteins that provide new insights into heterotrophic plant metabolism and control of gene expression. They include several new proteins that were not previously known to localize to plastids. The etioplast proteins were compared with proteomes from Arabidopsis chloroplasts and plastid from tobacco Bright Yellow 2 cells. Together with computational structure analyses of proteins without functional annotations, this comparative proteome analysis revealed novel etioplast-specific proteins. These include components of the plastid gene expression machinery such as two RNA helicases, an RNase II-like hydrolytic exonuclease, and a site 2 protease-like metalloprotease all of which were not known previously to localize to the plastid and are indicative for so far unknown regulatory mechanisms of plastid gene expression. All etioplast protein identifications and related data were integrated into a data base that is freely available upon request.

  5. Regulatory analysis on criteria for the release of patients administered radioactive material

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, S.; McGuire, S.A. [Nuclear Regulatory Commission, Washington, DC (United States). Div. of Regulatory Applications; Behling, U.H.; Behling, K.; Goldin, D. [Cohen (S.) and Associates, Inc., McLean, VA (United States)

    1994-05-01

    The Nuclear Regulatory Commission (NRC) has received two petitions to amend its regulations in 10 CFR Parts 20 and 35 as they apply to doses received by members of the public exposed to patients released from a hospital after they have been administered radioactive material. While the two petitions are not identical they both request that the NRC establish a dose limit of 5 millisieverts (0.5 rem) per year for individuals exposed to patients who have been administered radioactive materials. This Regulatory Analysis evaluates three alternatives. Alternative 1 is for the NRC to amend its patient release criteria in 10 CFR 35.75 to use the more stringent dose limit of 1 millisievert per year in 10 CFR 20.1301(a) for its patient release criteria. Alternative 2 is for the NRC to continue using the existing patient release criteria in 10 CFR 35.75 of 1,110 megabecquerels of activity or a dose rate at one meter from the patient of 0.05 millisievert per hour. Alternative 3 is for the NRC to amend the patient release criteria in 10 CFR 35.75 to specify a dose limit of 5 millisieverts for patient release. The evaluation indicates that Alternative 1 would cause a prohibitively large increase in the national health care cost from retaining patients in a hospital longer and would cause significant personal and psychological costs to patients and their families. The choice of Alternatives 2 or 3 would affect only thyroid cancer patients treated with iodine-131. For those patients, Alternative 3 would result in less hospitalization than Alternative 2. Alternative 3 has a potential decrease in national health care cost of $30,000,000 per year but would increase the potential collective dose from released therapy patients by about 2,700 person-rem per year, mainly to family members.

  6. Environmental impacts of combining pig slurry acidification and separation under different regulatory regimes - a life cycle assessment

    DEFF Research Database (Denmark)

    ten Hoeve, Marieke; Gomez Muñoz, Beatriz; Jensen, Lars Stoumann

    2016-01-01

    -house acidification and separation on marine eutrophication potential compared to these technologies individually. The model was sensitive to the chosen ammonia emission coefficients and to the choice of inclusion of indirect nitrous oxide emissions, since scenarios changed ranking for certain impact categories.......Global livestock production is increasing rapidly, leading to larger amounts of manure and environmental impacts. Technologies that can be applied to treat manure in order to decrease certain environmental impacts include separation and acidification. In this study, a life cycle assessment was used...... to investigate the environmental effects of slurry acidification and separation, and whether there were synergetic environmental benefits to combining these technologies. Furthermore, an analysis was undertaken into the effect of implementing regulations restricting the P application rate to soils...

  7. Fort Drum Preliminary Fiscal Impact Analysis.

    Science.gov (United States)

    1986-02-01

    of inmigrants 0 Fiscal histories, projections, and impacts for counties, cities, towns, villages, school districts, and the state. The results of...distribution of the inmigrating population within the three counties. Thus, an accurate forecast of the expected distribution of the inmigrating population is a...The distribution of inmigration to the school districts was made using the analysis explained in Chapter 3. Children associated with 800 new on-post

  8. Genome-Scale Analysis of Cell-Specific Regulatory Codes Using Nuclear Enzymes.

    Science.gov (United States)

    Baek, Songjoon; Sung, Myong-Hee

    2016-01-01

    High-throughput sequencing technologies have made it possible for biologists to generate genome-wide profiles of chromatin features at the nucleotide resolution. Enzymes such as nucleases or transposes have been instrumental as a chromatin-probing agent due to their ability to target accessible chromatin for cleavage or insertion. On the scale of a few hundred base pairs, preferential action of the nuclear enzymes on accessible chromatin allows mapping of cell state-specific accessibility in vivo. Such accessible regions contain functionally important regulatory sites, including promoters and enhancers, which undergo active remodeling for cells adapting in a dynamic environment. DNase-seq and the more recent ATAC-seq are two assays that are gaining popularity. Deep sequencing of DNA libraries from these assays, termed genomic footprinting, has been proposed to enable the comprehensive construction of protein occupancy profiles over the genome at the nucleotide level. Recent studies have discovered limitations of genomic footprinting which reduce the scope of detectable proteins. In addition, the identification of putative factors that bind to the observed footprints remains challenging. Despite these caveats, the methodology still presents significant advantages over alternative techniques such as ChIP-seq or FAIRE-seq. Here we describe computational approaches and tools for analysis of chromatin accessibility and genomic footprinting. Proper experimental design and assay-specific data analysis ensure the detection sensitivity and maximize retrievable information. The enzyme-based chromatin profiling approaches represent a powerful and evolving methodology which facilitates our understanding of how the genome is regulated.

  9. The impact of gene expression variation on the robustness and evolvability of a developmental gene regulatory network.

    Directory of Open Access Journals (Sweden)

    David A Garfield

    2013-10-01

    Full Text Available Regulatory interactions buffer development against genetic and environmental perturbations, but adaptation requires phenotypes to change. We investigated the relationship between robustness and evolvability within the gene regulatory network underlying development of the larval skeleton in the sea urchin Strongylocentrotus purpuratus. We find extensive variation in gene expression in this network throughout development in a natural population, some of which has a heritable genetic basis. Switch-like regulatory interactions predominate during early development, buffer expression variation, and may promote the accumulation of cryptic genetic variation affecting early stages. Regulatory interactions during later development are typically more sensitive (linear, allowing variation in expression to affect downstream target genes. Variation in skeletal morphology is associated primarily with expression variation of a few, primarily structural, genes at terminal positions within the network. These results indicate that the position and properties of gene interactions within a network can have important evolutionary consequences independent of their immediate regulatory role.

  10. Techniques of analyzing the impacts of certain electric-utility ratemaking and regulatory-policy concepts. Bibliography

    Energy Technology Data Exchange (ETDEWEB)

    None

    1980-08-01

    This bibliography provides documentation for use by state public utility commissions and major nonregulated utilities in evaluating the applicability of a wide range of electric utility rate design and regulatory concepts in light of certain regulatory objectives. Part I, Utility Regulatory Objectives, contains 2084 citations on conservation of energy and capital; efficient use of facilities and resources; and equitable rates to electricity consumers. Part II, Rate Design Concepts, contains 1238 citations on time-of-day rates; seasonally-varying rates; cost-of-service rates; interruptible rates (including the accompanying use of load management techniques); declining block rates; and lifeline rates. Part III, Regulatory Concepts, contains 1282 references on restrictions on master metering; procedures for review of automatic adjustment clauses; prohibitions of rate or regulatory discrimination against solar, wind, or other small energy systems; treatment of advertising expenses; and procedures to protect ratepayers from abrupt termination of service.

  11. Analysis of regulatory network involved in mechanical induction of embryonic stem cell differentiation.

    Directory of Open Access Journals (Sweden)

    Xinan Zhang

    Full Text Available Embryonic stem cells are conventionally differentiated by modulating specific growth factors in the cell culture media. Recently the effect of cellular mechanical microenvironment in inducing phenotype specific differentiation has attracted considerable attention. We have shown the possibility of inducing endoderm differentiation by culturing the stem cells on fibrin substrates of specific stiffness. Here, we analyze the regulatory network involved in such mechanically induced endoderm differentiation under two different experimental configurations of 2-dimensional and 3-dimensional culture, respectively. Mouse embryonic stem cells are differentiated on an array of substrates of varying mechanical properties and analyzed for relevant endoderm markers. The experimental data set is further analyzed for identification of co-regulated transcription factors across different substrate conditions using the technique of bi-clustering. Overlapped bi-clusters are identified following an optimization formulation, which is solved using an evolutionary algorithm. While typically such analysis is performed at the mean value of expression data across experimental repeats, the variability of stem cell systems reduces the confidence on such analysis of mean data. Bootstrapping technique is thus integrated with the bi-clustering algorithm to determine sets of robust bi-clusters, which is found to differ significantly from corresponding bi-clusters at the mean data value. Analysis of robust bi-clusters reveals an overall similar network interaction as has been reported for chemically induced endoderm or endodermal organs but with differences in patterning between 2-dimensional and 3-dimensional culture. Such analysis sheds light on the pathway of stem cell differentiation indicating the prospect of the two culture configurations for further maturation.

  12. The foreign experience of regulatory reform implementation and application of «regulatory guillotine»

    Directory of Open Access Journals (Sweden)

    N. M. Litvinova

    2014-09-01

    Full Text Available The foreign experience of regulatory reform implementation is considered. Particular attention is paid to the experience gained and the results of the use of “regulatory guillotine” as one of the kinds of regulatory reforms. The authors analyze the main preconditions and results of regulatory reforms and their impact on improved governance, creation of favorable conditions for business development, creating a positive investment climate. A certain degree of regulatory reform has become the standard for developed markets and for developing countries and are trying to take their place on stage one of the most developed countries. Study abroad experience in regulatory reforms in different countries of the world leads to the conclusion that the foundation for regulatory reform is a special system development and adoption of a special kind of legal acts - regulations. Unlike most legal acts, regulations, at the stage of the project should be accompanied by assessment or regulatory impact analysis, which provides comprehensive information about the possible positive or negative effects of the introduction of state regulation. Such adjustment shall be taken only when the overall benefits of regulation dominate the total cost of its implementation. The authors provide recommendations on the use of foreign experience in Ukraine

  13. A meta-analysis of multiple matched copy number and transcriptomics data sets for inferring gene regulatory relationships.

    Directory of Open Access Journals (Sweden)

    Richard Newton

    Full Text Available Inferring gene regulatory relationships from observational data is challenging. Manipulation and intervention is often required to unravel causal relationships unambiguously. However, gene copy number changes, as they frequently occur in cancer cells, might be considered natural manipulation experiments on gene expression. An increasing number of data sets on matched array comparative genomic hybridisation and transcriptomics experiments from a variety of cancer pathologies are becoming publicly available. Here we explore the potential of a meta-analysis of thirty such data sets. The aim of our analysis was to assess the potential of in silico inference of trans-acting gene regulatory relationships from this type of data. We found sufficient correlation signal in the data to infer gene regulatory relationships, with interesting similarities between data sets. A number of genes had highly correlated copy number and expression changes in many of the data sets and we present predicted potential trans-acted regulatory relationships for each of these genes. The study also investigates to what extent heterogeneity between cell types and between pathologies determines the number of statistically significant predictions available from a meta-analysis of experiments.

  14. A Benefit-Risk Analysis Approach to Capture Regulatory Decision-Making: Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Raju, G K; Gurumurthi, K; Domike, R; Kazandjian, D; Blumenthal, G; Pazdur, R; Woodcock, J

    2016-12-01

    Drug regulators around the world make decisions about drug approvability based on qualitative benefit-risk analyses. There is much interest in quantifying regulatory approaches to benefit and risk. In this work the use of a quantitative benefit-risk analysis was applied to regulatory decision-making about new drugs to treat advanced non-small cell lung cancer (NSCLC). Benefits and risks associated with 20 US Food and Drug Administration (FDA) decisions associated with a set of candidate treatments submitted between 2003 and 2015 were analyzed. For benefit analysis, the median overall survival (OS) was used where available. When not available, OS was estimated based on overall response rate (ORR) or progression-free survival (PFS). Risks were analyzed based on magnitude (or severity) of harm and likelihood of occurrence. Additionally, a sensitivity analysis was explored to demonstrate analysis of systematic uncertainty. FDA approval decision outcomes considered were found to be consistent with the benefit-risk logic.

  15. Regulatory agencies and regulatory risk

    OpenAIRE

    Knieps, Günter; Weiß, Hans-Jörg

    2007-01-01

    The aim of this paper is to show that regulatory risk is due to the discretionary behaviour of regulatory agencies, caused by a too extensive regulatory mandate provided by the legislator. The normative point of reference and a behavioural model of regulatory agencies based on the positive theory of regulation are presented. Regulatory risk with regard to the future behaviour of regulatory agencies is modelled as the consequence of the ex ante uncertainty about the relative influence of inter...

  16. Prognostic Impact of FoxP3+ Regulatory T Cells in Relation to CD8+ T Lymphocyte Density in Human Colon Carcinomas

    OpenAIRE

    Yoon, Harry H.; Jared M Orrock; Foster, Nathan R.; Sargent, Daniel J.; Thomas C. Smyrk; Sinicrope, Frank A

    2012-01-01

    BACKGROUND: T-lymphocyte infiltration into colon carcinomas can influence clinical outcome, and interactions among T cell subsets may be more informative than either subset alone. Our objective was to examine the prognostic impact of tumor-infiltrating FoxP3(+) regulatory T cells (Tregs) in relation to cytotoxic CD8(+) T lymphocytes in patients with colon carcinomas characterized by DNA mismatch repair (MMR) status who participated in adjuvant chemotherapy trials. METHODS: FoxP3(+) and CD8(+)...

  17. Partially observed bipartite network analysis to identify predictive connections in transcriptional regulatory networks

    Directory of Open Access Journals (Sweden)

    Woolf Peter J

    2011-05-01

    Full Text Available Abstract Background Messenger RNA expression is regulated by a complex interplay of different regulatory proteins. Unfortunately, directly measuring the individual activity of these regulatory proteins is difficult, leaving us with only the resulting gene expression pattern as a marker for the underlying regulatory network or regulator-gene associations. Furthermore, traditional methods to predict these regulator-gene associations do not define the relative importance of each association, leading to a large number of connections in the global regulatory network that, although true, are not useful. Results Here we present a Bayesian method that identifies which known transcriptional relationships in a regulatory network are consistent with a given body of static gene expression data by eliminating the non-relevant ones. The Partially Observed Bipartite Network (POBN approach developed here is tested using E. coli expression data and a transcriptional regulatory network derived from RegulonDB. When the regulatory network for E. coli was integrated with 266 E. coli gene chip observations, POBN identified 93 out of 570 connections that were either inconsistent or not adequately supported by the expression data. Conclusion POBN provides a systematic way to integrate known transcriptional networks with observed gene expression data to better identify which transcriptional pathways are likely responsible for the observed gene expression pattern.

  18. Molecular architecture of the regulatory Locus sae of Staphylococcus aureus and its impact on expression of virulence factors.

    Science.gov (United States)

    Steinhuber, Andrea; Goerke, Christiane; Bayer, Manfred G; Döring, Gerd; Wolz, Christiane

    2003-11-01

    We characterized the sae operon, a global regulator for virulence gene expression in Staphylococcus aureus. A Tn917 sae mutant was obtained by screening a Tn917 library of the agr mutant ISP479Mu for clones with altered hemolytic activity. Sequence analysis of the sae operon revealed two additional open reading frames (ORFs) (ORF3 and ORF4) upstream of the two-component regulatory genes saeR and saeS. Four overlapping sae-specific transcripts (T1 to T4) were detected by Northern blot analysis, and the transcriptional initiation points were mapped by primer extension analysis. The T1, T2, and T3 mRNAs are probably terminated at the same stem-loop sequence downstream of saeS. The T1 message (3.1 kb) initiates upstream of ORF4, T2 (2.4 kb) initiates upstream of ORF3, and T3 (2.0 kb) initiates in front of saeR. T4 (0.7 kb) represents a monocistronic mRNA encompassing ORF4 only. sae-specific transcripts were detectable in all of the 40 different clinical S. aureus isolates investigated. Transcript levels were at maximum during the post-exponential growth phase. The sae mutant showed a significantly reduced rate of invasion of human endothelial cells, consistent with diminished transcription and expression of fnbA. The expression of type 5 capsular polysaccharide is activated in the sae mutant of strain Newman, as shown by immunofluorescence and promoter-reporter fusion experiments. In summary, the sae operon constitutes a four-component regulator system which acts on virulence gene expression in S. aureus.

  19. PD-L1 Blockade Differentially Impacts Regulatory T Cells from HIV-Infected Individuals Depending on Plasma Viremia.

    Directory of Open Access Journals (Sweden)

    Cristina Peligero

    2015-12-01

    Full Text Available Blocking the PD-1/PD-L1 pathway has emerged as a potential therapy to restore impaired immune responses in human immunodeficiency virus (HIV-infected individuals. Most reports have studied the impact of the PD-L1 blockade on effector cells and neglected possible effects on regulatory T cells (Treg cells, which play an essential role in balancing immunopathology and antiviral effector responses. The aim of this study was to define the consequences of ex vivo PD-L1 blockade on Treg cells from HIV-infected individuals. We observed that HIV infection led to an increase in PD-1+ and PD-L1+ Treg cells. This upregulation correlated with disease progression and decreased under antiretroviral treatment. Treg cells from viremic individuals had a particularly high PD-1 expression and impaired proliferative capacity in comparison with Treg cells from individuals under antiretroviral treatment. PD-L1 blockade restored the proliferative capacity of Treg cells from viremic individuals but had no effect on its suppressive capacity. Moreover, it increased the viral production in cell cultures from viremic individuals. This increase in viral production correlated with an increase in Treg cell percentage and a reduction in the CD4/Treg and CD8/Treg cell ratios. In contrast to the effect of the PD-L1 blockade on Treg cells from viremic individuals, we did not observe a significant effect on the proliferative capacity of Treg cells from individuals in whom viremia was controlled (either spontaneously or by antiretroviral treatment. However, PD-L1 blockade resulted in an increased proliferative capacity of HIV-specific-CD8 T cells in all subjects. Taken together, our findings suggest that manipulating PD-L1 in vivo can be expected to influence the net gain of effector function depending on the subject's plasma viremia.

  20. 77 FR 28518 - Reducing Regulatory Burden

    Science.gov (United States)

    2012-05-15

    ..., and other advantages; distributive impacts; and equity). The regulatory process encourages public..., simplify, and harmonize regulations to reduce costs and promote certainty for businesses and the public... culture of retrospective review and analysis. DOE will continually engage in review of its rules...

  1. A Two-Component Regulatory System Impacts Extracellular Membrane-Derived Vesicle Production in Group A Streptococcus

    Directory of Open Access Journals (Sweden)

    Ulrike Resch

    2016-11-01

    Full Text Available Export of macromolecules via extracellular membrane-derived vesicles (MVs plays an important role in the biology of Gram-negative bacteria. Gram-positive bacteria have also recently been reported to produce MVs; however, the composition and mechanisms governing vesiculogenesis in Gram-positive bacteria remain undefined. Here, we describe MV production in the Gram-positive human pathogen group A streptococcus (GAS, the etiological agent of necrotizing fasciitis and streptococcal toxic shock syndrome. M1 serotype GAS isolates in culture exhibit MV structures both on the cell wall surface and in the near vicinity of bacterial cells. A comprehensive analysis of MV proteins identified both virulence-associated protein substrates of the general secretory pathway in addition to “anchorless surface proteins.” Characteristic differences in the contents, distributions, and fatty acid compositions of specific lipids between MVs and GAS cell membrane were also observed. Furthermore, deep RNA sequencing of vesicular RNAs revealed that GAS MVs contained differentially abundant RNA species relative to bacterial cellular RNA. MV production by GAS strains varied in a manner dependent on an intact two-component system, CovRS, with MV production negatively regulated by the system. Modulation of MV production through CovRS was found to be independent of both GAS cysteine protease SpeB and capsule biosynthesis. Our data provide an explanation for GAS secretion of macromolecules, including RNAs, lipids, and proteins, and illustrate a regulatory mechanism coordinating this secretory response.

  2. The differential impact of academic self-regulatory methods on academic achievement among university students with and without learning disabilities.

    Science.gov (United States)

    Ruban, Lilia M; McCoach, D Betsy; McGuire, Joan M; Reis, Sally M

    2003-01-01

    Although research on academic self-regulation has proliferated in recent years, no studies have investigated the question of whether the perceived usefulness and the use of standard self-regulated learning strategies and compensation strategies provide a differential prediction of academic achievement for university students with and without learning disabilities (LD). We developed and tested a model explaining interrelationships among self-regulatory variables and grade point average (GPA) using structural equation modeling and multiple group analysis for students with LD (n = 53) and without LD (n = 421). Data were gathered using a new instrument, the Learning Strategies and Study Skills survey. The results of this study indicate that students with LD differed significantly from students without LD in the relationships between their motivation for and use of standard self-regulated learning strategies and compensation strategies, which in turn provided a differential explanation of academic achievement for students with and without LD. These paths of influence and idiosyncrasies of academic self-regulation among students with LD were interpreted in terms of social cognitive theory, metacognitive theory, and research conducted in the LD field.

  3. Regulatory analysis on criteria for the release of patients administered radioactive material. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, S.; McGuire, S.A.

    1997-02-01

    This regulatory analysis was developed to respond to three petitions for rulemaking to amend 10 CFR parts 20 and 35 regarding release of patients administered radioactive material. The petitions requested revision of these regulations to remove the ambiguity that existed between the 1-millisievert (0.1-rem) total effective dose equivalent (TEDE) public dose limit in Part 20, adopted in 1991, and the activity-based release limit in 10 CFR 35.75 that, in some instances, would permit release of individuals in excess of the current public dose limit. Three alternatives for resolution of the petitions were evaluated. Under Alternative 1, NRC would amend its patient release criteria in 10 CFR 35.75 to match the annual public dose limit in Part 20 of 1 millisievert (0.1 rem) TEDE. Alternative 2 would maintain the status quo of using the activity-based release criteria currently found in 10 CFR 35.75. Under Alternative 3, the NRC would revise the release criteria in 10 CFR 35.75 to specify a dose limit of 5 millisieverts (0.5 rem) TEDE.

  4. Identification of causal genetic drivers of human disease through systems-level analysis of regulatory networks

    Science.gov (United States)

    Chen, James C.; Alvarez, Mariano J.; Talos, Flaminia; Dhruv, Harshil; Rieckhof, Gabrielle E.; Iyer, Archana; Diefes, Kristin L.; Aldape, Kenneth; Berens, Michael; Shen, Michael M.; Califano, Andrea

    2014-01-01

    SUMMARY Identification of driver mutations in human diseases is often limited by cohort size and availability of appropriate statistical models. We propose a novel framework for the systematic discovery of genetic alterations that are causal determinants of disease, by prioritizing genes upstream of functional disease drivers, within regulatory networks inferred de novo from experimental data. We tested this framework by identifying the genetic determinants of the mesenchymal subtype of glioblastoma. Our analysis uncovered KLHL9 deletions as upstream activators of two previously established master regulators of the subtype, C/EBPβ and C/EBPδ. Rescue of KLHL9 expression induced proteasomal degradation of C/EBP proteins, abrogated the mesenchymal signature, and reduced tumor viability in vitro and in vivo. Deletions of KLHL9 were confirmed in >50% of mesenchymal cases in an independent cohort, thus representing the most frequent genetic determinant of the subtype. The method generalized to study other human diseases, including breast cancer and Alzheimer’s disease. PMID:25303533

  5. Formal modeling and analysis of the MAL-associated biological regulatory network: insight into cerebral malaria.

    Directory of Open Access Journals (Sweden)

    Jamil Ahmad

    Full Text Available The discrete modeling formalism of René Thomas is a well known approach for the modeling and analysis of Biological Regulatory Networks (BRNs. This formalism uses a set of parameters which reflect the dynamics of the BRN under study. These parameters are initially unknown but may be deduced from the appropriately chosen observed dynamics of a BRN. The discrete model can be further enriched by using the model checking tool HyTech along with delay parameters. This paves the way to accurately analyse a BRN and to make predictions about critical trajectories which lead to a normal or diseased response. In this paper, we apply the formal discrete and hybrid (discrete and continuous modeling approaches to characterize behavior of the BRN associated with MyD88-adapter-like (MAL--a key protein involved with innate immune response to infections. In order to demonstrate the practical effectiveness of our current work, different trajectories and corresponding conditions that may lead to the development of cerebral malaria (CM are identified. Our results suggest that the system converges towards hyperinflammation if Bruton's tyrosine kinase (BTK remains constitutively active along with pre-existing high cytokine levels which may play an important role in CM pathogenesis.

  6. Mean field analysis of a spatial stochastic model of a gene regulatory network.

    Science.gov (United States)

    Sturrock, M; Murray, P J; Matzavinos, A; Chaplain, M A J

    2015-10-01

    A gene regulatory network may be defined as a collection of DNA segments which interact with each other indirectly through their RNA and protein products. Such a network is said to contain a negative feedback loop if its products inhibit gene transcription, and a positive feedback loop if a gene product promotes its own production. Negative feedback loops can create oscillations in mRNA and protein levels while positive feedback loops are primarily responsible for signal amplification. It is often the case in real biological systems that both negative and positive feedback loops operate in parameter regimes that result in low copy numbers of gene products. In this paper we investigate the spatio-temporal dynamics of a single feedback loop in a eukaryotic cell. We first develop a simplified spatial stochastic model of a canonical feedback system (either positive or negative). Using a Gillespie's algorithm, we compute sample trajectories and analyse their corresponding statistics. We then derive a system of equations that describe the spatio-temporal evolution of the stochastic means. Subsequently, we examine the spatially homogeneous case and compare the results of numerical simulations with the spatially explicit case. Finally, using a combination of steady-state analysis and data clustering techniques, we explore model behaviour across a subregion of the parameter space that is difficult to access experimentally and compare the parameter landscape of our spatio-temporal and spatially-homogeneous models.

  7. Mendeley Impact on Scientific Writing: Thematic Analysis

    Directory of Open Access Journals (Sweden)

    Kisman Salija

    2016-10-01

    Full Text Available The quality of scientific writing is based on its impact on knowledge development. This study aims at exposing the Mendeley impact on scientific writing. The thematic analysis was applied in this study to transcribe the recordings and translate as well as analyze the transcripts through NVivo 8 software. This study reveals that the identified themes appeared in this study are avoiding plagiarism, backup file, change citation style, personal library, and social network. This study recommends that due to the plagiarism deterrent is problematic in scientific writing; students are required to be educated on this issue. This study also reveals that research collaboration in internet connection could be the basis of building the real network by creating research community and organizing conference for knowledge sharing among the researchers.

  8. PlantPAN 2.0: an update of plant promoter analysis navigator for reconstructing transcriptional regulatory networks in plants.

    Science.gov (United States)

    Chow, Chi-Nga; Zheng, Han-Qin; Wu, Nai-Yun; Chien, Chia-Hung; Huang, Hsien-Da; Lee, Tzong-Yi; Chiang-Hsieh, Yi-Fan; Hou, Ping-Fu; Yang, Tien-Yi; Chang, Wen-Chi

    2016-01-01

    Transcription factors (TFs) are sequence-specific DNA-binding proteins acting as critical regulators of gene expression. The Plant Promoter Analysis Navigator (PlantPAN; http://PlantPAN2.itps.ncku.edu.tw) provides an informative resource for detecting transcription factor binding sites (TFBSs), corresponding TFs, and other important regulatory elements (CpG islands and tandem repeats) in a promoter or a set of plant promoters. Additionally, TFBSs, CpG islands, and tandem repeats in the conserve regions between similar gene promoters are also identified. The current PlantPAN release (version 2.0) contains 16 960 TFs and 1143 TF binding site matrices among 76 plant species. In addition to updating of the annotation information, adding experimentally verified TF matrices, and making improvements in the visualization of transcriptional regulatory networks, several new features and functions are incorporated. These features include: (i) comprehensive curation of TF information (response conditions, target genes, and sequence logos of binding motifs, etc.), (ii) co-expression profiles of TFs and their target genes under various conditions, (iii) protein-protein interactions among TFs and their co-factors, (iv) TF-target networks, and (v) downstream promoter elements. Furthermore, a dynamic transcriptional regulatory network under various conditions is provided in PlantPAN 2.0. The PlantPAN 2.0 is a systematic platform for plant promoter analysis and reconstructing transcriptional regulatory networks.

  9. When the model fits the frame: the impact of regulatory fit on efficacy appraisal and persuasion in health communication.

    Science.gov (United States)

    Bosone, Lucia; Martinez, Frédéric; Kalampalikis, Nikos

    2015-04-01

    In health-promotional campaigns, positive and negative role models can be deployed to illustrate the benefits or costs of certain behaviors. The main purpose of this article is to investigate why, how, and when exposure to role models strengthens the persuasiveness of a message, according to regulatory fit theory. We argue that exposure to a positive versus a negative model activates individuals' goals toward promotion rather than prevention. By means of two experiments, we demonstrate that high levels of persuasion occur when a message advertising healthy dietary habits offers a regulatory fit between its framing and the described role model. Our data also establish that the effects of such internal regulatory fit by vicarious experience depend on individuals' perceptions of response-efficacy and self-efficacy. Our findings constitute a significant theoretical complement to previous research on regulatory fit and contain valuable practical implications for health-promotional campaigns. © 2015 by the Society for Personality and Social Psychology, Inc.

  10. Structural characterization and regulatory element analysis of the heart isoform of cytochrome c oxidase VIa

    Science.gov (United States)

    Wan, B.; Moreadith, R. W.; Blomqvist, C. G. (Principal Investigator)

    1995-01-01

    In order to investigate the mechanism(s) governing the striated muscle-specific expression of cytochrome c oxidase VIaH we have characterized the murine gene and analyzed its transcriptional regulatory elements in skeletal myogenic cell lines. The gene is single copy, spans 689 base pairs (bp), and is comprised of three exons. The 5'-ends of transcripts from the gene are heterogeneous, but the most abundant transcript includes a 5'-untranslated region of 30 nucleotides. When fused to the luciferase reporter gene, the 3.5-kilobase 5'-flanking region of the gene directed the expression of the heterologous protein selectively in differentiated Sol8 cells and transgenic mice, recapitulating the pattern of expression of the endogenous gene. Deletion analysis identified a 300-bp fragment sufficient to direct the myotube-specific expression of luciferase in Sol8 cells. The region lacks an apparent TATA element, and sequence motifs predicted to bind NRF-1, NRF-2, ox-box, or PPAR factors known to regulate other nuclear genes encoding mitochondrial proteins are not evident. Mutational analysis, however, identified two cis-elements necessary for the high level expression of the reporter protein: a MEF2 consensus element at -90 to -81 bp and an E-box element at -147 to -142 bp. Additional E-box motifs at closely located positions were mutated without loss of transcriptional activity. The dependence of transcriptional activation of cytochrome c oxidase VIaH on cis-elements similar to those found in contractile protein genes suggests that the striated muscle-specific expression is coregulated by mechanisms that control the lineage-specific expression of several contractile and cytosolic proteins.

  11. Discourse-voice regulatory strategies in the psychotherapeutic interaction: a state-space dynamics analysis

    OpenAIRE

    Tomicic,Alemka; Martínez, Claudio; PÉREZ,J. CAROLA; Hollenstein, Tom; Angulo, Salvador; Gerstmann, Adam; Barroux, Isabelle; Krause, Mariane

    2015-01-01

    This study seeks to provide evidence of the dynamics associated with the configurations of discourse-voice regulatory strategies in patient–therapist interactions in relevant episodes within psychotherapeutic sessions. Its central assumption is that discourses manifest themselves differently in terms of their prosodic characteristics according to their regulatory functions in a system of interactions. The association between discourse and vocal quality in patients and therapists was analyzed ...

  12. Discourse-Voice Regulatory Strategies in the Psychotherapeutic Interaction: A State-Space Dynamics Analysis

    OpenAIRE

    Alemka eTomicic; Claudio eMartínez; J. Carola ePérez; Tom eHollenstein; Salvador eAngulo; Adam eGerstmann; Isabelle eBarroux; Mariane eKrause

    2015-01-01

    This study seeks to provide evidence of the dynamics associated with the configurations of discourse-voice regulatory strategies in patient-therapist interactions in relevant episodes within psychotherapeutic sessions. Its central assumption is that discourses manifest themselves differently in terms of their prosodic characteristics according to their regulatory functions in a system of interactions. The association between discourse and vocal quality in patients and therapists was analyzed ...

  13. Human immunodeficiency virus type 2 long terminal repeat: analysis of regulatory elements.

    OpenAIRE

    Arya, S. K.; Gallo, R C

    1988-01-01

    The long terminal repeats (LTRs) of the human immunodeficiency virus type 2 (HIV-2) and a related simian immunodeficiency virus (SIVmac) contain cis-acting positive regulatory elements upstream and the major transactivator gene (tat) response element and a possible negative regulatory element downstream of the transcriptional initiation site. The tat response element of HIV-2 and of SIVmac was more complex than that of HIV-1. Two structurally similar subelements within the HIV-2 tat response ...

  14. [Analysis of the cellular tropism of JC virus with archetypal regulatory region].

    Science.gov (United States)

    Hasegawa, Y

    1997-07-01

    JC virus (JCV) with an archetypal regulatory region (archetype) has been cloned from urines of a healthy individual. It has been suggested that the regulatory region of prototype JC virus (PML type) isolated from brain of PML patient was derived from that of the archetype by deletion and duplication. Biological characteristics of archetypal JCV, however, have not been fully studied. In the present study we examined the infectivity of archetypal JCV (CY), PML-type JCV (Mad-1) and Chimera JCV (Mad-1/CR-CY), in which the regulatory region is composed of CY and the other region Mad-1. DNAs from the three JCV types were transfected into COS-7 (monkey kidney cells transformed with SV40 T) and IMR-32 (human neuroblastoma cell). COS-7 was permissive for all three types, but IMR-32 was only infected with Mad-1. Infected DNAs were confirmed by Southern blotting, and the constancy of the regulatory regions before and after transmission was verified by DNA sequencing. The results showed that the viral regulatory region was related to viral cell tropism and that PML type regulatory region would be necessary for IMR-32 to propagate. The fact that COS-7 was susceptible for all three types may be explained by the function of SV40 T protein. In addition, we first succeeded in the propagation of CY in COS-7, which would provide a useful system to analyze the mechanism of persistent infection of archetypal JCV.

  15. Discourse-voice regulatory strategies in the psychotherapeutic interaction: a state-space dynamics analysis.

    Science.gov (United States)

    Tomicic, Alemka; Martínez, Claudio; Pérez, J Carola; Hollenstein, Tom; Angulo, Salvador; Gerstmann, Adam; Barroux, Isabelle; Krause, Mariane

    2015-01-01

    This study seeks to provide evidence of the dynamics associated with the configurations of discourse-voice regulatory strategies in patient-therapist interactions in relevant episodes within psychotherapeutic sessions. Its central assumption is that discourses manifest themselves differently in terms of their prosodic characteristics according to their regulatory functions in a system of interactions. The association between discourse and vocal quality in patients and therapists was analyzed in a sample of 153 relevant episodes taken from 164 sessions of five psychotherapies using the state space grid (SSG) method, a graphical tool based on the dynamic systems theory (DST). The results showed eight recurrent and stable discourse-voice regulatory strategies of the patients and three of the therapists. Also, four specific groups of these discourse-voice strategies were identified. The latter were interpreted as regulatory configurations, that is to say, as emergent self-organized groups of discourse-voice regulatory strategies constituting specific interactional systems. Both regulatory strategies and their configurations differed between two types of relevant episodes: Change Episodes and Rupture Episodes. As a whole, these results support the assumption that speaking and listening, as dimensions of the interaction that takes place during therapeutic conversation, occur at different levels. The study not only shows that these dimensions are dependent on each other, but also that they function as a complex and dynamic whole in therapeutic dialog, generating relational offers which allow the patient and the therapist to regulate each other and shape the psychotherapeutic process that characterizes each type of relevant episode.

  16. Analysis of flexible structures under lateral impact

    Energy Technology Data Exchange (ETDEWEB)

    Ramirez, D. F. [Paul C. Kizzo and Associates Inc., Seismic Structural Group, Oakland, CA 94612 (United States); Razavi, H. [AREVA Inc., Civil Seismic Group, San Jose, CA 95119 (United States)

    2012-07-01

    Three methods for analysis of flexible structures under lateral impact are presented. The first proposed method (Method A) consists of: (1) modifying an available deceleration on a rigid target with conservation principles to account for structural flexibility; and (2) transient nonlinear analysis of the structure with the corrected forcing function. The second proposed method (Method B) is similar to Method A in obtaining the forcing function but it solves the equations of motion of an idealized two-degree-of-freedom system instead of directly using conservation principles. The last method simply provides the maximum force in the structure using the conservation of energy and linear momentum. A coupled simulation is also performed in LS-DYNA and compared against the proposed methods. A case study is presented to illustrate the applicability of all three methods and the LS-DYNA simulation. (authors)

  17. The Complexity of Posttranscriptional Small RNA Regulatory Networks Revealed by In Silico Analysis of Gossypium arboreum L. Leaf, Flower and Boll Small Regulatory RNAs.

    Directory of Open Access Journals (Sweden)

    Hongtao Hu

    Full Text Available MicroRNAs (miRNAs and secondary small interfering RNAs (principally phased siRNAs or trans-acting siRNAs are two distinct subfamilies of small RNAs (sRNAs that are emerging as key regulators of posttranscriptional gene expression in plants. Both miRNAs and secondary-siRNAs (sec-siRNAs are processed from longer RNA precursors by DICER-LIKE proteins (DCLs. Gossypium arboreum L., also known as tree cotton or Asian cotton, is a diploid, possibly ancestral relative of tetraploid Gossypium hirsutum L., the predominant type of commercially grown cotton worldwide known as upland cotton. To understand the biological significance of these gene regulators in G. arboreum, a bioinformatics analysis was performed on G. arboreum small RNAs produced from G. arboreum leaf, flower, and boll tissues. Consequently, 263 miRNAs derived from 353 precursors, including 155 conserved miRNAs (cs-miRNAs and 108 novel lineage-specific miRNAs (ls-miRNAs. Along with miRNAs, 2,033 miRNA variants (isomiRNAs were identified as well. Those isomiRNAs with variation at the 3'-miRNA end were expressed at the highest levels, compared to other types of variants. In addition, 755 pha-siRNAs derived 319 pha-siRNA gene transcripts (PGTs were identified, and the potential pha-siRNA initiators were predicted. Also, 2,251 non-phased siRNAs were found as well, of which 1,088 appeared to be produced by so-called cis- or trans-cleavage of the PGTs observed at positions differing from pha-siRNAs. Of those sRNAs, 148 miRNAs/isomiRNAs and 274 phased/non-phased siRNAs were differentially expressed in one or more pairs of tissues examined. Target analysis revealed that target genes for both miRNAs and pha-siRNAs are involved a broad range of metabolic and enzymatic activities. We demonstrate that secondary siRNA production could result from initial cleavage of precursors by both miRNAs or isomiRNAs, and that subsequently produced phased and unphased siRNAs could result that also serve as triggers

  18. Emergent self-regulatory activity among young children during scientific inquiry: An analysis of six kindergarten children

    Science.gov (United States)

    Lomangino, Adrienne Gelpi

    2000-10-01

    This qualitative investigation extends the study of self-regulation to examine young children's developing self-regulated learning competencies. The framework for this research draws upon social cognitive, developmental, and sociocultural perspectives on self-regulation and research on children's scientific thinking. Taking a multiple case study approach, this study examines six kindergarten children's emerging self-regulatory competencies during inquiry-based science instruction. Data were collected during two inquiry-based science programs of study, one pertaining to light and shadow and a second pertaining to motion on inclined planes. Data sources included: videotaped records of the instruction, transcriptions of the videotapes, interviews with the children and teacher, student work, and field notes. Taking an inductive approach to analysis, patterns in the children's activity were identified through a recursive process of defining and refining categories that characterized the children's verbal and behavioral activity. Each case study examines a child's behavior within each phase of the inquiry for evidence of emerging self-regulatory competence. Analysis revealed nascent forms of goal-setting and planning, monitoring, resource management, seeking social assistance, and evaluating. Monitoring activity occurred more frequently than planning or evaluating. For several children, animating materials served to promote motivation. Children's efforts to support peers' activity and monitor the meaning of ongoing discourse contrast with common assumptions about children's attention to others' thinking. Variations in self-regulatory activity were found across phases of instruction. The children exhibited interpersonal self-regulatory efforts, in which monitoring and control of the self was entwined with the activity of others. Joint participation also played a critical role in supporting the metacognitive demands of self-regulation and prompting metacognitive awareness

  19. Applying centrality measures to impact analysis: A coauthorship network analysis

    CERN Document Server

    Yan, Erjia

    2010-01-01

    Many studies on coauthorship networks focus on network topology and network statistical mechanics. This article takes a different approach by studying micro-level network properties, with the aim to apply centrality measures to impact analysis. Using coauthorship data from 16 journals in the field of library and information science (LIS) with a time span of twenty years (1988-2007), we construct an evolving coauthorship network and calculate four centrality measures (closeness, betweenness, degree and PageRank) for authors in this network. We find out that the four centrality measures are significantly correlated with citation counts. We also discuss the usability of centrality measures in author ranking, and suggest that centrality measures can be useful indicators for impact analysis.

  20. Does flood risk information held within at risk population always have a positive impact? An evaluation of the effects of French regulatory tools in Orleans

    Directory of Open Access Journals (Sweden)

    Jadot Julien

    2016-01-01

    Full Text Available French law on major risk preventive information for population setup the objective to make the citizen able to act for his own safety and to participate through his behaviour to the civil security. To reach this objective, the policymakers developed 4 regulatory tools that have to be implemented by the local authorities. These 4 tools do not meet the success factors of risk communication measures aiming at inducing behavioural adaptation to face risks. This, added to the fact that people who die in the last floods events in France lost their lives due to either a lack of knowledge of the risk or to a risk taking behaviour, led us to question the impact of the preventive information regulatory tools. For the needs of our study we developed a risk perception and behaviour scale, helping us to classify the people of our sample. Our evaluation in Orléans shows that very few people know the regulatory tools and that their impact is quite low, far from the policymakers’ expectations. This highlight the real necessity to innovate in the field of flood risk communication.

  1. Update of Part 61 Impacts Analysis Methodology. Methodology report. Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    Oztunali, O.I.; Roles, G.W.

    1986-01-01

    Under contract to the US Nuclear Regulatory Commission, the Envirosphere Company has expanded and updated the impacts analysis methodology used during the development of the 10 CFR Part 61 rule to allow improved consideration of the costs and impacts of treatment and disposal of low-level waste that is close to or exceeds Class C concentrations. The modifications described in this report principally include: (1) an update of the low-level radioactive waste source term, (2) consideration of additional alternative disposal technologies, (3) expansion of the methodology used to calculate disposal costs, (4) consideration of an additional exposure pathway involving direct human contact with disposed waste due to a hypothetical drilling scenario, and (5) use of updated health physics analysis procedures (ICRP-30). Volume 1 of this report describes the calculational algorithms of the updated analysis methodology.

  2. Expression regulation of zebrafish interferon regulatory factor 9 by promoter analysis.

    Science.gov (United States)

    Shi, Jun; Zhang, Yi-Bing; Zhang, Jian-She; Gui, Jian-Fang

    2013-12-01

    We previously showed that a fish interferon (IFN) regulatory factor 9 (IRF9) homologue, crucian carp Carassius auratus IRF9, displays constitutively nuclear localization and involvement in fish IFN-dependent JAK-STAT signaling; however, little is known about the expression regulation of fish IRF9. Here, we characterized the expression of zebrafish IRF9 by promoter analysis. Zebrafish IRF9 gene promoter contained several putative transcription factor binding sites, including one ISRE (IFN-stimulated response element), one GAS (IFN gamma activation sequence) and three GATEs (IFNγ activated transcriptional element, GATE1/2/3). Further sequence analyses revealed that GAS and GATE motifs existed in all promoters of IRF9 from mammals and fishes. Luciferase assays confirmed that zebrafish IRF9 promoter could be activated by zebrafish IFNφs and zebrafish IFNγ2, as well as transcription factors IRF3, IRF7, and combination of IRF9 and STAT2. Treatment of recombinant crucian carp IFN protein or overexpression of zebrafish IFNγ2 both led to significant increase in crucian carp IRF9 mRNA and protein in cultured fish cells. Comparison of IFN-stimulated promoter activity revealed much more significant induction of zebrafish IRF9 by zebrafish IFNγ2 than by zebrafish IFNφs. Mutation analyses showed that the putative GAS and GATE3 contributed to zebrafish IFNγ2-triggered IRF9 expression, whereas the putative ISRE and the other two GATEs were not functional for induction of zebrafish IRF9. These results together indicated that the expression property of IRF9 might be conserved from fish to mammals and that some not yet identified mechanisms could exist in IRF9 gene transcription regulation in response to IFNs.

  3. Application of the Gini correlation coefficient to infer regulatory relationships in transcriptome analysis.

    Science.gov (United States)

    Ma, Chuang; Wang, Xiangfeng

    2012-09-01

    One of the computational challenges in plant systems biology is to accurately infer transcriptional regulation relationships based on correlation analyses of gene expression patterns. Despite several correlation methods that are applied in biology to analyze microarray data, concerns regarding the compatibility of these methods with the gene expression data profiled by high-throughput RNA transcriptome sequencing (RNA-Seq) technology have been raised. These concerns are mainly due to the fact that the distribution of read counts in RNA-Seq experiments is different from that of fluorescence intensities in microarray experiments. Therefore, a comprehensive evaluation of the existing correlation methods and, if necessary, introduction of novel methods into biology is appropriate. In this study, we compared four existing correlation methods used in microarray analysis and one novel method called the Gini correlation coefficient on previously published microarray-based and sequencing-based gene expression data in Arabidopsis (Arabidopsis thaliana) and maize (Zea mays). The comparisons were performed on more than 11,000 regulatory relationships in Arabidopsis, including 8,929 pairs of transcription factors and target genes. Our analyses pinpointed the strengths and weaknesses of each method and indicated that the Gini correlation can compensate for the shortcomings of the Pearson correlation, the Spearman correlation, the Kendall correlation, and the Tukey's biweight correlation. The Gini correlation method, with the other four evaluated methods in this study, was implemented as an R package named rsgcc that can be utilized as an alternative option for biologists to perform clustering analyses of gene expression patterns or transcriptional network analyses.

  4. Application of the Gini Correlation Coefficient to Infer Regulatory Relationships in Transcriptome Analysis[W][OA

    Science.gov (United States)

    Ma, Chuang; Wang, Xiangfeng

    2012-01-01

    One of the computational challenges in plant systems biology is to accurately infer transcriptional regulation relationships based on correlation analyses of gene expression patterns. Despite several correlation methods that are applied in biology to analyze microarray data, concerns regarding the compatibility of these methods with the gene expression data profiled by high-throughput RNA transcriptome sequencing (RNA-Seq) technology have been raised. These concerns are mainly due to the fact that the distribution of read counts in RNA-Seq experiments is different from that of fluorescence intensities in microarray experiments. Therefore, a comprehensive evaluation of the existing correlation methods and, if necessary, introduction of novel methods into biology is appropriate. In this study, we compared four existing correlation methods used in microarray analysis and one novel method called the Gini correlation coefficient on previously published microarray-based and sequencing-based gene expression data in Arabidopsis (Arabidopsis thaliana) and maize (Zea mays). The comparisons were performed on more than 11,000 regulatory relationships in Arabidopsis, including 8,929 pairs of transcription factors and target genes. Our analyses pinpointed the strengths and weaknesses of each method and indicated that the Gini correlation can compensate for the shortcomings of the Pearson correlation, the Spearman correlation, the Kendall correlation, and the Tukey’s biweight correlation. The Gini correlation method, with the other four evaluated methods in this study, was implemented as an R package named rsgcc that can be utilized as an alternative option for biologists to perform clustering analyses of gene expression patterns or transcriptional network analyses. PMID:22797655

  5. Proteomic analysis reveals metabolic and regulatory systems involved the syntrophic and axenic lifestyle of Syntrophomonas wolfei.

    Directory of Open Access Journals (Sweden)

    Jessica Rhea Sieber

    2015-02-01

    Full Text Available Microbial syntrophy is a vital metabolic interaction necessary for the complete oxidation of organic biomass to methane in all-anaerobic ecosystems. However, this process is thermodynamically constrained and represents an ecosystem-level metabolic bottleneck. To gain insight into the physiology of this process, a shotgun proteomic approach was used to quantify the protein landscape of the model syntrophic metabolizer, Syntrophomonas wolfei, grown axenically and syntrophically with Methanospirillum hungatei. Remarkably, the abundance of most proteins as represented by normalized spectral abundance factor (NSAF value changed very little between the pure and coculture growth conditions. Among the most abundant proteins detected were GroEL and GroES chaperonins, a small heat shock protein, and proteins involved in electron transfer, beta-oxidation, and ATP synthesis. Several putative energy conservation enzyme systems that utilize NADH and ferredoxin were present. The abundance of an EtfAB2 and the membrane-bound iron-sulfur oxidoreductase (Swol_0698 gene product delineated a potential conduit for electron transfer between acyl-CoA dehydrogenases and membrane redox carriers. Proteins detected only when S. wolfei was grown with M. hungatei included a zinc-dependent dehydrogenase with a GroES domain, whose gene is present in genomes in many organisms capable of syntrophy, and transcriptional regulators responsive to environmental stimuli or the physiological status of the cell. The proteomic analysis revealed an emphasis macromolecular stability and energy metabolism to S. wolfei and presence of regulatory mechanisms responsive to external stimuli and cellular physiological status.

  6. Systematic analysis of the regulatory functions of microRNAs in chicken hepatic lipid metabolism

    Science.gov (United States)

    Li, Hong; Ma, Zheng; Jia, Lijuan; Li, Yanmin; Xu, Chunlin; Wang, Taian; Han, Ruili; Jiang, Ruirui; Li, Zhuanjian; Sun, Guirong; Kang, Xiangtao; Liu, Xiaojun

    2016-01-01

    Laying performance is an important economic trait in hens, and this physiological process is largely influenced by the liver function. The livers of hens at 20- and 30-week-old stages were investigated using the next generation sequencing to identify the differences of microRNA expression profiles. Compared with the 20-week-old hens, 67 down- and 13 up-regulated microRNAs were verified to be significant differentially expressed (false discovery rate, FDR ≤ 0.05) (SDE) in the 30-week-old. We also identified 13 down- and 6 up-regulated novel differentially expressed (DE) microRNAs. miR-22-3p and miR-146b-5p, which exhibit critical roles in mammalian lipid metabolism, showed the most abundant expression and the highest fold-change, respectively. A total of 648 potential target genes of the SDE microRNAs were identified through an integrated analysis of microRNAs and the DE genes obtained in previous RNA-sequencing, including FADS1, FADS2, ELOVL6 and ACSL5, which are critical lipid metabolism-related regulators. Bioinformatic analyses revealed that target genes were mainly enriched in lipid-related metabolism processes. This work provides the first study of the expression patterns of hepatic microRNAs between 20- and 30-week old hens. The findings may serve as a fundamental resource for understanding the detailed functions of microRNAs in the molecular regulatory systems of lipid metabolism. PMID:27535581

  7. An epidemiological analysis of equine welfare data from regulatory inspections by the official competent authorities.

    Science.gov (United States)

    Hitchens, P L; Hultgren, J; Frössling, J; Emanuelson, U; Keeling, L J

    2016-12-09

    welfare if they also complied with documentation requirements. We present a novel approach for analysis of equine welfare data from regulatory inspections by the official competent authorities, and propose on-going analyses and benchmarking of trends in animal-based measures over time. We also suggest how such a database could be further improved to facilitate future epidemiological analyses of risk factors associated with poor equine welfare. The study has implications for other competent authorities and researchers collaborating in the area of animal welfare epidemiology.

  8. Comparative Genomic Analysis Reveals Habitat-Specific Genes and Regulatory Hubs within the Genus Novosphingobium

    Science.gov (United States)

    Kumar, Roshan; Verma, Helianthous; Haider, Shazia; Bajaj, Abhay; Sood, Utkarsh; Ponnusamy, Kalaiarasan; Nagar, Shekhar; Shakarad, Mallikarjun N.; Negi, Ram Krishan; Singh, Yogendra; Khurana, J. P.; Gilbert, Jack A.

    2017-01-01

    ABSTRACT Species belonging to the genus Novosphingobium are found in many different habitats and have been identified as metabolically versatile. Through comparative genomic analysis, we identified habitat-specific genes and regulatory hubs that could determine habitat selection for Novosphingobium spp. Genomes from 27 Novosphingobium strains isolated from diverse habitats such as rhizosphere soil, plant surfaces, heavily contaminated soils, and marine and freshwater environments were analyzed. Genome size and coding potential were widely variable, differing significantly between habitats. Phylogenetic relationships between strains were less likely to describe functional genotype similarity than the habitat from which they were isolated. In this study, strains (19 out of 27) with a recorded habitat of isolation, and at least 3 representative strains per habitat, comprised four ecological groups—rhizosphere, contaminated soil, marine, and freshwater. Sulfur acquisition and metabolism were the only core genomic traits to differ significantly in proportion between these ecological groups; for example, alkane sulfonate (ssuABCD) assimilation was found exclusively in all of the rhizospheric isolates. When we examined osmolytic regulation in Novosphingobium spp. through ectoine biosynthesis, which was assumed to be marine habitat specific, we found that it was also present in isolates from contaminated soil, suggesting its relevance beyond the marine system. Novosphingobium strains were also found to harbor a wide variety of mono- and dioxygenases, responsible for the metabolism of several aromatic compounds, suggesting their potential to act as degraders of a variety of xenobiotic compounds. Protein-protein interaction analysis revealed β-barrel outer membrane proteins as habitat-specific hubs in each of the four habitats—freshwater (Saro_1868), marine water (PP1Y_AT17644), rhizosphere (PMI02_00367), and soil (V474_17210). These outer membrane proteins could play a

  9. Comparative Genomic Analysis Reveals Habitat-Specific Genes and Regulatory Hubs within the Genus Novosphingobium.

    Science.gov (United States)

    Kumar, Roshan; Verma, Helianthous; Haider, Shazia; Bajaj, Abhay; Sood, Utkarsh; Ponnusamy, Kalaiarasan; Nagar, Shekhar; Shakarad, Mallikarjun N; Negi, Ram Krishan; Singh, Yogendra; Khurana, J P; Gilbert, Jack A; Lal, Rup

    2017-01-01

    Species belonging to the genus Novosphingobium are found in many different habitats and have been identified as metabolically versatile. Through comparative genomic analysis, we identified habitat-specific genes and regulatory hubs that could determine habitat selection for Novosphingobium spp. Genomes from 27 Novosphingobium strains isolated from diverse habitats such as rhizosphere soil, plant surfaces, heavily contaminated soils, and marine and freshwater environments were analyzed. Genome size and coding potential were widely variable, differing significantly between habitats. Phylogenetic relationships between strains were less likely to describe functional genotype similarity than the habitat from which they were isolated. In this study, strains (19 out of 27) with a recorded habitat of isolation, and at least 3 representative strains per habitat, comprised four ecological groups-rhizosphere, contaminated soil, marine, and freshwater. Sulfur acquisition and metabolism were the only core genomic traits to differ significantly in proportion between these ecological groups; for example, alkane sulfonate (ssuABCD) assimilation was found exclusively in all of the rhizospheric isolates. When we examined osmolytic regulation in Novosphingobium spp. through ectoine biosynthesis, which was assumed to be marine habitat specific, we found that it was also present in isolates from contaminated soil, suggesting its relevance beyond the marine system. Novosphingobium strains were also found to harbor a wide variety of mono- and dioxygenases, responsible for the metabolism of several aromatic compounds, suggesting their potential to act as degraders of a variety of xenobiotic compounds. Protein-protein interaction analysis revealed β-barrel outer membrane proteins as habitat-specific hubs in each of the four habitats-freshwater (Saro_1868), marine water (PP1Y_AT17644), rhizosphere (PMI02_00367), and soil (V474_17210). These outer membrane proteins could play a key role in

  10. Bayesian non-negative factor analysis for reconstructing transcription factor mediated regulatory networks

    Directory of Open Access Journals (Sweden)

    Chen Yidong

    2011-10-01

    Full Text Available Abstract Background Transcriptional regulation by transcription factor (TF controls the time and abundance of mRNA transcription. Due to the limitation of current proteomics technologies, large scale measurements of protein level activities of TFs is usually infeasible, making computational reconstruction of transcriptional regulatory network a difficult task. Results We proposed here a novel Bayesian non-negative factor model for TF mediated regulatory networks. Particularly, the non-negative TF activities and sample clustering effect are modeled as the factors from a Dirichlet process mixture of rectified Gaussian distributions, and the sparse regulatory coefficients are modeled as the loadings from a sparse distribution that constrains its sparsity using knowledge from database; meantime, a Gibbs sampling solution was developed to infer the underlying network structure and the unknown TF activities simultaneously. The developed approach has been applied to simulated system and breast cancer gene expression data. Result shows that, the proposed method was able to systematically uncover TF mediated transcriptional regulatory network structure, the regulatory coefficients, the TF protein level activities and the sample clustering effect. The regulation target prediction result is highly coordinated with the prior knowledge, and sample clustering result shows superior performance over previous molecular based clustering method. Conclusions The results demonstrated the validity and effectiveness of the proposed approach in reconstructing transcriptional networks mediated by TFs through simulated systems and real data.

  11. An Analysis of Regulatory Strategies for Recycling and Re-Use of Metals in Australia

    Directory of Open Access Journals (Sweden)

    Wayne Gumley

    2014-04-01

    Full Text Available This article considers regulatory strategies that promote more efficient use of material inputs within the Australian economy, with particular focus on recycling and recovery of metals, drawing upon the concept of a “circular economy”. It briefly reviews the nature of regulation and trends in regulatory strategies within changing policy contexts, and then examines the regulatory framework applicable to the various phases in the life cycle of metals, ranging from extraction of minerals to processing and assimilation of metals into finished products, through to eventual disposal of products as waste. Discussion focuses upon the regulatory strategies applied in each phase and the changing roles of government and business operators within global distribution networks. It is concluded that the prevailing political agenda favoring deregulation and reduced taxation may be a major barrier to development of new styles of regulation and more effective use of taxation powers that is needed to support a more circular economy in metals. The implication for future research is the need to substantiate the outcomes of reflexive regulatory strategies with well-designed empirical studies.

  12. Analysis of impact of large commercial aircraft on a prestressed containment building

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyoungsoo, E-mail: kylee@pvamu.edu [Center for Energy and Environmental Sustainability, Prairie View A and M University, Prairie view, TX, 77446 (United States); Han, Sang Eul, E-mail: hsang@inha.ac.kr [Department of Architectural Engineering, School of Architecture, Inha University, 253 Yonghyundong Nam-gu, Incheon, 402-751 (Korea, Republic of); Hong, Jung-Wuk, E-mail: j.hong@kaist.ac.kr [Department of Civil and Environmental Engineering, KAIST, 373-1 Guseon-dong, Yuseong-gu, Daejeon, 305-701 (Korea, Republic of)

    2013-12-15

    Highlights: • Aircraft impact analyses are performed using the missile–target interaction method. • A large commercial B747 aircraft is considered with erosion effect. • The rigid wall impact test shows the validity of the developed aircraft model. • The parametric studies on the fictitious containment building are performed. • The plastic failure of the target is governed by the impulse of aircraft at the first momentum peak. - Abstract: In this paper, the results of nonlinear dynamic analyses of a concrete containment building under extreme loads are presented. The impact of a large commercial B747 airliner is investigated as the extreme load, and a rigid wall impact test is performed using commercial nonlinear finite element codes. The impact forces exerted by the aircraft are verified compared with the time-dependent impact force provided by OECD/NEA (2002), which was calculated based on the so-called Riera method. The rigid wall impact analysis shows that the finite element model of a B747 is appropriate for the purpose of the aircraft crash analysis exposed to the external hazard of “Beyond Design-Basis Events” defined by U.S. Nuclear Regulatory Commission. Finally, the applicability of this methodology is further studied and verified by conducting parametric studies on the critical infrastructures of nuclear power plant containment structures.

  13. 10 CFR 503.13 - Environmental impact analysis.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Environmental impact analysis. 503.13 Section 503.13... Exemptions § 503.13 Environmental impact analysis. In order to enable OFE to comply with NEPA, a petitioner..., and land resources; (3) Direct and indirect environmental impacts of the proposed action including...

  14. Controllability analysis of transcriptional regulatory networks reveals circular control patterns among transcription factors

    DEFF Research Database (Denmark)

    Österlund, Tobias; Bordel, Sergio; Nielsen, Jens

    2015-01-01

    Transcriptional regulation is the most committed type of regulation in living cells where transcription factors (TFs) control the expression of their target genes and TF expression is controlled by other TFs forming complex transcriptional regulatory networks that can be highly interconnected. Here...... we analyze the topology and organization of nine transcriptional regulatory networks for E. coli, yeast, mouse and human, and we evaluate how the structure of these networks influences two of their key properties, namely controllability and stability. We calculate the controllability for each network...... as a measure of the organization and interconnectivity of the network. We find that the number of driver nodes n(D) needed to control the whole network is 64% of the TFs in the E. coli transcriptional regulatory network in contrast to only 17% for the yeast network, 4% for the mouse network and 8...

  15. Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in the United States. Preliminary background report

    Energy Technology Data Exchange (ETDEWEB)

    Feurer, D.A.; Weaver, C.L.; Gallagher, K.C.; Hejna, D.; Rielley, K.J.

    1980-01-01

    This report is one of a series of preliminary reports describing the laws and regulatory programs of the United States and each of the 50 states affecting the siting and operation of energy generating facilities likely to be used in Integrated Community Energy Systems (ICES). Public utility regulatory statutes, energy facility siting programs, and municipal franchising authority are examined to identify how they may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES. This report describes laws and regulatory programs in the United States. Subsequent reports will (1) describe public utility rate regulatory procedures and practices as they might affect an ICES, (2) analyze each of the aforementioned regulatory programs to identify impediments to the development of ICES, and (3) recommend potential changes in legislation and regulatory practices and procedures to overcome such impediments.

  16. The safety, efficacy and regulatory triangle in drug development: Impact for animal models and the use of animals.

    Science.gov (United States)

    van Meer, Peter J K; Graham, Melanie L; Schuurman, Henk-Jan

    2015-07-15

    Nonclinical studies in animals are conducted to demonstrate proof-of-concept, mechanism of action and safety of new drugs. For a large part, in particular safety assessment, studies are done in compliance with international regulatory guidance. However, animal models supporting the initiation of clinical trials have their limitations, related to uncertainty regarding the predictive value for a clinical condition. The 3Rs principles (refinement, reduction and replacement) are better applied nowadays, with a more comprehensive application with respect to the original definition. This regards also regulatory guidance, so that opportunities exist to revise or reduce regulatory guidance with the perspective that the optimal balance between scientifically relevant data and animal wellbeing or a reduction in animal use can be achieved. In this manuscript we review the connections in the triangle between nonclinical efficacy/safety studies and regulatory aspects, with focus on in vivo testing of drugs. These connections differ for different drugs (chemistry-based low molecular weight compounds, recombinant proteins, cell therapy or gene therapy products). Regarding animal models and their translational value we focus on regulatory aspects and indications where scientific outcomes warrant changes, reduction or replacement, like for, e.g., biosimilar evaluation and safety testing of monoclonal antibodies. On the other hand, we present applications where translational value has been clearly demonstrated, e.g., immunosuppressives in transplantation. Especially for drugs of more recent date like recombinant proteins, cell therapy products and gene therapy products, a regulatory approach that allows the possibility to conduct combined efficacy/safety testing in validated animal models should strengthen scientific outcomes and improve translational value, while reducing the numbers of animals necessary. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Controllability analysis of transcriptional regulatory networks reveals circular control patterns among transcription factors.

    Science.gov (United States)

    Österlund, Tobias; Bordel, Sergio; Nielsen, Jens

    2015-05-01

    Transcriptional regulation is the most committed type of regulation in living cells where transcription factors (TFs) control the expression of their target genes and TF expression is controlled by other TFs forming complex transcriptional regulatory networks that can be highly interconnected. Here we analyze the topology and organization of nine transcriptional regulatory networks for E. coli, yeast, mouse and human, and we evaluate how the structure of these networks influences two of their key properties, namely controllability and stability. We calculate the controllability for each network as a measure of the organization and interconnectivity of the network. We find that the number of driver nodes nD needed to control the whole network is 64% of the TFs in the E. coli transcriptional regulatory network in contrast to only 17% for the yeast network, 4% for the mouse network and 8% for the human network. The high controllability (low number of drivers needed to control the system) in yeast, mouse and human is due to the presence of internal loops in their regulatory networks where the TFs regulate each other in a circular fashion. We refer to these internal loops as circular control motifs (CCM). The E. coli transcriptional regulatory network, which does not have any CCMs, shows a hierarchical structure of the transcriptional regulatory network in contrast to the eukaryal networks. The presence of CCMs also has influence on the stability of these networks, as the presence of cycles can be associated with potential unstable steady-states where even small changes in binding affinities can cause dramatic rearrangements of the state of the network.

  18. Discourse-Voice Regulatory Strategies in the Psychotherapeutic Interaction: A State-Space Dynamics Analysis

    Directory of Open Access Journals (Sweden)

    Alemka eTomicic

    2015-04-01

    Full Text Available This study seeks to provide evidence of the dynamics associated with the configurations of discourse-voice regulatory strategies in patient-therapist interactions in relevant episodes within psychotherapeutic sessions. Its central assumption is that discourses manifest themselves differently in terms of their prosodic characteristics according to their regulatory functions in a system of interactions. The association between discourse and vocal quality in patients and therapists was analyzed in a sample of 153 relevant episodes taken from 164 sessions of five psychotherapies using the State Space Grid (SSG method, a graphical tool based on the Dynamic Systems Theory (DST. The results showed eight recurrent and stable discourse-voice regulatory strategies of the patients and three of the therapists. Also, four specific groups of these discourse-voice strategies were identified. The latter were interpreted as regulatory configurations, that is to say, as emergent self-organized groups of discourse-voice regulatory strategies constituting specific interactional systems. Both regulatory strategies and their configurations differed between two types of relevant episodes: Change Episodes and Rupture Episodes. As a whole, these results support the assumption that speaking and listening, as dimensions of the interaction that takes place during therapeutic conversation, occur at different levels. The study not only shows that these dimensions are dependent on each other, but also that they function as a complex and dynamic whole in therapeutic dialogue, generating relational offers which allow the patient and the therapist to regulate each other and shape the psychotherapeutic process that characterizes each type of relevant episode.

  19. Modeling of hysteresis in gene regulatory networks.

    Science.gov (United States)

    Hu, J; Qin, K R; Xiang, C; Lee, T H

    2012-08-01

    Hysteresis, observed in many gene regulatory networks, has a pivotal impact on biological systems, which enhances the robustness of cell functions. In this paper, a general model is proposed to describe the hysteretic gene regulatory network by combining the hysteresis component and the transient dynamics. The Bouc-Wen hysteresis model is modified to describe the hysteresis component in the mammalian gene regulatory networks. Rigorous mathematical analysis on the dynamical properties of the model is presented to ensure the bounded-input-bounded-output (BIBO) stability and demonstrates that the original Bouc-Wen model can only generate a clockwise hysteresis loop while the modified model can describe both clockwise and counter clockwise hysteresis loops. Simulation studies have shown that the hysteresis loops from our model are consistent with the experimental observations in three mammalian gene regulatory networks and two E.coli gene regulatory networks, which demonstrate the ability and accuracy of the mathematical model to emulate natural gene expression behavior with hysteresis. A comparison study has also been conducted to show that this model fits the experiment data significantly better than previous ones in the literature. The successful modeling of the hysteresis in all the five hysteretic gene regulatory networks suggests that the new model has the potential to be a unified framework for modeling hysteresis in gene regulatory networks and provide better understanding of the general mechanism that drives the hysteretic function.

  20. Twin-Peak Financial Regulatory Regime in China: A Desirability Analysis

    DEFF Research Database (Denmark)

    Hu, Chenchen

    2015-01-01

    speed of the expansion of shadow banking activities. The banking activity expansion and the emergence of financial conglomerates have been challenging the effectiveness of the current institutional regulatory structure: the fragmented "One Bank and Three Commissions" system and the "Joint Meeting...... as a "deep context". By drawing on the Australia experience of the twin-peak reform and discussing the new ecology of the Chinese financial markets, the article attempts to answer the question of the desirability of a twin-peak regulatory regime in China....

  1. Analysis of the impact of safeguards criteria

    Energy Technology Data Exchange (ETDEWEB)

    Mullen, M.F.; Reardon, P.T.

    1981-01-01

    As part of the US Program of Technical Assistance to IAEA Safeguards, the Pacific Northwest Laboratory (PNL) was asked to assist in developing and demonstrating a model for assessing the impact of setting criteria for the application of IAEA safeguards. This report presents the results of PNL's work on the task. The report is in three parts. The first explains the technical approach and methodology. The second contains an example application of the methodology. The third presents the conclusions of the study. PNL used the model and computer programs developed as part of Task C.5 (Estimation of Inspection Efforts) of the Program of Technical Assistance. The example application of the methodology involves low-enriched uranium conversion and fuel fabrication facilities. The effects of variations in seven parameters are considered: false alarm probability, goal probability of detection, detection goal quantity, the plant operator's measurement capability, the inspector's variables measurement capability, the inspector's attributes measurement capability, and annual plant throughput. Among the key results and conclusions of the analysis are the following: the variables with the greatest impact on the probability of detection are the inspector's measurement capability, the goal quantity, and the throughput; the variables with the greatest impact on inspection costs are the throughput, the goal quantity, and the goal probability of detection; there are important interactions between variables. That is, the effects of a given variable often depends on the level or value of some other variable. With the methodology used in this study, these interactions can be quantitatively analyzed; reasonably good approximate prediction equations can be developed using the methodology described here.

  2. Analysis for making a regulatory decision to equipment of industrial gammagraphy in Argentin; Analisis para la toma de decision regulatoria sobre equipos de gammagrafia industrial en Argentina

    Energy Technology Data Exchange (ETDEWEB)

    Ermacora, Marcela G.; Vidal, Dora N.; Alonso, Maria T., E-mail: mermacora@arn.gob.ar, E-mail: dvidal@arn.gob.ar, E-mail: malonso@arn.gob.ar [Autoridad Regulatoria Nuclear (ARN), Buenos Aires (Argentina)

    2013-10-01

    Industrial gammagraphy is a practice widely used as a nondestructive testing technique in Argentina. Experience worldwide has shown the need for an improvement in the intrinsic safety of the equipment used in this lab. In response to this reason, the board of the Nuclear Regulatory Authority (ARN) has considered a proposal to withdraw service movement and much of the equipment inventory scan belonging to industrial facilities nationwide. The main objective of this paper is to present the results of the analysis performed to support the above proposal. The main elements of evaluation can be summarized as follows: I) the teams that do not conform to international recommendations regarding compliance with key safety requirements of international standards such as ISO 3999:2004 (E) {sup R}adiation protection - Industrial Apparatus for gamma radiography - Specifications for performance, design and tests {sup ;} II) the decision by some manufacturers to discontinue production of certain models of equipment and the provision of spare parts, and III) the validity of certificates bulk type B (U) for transport. In conclusion, it highlights the importance of a regulatory decision supplementary to the Standard AR 7.9.1 concerning the operation of scan equipment industry, based on current international recommendations and Argentina's commitment to good practice and safety culture which can lead to a positive impact on radiation safety in this art.

  3. Dissecting the regulatory microenvironment of a large animal model of non-Hodgkin lymphoma: evidence of a negative prognostic impact of FOXP3+ T cells in canine B cell lymphoma.

    Science.gov (United States)

    Pinheiro, Dammy; Chang, Yu-Mei; Bryant, Hannah; Szladovits, Balazs; Dalessandri, Tim; Davison, Lucy J; Yallop, Elizabeth; Mills, Emily; Leo, Chiara; Lara, Ana; Stell, Anneliese; Polton, Gerry; Garden, Oliver A

    2014-01-01

    The cancer microenvironment plays a pivotal role in oncogenesis, containing a number of regulatory cells that attenuate the anti-neoplastic immune response. While the negative prognostic impact of regulatory T cells (Tregs) in the context of most solid tissue tumors is well established, their role in lymphoid malignancies remains unclear. T cells expressing FOXP3 and Helios were documented in the fine needle aspirates of affected lymph nodes of dogs with spontaneous multicentric B cell lymphoma (BCL), proposed to be a model for human non-Hodgkin lymphoma. Multivariable analysis revealed that the frequency of lymph node FOXP3(+) T cells was an independent negative prognostic factor, impacting both progression-free survival (hazard ratio 1.10; p = 0.01) and overall survival (hazard ratio 1.61; p = 0.01) when comparing dogs showing higher than the median FOXP3 expression with those showing the median value of FOXP3 expression or less. Taken together, these data suggest the existence of a population of Tregs operational in canine multicentric BCL that resembles thymic Tregs, which we speculate are co-opted by the tumor from the periphery. We suggest that canine multicentric BCL represents a robust large animal model of human diffuse large BCL, showing clinical, cytological and immunophenotypic similarities with the disease in man, allowing comparative studies of immunoregulatory mechanisms.

  4. Patient-Focused Benefit-Risk Analysis to Inform Regulatory Decisions : The European Union Perspective

    NARCIS (Netherlands)

    Muehlbacher, Axel C.; Juhnke, Christin; Beyer, Andrea R.; Garner, Sarah

    2016-01-01

    Regulatory decisions are often based on multiple clinical end points, but the perspectives used to judge the relative importance of those end points are predominantly those of expert decision makers rather than of the patient. However, there is a growing awareness that active patient and public

  5. New families of human regulatory RNA structures identified by comparative analysis of vertebrate genomes

    DEFF Research Database (Denmark)

    Parker, Brian John; Moltke, Ida; Roth, Adam Anders Edvin

    2011-01-01

    -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...

  6. Case Study for Effectiveness Analysis on Nuclear Regulatory Infrastructure Support for Emerging Nuclear Energy Countries

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Y. E.; Byeon, M. J.; Yoo, J. W.; Lee, J. M.; Lim, J. H. [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2016-10-15

    The donor countries need to make decisions on various steps such as whether to fully accept newcomers’ requests, the depth of support, and how the supportive action will be carried out. Such is not an easy task due to limited time, resources, manpower, etc. Thus, creating an infrastructure to support emerging nuclear energy countries is needed. This paper suggests the resource portfolio concept used in business management and aims to analyze the validity of supporting the new entrants’ development of regulatory infrastructure as a case study. This study tries to develop a very simple Excel-based tool for assessing the supporting strategy quantitatively and screening the activities that is projected to be less effective and attractive. There are many countries, so called newcomers, which have expressed interests in developing their own nuclear power program. It has been recognized by the international community that every country considering embarking upon their own nuclear power program should establish their nuclear safety infrastructure to sustain a high level of nuclear safety. The newcomers have requested for considerable assistance from the IAEA and they already have bilateral cooperation programs with the advanced countries with matured nuclear regulatory programs. Currently, the regulatory bodies that provide support are confronted with two responsibilities as follows; the primary objective of the regulatory bodies is to ensure that the operator fulfills the responsibility to protect human health.

  7. Deciphering ascorbic acid regulatory pathways in ripening tomato fruit using a weighted gene correlation network analysis approach.

    Science.gov (United States)

    Gao, Chao; Ju, Zheng; Li, Shan; Zuo, Jinhua; Fu, Daqi; Tian, Huiqin; Luo, Yunbo; Zhu, Benzhong

    2013-11-01

    Genotype is generally determined by the co-expression of diverse genes and multiple regulatory pathways in plants. Gene co-expression analysis combining with physiological trait data provides very important information about the gene function and regulatory mechanism. L-Ascorbic acid (AsA), which is an essential nutrient component for human health and plant metabolism, plays key roles in diverse biological processes such as cell cycle, cell expansion, stress resistance, hormone synthesis, and signaling. Here, we applied a weighted gene correlation network analysis approach based on gene expression values and AsA content data in ripening tomato (Solanum lycopersicum L.) fruit with different AsA content levels, which leads to identification of AsA relevant modules and vital genes in AsA regulatory pathways. Twenty-four modules were compartmentalized according to gene expression profiling. Among these modules, one negatively related module containing genes involved in redox processes and one positively related module enriched with genes involved in AsA biosynthetic and recycling pathways were further analyzed. The present work herein indicates that redox pathways as well as hormone-signal pathways are closely correlated with AsA accumulation in ripening tomato fruit, and allowed us to prioritize candidate genes for follow-up studies to dissect this interplay at the biochemical and molecular level.

  8. Deciphering Ascorbic Acid Regulatory Pathways in Ripening Tomato Fruit Using a Weighted Gene Correlation Network Analysis Approach

    Institute of Scientific and Technical Information of China (English)

    Chao Gao; Zheng Ju; Shan Li; Jinhua Zuo; Daqi Fu; Huiqin Tian; Yunbo Luo; Benzhong Zhu

    2013-01-01

    Genotype is generally determined by the co-expression of diverse genes and multiple regulatory pathways in plants. Gene co-expression analysis combining with physiological trait data provides very important information about the gene function and regulatory mechanism. L-Ascorbic acid (AsA), which is an essential nutrient component for human health and plant metabolism, plays key roles in diverse biological processes such as cell cycle, cell expansion, stress resistance, hormone synthesis, and signaling. Here, we applied a weighted gene correlation network analysis approach based on gene expression values and AsA content data in ripening tomato (Solanum lycopersicum L.) fruit with different AsA content levels, which leads to identification of AsA relevant modules and vital genes in AsA regulatory pathways. Twenty-four modules were compartmentalized according to gene expression profiling. Among these modules, one negatively related module containing genes involved in redox processes and one positively related module enriched with genes involved in AsA biosynthetic and recycling pathways were further analyzed. The present work herein indicates that redox pathways as well as hormone-signal pathways are closely correlated with AsA accumulation in ripening tomato fruit, and allowed us to prioritize candidate genes for follow-up studies to dissect this interplay at the biochemical and molecular level.

  9. The Proportion of Regulatory T Cells in Patients with Rheumatoid Arthritis: A Meta-Analysis

    Science.gov (United States)

    Morita, Takayoshi; Shima, Yoshihito; Wing, James Badger; Sakaguchi, Shimon; Kumanogoh, Atsushi

    2016-01-01

    Background Regulatory T cells (Tregs) have important functions in peripheral immune tolerance. Dysfunction of Tregs is considered to be a pivotal cause of autoimmune diseases, including rheumatoid arthritis (RA). However, previous reports describing the proportion of Tregs among CD4+ T cells in RA patients were controversial because a range of markers are used to identify Tregs with little consensus. To clarify the status of Tregs in RA, we investigated the proportion of Tregs with focusing on the definitions of them. Methods We identified the studies reporting the proportion of Tregs in RA patients using PubMed and Google Scholar. We performed a systematic review of them and a meta-analysis to evaluate the proportion of Tregs (FOXP3-positive and/or CD25-positive) among CD4+ T cells in peripheral blood (PB) and synovial fluid (SF) of RA patients and control subjects. Results A total 31 studies were selected. The proportion of Tregs defined by all definitions among CD4+ T cells in PB was not significantly different between RA patients and control subjects (-0.65, [-1.30, 0.01]). Then we performed sub-analyses based on individual definitions. The proportion of Tregs defined by either CD25 or FOXP3 alone did not differ between RA patients and control subjects. The proportion of Tregs defined by both FOXP3 and CD25 was lower in RA patients than that in control subjects (-2.42 [-3.49, -1.34]). The proportion of Tregs defined by both FOXP3 and CD25 was higher in SF than that in PB among RA patients (3.27 [0.40, 6.14]). Conclusion The status of Tregs varied according to the definition system. The proportion of Tregs defined by stricter and functionally validated methods decreased in PB and increased in SF among RA patients. If the proportion of Tregs differs in RA, accurate and functionally relevant definitions of Tregs are necessary to elucidate their status in RA. PMID:27622457

  10. Monitoring regulatory T cells in clinical samples: consensus on an essential marker set and gating strategy for regulatory T cell analysis by flow cytometry.

    Science.gov (United States)

    Santegoets, Saskia J A M; Dijkgraaf, Eveline M; Battaglia, Alessandra; Beckhove, Philipp; Britten, Cedrik M; Gallimore, Awen; Godkin, Andrew; Gouttefangeas, Cecile; de Gruijl, Tanja D; Koenen, Hans J P M; Scheffold, Alexander; Shevach, Ethan M; Staats, Janet; Taskén, Kjetil; Whiteside, Theresa L; Kroep, Judith R; Welters, Marij J P; van der Burg, Sjoerd H

    2015-10-01

    Regulatory T cell (Treg)-mediated immunosuppression is considered a major obstacle for successful cancer immunotherapy. The association between clinical outcome and Tregs is being studied extensively in clinical trials, but unfortunately, no consensus has been reached about (a) the markers and (b) the gating strategy required to define human Tregs in this context, making it difficult to draw final conclusions. Therefore, we have organized an international workshop on the detection and functional testing of Tregs with leading experts in the field, and 40 participants discussing different analyses and the importance of different markers and context in which Tregs were analyzed. This resulted in a rationally composed ranking list of "Treg markers". Subsequently, the proposed Treg markers were tested to get insight into the overlap/differences between the most frequently used Treg definitions and their utility for Treg detection in various human tissues. Here, we conclude that the CD3, CD4, CD25, CD127, and FoxP3 markers are the minimally required markers to define human Treg cells. Staining for Ki67 and CD45RA showed to provide additional information on the activation status of Tregs. The use of markers was validated in a series of PBMC from healthy donors and cancer patients, as well as in tumor-draining lymph nodes and freshly isolated tumors. In conclusion, we propose an essential marker set comprising antibodies to CD3, CD4, CD25, CD127, Foxp3, Ki67, and CD45RA and a corresponding robust gating strategy for the context-dependent analysis of Tregs by flow cytometry.

  11. Mission Risk Reduction Regulatory Change Management

    Science.gov (United States)

    Scroggins, Sharon

    2007-01-01

    NASA Headquarters Environmental Management Division supports NASA's mission to pioneer the future in space exploration, scientific discovery, and aeronautics research by integrating environmental considerations into programs and projects early-on, thereby proactively reducing NASA's exposure to institutional, programmatic and operational risk. As part of this effort, NASA established the Principal Center for Regulatory Risk Analysis and Communication (RRAC PC) as a resource for detecting, analyzing, and communicating environmental regulatory risks to the NASA stakeholder community. The RRAC PC focuses on detecting emerging environmental regulations and other operational change drivers that may pose risks to NASA programs and facilities, and effectively communicating the potential risks. For example, regulatory change may restrict how and where certain activities or operations may be conducted. Regulatory change can also directly affect the ability to use certain materials by mandating a production phase-out or restricting usage applications of certain materials. Regulatory change can result in significant adverse impacts to NASA programs and facilities due to NASA's stringent performance requirements for materials and components related to human-rated space vehicles. Even if a regulation does not directly affect NASA operations, U.S. and international regulations can pose program risks indirectly through requirements levied on manufacturers and vendors of components and materials. For example, manufacturers can change their formulations to comply with new regulatory requirements. Such changes can require time-consuming and costly requalification certification for use in human spaceflight programs. The RRAC PC has implemented a system for proactively managing regulatory change to minimize potential adverse impacts to NASA programs and facilities. This presentation highlights the process utilized by the RRACPC to communicate regulatory change and the associated

  12. Regulatory Compliance and Environmental Benefit Analysis of Combined Heat and Power (CHP Systems in Taiwan

    Directory of Open Access Journals (Sweden)

    Wen-Tien Tsai

    2013-01-01

    Full Text Available The energy conservation achieved by utilizing waste heat in the energy and industrial sectors has became more and more important after the energy crisis in the 1970s because it plays a vital role in the potential energy-efficiency improvement. In this regard, cogeneration (combined heat and power, CHP systems are thus becoming attractive due to the energy, economic, and environmental policies for pursuing stable electricity supply, sustainable development and environmental pollution mitigation in Taiwan. The objective of this paper is to present an updated analysis of CHP systems in Taiwan during the period from 1990 to 2010. The description in the paper is thus based on an analysis of electricity supply/consumption and its sources from CHP systems during the past two decades, and centered on two important regulations in compliance with CHP systems (i.e., Energy Management Law and Environmental Impact Assessment Act. Based on the total net power generation from CHP systems (i.e., 35,626 GWh in 2011, it was found that the carbon dioxide reduction benefits were estimated to be around 20,000 Gg.

  13. Neuraminidase inhibitors for influenza: a systematic review and meta-analysis of regulatory and mortality data.

    Science.gov (United States)

    Heneghan, Carl J; Onakpoya, Igho; Jones, Mark A; Doshi, Peter; Del Mar, Chris B; Hama, Rokuro; Thompson, Matthew J; Spencer, Elizabeth A; Mahtani, Kamal R; Nunan, David; Howick, Jeremy; Jefferson, Tom

    2016-01-01

    BACKGROUND Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used clinically worldwide. OBJECTIVES To (1) describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports (CSRs) of published and unpublished randomised, placebo-controlled trials and regulatory comments; and (2) determine the effect of oseltamivir (Tamiflu(®), Roche) treatment on mortality in patients with 2009A/H1N1 influenza. METHODS We searched trial registries, electronic databases and corresponded with regulators and sponsors to identify randomised trials of NIs. We requested full CSRs and accessed regulators' comments. We included only those trials for which we had CSRs. To examine the effects of oseltamivir on 2009A/H1N1 influenza mortality, we requested individual patient data (IPD) from corresponding authors of all included observational studies. RESULTS Effect of oseltamivir and zanamivir (Relenza®, GlaxoSmithKline) in the prevention and treatment of influenza: Oseltamivir reduced the time to first alleviation of symptoms in adults by 16.8 hours [95% confidence interval (CI) 8.4 to 25.1 hours]. Zanamivir reduced the time to first alleviation of symptoms in adults by 0.60 days (95% CI 0.39 to 0.81 days). Oseltamivir reduced unverified pneumonia in adult treatment [risk difference (RD) 1.00%, 95% CI 0.22% to 1.49%]; similar findings were observed with zanamivir prophylaxis in adults (RD 0.32%, 95% CI 0.09% to 0.41%). Oseltamivir treatment of adults increased the risk of nausea (RD 3.66%, 95% CI 0.90% to 7.39%) and vomiting (RD 4.56%, 95% CI 2.39% to 7.58%). In the treatment of children, oseltamivir induced vomiting (RD 5.34%, 95% CI 1.75% to 10.29%). Both oseltamivir and zanamivir prophylaxis reduced the risk of symptomatic influenza in individuals (oseltamivir RD 3.05%, 95% CI 1.83% to 3.88%; zanamivir RD 1.98%, 95% CI 0.98% to

  14. Analysis of Necessity of Transforming Electrical Grid Access Training and Examination Regulatory Agency Mode

    Institute of Scientific and Technical Information of China (English)

    JI Tuo; SUN Qi; ZHOU Wan-lan

    2016-01-01

    There are numerous electricians, but only a few of them have obtained certificate. Training and examination agencies provide services relating to training, examination, and certificate application and so on. Thus, training resources are not rationally utilized, and the increased training demand cannot be fully satisfied. Under such circumstances, it is recommended to transform the regulatory agency mode by establishing a scientific management process, and put forward a new mode of electrical grid access training and examination to better meet related demands. Under the coordination of examination center regulatory agency, uniform training program, training materials, charging standard, examination and certificate can be guaranteed. This project is carried out as an effort to improve the quality of electronic-engineering training and examination, so that electricity accident rate can be reduced, and the security of electrical grid operation can be guaranteed to boost the rapidly developing economy.

  15. CARRIE web service: automated transcriptional regulatory network inference and interactive analysis.

    Science.gov (United States)

    Haverty, Peter M; Frith, Martin C; Weng, Zhiping

    2004-07-01

    We present an intuitive and interactive web service for CARRIE (Computational Ascertainment of Regulatory Relationships Inferred from Expression). CARRIE is a computational method that analyzes microarray and promoter sequence data to infer a transcriptional regulatory network from the response to a specific stimulus. This service displays an interactive graph of the inferred network and provides easy access to the evidence for the involvement of each gene in the network. We provide functionality to include network data in KEGG XML (KGML) format in this graph. Our service also provides Gene Ontology annotation to aid the user in forming hypotheses about the role of each gene in the cellular response. The CARRIE web service is freely available at http://zlab.bu.edu/CARRIE-web.

  16. Opinions and perceptions regarding the impact of new regulatory guidelines: A survey in Indian Clinical Trial Investigators

    Directory of Open Access Journals (Sweden)

    Rashmi Kadam

    2016-01-01

    Full Text Available Background: Clinical research in India experienced dramatic changes with series of stringent guidelines introduced by regulatory authorities. These guidelines posed significant challenges for the clinical trial industry. Objective: To assess the perceptions and opinion of Indian Investigators about the new regulatory guidelines. Methods: We developed a survey questionnaire on recent regulatory guidelines which was hosted on a web portal. Seventy-three investigators from India participated in the survey. Results: Central registration of Ethics Committees (ECs was agreed by 90.1% participants, 76.8% participants agreed to compensation of subjects for study related Serious Adverse Events (SAE's. The compulsion to include government sites in clinical trials was not agreed by 49.3% participants while 21.2% agreed to it. Restriction on a number of trials per investigator was agreed by 49.3% of participants while 40.9% disagreed. Participants (50.7% disagreed to the introduction of audio-video (AV recording of informed consent, 36.6% agreed and 12.7% were neutral. Discussion: Participants observed that post central registration; ECs have improved systems with adequate member composition, functional Standard Operating Procedures, and timely approvals. Participants agreed that compensation of study related SAE's would assure subject protection and safety. The introduction of AV consenting was strongly debated sighting sociocultural issues in the implementation of the same. Conclusion: Participants endorsed guidelines pertaining to the central registration of ECs, SAE related compensation. Restrictions on a number of trials per investigator and AV consenting were debated ardently. The response of the survey participants who are clinical trial investigators in India showed general acceptance, effectiveness and anticipated compliance to the new regulatory guidelines.

  17. Patient-Focused Benefit-Risk Analysis to Inform Regulatory Decisions: The European Union Perspective.

    Science.gov (United States)

    Mühlbacher, Axel C; Juhnke, Christin; Beyer, Andrea R; Garner, Sarah

    Regulatory decisions are often based on multiple clinical end points, but the perspectives used to judge the relative importance of those end points are predominantly those of expert decision makers rather than of the patient. However, there is a growing awareness that active patient and public participation can improve decision making, increase acceptance of decisions, and improve adherence to treatments. The assessment of risk versus benefit requires not only information on clinical outcomes but also value judgments about which outcomes are important and whether the potential benefits outweigh the harms. There are a number of mechanisms for capturing the input of patients, and regulatory bodies within the European Union are participating in several initiatives. These can include patients directly participating in the regulatory decision-making process or using information derived from patients in empirical studies as part of the evidence considered. One promising method that is being explored is the elicitation of "patient preferences." Preferences, in this context, refer to the individual's evaluation of health outcomes and can be understood as statements regarding the relative desirability of a range of treatment options, treatment characteristics, and health states. Several methods for preference measurement have been proposed, and pilot studies have been undertaken to use patient preference information in regulatory decision making. This article describes how preferences are currently being considered in the benefit-risk assessment context, and shows how different methods of preference elicitation are used to support decision making within the European context. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  18. The Michigan regulatory incentives study for electric utilities

    Energy Technology Data Exchange (ETDEWEB)

    Reid, M.W.; Weaver, E.M. (Barakat and Chamberlin, Inc., Oakland, CA (United States))

    1991-06-17

    This is the final report of Phase I of the Michigan Regulatory Incentives Study for Electric Utilities, a three-phase review of Michigan's regulatory system and its effects on resource selection by electric utilities. The goal of Phase I is to identify and analyze financial incentive mechanisms that encourage selection of resources in accord with the principles of integrated resource planning (IRP) or least-cost planning (LCP). Subsequent study phases will involve further analysis of options and possibly a collaborative formal effort to propose regulatory changes. The Phase I analysis proceeded in three steps: (1) identification and review of existing regulatory practices that affect utilities; selection of resources, particularly DSM; (2) preliminary analysis of ten financial mechanisms, and selection of three for further study; (3) detailed analysis of the three mechanisms, including consideration of how they could be implemented in Michigan and financial modeling of their likely impacts on utilities and ratepayers.

  19. Identifying significant genetic regulatory networks in the prostate cancer from microarray data based on transcription factor analysis and conditional independency

    Directory of Open Access Journals (Sweden)

    Yeh Cheng-Yu

    2009-12-01

    Full Text Available Abstract Background Prostate cancer is a world wide leading cancer and it is characterized by its aggressive metastasis. According to the clinical heterogeneity, prostate cancer displays different stages and grades related to the aggressive metastasis disease. Although numerous studies used microarray analysis and traditional clustering method to identify the individual genes during the disease processes, the important gene regulations remain unclear. We present a computational method for inferring genetic regulatory networks from micorarray data automatically with transcription factor analysis and conditional independence testing to explore the potential significant gene regulatory networks that are correlated with cancer, tumor grade and stage in the prostate cancer. Results To deal with missing values in microarray data, we used a K-nearest-neighbors (KNN algorithm to determine the precise expression values. We applied web services technology to wrap the bioinformatics toolkits and databases to automatically extract the promoter regions of DNA sequences and predicted the transcription factors that regulate the gene expressions. We adopt the microarray datasets consists of 62 primary tumors, 41 normal prostate tissues from Stanford Microarray Database (SMD as a target dataset to evaluate our method. The predicted results showed that the possible biomarker genes related to cancer and denoted the androgen functions and processes may be in the development of the prostate cancer and promote the cell death in cell cycle. Our predicted results showed that sub-networks of genes SREBF1, STAT6 and PBX1 are strongly related to a high extent while ETS transcription factors ELK1, JUN and EGR2 are related to a low extent. Gene SLC22A3 may explain clinically the differentiation associated with the high grade cancer compared with low grade cancer. Enhancer of Zeste Homolg 2 (EZH2 regulated by RUNX1 and STAT3 is correlated to the pathological stage

  20. Comparative analysis of the transcription-factor gene regulatory networks of E. coli and S. cerevisiae

    Directory of Open Access Journals (Sweden)

    Santillán Moisés

    2008-01-01

    Full Text Available Abstract Background The regulatory interactions between transcription factors (TF and regulated genes (RG in a species genome can be lumped together in a single directed graph. The TF's and RG's conform the nodes of this graph, while links are drawn whenever a transcription factor regulates a gene's expression. Projections onto TF nodes can be constructed by linking every two nodes regulating a common gene. Similarly, projections onto RG nodes can be made by linking every two regulated genes sharing at least one common regulator. Recent studies of the connectivity pattern in the transcription-factor regulatory network of many organisms have revealed some interesting properties. However, the differences between TF and RG nodes have not been widely explored. Results After analysing the RG and TF projections of the transcription-factor gene regulatory networks of Escherichia coli and Saccharomyces cerevisiae, we found several common characteristic as well as some noticeable differences. To better understand these differences, we compared the properties of the E. coli and S. cerevisiae RG- and TF-projected networks with those of the corresponding projections built from randomized versions of the original bipartite networks. These last results indicate that the observed differences are mostly due to the very different ratios of TF to RG counts of the E. coli and S. cerevisiae bipartite networks, rather than to their having different connectivity patterns. Conclusion Since E. coli is a prokaryotic organism while S. cerevisiae is eukaryotic, there are important differences between them concerning processing of mRNA before translation, DNA packing, amount of junk DNA, and gene regulation. From the results in this paper we conclude that the most important effect such differences have had on the development of the corresponding transcription-factor gene regulatory networks is their very different ratios of TF to RG numbers. This ratio is more than three

  1. Genome-wide analysis of the regulatory function mediated by the small regulatory psm-mec RNA of methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Cheung, Gordon Y C; Villaruz, Amer E; Joo, Hwang-Soo; Duong, Anthony C; Yeh, Anthony J; Nguyen, Thuan H; Sturdevant, Daniel E; Queck, S Y; Otto, M

    2014-07-01

    Several methicillin resistance (SCCmec) clusters characteristic of hospital-associated methicillin-resistant Staphylococcus aureus (MRSA) strains harbor the psm-mec locus. In addition to encoding the cytolysin, phenol-soluble modulin (PSM)-mec, this locus has been attributed gene regulatory functions. Here we employed genome-wide transcriptional profiling to define the regulatory function of the psm-mec locus. The immune evasion factor protein A emerged as the primary conserved and strongly regulated target of psm-mec, an effect we show is mediated by the psm-mec RNA. Furthermore, the psm-mec locus exerted regulatory effects that were more moderate in extent. For example, expression of PSM-mec limited expression of mecA, thereby decreasing methicillin resistance. Our study shows that the psm-mec locus has a rare dual regulatory RNA and encoded cytolysin function. Furthermore, our findings reveal a specific mechanism underscoring the recently emerging concept that S. aureus strains balance pronounced virulence and high expression of antibiotic resistance.

  2. Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in the United States. Preliminary background report

    Energy Technology Data Exchange (ETDEWEB)

    Feurer, D.A.; Weaver, C.L.; Gallagher, K.C.; Hejna, D.; Rielley, K.J.

    1980-01-01

    This report is a summary of a series of preliminary reports describing the laws and regulatory programs of the United states and each of the 50 states affecting the siting and operation of energy generating facilities likely to be used in Integrated Community Energy Systems (ICES). A brief summary of public utility regulatory programs, energy facility siting programs, and municipal franchising authority is presented in this report to identify how such programs and authority may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES. Subsequent reports will (1) describe public utility rate regulatory procedures and practices as they might affect an ICES, (2) analyze each of the aforementioned regulatory programs to identify impediments to the development of ICES, and (3) recommend potential changes in legislation and regulatory practices and procedures to overcome such impediments.

  3. Regulating Cannabis Social Clubs: A comparative analysis of legal and self-regulatory practices in Spain, Belgium and Uruguay.

    Science.gov (United States)

    Decorte, Tom; Pardal, Mafalda; Queirolo, Rosario; Boidi, Maria Fernanda; Sánchez Avilés, Constanza; Parés Franquero, Òscar

    2017-05-01

    Cannabis Social Clubs (CSCs) are a model of non-profit production and distribution of cannabis among a closed circuit of adult cannabis users. CSCs are now operating in several countries around the world, albeit under very different legal regimes and in different socio-political contexts. In this paper we describe and compare the legal framework and the self-regulatory practices of Cannabis Social Clubs in three countries (Spain, Belgium, and Uruguay). The objective of our comparative analysis is to investigate how CSCs operate in each of these countries. To foster discussions about how one might regulate CSCs to promote public health objectives, we conclude this paper with a discussion on the balance between adequate governmental control and self-regulatory competences of CSCs. The data used for this analysis stem from independently conducted local studies by the authors in their countries. Although the particular designs of the studies differ, the data in all three countries was collected through similar data collection methods: analysis of (legal and other documents), field visits to the clubs, interviews with staff members, media content analysis. We identified a number of similarities and differences among the CSCs' practices in the three countries. Formal registration as non-profit association seems to be a common standard among CSCs. We found nevertheless great variation in terms of the size of these organisations. Generally, only adult nationals and/or residents are able to join the CSCs, upon the payment of a membership fee. While production seems to be guided by consumption estimates of the members (Spain and Belgium) or by the legal framework (Uruguay), the thresholds applied by the clubs vary significantly across countries. Quality control practices remain an issue in the three settings studied here. The CSCs have developed different arrangements with regards to the distribution of cannabis to their members. By uncovering the current practices of CSCs

  4. Integrating health and environmental impact analysis.

    Science.gov (United States)

    Reis, S; Morris, G; Fleming, L E; Beck, S; Taylor, T; White, M; Depledge, M H; Steinle, S; Sabel, C E; Cowie, H; Hurley, F; Dick, J McP; Smith, R I; Austen, M

    2015-10-01

    Scientific investigations have progressively refined our understanding of the influence of the environment on human health, and the many adverse impacts that human activities exert on the environment, from the local to the planetary level. Nonetheless, throughout the modern public health era, health has been pursued as though our lives and lifestyles are disconnected from ecosystems and their component organisms. The inadequacy of the societal and public health response to obesity, health inequities, and especially global environmental and climate change now calls for an ecological approach which addresses human activity in all its social, economic and cultural complexity. The new approach must be integral to, and interactive, with the natural environment. We see the continuing failure to truly integrate human health and environmental impact analysis as deeply damaging, and we propose a new conceptual model, the ecosystems-enriched Drivers, Pressures, State, Exposure, Effects, Actions or 'eDPSEEA' model, to address this shortcoming. The model recognizes convergence between the concept of ecosystems services which provides a human health and well-being slant to the value of ecosystems while equally emphasizing the health of the environment, and the growing calls for 'ecological public health' as a response to global environmental concerns now suffusing the discourse in public health. More revolution than evolution, ecological public health will demand new perspectives regarding the interconnections among society, the economy, the environment and our health and well-being. Success must be built on collaborations between the disparate scientific communities of the environmental sciences and public health as well as interactions with social scientists, economists and the legal profession. It will require outreach to political and other stakeholders including a currently largely disengaged general public. The need for an effective and robust science-policy interface has

  5. A comparative analysis of the evolution, expression, and cis-regulatory element of polygalacturonase genes in grasses and dicots.

    Science.gov (United States)

    Liang, Ying; Yu, Youjian; Cui, Jinlong; Lyu, Meiling; Xu, Liai; Cao, Jiashu

    2016-11-01

    Cell walls are a distinguishing characteristic of plants essential to their survival. The pectin content of primary cell walls in grasses and dicots is distinctly different. Polygalacturonases (PGs) can degrade pectins and participate in multiple developmental processes of plants. This study comprehensively compared the evolution, expression, and cis-regulatory element of PGs in grasses and dicots. A total of 577 PGs identified from five grasses and five dicots fell into seven clades. Evolutionary analysis demonstrated the distinct differences between grasses and dicots in patterns of gene duplication and loss, and evolutionary rates. Grasses generally contained much fewer clade C and F members than dicots. We found that this disparity was the result of less duplication and more gene losses in grasses. More duplications occurred in clades D and E, and expression analysis showed that most of clade E members were expressed ubiquitously at a high overall level and clade D members were closely related to male reproduction in both grasses and dicots, suggesting their biological functions were highly conserved across species. In addition to the general role in reproductive development, PGs of clades C and F specifically played roles in root development in dicots, shedding light on organ differentiation between the two groups of plants. A regulatory element analysis of clade C and F members implied that possible functions of PGs in specific biological responses contributed to their expansion and preservation. This work can improve the knowledge of PGs in plants generally and in grasses specifically and is beneficial to functional studies.

  6. An eQTL mapping approach reveals that rare variants in the SEMA5A regulatory network impact autism risk.

    Science.gov (United States)

    Cheng, Ye; Quinn, Jeffrey Francis; Weiss, Lauren Anne

    2013-07-15

    To date, genome-wide single nucleotide polymorphism (SNP) and copy number variant (CNV) association studies of autism spectrum disorders (ASDs) have led to promising signals but not to easily interpretable or translatable results. Our own genome-wide association study (GWAS) showed significant association to an intergenic SNP near Semaphorin 5A (SEMA5A) and provided evidence for reduced expression of the same gene. In a novel GWAS follow-up approach, we map an expression regulatory pathway for a GWAS candidate gene, SEMA5A, in silico by using population expression and genotype data sets. We find that the SEMA5A regulatory network significantly overlaps rare autism-specific CNVs. The SEMA5A regulatory network includes previous autism candidate genes and regions, including MACROD2, A2BP1, MCPH1, MAST4, CDH8, CADM1, FOXP1, AUTS2, MBD5, 7q21, 20p, USH2A, KIRREL3, DBF4B and RELN, among others. Our results provide: (i) a novel data-derived network implicated in autism, (ii) evidence that the same pathway seeded by an initial SNP association shows association with rare genetic variation in ASDs, (iii) a potential mechanism of action and interpretation for the previous autism candidate genes and genetic variants that fall in this network, and (iv) a novel approach that can be applied to other candidate genes for complex genetic disorders. We take a step towards better understanding of the significance of SEMA5A pathways in autism that can guide interpretation of many other genetic results in ASDs.

  7. Quantitative and functional analysis of CD69(+) T regulatory lymphocytes in patients with periodontal disease.

    Science.gov (United States)

    Vitales-Noyola, Marlen; Martínez-Martínez, Rita; Loyola-Rodríguez, Juan P; Baranda, Lourdes; Niño-Moreno, Perla; González-Amaro, Roberto

    2017-08-01

    Periodontal disease is chronic inflammatory process that affects the attachment structures of the teeth and constitutes a significant cause of tooth loss in adults. Although different bacteria play an important role in the triggering of this condition, the progression and severity of the disease are strongly affected by the host immune response, which is under the control of different immune regulatory mechanisms, including T regulatory (Treg) cells. The aim of this study was to assess the frequency and function of CD69(+) Treg lymphocytes in patients with chronic periodontal disease. Peripheral blood samples (n = 33) and gingival tissue (n = 9) were obtained from patients with chronic periodontal disease. Blood samples from 25 healthy individuals were also studied. Levels of CD69(+) Treg lymphocytes in peripheral blood and gingival tissue were determined by six-color multiparametric flow cytometry, immunofluorescence, and immunohistochemistry. The immune regulatory function of CD69(+) Treg cells was tested by an in vitro assay of inhibition of lymphocyte activation. Percentages of CD69(+) Treg cells were significantly higher in the peripheral blood from patients with active periodontal disease compared to healthy controls, and these percentages inversely correlated with the periodontal attachment loss. Increased numbers of these Treg cells were detected in the gingival tissue from active PD patients compared to their peripheral blood. However, the suppressive function of CD69(+) Treg cells was significantly diminished in patients with periodontal disease compared to healthy controls. Our data suggest that CD69(+) Treg cells seem to be another important piece in the complex immunopathogenesis of periodontal disease. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Systematic genetic analysis of transcription factors to map the fission yeast transcription-regulatory network.

    Science.gov (United States)

    Chua, Gordon

    2013-12-01

    Mapping transcriptional-regulatory networks requires the identification of target genes, binding specificities and signalling pathways of transcription factors. However, the characterization of each transcription factor sufficiently for deciphering such networks remains laborious. The recent availability of overexpression and deletion strains for almost all of the transcription factor genes in the fission yeast Schizosaccharomyces pombe provides a valuable resource to better investigate transcription factors using systematic genetics. In the present paper, I review and discuss the utility of these strain collections combined with transcriptome profiling and genome-wide chromatin immunoprecipitation to identify the target genes of transcription factors.

  9. Rationale for Selection of Pesticides, Herbicides, and Related Compounds from the Hanford SST/DST Waste Considered for Analysis in Support of the Regulatory DQO (Privatization)

    Energy Technology Data Exchange (ETDEWEB)

    Wiemers, K.D.; Daling, P.; Meier, K.

    1999-01-04

    Regulated pesticides, herbicides, miticides, and fungicides were evaluated for their potential past and current use at the Hanford Site. The starting list of these compounds is based on regulatory analyte input lists discussed in the Regulatory DQO. Twelve pesticide, herbicide, miticide, and fungicide compounds are identified for analysis in the Hanford SST and DST waste in support of the Regulatory DQO. The compounds considered for additional analyses are non-detected, considered stable in the tank waste matrix, and of higher toxicity/carcinogenicity.

  10. Rationale for Selection of Pesticides, Herbicides, and Related Compounds from the Hanford SST/DST Waste Considered for Analysis in Support of the Regulatory DQO (Privatization)

    Energy Technology Data Exchange (ETDEWEB)

    Wiemers, K.D.; Daling, P.; Meier, K.

    1999-01-04

    Regulated pesticides, herbicides, miticides, and fungicides were evaluated for their potential past and current use at the Hanford Site. The starting list of these compounds is based on regulatory analyte input lists discussed in the Regulatory DQO. Twelve pesticide, herbicide, miticide, and fungicide compounds are identified for analysis in the Hanford SST and DST waste in support of the Regulatory DQO. The compounds considered for additional analyses are non-detected, considered stable in the tank waste matrix, and of higher toxicity/carcinogenicity.

  11. Analysis of 12 electric power system outages/disturbances impacting the Florida Peninsula

    Energy Technology Data Exchange (ETDEWEB)

    None

    1980-12-01

    Between January 3 and August 3, 1979, there were 12 occasions on which electric power was curtailed or public appeals were made to customers to reduce their load in Peninsular Florida due to bulk electric power supply problems. The Economic Regulatory Administration (ERA) of the US DOE, pursuant to its electric power supply adequacy and reliability responsibilities, initiated a twofold analysis of the bulk power supply situation in Florida. The first phase of the analysis evaluated the technical and engineering aspects of the overall Florida bulk power supply system with special attention given to the City of Jacksonville's electric system. The second phase evaluated the socioeconomic impacts of the bulk power supply outages on residential customers in Jacksonville. The 12 disturbances are described and a comparative analysis of the causes is presented. (LCL)

  12. Integrative analysis of the zinc finger transcription factor Lame duck in the Drosophila myogenic gene regulatory network.

    Science.gov (United States)

    Busser, Brian W; Huang, Di; Rogacki, Kevin R; Lane, Elizabeth A; Shokri, Leila; Ni, Ting; Gamble, Caitlin E; Gisselbrecht, Stephen S; Zhu, Jun; Bulyk, Martha L; Ovcharenko, Ivan; Michelson, Alan M

    2012-12-11

    Contemporary high-throughput technologies permit the rapid identification of transcription factor (TF) target genes on a genome-wide scale, yet the functional significance of TFs requires knowledge of target gene expression patterns, cooperating TFs, and cis-regulatory element (CRE) structures. Here we investigated the myogenic regulatory network downstream of the Drosophila zinc finger TF Lame duck (Lmd) by combining both previously published and newly performed genomic data sets, including ChIP sequencing (ChIP-seq), genome-wide mRNA profiling, cell-specific expression patterns of putative transcriptional targets, analysis of histone mark signatures, studies of TF cooccupancy by additional mesodermal regulators, TF binding site determination using protein binding microarrays (PBMs), and machine learning of candidate CRE motif compositions. Our findings suggest that Lmd orchestrates an extensive myogenic regulatory network, a conclusion supported by the identification of Lmd-dependent genes, histone signatures of Lmd-bound genomic regions, and the relationship of these features to cell-specific gene expression patterns. The heterogeneous cooccupancy of Lmd-bound regions with additional mesodermal regulators revealed that different transcriptional inputs are used to mediate similar myogenic gene expression patterns. Machine learning further demonstrated diverse combinatorial motif patterns within tissue-specific Lmd-bound regions. PBM analysis established the complete spectrum of Lmd DNA binding specificities, and site-directed mutagenesis of Lmd and additional newly discovered motifs in known enhancers demonstrated the critical role of these TF binding sites in supporting full enhancer activity. Collectively, these findings provide insights into the transcriptional codes regulating muscle gene expression and offer a generalizable approach for similar studies in other systems.

  13. Genomic analysis of host - Peste des petits ruminants vaccine viral transcriptome uncovers transcription factors modulating immune regulatory pathways.

    Science.gov (United States)

    Manjunath, Siddappa; Kumar, Gandham Ravi; Mishra, Bishnu Prasad; Mishra, Bina; Sahoo, Aditya Prasad; Joshi, Chaitanya G; Tiwari, Ashok K; Rajak, Kaushal Kishore; Janga, Sarath Chandra

    2015-02-24

    Peste des petits ruminants (PPR), is an acute transboundary viral disease of economic importance, affecting goats and sheep. Mass vaccination programs around the world resulted in the decline of PPR outbreaks. Sungri 96 is a live attenuated vaccine, widely used in Northern India against PPR. This vaccine virus, isolated from goat works efficiently both in sheep and goat. Global gene expression changes under PPR vaccine virus infection are not yet well defined. Therefore, in this study we investigated the host-vaccine virus interactions by infecting the peripheral blood mononuclear cells isolated from goat with PPRV (Sungri 96 vaccine virus), to quantify the global changes in the transcriptomic signature by RNA-sequencing. Viral genome of Sungri 96 vaccine virus was assembled from the PPRV infected transcriptome confirming the infection and demonstrating the feasibility of building a complete non-host genome from the blood transcriptome. Comparison of infected transcriptome with control transcriptome revealed 985 differentially expressed genes. Functional analysis showed enrichment of immune regulatory pathways under PPRV infection. Key genes involved in immune system regulation, spliceosomal and apoptotic pathways were identified to be dysregulated. Network analysis revealed that the protein - protein interaction network among differentially expressed genes is significantly disrupted in infected state. Several genes encoding TFs that govern immune regulatory pathways were identified to co-regulate the differentially expressed genes. These data provide insights into the host - PPRV vaccine virus interactome for the first time. Our findings suggested dysregulation of immune regulatory pathways and genes encoding Transcription Factors (TFs) that govern these pathways in response to viral infection.

  14. The impact of implementation of the Canadian regulatory requirements on the quality of natural health products: the glucosamine case.

    Science.gov (United States)

    Aghazadeh-Habashi, Ali; Duke, John; Jamali, Fakhreddin

    2014-01-01

    We investigated whether the recent implementation of the regulatory requirements for the entry to the Canadian market of natural products has resulted in improved quality of the available glucosamine products. Eleven available products, of which 8 had been tested in 2002 (7 had contained substantially lower than the label claim of the active ingredient), and a European pharmaceutical grade tablet were assayed for their glucosamine content. The potassium and sodium contents of the products were also tested. Nine of the 11 Canadian products and the European tablet had more than 91% of the label claim of the active ingredient, hence, met the criterion. Two products contained 71 and 78% label claim. The electrolyte contents were very variable but constituted only a small fraction of the daily requirements. Most tested glucosamine products passed the Health Canada requirements. This improvement is likely due to the publicity regarding the low quality of the products in the past and also a result, at least in part, of the introduction of the new regulatory requirements. The sub-standard quality of a few tested products is still of concern.

  15. CodY orchestrates the expression of virulence determinants in emetic Bacillus cereus by impacting key regulatory circuits.

    Science.gov (United States)

    Frenzel, Elrike; Doll, Viktoria; Pauthner, Matthias; Lücking, Genia; Scherer, Siegfried; Ehling-Schulz, Monika

    2012-07-01

    Bacillus cereus causes gastrointestinal diseases and local and systemic infections elicited by the depsipeptide cereulide, enterotoxins, phospholipases, cytolysins and proteases. The PlcR-PapR quorum sensing system activates the expression of several virulence factors, whereas the Spo0A-AbrB regulatory circuit partially controls the plasmid-borne cereulide synthetase (ces) operon. Here, we show that CodY, a nutrient-responsive regulator of Gram-positive bacteria, has a profound effect on both regulatory systems, which have been assumed to operate independently of each other. Deletion of codY resulted in downregulation of virulence genes belonging to the PlcR regulon and a concomitant upregulation of the ces genes. CodY was found to be a repressor of the ces operon, but did not interact with the promoter regions of PlcR-dependent virulence genes in vitro, suggesting an indirect regulation of the latter. Furthermore, CodY binds to the promoter of the immune inhibitor metalloprotease InhA1, demonstrating that CodY directly links B. cereus metabolism to virulence. In vivo studies using a Galleria mellonella infection model, showed that the codY mutant was substantially attenuated, highlighting the importance of CodY as a key regulator of pathogenicity. Our results demonstrate that CodY profoundly modulates the virulence of B. cereus, possibly controlling the development of pathogenic traits in suitable host environments.

  16. Impacts of different regulatory regimes in the unitization of production; Impactos dos diferentes regimes regulatorios na individualizacao da producao

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Vinicius Farias; Moreira, Robson Prates [Petroleo Brasileiro S.A. (PETROBRAS), Rio de Janeiro, RJ (Brazil)

    2012-07-01

    The unitization process is required in most regulatory models around the world when it identifies that a reservoir straddles to out of the contracted area. This procedure aims to ensure a greater exploitation of petroleum. In Brazil is no different; however there are still many ambiguities in this process. The introduction of new tax regimes in the country broadened the doubts, as we may have a reservoir straddling between concession, production sharing, assignment of rights areas and areas not yet contracted. The objective of the present paper is to explore the uncertainties that must be addressed by the oil and gas sector in order to ensure low legal, regulatory and fiscal risks in the oil industry. The main topics discussed are the rules for production allocation, reserves and expenditures, the ANP and PPSA roles' conflicts, restriction of parties' rights, adjustment of contractual rules and also mitigate or eliminate economic, financial and fiscal uncertainties. This article does not propose solutions to all lacks raised. (author)

  17. Analysis of long-range interactions in primary human cells identifies cooperative CFTR regulatory elements.

    Science.gov (United States)

    Moisan, Stéphanie; Berlivet, Soizik; Ka, Chandran; Le Gac, Gérald; Dostie, Josée; Férec, Claude

    2016-04-07

    A mechanism by which control DNA elements regulate transcription over large linear genomic distances is by achieving close physical proximity with genes, and looping of the intervening chromatin paths. Alterations of such regulatory 'chromatin looping' systems are likely to play a critical role in human genetic disease at large. Here, we studied the spatial organization of a ≈790 kb locus encompassing the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Dysregulation of CFTR is responsible for cystic fibrosis, which is the most common lethal genetic disorder in Caucasian populations. CFTR is a relatively large gene of 189 kb with a rather complex tissue-specific and temporal expression profile. We used chromatin conformation at the CFTR locus to identify new DNA sequences that regulate its transcription. By comparing 5C chromatin interaction maps of the CFTR locus in expressing and non-expressing human primary cells, we identified several new contact points between the CFTR promoter and its surroundings, in addition to regions featuring previously described regulatory elements. We demonstrate that two of these novel interacting regions cooperatively increase CFTR expression, and suggest that the new enhancer elements located on either side of the gene are brought together through chromatin looping via CTCF.

  18. Transcriptome analysis of the Brucella abortus BvrR/BvrS two-component regulatory system.

    Directory of Open Access Journals (Sweden)

    Cristina Viadas

    Full Text Available BACKGROUND: The two-component BvrR/BvrS system is essential for Brucella abortus virulence. It was shown previously that its dysfunction alters the expression of some major outer membrane proteins and the pattern of lipid A acylation. To determine the genes regulated by BvrR/BvrS, we performed a whole-genome microarray analysis using B. abortus RNA obtained from wild type and bvrR mutant cells grown in the same conditions. METHODOLOGY/PRINCIPAL FINDINGS: A total of 127 differentially expressed genes were found: 83 were over expressed and 44 were less expressed in the bvrR mutant. Two operons, the phosphotransferase system and the maltose transport system, were down-regulated. Several genes involved in cell envelope or outer membrane biogenesis were differentially expressed: genes for outer membrane proteins (omp25a, omp25d, lipoproteins, LPS and fatty acid biosynthesis, stress response proteins, chaperones, flagellar genes, and twelve genes encoding ABC transport systems. Ten genes related with carbon metabolism (pckA and fumB among others were up-regulated in the bvrR mutant, and denitrification genes (nirK, norC and nosZ were also regulated. Notably, seven transcriptional regulators were affected, including VjbR, ExoR and OmpR that were less expressed in the bvrR mutant. Finally, the expression of eleven genes which have been previously related with Brucella virulence was also altered. CONCLUSIONS/SIGNIFICANCE: All these data corroborate the impact of BvrR/BvrS on cell envelope modulation, confirm that this system controls the carbon and nitrogen metabolism, and suggest a cross-talk among some regulators to adjust the Brucella physiology to the shift expected to occur during the transit from the extracellular to the intracellular niche.

  19. A meta-analysis of caloric restriction gene expression profiles to infer common signatures and regulatory mechanisms.

    Science.gov (United States)

    Plank, Michael; Wuttke, Daniel; van Dam, Sipko; Clarke, Susan A; de Magalhães, João Pedro

    2012-04-01

    Caloric restriction, a reduction in calorie intake without malnutrition, retards age-related degeneration and extends lifespan in several organisms. CR induces multiple changes, yet its underlying mechanisms remain poorly understood. In this work, we first performed a meta-analysis of microarray CR studies in mammals and identified genes and processes robustly altered due to CR. Our results reveal a complex array of CR-induced changes and we re-identified several genes and processes previously associated with CR, such as growth hormone signalling, lipid metabolism and immune response. Moreover, our results highlight novel associations with CR, such as retinol metabolism and copper ion detoxification, as well as hint of a strong effect of CR on circadian rhythms that in turn may contribute to metabolic changes. Analyses of our signatures by integrating co-expression data, information on genetic mutants, and transcription factor binding site analysis revealed candidate regulators of transcriptional modules in CR. Our results hint at a transcriptional module involved in sterol metabolism regulated by Srebf1. A putative regulatory role of Ppara was also identified. Overall, our conserved molecular signatures of CR provide a comprehensive picture of CR-induced changes and help understand its regulatory mechanisms.

  20. From molecule to market access: drug regulatory science as an upcoming discipline.

    Science.gov (United States)

    Gispen-de Wied, Christine C; Leufkens, Hubertus G M

    2013-11-05

    Regulatory science as a discipline has evolved over the past years with the object to boost and promote scientific rationale behind benefit/risk and decision making by regulatory authorities. The European Medicines Agency, EMA, the Food and Drug Administration, FDA, and the Japanese Pharmaceutical and Medical Devices Agency, PMDA, highlighted in their distinct ways the importance of regulatory science as a basis of good quality assessment in their strategic plans. The Medicines Evaluation Board, MEB, states: 'regulatory science is the science of developing and validating new standards and tools to evaluate and assess the benefit/risk of medicinal products, facilitating sound and transparent regulatory decision making'. Through analysis of regulatory frameworks itself and their effectiveness, however, regulatory science can also advance knowledge of these systems in general. The comprehensive guidance that is issued to complete an application dossier for regulatory product approval has seldomly been scrutinized for its efficiency. Since it is the task of regulatory authorities to protect and promote public health, it is understood that they take a cautious approach in regulating drugs prior to market access. In general, the authorities are among the first to be blamed if dangerous or useless drugs were allowed to the market. Yet, building a regulatory framework that is not challenged continuously in terms of deliverables for public health and cost-effectiveness, might be counterproductive in the end. Regulatory science and research can help understand how and why regulatory decisions are made, and where renewed discussions may be warranted. The MEB supports regulatory science as an R&D activity to fuel primary regulatory processes on product evaluation and vigilance, but also invests in a 'looking into the mirror' approach. Along the line of the drug life-cycle, publicly available data are reviewed and their regulatory impact highlighted. If made explicit

  1. Comparative analysis of acute and chronic corticosteroid pharmacogenomic effects in rat liver: Transcriptional dynamics and regulatory structures

    Directory of Open Access Journals (Sweden)

    DuBois Debra C

    2010-10-01

    Full Text Available Abstract Background Comprehensively understanding corticosteroid pharmacogenomic effects is an essential step towards an insight into the underlying molecular mechanisms for both beneficial and detrimental clinical effects. Nevertheless, even in a single tissue different methods of corticosteroid administration can induce different patterns of expression and regulatory control structures. Therefore, rich in vivo datasets of pharmacological time-series with two dosing regimens sampled from rat liver are examined for temporal patterns of changes in gene expression and their regulatory commonalities. Results The study addresses two issues, including (1 identifying significant transcriptional modules coupled with dynamic expression patterns and (2 predicting relevant common transcriptional controls to better understand the underlying mechanisms of corticosteroid adverse effects. Following the orientation of meta-analysis, an extended computational approach that explores the concept of agreement matrix from consensus clustering has been proposed with the aims of identifying gene clusters that share common expression patterns across multiple dosing regimens as well as handling challenges in the analysis of microarray data from heterogeneous sources, e.g. different platforms and time-grids in this study. Six significant transcriptional modules coupled with typical patterns of expression have been identified. Functional analysis reveals that virtually all enriched functions (gene ontologies, pathways in these modules are shown to be related to metabolic processes, implying the importance of these modules in adverse effects under the administration of corticosteroids. Relevant putative transcriptional regulators (e.g. RXRF, FKHD, SP1F are also predicted to provide another source of information towards better understanding the complexities of expression patterns and the underlying regulatory mechanisms of those modules. Conclusions We have proposed a

  2. From frequent hurricanes to the Deepwater Horizon oil spill in coastal Louisiana: the impact of regulatory change

    Directory of Open Access Journals (Sweden)

    So-Min Cheong

    2014-06-01

    Full Text Available The issue of whether adaptations to past disasters can impede adaptation to new disasters of a different type or intensity will be analyzed by examining the transition from frequent hurricanes to the Deepwater Horizon oil spill in coastal Louisiana. In particular, the effects of changed regulatory structures from the Stafford Act to the Oil Pollution Act of 1990 in response to the Deepwater Horizon oil spill are investigated. The article describes how the federal, state, and local governments adjust. In addition, it illustrates the shifting focus on the environment with the activation of the Oil Pollution Act and the Clean Water Act. It wraps up with a discussion of the uncertainty that is pervasive in the case of the oil spill derived from changed regulations and the novelty of the disaster.

  3. Nuclear Forensic Science: Analysis of Nuclear Material Out of Regulatory Control

    Science.gov (United States)

    Kristo, Michael J.; Gaffney, Amy M.; Marks, Naomi; Knight, Kim; Cassata, William S.; Hutcheon, Ian D.

    2016-06-01

    Nuclear forensic science seeks to identify the origin of nuclear materials found outside regulatory control. It is increasingly recognized as an integral part of a robust nuclear security program. This review highlights areas of active, evolving research in nuclear forensics, with a focus on analytical techniques commonly employed in Earth and planetary sciences. Applications of nuclear forensics to uranium ore concentrates (UOCs) are discussed first. UOCs have become an attractive target for nuclear forensic researchers because of the richness in impurities compared to materials produced later in the fuel cycle. The development of chronometric methods for age dating nuclear materials is then discussed, with an emphasis on improvements in accuracy that have been gained from measurements of multiple radioisotopic systems. Finally, papers that report on casework are reviewed, to provide a window into current scientific practice.

  4. Modeling disease risk through analysis of physical interactions between genetic variants within chromatin regulatory circuitry.

    Science.gov (United States)

    Corradin, Olivia; Cohen, Andrea J; Luppino, Jennifer M; Bayles, Ian M; Schumacher, Fredrick R; Scacheri, Peter C

    2016-11-01

    SNPs associated with disease susceptibility often reside in enhancer clusters, or super-enhancers. Constituents of these enhancer clusters cooperate to regulate target genes and often extend beyond the linkage disequilibrium (LD) blocks containing risk SNPs identified in genome-wide association studies (GWAS). We identified 'outside variants', defined as SNPs in weak LD with GWAS risk SNPs that physically interact with risk SNPs as part of a target gene's regulatory circuitry. These outside variants further explain variation in target gene expression beyond that explained by GWAS-associated SNPs. Additionally, the clinical risk associated with GWAS SNPs is considerably modified by the genotype of outside variants. Collectively, these findings suggest a potential model in which outside variants and GWAS SNPs that physically interact in 3D chromatin collude to influence target transcript levels as well as clinical risk. This model offers an additional hypothesis for the source of missing heritability for complex traits.

  5. Applying quantitative benefit-risk analysis to aid regulatory decision making in diagnostic imaging: methods, challenges, and opportunities.

    Science.gov (United States)

    Agapova, Maria; Devine, Emily Beth; Bresnahan, Brian W; Higashi, Mitchell K; Garrison, Louis P

    2014-09-01

    Health agencies making regulatory marketing-authorization decisions use qualitative and quantitative approaches to assess expected benefits and expected risks associated with medical interventions. There is, however, no universal standard approach that regulatory agencies consistently use to conduct benefit-risk assessment (BRA) for pharmaceuticals or medical devices, including for imaging technologies. Economics, health services research, and health outcomes research use quantitative approaches to elicit preferences of stakeholders, identify priorities, and model health conditions and health intervention effects. Challenges to BRA in medical devices are outlined, highlighting additional barriers in radiology. Three quantitative methods--multi-criteria decision analysis, health outcomes modeling and stated-choice survey--are assessed using criteria that are important in balancing benefits and risks of medical devices and imaging technologies. To be useful in regulatory BRA, quantitative methods need to: aggregate multiple benefits and risks, incorporate qualitative considerations, account for uncertainty, and make clear whose preferences/priorities are being used. Each quantitative method performs differently across these criteria and little is known about how BRA estimates and conclusions vary by approach. While no specific quantitative method is likely to be the strongest in all of the important areas, quantitative methods may have a place in BRA of medical devices and radiology. Quantitative BRA approaches have been more widely applied in medicines, with fewer BRAs in devices. Despite substantial differences in characteristics of pharmaceuticals and devices, BRA methods may be as applicable to medical devices and imaging technologies as they are to pharmaceuticals. Further research to guide the development and selection of quantitative BRA methods for medical devices and imaging technologies is needed. Copyright © 2014 AUR. Published by Elsevier Inc. All rights

  6. Genome-wide identification of the regulatory targets of a transcription factor using biochemical characterization and computational genomic analysis

    Directory of Open Access Journals (Sweden)

    Jolly Emmitt R

    2005-11-01

    Full Text Available Abstract Background A major challenge in computational genomics is the development of methodologies that allow accurate genome-wide prediction of the regulatory targets of a transcription factor. We present a method for target identification that combines experimental characterization of binding requirements with computational genomic analysis. Results Our method identified potential target genes of the transcription factor Ndt80, a key transcriptional regulator involved in yeast sporulation, using the combined information of binding affinity, positional distribution, and conservation of the binding sites across multiple species. We have also developed a mathematical approach to compute the false positive rate and the total number of targets in the genome based on the multiple selection criteria. Conclusion We have shown that combining biochemical characterization and computational genomic analysis leads to accurate identification of the genome-wide targets of a transcription factor. The method can be extended to other transcription factors and can complement other genomic approaches to transcriptional regulation.

  7. Formal modeling and analysis of ER-α associated Biological Regulatory Network in breast cancer

    Directory of Open Access Journals (Sweden)

    Samra Khalid

    2016-10-01

    Full Text Available Background Breast cancer (BC is one of the leading cause of death among females worldwide. The increasing incidence of BC is due to various genetic and environmental changes which lead to the disruption of cellular signaling network(s. It is a complex disease in which several interlinking signaling cascades play a crucial role in establishing a complex regulatory network. The logical modeling approach of René Thomas has been applied to analyze the behavior of estrogen receptor-alpha (ER-α associated Biological Regulatory Network (BRN for a small part of complex events that leads to BC metastasis. Methods A discrete model was constructed using the kinetic logic formalism and its set of logical parameters were obtained using the model checking technique implemented in the SMBioNet software which is consistent with biological observations. The discrete model was further enriched with continuous dynamics by converting it into an equivalent Petri Net (PN to analyze the logical parameters of the involved entities. Results In-silico based discrete and continuous modeling of ER-α associated signaling network involved in BC provides information about behaviors and gene-gene interaction in detail. The dynamics of discrete model revealed, imperative behaviors represented as cyclic paths and trajectories leading to pathogenic states such as metastasis. Results suggest that the increased expressions of receptors ER-α, IGF-1R and EGFR slow down the activity of tumor suppressor genes (TSGs such as BRCA1, p53 and Mdm2 which can lead to metastasis. Therefore, IGF-1R and EGFR are considered as important inhibitory targets to control the metastasis in BC. Conclusion The in-silico approaches allow us to increase our understanding of the functional properties of living organisms. It opens new avenues of investigations of multiple inhibitory targets (ER-α, IGF-1R and EGFR for wet lab experiments as well as provided valuable insights in the treatment of cancers

  8. Mutations in complement regulatory proteins predispose to preeclampsia: a genetic analysis of the PROMISSE cohort.

    Directory of Open Access Journals (Sweden)

    Jane E Salmon

    2011-03-01

    Full Text Available BACKGROUND: Pregnancy in women with systemic lupus erythematosus (SLE or antiphospholipid antibodies (APL Ab--autoimmune conditions characterized by complement-mediated injury--is associated with increased risk of preeclampsia and miscarriage. Our previous studies in mice indicate that complement activation targeted to the placenta drives angiogenic imbalance and placental insufficiency. METHODS AND FINDINGS: We use PROMISSE, a prospective study of 250 pregnant patients with SLE and/or APL Ab, to test the hypothesis in humans that impaired capacity to limit complement activation predisposes to preeclampsia. We sequenced genes encoding three complement regulatory proteins--membrane cofactor protein (MCP, complement factor I (CFI, and complement factor H (CFH--in 40 patients who had preeclampsia and found heterozygous mutations in seven (18%. Five of these patients had risk variants in MCP or CFI that were previously identified in atypical hemolytic uremic syndrome, a disease characterized by endothelial damage. One had a novel mutation in MCP that impairs regulation of C4b. These findings constitute, to our knowledge, the first genetic defects associated with preeclampsia in SLE and/or APL Ab. We confirmed the association of hypomorphic variants of MCP and CFI in a cohort of non-autoimmune preeclampsia patients in which five of 59 were heterozygous for mutations. CONCLUSION: The presence of risk variants in complement regulatory proteins in patients with SLE and/or APL Ab who develop preeclampsia, as well as in preeclampsia patients lacking autoimmune disease, links complement activation to disease pathogenesis and suggests new targets for treatment of this important public health problem. STUDY REGISTRATION: ClinicalTrials.gov NCT00198068.

  9. Construction and analysis of an integrated regulatory network derived from high-throughput sequencing data.

    Directory of Open Access Journals (Sweden)

    Chao Cheng

    2011-11-01

    Full Text Available We present a network framework for analyzing multi-level regulation in higher eukaryotes based on systematic integration of various high-throughput datasets. The network, namely the integrated regulatory network, consists of three major types of regulation: TF→gene, TF→miRNA and miRNA→gene. We identified the target genes and target miRNAs for a set of TFs based on the ChIP-Seq binding profiles, the predicted targets of miRNAs using annotated 3'UTR sequences and conservation information. Making use of the system-wide RNA-Seq profiles, we classified transcription factors into positive and negative regulators and assigned a sign for each regulatory interaction. Other types of edges such as protein-protein interactions and potential intra-regulations between miRNAs based on the embedding of miRNAs in their host genes were further incorporated. We examined the topological structures of the network, including its hierarchical organization and motif enrichment. We found that transcription factors downstream of the hierarchy distinguish themselves by expressing more uniformly at various tissues, have more interacting partners, and are more likely to be essential. We found an over-representation of notable network motifs, including a FFL in which a miRNA cost-effectively shuts down a transcription factor and its target. We used data of C. elegans from the modENCODE project as a primary model to illustrate our framework, but further verified the results using other two data sets. As more and more genome-wide ChIP-Seq and RNA-Seq data becomes available in the near future, our methods of data integration have various potential applications.

  10. Network analysis of transcriptomics expands regulatory landscapes in Synechococcus sp. PCC 7002

    Energy Technology Data Exchange (ETDEWEB)

    McClure, Ryan S.; Overall, Christopher C.; McDermott, Jason E.; Hill, Eric A.; Markillie, Lye Meng; McCue, Lee Ann; Taylor, Ronald C.; Ludwig, Marcus; Bryant, Donald A.; Beliaev, Alexander S.

    2016-08-27

    Cyanobacterial regulation of gene expression must contend with a genome organization that lacks apparent functional context, as the majority of cellular processes and metabolic pathways are encoded by genes found at disparate locations across the genome. In addition, the fact that coordinated regulation of cyanobacterial cellular machinery takes place with significantly fewer transcription factors, compared to other Eubacteria, suggests the involvement of post-transcriptional mechanisms and regulatory adaptations which are not fully understood. Global transcript abundance from model cyanobacterium Synechococcus sp. PCC 7002 grown under 42 different conditions was analyzed using context-likelihood of relatedness. The resulting 903-gene network, which was organized into 11 modules, not only allowed classification of cyanobacterial responses to specific environmental variables but provided insight into the transcriptional network topology and led to the expansion of predicted regulons. When used in conjunction with genome sequence, the global transcript abundance allowed identification of putative post-transcriptional changes in expression as well as novel potential targets of both DNA binding proteins and asRNA regulators. The results offer a new perspective into the multi-level regulation that governs cellular adaptations of fast-growing physiologically robust cyanobacterium Synechococcus sp. PCC 7002 to changing environmental variables. It also extends a methodological knowledge-based framework for studying multi-scale regulatory mechanisms that operate in cyanobacteria. Finally, it provides valuable context for integrating systems-level data to enhance evidence-driven genomic annotation, especially in organisms where traditional context analyses cannot be implemented due to lack of operon-based functional organization.

  11. Formal modeling and analysis of ER-α associated Biological Regulatory Network in breast cancer

    Science.gov (United States)

    Tareen, Samar H.K.; Siddiqa, Amnah; Bibi, Zurah; Ahmad, Jamil

    2016-01-01

    Background Breast cancer (BC) is one of the leading cause of death among females worldwide. The increasing incidence of BC is due to various genetic and environmental changes which lead to the disruption of cellular signaling network(s). It is a complex disease in which several interlinking signaling cascades play a crucial role in establishing a complex regulatory network. The logical modeling approach of René Thomas has been applied to analyze the behavior of estrogen receptor-alpha (ER-α) associated Biological Regulatory Network (BRN) for a small part of complex events that leads to BC metastasis. Methods A discrete model was constructed using the kinetic logic formalism and its set of logical parameters were obtained using the model checking technique implemented in the SMBioNet software which is consistent with biological observations. The discrete model was further enriched with continuous dynamics by converting it into an equivalent Petri Net (PN) to analyze the logical parameters of the involved entities. Results In-silico based discrete and continuous modeling of ER-α associated signaling network involved in BC provides information about behaviors and gene-gene interaction in detail. The dynamics of discrete model revealed, imperative behaviors represented as cyclic paths and trajectories leading to pathogenic states such as metastasis. Results suggest that the increased expressions of receptors ER-α, IGF-1R and EGFR slow down the activity of tumor suppressor genes (TSGs) such as BRCA1, p53 and Mdm2 which can lead to metastasis. Therefore, IGF-1R and EGFR are considered as important inhibitory targets to control the metastasis in BC. Conclusion The in-silico approaches allow us to increase our understanding of the functional properties of living organisms. It opens new avenues of investigations of multiple inhibitory targets (ER-α, IGF-1R and EGFR) for wet lab experiments as well as provided valuable insights in the treatment of cancers such as BC.

  12. Regional analysis and environmental impact assessment

    Energy Technology Data Exchange (ETDEWEB)

    Parzyck, D.C.; Brocksen, R.W.; Emanuel, W.R.

    1976-01-01

    This paper presents a number of techniques that can be used to assess environmental impacts on a regional scale. Regional methodologies have been developed which examine impacts upon aquatic and terrestrial biota in regions through consideration of changes in land use, land cover, air quality, water resource use, and water quality. Techniques used to assess long-range atmospheric transport, water resources, effects on sensitive forest and animal species, and impacts on man are presented in this paper, along with an optimization approach which serves to integrate the analytical techniques in an overall assessment framework. A brief review of the research approach and certain modeling techniques used within one regional studies program is provided. While it is not an all inclusive report on regional analyses, it does present an illustration of the types of analyses that can be performed on a regional scale.

  13. Reduction of regulatory risk: a network economic approach

    OpenAIRE

    Knieps, Günter; Weiß, Hans-Jörg

    2007-01-01

    Several definitions of regulatory risk are known from the literature. From the perspective of regulatory reform it is important to differentiate between the impact of a given regulatory scheme on the firm's risk exposure and the risk arising from discretionary behavior of regulatory agencies. Whereas the conse-quences of effective regulation in principle are known and accepted, excessive regulatory discretion may cause a strong need for regulatory reform. Regulatory reform focussing on the re...

  14. Integrative bioinformatics analysis of genomic and proteomic approaches to understand the transcriptional regulatory program in coronary artery disease pathways.

    Directory of Open Access Journals (Sweden)

    Rajani Kanth Vangala

    Full Text Available Patients with cardiovascular disease show a panel of differentially regulated serum biomarkers indicative of modulation of several pathways from disease onset to progression. Few of these biomarkers have been proposed for multimarker risk prediction methods. However, the underlying mechanism of the expression changes and modulation of the pathways is not yet addressed in entirety. Our present work focuses on understanding the regulatory mechanisms at transcriptional level by identifying the core and specific transcription factors that regulate the coronary artery disease associated pathways. Using the principles of systems biology we integrated the genomics and proteomics data with computational tools. We selected biomarkers from 7 different pathways based on their association with the disease and assayed 24 biomarkers along with gene expression studies and built network modules which are highly regulated by 5 core regulators PPARG, EGR1, ETV1, KLF7 and ESRRA. These network modules in turn comprise of biomarkers from different pathways showing that the core regulatory transcription factors may work together in differential regulation of several pathways potentially leading to the disease. This kind of analysis can enhance the elucidation of mechanisms in the disease and give better strategies of developing multimarker module based risk predictions.

  15. Integrative bioinformatics analysis of genomic and proteomic approaches to understand the transcriptional regulatory program in coronary artery disease pathways.

    Science.gov (United States)

    Vangala, Rajani Kanth; Ravindran, Vandana; Ghatge, Madan; Shanker, Jayashree; Arvind, Prathima; Bindu, Hima; Shekar, Meghala; Rao, Veena S

    2013-01-01

    Patients with cardiovascular disease show a panel of differentially regulated serum biomarkers indicative of modulation of several pathways from disease onset to progression. Few of these biomarkers have been proposed for multimarker risk prediction methods. However, the underlying mechanism of the expression changes and modulation of the pathways is not yet addressed in entirety. Our present work focuses on understanding the regulatory mechanisms at transcriptional level by identifying the core and specific transcription factors that regulate the coronary artery disease associated pathways. Using the principles of systems biology we integrated the genomics and proteomics data with computational tools. We selected biomarkers from 7 different pathways based on their association with the disease and assayed 24 biomarkers along with gene expression studies and built network modules which are highly regulated by 5 core regulators PPARG, EGR1, ETV1, KLF7 and ESRRA. These network modules in turn comprise of biomarkers from different pathways showing that the core regulatory transcription factors may work together in differential regulation of several pathways potentially leading to the disease. This kind of analysis can enhance the elucidation of mechanisms in the disease and give better strategies of developing multimarker module based risk predictions.

  16. On the local optimal solutions of metabolic regulatory networks using information guided genetic algorithm approach and clustering analysis.

    Science.gov (United States)

    Zheng, Ying; Yeh, Chen-Wei; Yang, Chi-Da; Jang, Shi-Shang; Chu, I-Ming

    2007-08-31

    Biological information generated by high-throughput technology has made systems approach feasible for many biological problems. By this approach, optimization of metabolic pathway has been successfully applied in the amino acid production. However, in this technique, gene modifications of metabolic control architecture as well as enzyme expression levels are coupled and result in a mixed integer nonlinear programming problem. Furthermore, the stoichiometric complexity of metabolic pathway, along with strong nonlinear behaviour of the regulatory kinetic models, directs a highly rugged contour in the whole optimization problem. There may exist local optimal solutions wherein the same level of production through different flux distributions compared with global optimum. The purpose of this work is to develop a novel stochastic optimization approach-information guided genetic algorithm (IGA) to discover the local optima with different levels of modification of the regulatory loop and production rates. The novelties of this work include the information theory, local search, and clustering analysis to discover the local optima which have physical meaning among the qualified solutions.

  17. Mass Spectrometric Analysis of TRPM6 and TRPM7 Phosphorylation Reveals Regulatory Mechanisms of the Channel-Kinases

    Science.gov (United States)

    Cai, Na; Bai, Zhiyong; Nanda, Vikas; Runnels, Loren W.

    2017-01-01

    TRPM7 and TRPM6 were the first identified bifunctional channels to contain their own kinase domains, but how these channel-kinases are regulated is poorly understood. Previous studies identified numerous phosphorylation sites on TRPM7, but very little is known about TRPM6 phosphorylation or sites on TRPM7 transphosphorylated by TRPM6. Our mass spectrometric analysis of homomeric and heteromeric TRPM7 and TRPM6 channels identified phosphorylation sites on both proteins, as well as several prominent sites on TRPM7 that are commonly modified through autophosphorylation and transphosphorylation by TRPM6. We conducted a series of amino acid substitution analyses and identified S1777, in TRPM7’s catalytic domain, and S1565, in TRPM7’s exchange domain that mediates kinase dimerization, as potential regulatory sites. The phosphomimetic S1777D substitution disrupted catalytic activity, most likely by causing an electrostatic perturbation at the active site. The S1565D phosphomimetic substitution also inactivated the kinase but did so without interfering with kinase dimerization. Molecular modeling indicates that phosphorylation of S1565 is predicted to structurally affect TRPM7’s functionally conserved N/D loop, which is thought to influence the access of substrate to the active site pocket. We propose that phosphorylation of S1565 within the exchange domain functions as a regulatory switch to control TRPM7 catalytic activity. PMID:28220887

  18. An Improved Integral Inequality to Stability Analysis of Genetic Regulatory Networks With Interval Time-Varying Delays.

    Science.gov (United States)

    Zhang, Xian; Wu, Ligang; Cui, Shaochun

    2015-01-01

    This paper focuses on stability analysis for a class of genetic regulatory networks with interval time-varying delays. An improved integral inequality concerning on double-integral items is first established. Then, we use the improved integral inequality to deal with the resultant double-integral items in the derivative of the involved Lyapunov-Krasovskii functional. As a result, a delay-range-dependent and delay-rate-dependent asymptotical stability criterion is established for genetic regulatory networks with differential time-varying delays. Furthermore, it is theoretically proven that the stability criterion proposed here is less conservative than the corresponding one in [Neurocomputing, 2012, 93: 19-26]. Based on the obtained result, another stability criterion is given under the case that the information of the derivatives of delays is unknown. Finally, the effectiveness of the approach proposed in this paper is illustrated by a pair of numerical examples which give the comparisons of stability criteria proposed in this paper and some literature.

  19. Comparative analysis of the ATRX promoter and 5' regulatory region reveals conserved regulatory elements which are linked to roles in neurodevelopment, alpha-globin regulation and testicular function

    Directory of Open Access Journals (Sweden)

    Argentaro Anthony

    2011-06-01

    Full Text Available Abstract Background ATRX is a tightly-regulated multifunctional protein with crucial roles in mammalian development. Mutations in the ATRX gene cause ATR-X syndrome, an X-linked recessive developmental disorder resulting in severe mental retardation and mild alpha-thalassemia with facial, skeletal and genital abnormalities. Although ubiquitously expressed the clinical features of the syndrome indicate that ATRX is not likely to be a global regulator of gene expression but involved in regulating specific target genes. The regulation of ATRX expression is not well understood and this is reflected by the current lack of identified upstream regulators. The availability of genomic data from a range of species and the very highly conserved 5' regulatory regions of the ATRX gene has allowed us to investigate putative transcription factor binding sites (TFBSs in evolutionarily conserved regions of the mammalian ATRX promoter. Results We identified 12 highly conserved TFBSs of key gene regulators involved in biologically relevant processes such as neural and testis development and alpha-globin regulation. Conclusions Our results reveal potentially important regulatory elements in the ATRX gene which may lead to the identification of upstream regulators of ATRX and aid in the understanding of the molecular mechanisms that underlie ATR-X syndrome.

  20. Regulatory Volume Decrease in Neural Precursor Cells: Taurine Efflux and Gene Microarray Analysis

    Directory of Open Access Journals (Sweden)

    Reyna Hernández-Benítez

    2014-11-01

    Full Text Available Background/Aims: Neural stem/ progenitor cells (NPCs endure important changes in cell volume during growth, proliferation and migration. As a first approach to know about NPC response to cell volume changes, the Regulatory Volume Decrease (RVD subsequent to hypotonic swelling was investigated. Methods: NPCs obtained from the mesencephalon and the subventricular zone of embryonic and adult mice, respectively, were grown and cultured as neurospheres. Cell volume changes were measured by large-angle light-scattering and taurine efflux by [3H]-taurine. Expression of genes encoding molecules related to RVD was analysed using a DNA microarray obtained from NPC samples. Results: Embryonic and adult NPCs exposed to osmolarity reduction (H15, H30, H40 exhibited rapid swelling followed by RVD. The magnitude, efficiency and pharmacological profile, of RVD and of [3H]-taurine osmosensitive efflux were comparable to those found in cultured brain cells, astrocytes and neurons. The relative expression of genes encoding molecules related to volume regulation, i.e. K+ and Cl- channels, cotransporters, exchangers and aquaporins were identified in NPCs. Conclusion: NPCs show the ability to respond to hypotonic-evoked volume changes by adaptative recovery processes, similar to those found in other cultured brain cells. Genes related to molecules involved in RVD were found expressed in NPCs.

  1. Investigation and Analysis of Indian Power Grid after Regulatory Reforms & Dynamic Pricing

    Directory of Open Access Journals (Sweden)

    Ibraheem

    2010-05-01

    Full Text Available Indian power system is now a national grid with 156GW of grid capacity and approximately 19.5GW of captive generation. It has passed the horrible operation phase of last decade of the twentieth century. Though the growth rate of capacity is still trying to chase the growth rate of the load since very long but the operation and control of the system has became smooth. The obvious credit goes to restructuring and concurrent regulations encouraging discipline in the operation and control of the system. In the process of transformation structural as well as policy both the types of amendments played their role. A new kind of environment is created in the system through the new tariff structure referred as Availability Based Tariff and competition is created opening the way for furthergrowth of the system to initiate activities suitable to well developed power markets. This paper investigates into operation of the grid in the light of performance indices of the power systems after regulatory reforms and restructuring at the central as well as state level.

  2. Steady-State Analysis of Genetic Regulatory Networks Modelled by Probabilistic Boolean Networks

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2006-04-01

    Full Text Available Probabilistic Boolean networks (PBNs have recently been introduced as a promising class of models of genetic regulatory networks. The dynamic behaviour of PBNs can be analysed in the context of Markov chains. A key goal is the determination of the steady-state (long-run behaviour of a PBN by analysing the corresponding Markov chain. This allows one to compute the long-term influence of a gene on another gene or determine the long-term joint probabilistic behaviour of a few selected genes. Because matrix-based methods quickly become prohibitive for large sizes of networks, we propose the use of Monte Carlo methods. However, the rate of convergence to the stationary distribution becomes a central issue. We discuss several approaches for determining the number of iterations necessary to achieve convergence of the Markov chain corresponding to a PBN. Using a recently introduced method based on the theory of two-state Markov chains, we illustrate the approach on a sub-network designed from human glioma gene expression data and determine the joint steadystate probabilities for several groups of genes.

  3. ANALYSIS OF THE NEW REGULATORY BIOETHICAL REVIEW FRAMEWORK FOR CLINICAL TRIALS IN TURKEY.

    Science.gov (United States)

    Ilgili, Onder; Arda, Berna; Munir, Kerim

    2014-04-01

    We conducted a descriptive study of the existing research ethics committee (REC) review structure in Turkey with respect to clinical trials and discuss what can be expected in the future under the new regulation that came into effect in April 2013. We identified 78 RECs in Turkey under the Ministry of Health (MOH) as of September 2012, categorised under geographic location, type and institution. We identified REC member lists from the MOH in the same month and further characterize them under: membership number, gender, and speciality. MOH, universities, national nongovernmental organizations such as the Turkish Medical Association and the Turkish Bioethics Association, as well as clinical research and pharmaceutical bodies are intensively interested in the enhancement of the current system of research ethics review in the country. The European Union and Council directives have been important sources that have guided new developments. Proper evaluation of the existing system and introduction of new regulatory framework are expected to further clarify the obstacles and offer opportunities for institutions, researchers, REC members and administrators.

  4. DNA Methylation Analysis of HTR2A Regulatory Region in Leukocytes of Autistic Subjects.

    Science.gov (United States)

    Hranilovic, Dubravka; Blazevic, Sofia; Stefulj, Jasminka; Zill, Peter

    2016-02-01

    Disturbed brain and peripheral serotonin homeostasis is often found in subjects with autism spectrum disorder (ASD). The role of the serotonin receptor 2A (HTR2A) in the regulation of central and peripheral serotonin homeostasis, as well as its altered expression in autistic subjects, have implicated the HTR2A gene as a major candidate for the serotonin disturbance seen in autism. Several studies, yielding so far inconclusive results, have attempted to associate autism with a functional SNP -1438 G/A (rs6311) in the HTR2A promoter region, while possible contribution of epigenetic mechanisms, such as DNA methylation, to HTR2A dysregulation in autism has not yet been investigated. In this study, we compared the mean DNA methylation within the regulatory region of the HTR2A gene between autistic and control subjects. DNA methylation was analysed in peripheral blood leukocytes using bisulfite conversion and sequencing of the HTR2A region containing rs6311 polymorphism. Autistic subjects of rs6311 AG genotype displayed higher mean methylation levels within the analysed region than the corresponding controls (P < 0.05), while there was no statistically significant difference for AA and GG carriers. Our study provides preliminary evidence for increased HTR2A promoter methylation in leukocytes of a portion of adult autistic subjects, indicating that epigenetic mechanisms might contribute to HTR2A dysregulation observed in individuals with ASD.

  5. Cross-impact analysis experimentation using two techniques to ...

    African Journals Online (AJOL)

    coherency. This paper describes cross-impact analysis experimentation in which a Monte ..... [4] is used to accomplish this computational task. Using this method ..... 202–222 in Baldwin MM (Ed), Portraits of complexity: Applications of systems.

  6. Analysis of the Younger Dryas Impact Layer

    Energy Technology Data Exchange (ETDEWEB)

    Firestone, Richard B.; West, Allen; Revay, Zsolt; Hagstrum, Jonathon T,; Belgya, Thomas; Hee, Shane S. Que; Smith, Alan R.

    2010-02-27

    We have uncovered a thin layer of magnetic grains and microspherules, carbon spherules, and glass-like carbon at nine sites across North America, a site in Belgium, and throughout the rims of 16 Carolina Bays. It is consistent with the ejecta layer from an impact event and has been dated to 12.9 ka BP coinciding with the onset of Younger Dryas (YD) cooling and widespread megafaunal extinctions in North America. At many locations the impact layer is directly below a black mat marking the sudden disappearance of the megafauna and Clovis people. The distribution pattern of the Younger Dryas boundary (YDB) ejecta layer is consistent with an impact near the Great Lakes that deposited terrestrial-like ejecta near the impact site and unusual, titanium-rich projectile-like ejecta further away. High water content associated with the ejecta, up to 28 at. percent hydrogen (H), suggests the impact occurred over the Laurentide Ice Sheet. YDB microspherules and magnetic grains are highly enriched in TiO{sub 2}. Magnetic grains from several sites are enriched in iridium (Ir), up to 117 ppb. The TiO{sub 2}/FeO, K/Th, TiO{sub 2}/Zr, Al{sub 2}O{sub 3}/FeO+MgO, CaO/Al{sub 2}O{sub 3}, REE/ chondrite, FeO/MnO ratios and SiO{sub 2}, Na{sub 2}O, K{sub 2}O, Cr{sub 2}O{sub 3}, Ni, Co, U, Th and other trace element abundances are inconsistent with all terrestrial and extraterrestrial (ET) sources except for KREEP, a lunar igneous rock rich in potassium (K), rare-earth elements (REE), phosphorus (P), and other incompatible elements including U and Th. Normal Fe, Ti, and {sup 238}U/{sup 235}U isotopic abundances were found in the magnetic grains, but {sup 234}U was enriched over equilibrium values by 50 percent in Murray Springs and by 130 percent in Belgium. 40K abundance is enriched by up to 100 percent in YDB sediments and Clovis chert artifacts. Highly vesicular carbon spherules containing nanodiamonds, glass-like carbon, charcoal and soot found in large quantities in the YDB layer are

  7. Flood Progression Modelling and Impact Analysis

    DEFF Research Database (Denmark)

    Mioc, Darka; Anton, François; Nickerson, B.

    People living in the lower valley of the St. John River, New Brunswick, Canada, frequently experience flooding when the river overflows its banks during spring ice melt and rain. To better prepare the population of New Brunswick for extreme flooding, we developed a new flood prediction model...... that computes floodplain polygons before the flood occurs. This allows emergency managers to access the impact of the flood before it occurs and make the early decisions for evacuation of the population and flood rescue. This research shows that the use of GIS and LiDAR technologies combined with hydrological...... modelling can significantly improve the decision making and visualization of flood impact needed for emergency planning and flood rescue. Furthermore, the 3D GIS application we developed for modelling flooded buildings and infrastructure provides a better platform for modelling and visualizing flood...

  8. Report to the US Nuclear Regulatory Commission on analysis and evaluation of operational data - 1987: Power reactors

    Energy Technology Data Exchange (ETDEWEB)

    None

    1988-10-01

    This annual report of the US Nuclear Regulatory Commission's Office for Analysis and Evaluation of Operational Data (AEOD) is devoted to the activities performed during 1987. The report is published in two volumes. NUREG-1272, Vol. 2, No. 1, covers Power Reactors and presents an overview of the operating experience of the nuclear power industry, with comments regarding the trends of some key performance measures. The report also includes the principal findings and issues identified in AEOD studies over the past year, and summarizes information from Licensee Event Reports, the NRC's Operations Center, and Diagnostic Evaluations. NUREG-1272, Vol. 2, No. 2, covers Nonreactors and presents a review of the nonreactors events and misadministration reports that were reported in 1987 and a brief synopsis of AEOD studies published in 1987. Each volume contains a list of the AEOD Reports issued for 1980-1987.

  9. Change impact analysis for software product lines

    Directory of Open Access Journals (Sweden)

    Jihen Maâzoun

    2016-10-01

    Full Text Available A software product line (SPL represents a family of products in a given application domain. Each SPL is constructed to provide for the derivation of new products by covering a wide range of features in its domain. Nevertheless, over time, some domain features may become obsolete with the apparition of new features while others may become refined. Accordingly, the SPL must be maintained to account for the domain evolution. Such evolution requires a means for managing the impact of changes on the SPL models, including the feature model and design. This paper presents an automated method that analyzes feature model evolution, traces their impact on the SPL design, and offers a set of recommendations to ensure the consistency of both models. The proposed method defines a set of new metrics adapted to SPL evolution to identify the effort needed to maintain the SPL models consistently and with a quality as good as the original models. The method and its tool are illustrated through an example of an SPL in the Text Editing domain. In addition, they are experimentally evaluated in terms of both the quality of the maintained SPL models and the precision of the impact change management.

  10. A Change Impact Analysis to Characterize Evolving Program Behaviors

    Science.gov (United States)

    Rungta, Neha Shyam; Person, Suzette; Branchaud, Joshua

    2012-01-01

    Change impact analysis techniques estimate the potential effects of changes made to software. Directed Incremental Symbolic Execution (DiSE) is an intraprocedural technique for characterizing the impact of software changes on program behaviors. DiSE first estimates the impact of the changes on the source code using program slicing techniques, and then uses the impact sets to guide symbolic execution to generate path conditions that characterize impacted program behaviors. DiSE, however, cannot reason about the flow of impact between methods and will fail to generate path conditions for certain impacted program behaviors. In this work, we present iDiSE, an extension to DiSE that performs an interprocedural analysis. iDiSE combines static and dynamic calling context information to efficiently generate impacted program behaviors across calling contexts. Information about impacted program behaviors is useful for testing, verification, and debugging of evolving programs. We present a case-study of our implementation of the iDiSE algorithm to demonstrate its efficiency at computing impacted program behaviors. Traditional notions of coverage are insufficient for characterizing the testing efforts used to validate evolving program behaviors because they do not take into account the impact of changes to the code. In this work we present novel definitions of impacted coverage metrics that are useful for evaluating the testing effort required to test evolving programs. We then describe how the notions of impacted coverage can be used to configure techniques such as DiSE and iDiSE in order to support regression testing related tasks. We also discuss how DiSE and iDiSE can be configured for debugging finding the root cause of errors introduced by changes made to the code. In our empirical evaluation we demonstrate that the configurations of DiSE and iDiSE can be used to support various software maintenance tasks

  11. Analysis of high velocity impact on hybrid composite fan blades

    Science.gov (United States)

    Chamis, C. C.; Sinclair, J. H.

    1979-01-01

    This paper describes recent developments in the analysis of high velocity impact of composite blades using a computerized capability which consists of coupling a composites mechanics code with the direct-time integration features of NASTRAN. The application of the capability to determine the linear dynamic response of an intraply hybrid composite aircraft engine fan blade is described in detail. The predicted results agree with measured data. The results also show that the impact stresses reach sufficiently high magnitudes to cause failures in the impact region at early times of the impact event.

  12. Preferential Regulatory Treatment and Banks' Demand for Government Bonds

    NARCIS (Netherlands)

    Bonner, Clemens

    2015-01-01

    The purpose of this paper is to analyze the impact of preferential regulatory treatment on banks’ demand for government bonds. Using unique transaction-level data, our analysis suggests that preferential treatment in microprudential liquidity and capital regulation significantly increases banks’ dem

  13. REGULATORY AND PRACTICAL MATTERS REGARDING CHILD PROTECTION IN ROMANIA

    Directory of Open Access Journals (Sweden)

    Mihaela Tofan

    2013-11-01

    Full Text Available Social protection of children as prerequisite of social economy is a topic of theoretical and practical analysis over Romanian law system. Addressing the regulatory framework in force and following the practical impact of the effects that legal rules may generate, the article leads to conclusions on improving and developing institutions and mechanisms that support the coherent functioning of the social economy.

  14. Preferential Regulatory Treatment and Banks' Demand for Government Bonds

    NARCIS (Netherlands)

    Bonner, Clemens

    2015-01-01

    The purpose of this paper is to analyze the impact of preferential regulatory treatment on banks’ demand for government bonds. Using unique transaction-level data, our analysis suggests that preferential treatment in microprudential liquidity and capital regulation significantly increases banks’

  15. Preferential Regulatory Treatment and Banks' Demand for Government Bonds

    NARCIS (Netherlands)

    Bonner, Clemens

    2015-01-01

    The purpose of this paper is to analyze the impact of preferential regulatory treatment on banks’ demand for government bonds. Using unique transaction-level data, our analysis suggests that preferential treatment in microprudential liquidity and capital regulation significantly increases banks’ dem

  16. Transcriptome Analysis of an Insecticide Resistant Housefly Strain: Insights about SNPs and Regulatory Elements in Cytochrome P450 Genes.

    Directory of Open Access Journals (Sweden)

    Khalid Mahmood

    Full Text Available Insecticide resistance in the housefly, Musca domestica, has been investigated for more than 60 years. It will enter a new era after the recent publication of the housefly genome and the development of multiple next generation sequencing technologies. The genetic background of the xenobiotic response can now be investigated in greater detail. Here, we investigate the 454-pyrosequencing transcriptome of the spinosad-resistant 791spin strain in relation to the housefly genome with focus on P450 genes.The de novo assembly of clean reads gave 35,834 contigs consisting of 21,780 sequences of the spinosad resistant strain. The 3,648 sequences were annotated with an enzyme code EC number and were mapped to 124 KEGG pathways with metabolic processes as most highly represented pathway. One hundred and twenty contigs were annotated as P450s covering 44 different P450 genes of housefly. Eight differentially expressed P450s genes were identified and investigated for SNPs, CpG islands and common regulatory motifs in promoter and coding regions. Functional annotation clustering of metabolic related genes and motif analysis of P450s revealed their association with epigenetic, transcription and gene expression related functions. The sequence variation analysis resulted in 12 SNPs and eight of them found in cyp6d1. There is variation in location, size and frequency of CpG islands and specific motifs were also identified in these P450s. Moreover, identified motifs were associated to GO terms and transcription factors using bioinformatic tools.Transcriptome data of a spinosad resistant strain provide together with genome data fundamental support for future research to understand evolution of resistance in houseflies. Here, we report for the first time the SNPs, CpG islands and common regulatory motifs in differentially expressed P450s. Taken together our findings will serve as a stepping stone to advance understanding of the mechanism and role of P450s in

  17. RNA-Sequencing Analysis Reveals a Regulatory Role for Transcription Factor Fezf2 in the Mature Motor Cortex

    Directory of Open Access Journals (Sweden)

    Alison J. Clare

    2017-09-01

    Full Text Available Forebrain embryonic zinc finger (Fezf2 encodes a transcription factor essential for the specification of layer 5 projection neurons (PNs in the developing cerebral cortex. As with many developmental transcription factors, Fezf2 continues to be expressed into adulthood, suggesting it remains crucial to the maintenance of neuronal phenotypes. Despite the continued expression, a function has yet to be explored for Fezf2 in the PNs of the developed cortex. Here, we investigated the role of Fezf2 in mature neurons, using lentiviral-mediated delivery of a shRNA to conditionally knockdown the expression of Fezf2 in the mouse primary motor cortex (M1. RNA-sequencing analysis of Fezf2-reduced M1 revealed significant changes to the transcriptome, identifying a regulatory role for Fezf2 in the mature M1. Kyoto Encyclopedia Genes and Genomes (KEGG pathway analyses of Fezf2-regulated genes indicated a role in neuronal signaling and plasticity, with significant enrichment of neuroactive ligand-receptor interaction, cell adhesion molecules and calcium signaling pathways. Gene Ontology analysis supported a functional role for Fezf2-regulated genes in neuronal transmission and additionally indicated an importance in the regulation of behavior. Using the mammalian phenotype ontology database, we identified a significant overrepresentation of Fezf2-regulated genes associated with specific behavior phenotypes, including associative learning, social interaction, locomotor activation and hyperactivity. These roles were distinct from that of Fezf2-regulated genes identified in development, indicating a dynamic transition in Fezf2 function. Together our findings demonstrate a regulatory role for Fezf2 in the mature brain, with Fezf2-regulated genes having functional roles in sustaining normal neuronal and behavioral phenotypes. These results support the hypothesis that developmental transcription factors are important for maintaining neuron transcriptomes and that

  18. Pineal function: impact of microarray analysis

    DEFF Research Database (Denmark)

    Klein, David C; Bailey, Michael J; Carter, David A

    2009-01-01

    Microarray analysis has provided a new understanding of pineal function by identifying genes that are highly expressed in this tissue relative to other tissues and also by identifying over 600 genes that are expressed on a 24-h schedule. This effort has highlighted surprising similarity...... foundation that microarray analysis has provided will broadly support future research on pineal function....

  19. Comparative analysis of regulatory roles of P38 signaling pathway in 8 types liver cell during liver regeneration.

    Science.gov (United States)

    Yang, Xianguang; Zhu, Lin; Zhao, Weiming; Shi, Yaohuang; He, Chuncui; Xu, Cunshuan

    2016-12-05

    P38MAPK signaling pathway was closely related to cell proliferation, apoptosis, cell differentiation, cell survival, cell death, and so on. However, the regulatory mechanism of P38MAPK signaling pathway in liver regeneration (LR) was unclear. In order to further reveal the roles of P38MAPK signaling pathway in rat liver regeneration, Ingenuity Pathway Analysis (IPA) software and related data sites were used to construct P38MAPK signaling pathway, and the pathway was confirmed by relevant documents literature. The expression changes of P38MAPK signaling pathway-related gene in eight type cells were further analyzed by Rat Genome 230 2.0 Array, and the results showed that 95 genes in P38MAPK signaling pathway had significant changes. H-cluster analysis showed that hepatocyte cell (HC), pit cell (PC), oval cell (OC) and biliary epithelial cell (BEC) are clustered together; and the same as Kupffer cell (KC), sinusoidal endothelial cell (SEC), dendritic cell (DC) and hepatic stellate cell (HSC). IPA software and expression analysis systematic explorer (EASE) were applied to functional enrichment analysis, and the results showed that P38MAPK signaling pathway was mainly involved in apoptosis, cell death, cell proliferation, cell survival, cell viability, activation, cell cycle progression, necrosis, synthesis of DNA and other physical activity during LR. In conclusion, P38MAPK signaling pathway regulated various physiological activities of LR through multiple signaling pathways.

  20. Integrated analysis environment for high impact systems

    Energy Technology Data Exchange (ETDEWEB)

    Martinez, M. [Sandia National Labs., Albuquerque, NM (United States); Davis, J.; Scott, J.; Sztipanovits, J.; Karsai, G. [Vanderbilt Univ., Nashville, TN (United States). Measurement and Computing Systems Lab.

    1998-02-01

    Modeling and analysis of high consequence, high assurance systems requires special modeling considerations. System safety and reliability information must be captured in the models. Previously, high consequence systems were modeled using separate, disjoint models for safety, reliability, and security. The MultiGraph Architecture facilitates the implementation of a model integrated system for modeling and analysis of high assurance systems. Model integrated computing allows an integrated modeling technique to be applied to high consequence systems. Among the tools used for analyzing safety and reliability are a behavioral simulator and an automatic fault tree generation and analysis tool. Symbolic model checking techniques are used to efficiently investigate the system models. A method for converting finite state machine models to ordered binary decision diagrams allows the application of symbolic model checking routines to the integrated system models. This integrated approach to modeling and analysis of high consequence systems ensures consistency between the models and the different analysis tools.

  1. A Single Host-Derived Glycan Impacts Key Regulatory Nodes of Symbiont Metabolism in a Coevolved Mutualism.

    Science.gov (United States)

    Pan, Min; Schwartzman, Julia A; Dunn, Anne K; Lu, Zuhong; Ruby, Edward G

    2015-07-14

    a regulatory glycan is sufficient to shift symbiont carbohydrate catabolism, acetate homeostasis, and oxygen consumption. Copyright © 2015 Pan et al.

  2. Impact of birth weight and gender on early postnatal hypothalamic energy balance regulatory gene expression in the young lamb.

    Science.gov (United States)

    Adam, C L; Bake, T; Findlay, P A; Milne, J S; Aitken, R P; Wallace, J M

    2013-11-01

    Intra-uterine growth restriction (IUGR) is involved in developmental metabolic programming and here we test the hypothesis that IUGR affects the developing hypothalamic energy balance regulatory pathways in a sex-specific manner. This experiment investigated early postnatal hypothalamic gene expression for six primary leptin- and insulin-sensitive neuropeptides and receptors in male and female IUGR (n = 8 and 9, respectively) and normal (N) birth weight lambs (n = 8 per gender) gestated and suckled by overnourished mothers. IUGR lambs were smaller at birth, had increased fractional growth rates (FGR), lower final body weight (11 weeks) and similar body fat content compared with N lambs, while males had higher final body weight and insulinemia but lower body fat and leptinemia than females. In situ hybridization revealed greater gene expression in the hypothalamic arcuate nucleus at 11 weeks for anorexigenic genes in females and orexigenic genes in males, with no effect of IUGR. Leptinemia correlated with gene expression for neuropeptide Y (NPY, negatively) in both sexes and pro-opiomelanocortin (POMC, positively) in females but with leptin receptor (negatively) only in males. Current FGR for girth correlated negatively with gene expression for NPY in males and POMC in females. Neither IUGR nor gender affected suckling activity (proxy for appetite) assessed at 3 weeks, but final NPY gene expression correlated with suckling weight gain in males. This study has revealed no effect of IUGR on early postnatal hypothalamic energy balance gene expression but a major effect of gender associated with major sex differences in adiposity and leptinemia. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

  3. Immunohistochemical analysis of FoxP3+ regulatory T cells in lower lip squamous cell carcinomas

    Directory of Open Access Journals (Sweden)

    Fernando Antonio Portela da CUNHA FILHO

    Full Text Available Abstract: The aim of this study was to determine the number of FoxP3+ regulatory T (Treg cells in the microenvironment of lower lip squamous cell carcinomas (LLSCCs and to correlate the findings with clinicopathological parameters (tumor size/extent, regional lymph node metastasis, clinical stage, and histopathological grade of malignancy. Fifty cases of LLSCC were selected. Lymphocytes exhibiting nuclear immunostaining for FoxP3 were quantified in 10 microscopic fields at the deep invasive front of LLSCCs. The results were analyzed statistically using the nonparametric Mann-Whitney test and Fisher's exact test. FoxP3+ lymphocytes were observed in all cases studied. The number of these cells tended to be higher in smaller tumors, tumors without regional lymph node metastasis, and tumors in early clinical stages, but the difference was not statistically significant (p > 0.05. Low-grade tumors contained a larger number of FoxP3+ lymphocytes than high-grade tumors (p = 0.019. Tumors with an intense inflammatory infiltrate exhibited a larger number of Treg cells (p = 0.035. On the other hand, the number of FoxP3+ lymphocytes was smaller in tumors arranged in small cell clusters (p = 0.003. No significant differences in the number of FoxP3+ lymphocytes were observed according to the degree of keratinization (p = 0.525 or nuclear pleomorphism (p = 0.343. The results suggest the participation of Treg cells in immune and inflammatory responses in the microenvironment of LLSCCs. These cells may play a more important role in early stages rather than in advanced stages of lip carcinogenesis.

  4. [Analysis of regulatory basis for organization of clinical nutrition in medical institutions of the Russian Federation].

    Science.gov (United States)

    Tutel'ian, V A; Sharafetdinov, Kh Kh; Pogozheva, A V; Plotnikova, O A

    2013-01-01

    The article analyzes regulatory basis for organization of clinical nutrition in medical institutions of Russia. It is shown that the strategy of therapeutic measures in acute and chronic diseases a central place to take dietary therapy with adequate provision of energy and plastic body's needs, correction of metabolic disorders and risk factors for comorbidity. Prior to the confirmation of the order of Ministry of Health of Russia from 05.08.2003, No 330 "On measures to improve nutritional care in health care institutions in the Russian Federation" clinical nutrition in medical institutions was based on the nosological principle, in the form of daily diet--a diet designed for each concrete Diseases which are identified by a number from 1 to 15. According to the order of Ministry of Health of Russia from 05.08.2003, No 330 in the health care practice has introduced a new range of diets (system standard diets), which is based on the principle of adapting the chemical composition and energy value of the diet to the individual clinical and pathogenic features of the disease and combines previously used diet numbering system. It is shown that the organization of clinical nutrition should be based on common requirements imposed on the federal level and at the level of the subject of the Russian Federation. In order to optimize clinical nutrition is necessary to determine the methodological approaches to personalization through the introduction of diet in health care practice of modern innovative technologies health food, performing preventive and treatment of the problem (implementation of Article 39 of the Federal Law of 21.11.2011 No 323--FZ "On the basis of health protection in the Russian Federation", the Order of the Government of the Russian Federation of 25.10.2010 No 1873-r "On the basis of the state policy in the field of nutrition to 2020 year").

  5. Computation and Asymptotic Analysis in the Impact Problem

    Institute of Scientific and Technical Information of China (English)

    Lei Hou; Lin Qiu

    2009-01-01

    Non-linear numerical method is applied to solve the viscons-elastic-plastic material impact problem.The finite element simulation agrees with the celebrated European crash safety analysis.The complex material stress distribution in the large deformation has been obtained,when the impact happens.Also the posterior-estimate solver and asymptotic analysis have been used for the sensitive pre-stage deformation before the impact happening.This part of simulation is very interesting for the passive safety in automotive protection devices.It is an important part of the mathematical modelling.

  6. Empirical Analysis on the Path Selection of Optimizing Organization Structure of Financial Regulatory in China%我国金融监管组织架构优化路径选择的实证分析

    Institute of Scientific and Technical Information of China (English)

    张鹏; 胡传雨

    2011-01-01

    To unify regulatory organization structure has been a trend to change organization structure of financial regulatory. But due to the different financial development levels and operating environment in various countries, the path selection to optimize the organization structure has also differences. The factors which affect the changes of organization structure of financial regulatory are institutional factors, financial factors and management factors. In this paper, we do the empirical analysis on the impact factors of organization structure changes of financial regulatory by selecting representative samples of 33 countries and constructing the ordered Logit model, and then analyze the organization structure of financial regulatory in China. The results show that China's current organizational structure of separate supervision is appropriate. With the development of China's financial sector and mixed - depth, we must first improve governance, and then integrate the financial regulatory agencies gradually, ultimately establish a unified regulatory organization.%统一监管组织架构已成为金融监管组织架构变迁的一种趋势,但由于各国金融业的发展程度和经营环境不同,金融监管组织架构优化的路径选择也就有差异。影响金融监管组织架构变迁的因素有体制因素、金融因素和治理因素。选取33个代表性国家样本,构建有序Logit模型对影响金融监管组织架构变迁的因素进行实证分析,并运用有序蚴模型对中国金融监管组织架构进行分析,结果表明,目前中国分业监管组织架构是合适的,随著中国金融业的发展和混业经营的深入,中国应首先提高治理水平,然后逐渐整合金融监管机构,最终建立统一监管组织架构。

  7. Putative regulatory sites unraveled by network-embedded thermodynamic analysis of metabolome data

    NARCIS (Netherlands)

    Kümmel, Anne; Panke, Sven; Heinemann, Matthias

    2006-01-01

    As one of the most recent members of the omics family, large-scale quantitative metabolomics data are currently complementing our systems biology data pool and offer the chance to integrate the metabolite level into the functional analysis of cellular networks. Network-embedded thermodynamic analysi

  8. Combined Analysis of Variation in Core, Accessory and Regulatory Genome Regions Provides a Super-Resolution View into the Evolution of Bacterial Populations

    Science.gov (United States)

    McNally, Alan; Oren, Yaara; Kelly, Darren; Sreecharan, Tristan; Vehkala, Minna; Välimäki, Niko; Prentice, Michael B.; Ashour, Amgad; Avram, Oren; Pupko, Tal; Literak, Ivan; Guenther, Sebastian; Schaufler, Katharina; Wieler, Lothar H.; Zhiyong, Zong; Sheppard, Samuel K.; Corander, Jukka

    2016-01-01

    The use of whole-genome phylogenetic analysis has revolutionized our understanding of the evolution and spread of many important bacterial pathogens due to the high resolution view it provides. However, the majority of such analyses do not consider the potential role of accessory genes when inferring evolutionary trajectories. Moreover, the recently discovered importance of the switching of gene regulatory elements suggests that an exhaustive analysis, combining information from core and accessory genes with regulatory elements could provide unparalleled detail of the evolution of a bacterial population. Here we demonstrate this principle by applying it to a worldwide multi-host sample of the important pathogenic E. coli lineage ST131. Our approach reveals the existence of multiple circulating subtypes of the major drug–resistant clade of ST131 and provides the first ever population level evidence of core genome substitutions in gene regulatory regions associated with the acquisition and maintenance of different accessory genome elements. PMID:27618184

  9. An enhanced archive facilitating climate impacts analysis

    Science.gov (United States)

    Maurer, E.P.; Brekke, L.; Pruitt, T.; Thrasher, B.; Long, J.; Duffy, P.; Dettinger, M.; Cayan, D.; Arnold, J.

    2014-01-01

    We describe the expansion of a publicly available archive of downscaled climate and hydrology projections for the United States. Those studying or planning to adapt to future climate impacts demand downscaled climate model output for local or regional use. The archive we describe attempts to fulfill this need by providing data in several formats, selectable to meet user needs. Our archive has served as a resource for climate impacts modelers, water managers, educators, and others. Over 1,400 individuals have transferred more than 50 TB of data from the archive. In response to user demands, the archive has expanded from monthly downscaled data to include daily data to facilitate investigations of phenomena sensitive to daily to monthly temperature and precipitation, including extremes in these quantities. New developments include downscaled output from the new Coupled Model Intercomparison Project phase 5 (CMIP5) climate model simulations at both the monthly and daily time scales, as well as simulations of surface hydrologi- cal variables. The web interface allows the extraction of individual projections or ensemble statistics for user-defined regions, promoting the rapid assessment of model consensus and uncertainty for future projections of precipitation, temperature, and hydrology. The archive is accessible online (http://gdo-dcp.ucllnl.org/downscaled_ cmip_projections).

  10. Diagnostic imaging analysis of the impacted mesiodens

    Energy Technology Data Exchange (ETDEWEB)

    Noh, Jeong Jun; Choi, Bo Ram; Jeong, Hwan Seok; Huh, Kyung Hoe; Yi, Won Jin; Heo, Min Suk; Lee, Sam Sun; Choi, Soon Chul [School of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    2010-06-15

    The research was performed to predict the three dimensional relationship between the impacted mesiodens and the maxillary central incisors and the proximity with the anatomic structures by comparing their panoramic images with the CT images. Among the patients visiting Seoul National University Dental Hospital from April 2003 to July 2007, those with mesiodens were selected (154 mesiodens of 120 patients). The numbers, shapes, orientation and positional relationship of mesiodens with maxillary central incisors were investigated in the panoramic images. The proximity with the anatomical structures and complications were investigated in the CT images as well. The sex ratio (M : F) was 2.28 : 1 and the mean number of mesiodens per one patient was 1.28. Conical shape was 84.4% and inverted orientation was 51.9%. There were more cases of anatomical structures encroachment, especially on the nasal floor and nasopalatine duct, when the mesiodens was not superimposed with the central incisor. There were, however, many cases of the nasopalatine duct encroachment when the mesiodens was superimpoised with the apical 1/3 of central incisor (52.6%). Delayed eruption (55.6%), crown rotation (66.7%) and crown resorption (100%) were observed when the mesiodens was superimposed with the crown of the central incisor. It is possible to predict three dimensional relationship between the impacted mesiodens and the maxillary central incisors in the panoramic images, but more details should be confirmed by the CT images when necessary.

  11. The global economic and regulatory determinants of household food waste generation: A cross-country analysis.

    Science.gov (United States)

    Chalak, Ali; Abou-Daher, Chaza; Chaaban, Jad; Abiad, Mohamad G

    2016-02-01

    Food is generally wasted all along the supply chain, with an estimated loss of 35percent generated at the consumer level. Consequently, household food waste constitutes a sizable proportion of the total waste generated throughout the food supply chain. Yet such wastes vary drastically between developed and developing countries. Using data collected from 44 countries with various income levels, this paper investigates the impact of legislation and economic incentives on household food waste generation. The obtained results indicate that well-defined regulations, policies and strategies are more effective than fiscal measures in mitigating household food waste generation.

  12. Proteomic analysis of iron acquisition, metabolic and regulatory responses of Yersinia pestis to iron starvation

    Directory of Open Access Journals (Sweden)

    Fleischmann Robert D

    2010-01-01

    Full Text Available Abstract Background The Gram-negative bacterium Yersinia pestis is the causative agent of the bubonic plague. Efficient iron acquisition systems are critical to the ability of Y. pestis to infect, spread and grow in mammalian hosts, because iron is sequestered and is considered part of the innate host immune defence against invading pathogens. We used a proteomic approach to determine expression changes of iron uptake systems and intracellular consequences of iron deficiency in the Y. pestis strain KIM6+ at two physiologically relevant temperatures (26°C and 37°C. Results Differential protein display was performed for three Y. pestis subcellular fractions. Five characterized Y. pestis iron/siderophore acquisition systems (Ybt, Yfe, Yfu, Yiu and Hmu and a putative iron/chelate outer membrane receptor (Y0850 were increased in abundance in iron-starved cells. The iron-sulfur (Fe-S cluster assembly system Suf, adapted to oxidative stress and iron starvation in E. coli, was also more abundant, suggesting functional activity of Suf in Y. pestis under iron-limiting conditions. Metabolic and reactive oxygen-deactivating enzymes dependent on Fe-S clusters or other iron cofactors were decreased in abundance in iron-depleted cells. This data was consistent with lower activities of aconitase and catalase in iron-starved vs. iron-rich cells. In contrast, pyruvate oxidase B which metabolizes pyruvate via electron transfer to ubiquinone-8 for direct utilization in the respiratory chain was strongly increased in abundance and activity in iron-depleted cells. Conclusions Many protein abundance differences were indicative of the important regulatory role of the ferric uptake regulator Fur. Iron deficiency seems to result in a coordinated shift from iron-utilizing to iron-independent biochemical pathways in the cytoplasm of Y. pestis. With growth temperature as an additional variable in proteomic comparisons of the Y. pestis fractions (26°C and 37°C, there was

  13. Spatiotemporal trend analysis of metal concentrations in sediments of a residential California stream with toxicity and regulatory implications.

    Science.gov (United States)

    Hall, Lenwood W; Anderson, Ronald D; Killen, William D

    2017-06-07

    The objective of this study was to determine if concentrations of arsenic, cadmium, chromium, copper, lead, nickel and zinc measured in the sediments of a residential stream in California (Pleasant Grove Creek) have changed temporally or spatially from 2006 to 2016. Threshold Effect Levels (TELs), conservative ecological effects benchmarks, and exceedances for the seven metals were also evaluated over the 11-year time period to provide insight into potential metal toxicity to resident benthic communities. In addition, the bioavailability of metals in sediments was also determined by calculating Simultaneous Extracted Metal/Acid Volatle Sulfide (SEM/AVS) ratios to allow an additional assessment of toxicity. Regulatory implications of this data set and the role of metal toxicity are also discussed. Stream-wide temporal trend analysis showed no statistically significant trends for any of the metals. However, spatial analysis for several sites located near storm drains did show a significant increase for most metals over the 11-year period. TEL exceedances during the 7 years of sampling, spanning 2006-2016, were reported for all metals with the number of exceedances ranging from 47 for copper and zinc to 1 for lead. A spatial analysis showed that the highest number of TEL exceedances and the highest number of SEM/AVS ratios greater than one with at least one metal exceeding a TEL occurred at upstream sites. The potentially toxic metal concentrations reported in Pleasant Grove Creek should be used in the 303 (d) listing process for impaired water bodies in California.

  14. Regulatory analysis for the resolution of Generic Safety Issue 29: Bolting degradation or failure in nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Chang, T.Y.

    1991-09-01

    Generic Safety Issue (GSI)-29 deals with staff concerns about public risk due to degradation or failure of safety-related bolting in nuclear power plants. The issue was initiated in November 1982. Value-impact studies of a mandatory program on safety-related bolting for operating plants were inconclusive: therefore, additional regulatory requirements for operating plants could not be justified in accordance with provisions of 10 CFR 50.109. In addition, based on operating experience with bolting in both nuclear and conventional power plants, the actions already taken through bulletins, generic letters, and information notices, and the industry-proposed actions, the staff concluded that a sufficient technical basis exists for the resolution of GSI-29. The staff further concluded that leakage of bolted pressure joints is possible but catastrophic failure of a reactor coolant pressure boundary joint that will lead to significant accident sequences is highly unlikely. For future plants, it was concluded that a new Standard Review Plant section should be developed to codify existing bolting requirements and industry-developed initiatives. 9 refs., 1 tab.

  15. Functional Analysis of Multiple Transcription Factor Sites in a Regulatory Element of Human ε-Globin Gene

    Institute of Scientific and Technical Information of China (English)

    Chun-Hui HOU; Jian HUANG; Ruo-Lan QIAN

    2004-01-01

    The developmental control of the human ε-globin gene expression is mediated by transcriptional regulatory elements in the 5' flanking DNA of this gene. A previously identified negative regulatory element (-3028 to -2902 bp, termed ε-NRAII) was analyzed and one putative NF-κB site and two GATA sites locate at -3004 bp, -2975 bp and -2948 bp were characterized. Electrophoresis mobility shift assay (EMSA)showed that the putative NF-κB site was specifically bound by nuclear proteins of K562 cells. Data obtained from transient transfection showed that the expression of reporter gene could be upregulated about 50% or 100% respectively when ε-NRAII was inserted upstream of the SV40 promoter or ε-globin gene proximal promoter (-177 bp to +1 bp), suggesting that ε-NRAII might not be a classic silencer. Mutation in the putative NF-κB site or in the GATA site (at-2975 bp) slightly reduced the expression of reporter gene driven by SV40 promoter or ε-globin gene proximal promoter. However, the mutation of GATA site at -2948 bp remarkably reduced the reporter gene activity driven by SV40 promoter, but not by ε-globin gene proximal promoter. Further mutation analysis showed that the negative effect of mutation in GATA site at -2948 bp on SV40 promoter was not affected by the mutation of the putative NF-κB site, whereas it could be abolished by the mutation of GATA site at -2975 bp. Furthermore, the mutation of both GATA sites could synergistically reduce the reporter gene activity driven by ε-globin gene proximal promoter. Those results suggested that ε-NRAII might function differently on the SV40 promoter and ε-globin gene proximal promoter.

  16. Molecular Analysis of the Clavulanic Acid Regulatory Gene Isolated from an Iranian Strain of Streptomyces Clavuligerus, PTCC 1709

    Directory of Open Access Journals (Sweden)

    Hasan Korbekandi

    2011-01-01

    Full Text Available Objective: The clavulanic acid regulatory gene (claR is in the clavulanic acid biosyntheticgene cluster that encodes ClaR. This protein is a putative regulator of the late steps ofclavulanic acid biosynthesis. The aim of this research is the molecular cloning of claR,isolated from the Iranian strain of Streptomyces clavuligerus (S. clavuligerus.Materials and Methods: In this experimental study, two different strains of S. clavuligeruswere used (PTCC 1705 and DSM 738, of which there is no claR sequence record forstrain PTCC 1705 in all three main gene banks. The specific designed primers were subjectedto a few base modifications for introduction of the recognition sites of BamHI andClaI. The claR gene was amplified by polymerase chain reaction (PCR using DNA isolatedfrom S. clavuligerus PTCC 1705. Nested-PCR, restriction fragment length polymorphism(PCR-RFLP, and sequencing were used for molecular analysis of the claR gene.The confirmed claR was subjected to double digestion with BamHI and ClaI. The cut claRwas ligated into a pBluescript (pBs vector and transformed into E. coli.Results: The entire sequence of the isolated claR (Iranian strain was identified. Thepresence of the recombinant vector in the transformed colonies was confirmed by thecolony-PCR procedure. The correct structure of the recombinant vector, isolated from thetransformed E. coli, was confirmed using gel electrophoresis, PCR, and double digestionwith restriction enzymes.Conclusion: The constructed recombinant cassette, named pZSclaR, can be regardedas an appropriate tool for site directed mutagenesis and sub-cloning. At this time, claRhas been cloned accompanied with its precisely selected promoter so it could be used inexpression vectors. Hence the ClaR is known as a putative regulatory protein. The overproducedprotein could also be used for other related investigations, such as a mobilityshift assay.

  17. Equivalent Kelvin Impact Model for Seismic Pounding Analysis of Bridges

    Institute of Scientific and Technical Information of China (English)

    DING Yang; YUE Fuqing; LI Zhongxian

    2006-01-01

    Based on Hertz contact theory,a method to determine the parameters of Kelvin impact model for seismic pounding analysis of bridges is proposed.The impact stiffness of Kelvin model is determined by the ratio of maximum impact force to maximum contact deformation,which is calculated based on Hertz contact theory with considering the vibration effect.The restitution coefficient which has great influence on the damping coefficient of Kelvin impact model is investigated by numerical analysis.Numerical results indicate that the impact stiffness of Kelvin impact model increases with the increment of the Hertz contact stiffness,approaching velocity or the length ratio of short to long girders.Vibration effect has remarkable influence on the impact stiffness and cannot be neglected.The restitution coefficient decreases when approaching velocity increases or the length ratio of short girder to long girder decreasing.The practical ranges of impact stiffness and restitution coefficient are obtained as 3 × 108-6 × 108 N/m and 0.6-0.95 respectively.

  18. Integrating health and environmental impact analysis

    DEFF Research Database (Denmark)

    Reis, S; Morris, G.; Fleming, L. E.

    2015-01-01

    the interconnections among society, the economy, the environment and our health and well-being. Success must be built on collaborations between the disparate scientific communities of the environmental sciences and public health as well as interactions with social scientists, economists and the legal profession......Scientific investigations have progressively refined our understanding of the influence of the environment on human health, and the many adverse impacts that human activities exert on the environment, from the local to the planetary level. Nonetheless, throughout the modern public health era......, health has been pursued as though our lives and lifestyles are disconnected from ecosystems and their component organisms. The inadequacy of the societal and public health response to obesity, health inequities, and especially global environmental and climate change now calls for an ecological approach...

  19. The Impact of Action Learning on Analysis of Occupation

    Science.gov (United States)

    Fain, Elizabeth

    2011-01-01

    Technology and millennials have created a shift in the world and how it operates. This impact has been experienced in the field of occupational therapy education. As a result of this paradigm shift, an analysis of effective teaching methodologies was carried out to assess the most effective way to engage the millennials in an analysis of…

  20. The impact of Australian ETS news on wholesale spot electricity prices: An exploratory analysis

    Energy Technology Data Exchange (ETDEWEB)

    Chevallier, Julien, E-mail: julien.chevallier@dauphine.f [Universite Paris Dauphine, Place du Marechal de Lattre de Tassigny, 75775 Paris Cedex 16 (France)

    2010-08-15

    This article investigates the impact of news concerning the development of emissions trading in Australia (such as the Carbon Pollution Reduction Scheme (CPRS)) on wholesale electricity spot prices, by using a database of 117 news announcements from December 1, 1998 to July 1, 2009. As power producers constitute the bulk of the participants of the proposed Australian emissions trading scheme, regulatory changes (about allocation, banking, coverage, targets) are indeed likely to affect the five interconnected electricity markets in New South Wales, Queensland, South Australia, Victoria, and Tasmania. We assess these effects with an ARMA(1,1)-GARCH(1,1) model, where daily electricity spot prices are regressed against exogenous variables in the mean and variance equations. This article constitutes the first empirical analysis of Australian ETS news effects on electricity wholesale spot prices. Our results show two asymmetric types of news effects, depending on their information content.

  1. The impact of Australian ETS news on wholesale spot electricity prices. An exploratory analysis

    Energy Technology Data Exchange (ETDEWEB)

    Chevallier, Julien [Universite Paris Dauphine, Place du Marechal de Lattre de Tassigny, 75775 Paris Cedex 16 (France)

    2010-08-15

    This article investigates the impact of news concerning the development of emissions trading in Australia (such as the Carbon Pollution Reduction Scheme (CPRS)) on wholesale electricity spot prices, by using a database of 117 news announcements from December 1, 1998 to July 1, 2009. As power producers constitute the bulk of the participants of the proposed Australian emissions trading scheme, regulatory changes (about allocation, banking, coverage, targets) are indeed likely to affect the five interconnected electricity markets in New South Wales, Queensland, South Australia, Victoria, and Tasmania. We assess these effects with an ARMA(1,1)-GARCH(1,1) model, where daily electricity spot prices are regressed against exogenous variables in the mean and variance equations. This article constitutes the first empirical analysis of Australian ETS news effects on electricity wholesale spot prices. Our results show two asymmetric types of news effects, depending on their information content. (author)

  2. Pineal function : Impact of microarray analysis

    NARCIS (Netherlands)

    Klein, David C.; Bailey, Michael J.; Carter, David A.; Kim, Jong-so; Shi, Qiong; Ho, Anthony K.; Chik, Constance L.; Gaildrat, Pascaline; Morin, Fabrice; Ganguly, Surajit; Rath, Martin F.; Moller, Morten; Sugden, David; Rangel, Zoila G.; Munson, Peter J.; Weller, Joan L.; Coon, Steven L.

    2010-01-01

    Microarray analysis has provided a new understanding of pineal function by identifying genes that are highly expressed in this tissue relative to other tissues and also by identifying over 600 genes that are expressed on a 24-h schedule. This effort has highlighted surprising similarity to the retin

  3. Economic impact assessment in pest risk analysis

    NARCIS (Netherlands)

    Soliman, T.A.A.; Mourits, M.C.M.; Oude Lansink, A.G.J.M.; Werf, van der W.

    2010-01-01

    According to international treaties, phytosanitary measures against introduction and spread of invasive plant pests must be justified by a science-based pest risk analysis (PRA). Part of the PRA consists of an assessment of potential economic consequences. This paper evaluates the main available tec

  4. Key regulatory role of dermal fibroblasts in pigmentation as demonstrated using a reconstructed skin model: impact of photo-aging.

    Directory of Open Access Journals (Sweden)

    Christine Duval

    Full Text Available To study cutaneous pigmentation in a physiological context, we have previously developed a functional pigmented reconstructed skin model composed of a melanocyte-containing epidermis grown on a dermal equivalent comprising living fibroblasts. The present studies, using the same model, aimed to demonstrate that dermal fibroblasts influence skin pigmentation up to the macroscopic level. The proof of principle was performed with pigmented skins differing only in the fibroblast component. First, the in vitro system was reconstructed with or without fibroblasts in order to test the global influence of the presence of this cell type. We then assessed the impact of the origin of the fibroblast strain on the degree of pigmentation using fetal versus adult fibroblasts. In both experiments, impressive variation in skin pigmentation at the macroscopic level was observed and confirmed by quantitative parameters related to skin color, melanin content and melanocyte numbers. These data confirmed the responsiveness of the model and demonstrated that dermal fibroblasts do indeed impact the degree of skin pigmentation. We then hypothesized that a physiological state associated with pigmentary alterations such as photo-aging could be linked to dermal fibroblasts modifications that accumulate over time. Pigmentation of skin reconstructed using young unexposed fibroblasts (n = 3 was compared to that of tissues containing natural photo-aged fibroblasts (n = 3 which express a senescent phenotype. A stimulation of pigmentation in the presence of the natural photo-aged fibroblasts was revealed by a significant increase in the skin color (decrease in Luminance and an increase in both epidermal melanin content and melanogenic gene expression, thus confirming our hypothesis. Altogether, these data demonstrate that the level of pigmentation of the skin model is influenced by dermal fibroblasts and that natural photo-aged fibroblasts can contribute to the

  5. A watershed-based environmental and regulatory data analysis system for the forest products industry

    Science.gov (United States)

    John Beebe

    2012-01-01

    A watershed-based data analysis system was created as a tool for forest product companies to better understand potential implications from environmental regulations. Also known as the Receiving Water Database (RWDB), this data system was designed with the purpose of assisting companies that own pulp and paper mills, wood product facilities, and commercial timberlands...

  6. Putative regulatory sites unraveled by network-embedded thermodynamic analysis of metabolome data

    NARCIS (Netherlands)

    Kümmel, Anne; Panke, Sven; Heinemann, Matthias

    2006-01-01

    As one of the most recent members of the omics family, large-scale quantitative metabolomics data are currently complementing our systems biology data pool and offer the chance to integrate the metabolite level into the functional analysis of cellular networks. Network-embedded thermodynamic

  7. Metabolomic Analysis of Key Regulatory Metabolites in Hepatitis C Virus–infected Tree Shrews*

    Science.gov (United States)

    Sun, Hui; Zhang, Aihua; Yan, Guangli; Piao, Chengyu; Li, Weiyun; Sun, Chang; Wu, Xiuhong; Li, Xinghua; Chen, Yun; Wang, Xijun

    2013-01-01

    Metabolomics is a powerful new technology that allows the assessment of global low-molecular-weight metabolites in a biological system and which shows great potential in biomarker discovery. Analysis of the key metabolites in body fluids has become an important part of improving the diagnosis, prognosis, and therapy of diseases. Hepatitis C virus (HCV) is a major leading cause of liver disease worldwide and a serious burden on public health. However, the lack of a small-animal model has hampered the analysis of HCV pathogenesis. We hypothesize that an animal model (Tupaia belangeri chinensis) of HCV would produce a unique characterization of metabolic phenotypes. Ultra-performance liquid-chromatography/electrospray ionization-SYNAPT-high-definition mass spectrometry (UPLC/ESI-SYNAPT-HDMS) coupled with pattern recognition methods and system analysis was carried out to obtain comprehensive metabolomics profiling and pathways of large biological data sets. Taurine, hypotaurine, ether lipid, glycerophospholipid, arachidonic acid, tryptophan, and primary bile acid metabolism pathways were acutely perturbed, and 38 differential metabolites were identified. More important, five metabolite markers were selected via the “significance analysis for microarrays” method as the most discriminant and interesting biomarkers that were effective for the diagnosis of HCV. Network construction has led to the integration of metabolites associated with the multiple perturbation pathways. Integrated network analysis of the key metabolites yields highly related signaling pathways associated with the differentially expressed proteins, which suggests that the creation of new treatment paradigms targeting and activating these networks in their entirety, rather than single proteins, might be necessary for controlling and treating HCV efficiently. PMID:23264353

  8. Metabolomic analysis of key regulatory metabolites in hepatitis C virus-infected tree shrews.

    Science.gov (United States)

    Sun, Hui; Zhang, Aihua; Yan, Guangli; Piao, Chengyu; Li, Weiyun; Sun, Chang; Wu, Xiuhong; Li, Xinghua; Chen, Yun; Wang, Xijun

    2013-03-01

    Metabolomics is a powerful new technology that allows the assessment of global low-molecular-weight metabolites in a biological system and which shows great potential in biomarker discovery. Analysis of the key metabolites in body fluids has become an important part of improving the diagnosis, prognosis, and therapy of diseases. Hepatitis C virus (HCV) is a major leading cause of liver disease worldwide and a serious burden on public health. However, the lack of a small-animal model has hampered the analysis of HCV pathogenesis. We hypothesize that an animal model (Tupaia belangeri chinensis) of HCV would produce a unique characterization of metabolic phenotypes. Ultra-performance liquid-chromatography/electrospray ionization-SYNAPT-high-definition mass spectrometry (UPLC/ESI-SYNAPT-HDMS) coupled with pattern recognition methods and system analysis was carried out to obtain comprehensive metabolomics profiling and pathways of large biological data sets. Taurine, hypotaurine, ether lipid, glycerophospholipid, arachidonic acid, tryptophan, and primary bile acid metabolism pathways were acutely perturbed, and 38 differential metabolites were identified. More important, five metabolite markers were selected via the "significance analysis for microarrays" method as the most discriminant and interesting biomarkers that were effective for the diagnosis of HCV. Network construction has led to the integration of metabolites associated with the multiple perturbation pathways. Integrated network analysis of the key metabolites yields highly related signaling pathways associated with the differentially expressed proteins, which suggests that the creation of new treatment paradigms targeting and activating these networks in their entirety, rather than single proteins, might be necessary for controlling and treating HCV efficiently.

  9. Regulatory Anatomy

    DEFF Research Database (Denmark)

    Hoeyer, Klaus

    2015-01-01

    This article proposes the term “safety logics” to understand attempts within the European Union (EU) to harmonize member state legislation to ensure a safe and stable supply of human biological material for transplants and transfusions. With safety logics, I refer to assemblages of discourses, le...... they arise. In short, I expose the regulatory anatomy of the policy landscape....

  10. Reconstruction and analysis of transcription factor-miRNA co-regulatory feed-forward loops in human cancers using filter-wrapper feature selection.

    Directory of Open Access Journals (Sweden)

    Chen Peng

    Full Text Available BACKGROUND: As one of the most common types of co-regulatory motifs, feed-forward loops (FFLs control many cell functions and play an important role in human cancers. Therefore, it is crucial to reconstruct and analyze cancer-related FFLs that are controlled by transcription factor (TF and microRNA (miRNA simultaneously, in order to find out how miRNAs and TFs cooperate with each other in cancer cells and how they contribute to carcinogenesis. Current FFL studies rely on predicted regulation information and therefore suffer the false positive issue in prediction results. More critically, FFLs generated by existing approaches cannot represent the dynamic and conditional regulation relationship under different experimental conditions. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we proposed a novel filter-wrapper feature selection method to accurately identify co-regulatory mechanism by incorporating prior information from predicted regulatory interactions with parallel miRNA/mRNA expression datasets. By applying this method, we reconstructed 208 and 110 TF-miRNA co-regulatory FFLs from human pan-cancer and prostate datasets, respectively. Further analysis of these cancer-related FFLs showed that the top-ranking TF STAT3 and miRNA hsa-let-7e are key regulators implicated in human cancers, which have regulated targets significantly enriched in cellular process regulations and signaling pathways that are involved in carcinogenesis. CONCLUSIONS/SIGNIFICANCE: In this study, we introduced an efficient computational approach to reconstruct co-regulatory FFLs by accurately identifying gene co-regulatory interactions. The strength of the proposed feature selection method lies in the fact it can precisely filter out false positives in predicted regulatory interactions by quantitatively modeling the complex co-regulation of target genes mediated by TFs and miRNAs simultaneously. Moreover, the proposed feature selection method can be generally applied to

  11. Comparative genomic analysis of two-component regulatory proteins in Pseudomonas syringae

    DEFF Research Database (Denmark)

    Lavin, J.L.; Kiil, Kristoffer; Resano, O.

    2007-01-01

    important differences in TCS proteins among the three P. syringae pathovars. Conclusion: In this article we present a thorough analysis of the identification and distribution of TCS proteins among the sequenced genomes of P. syringae. We have identified differences in TCS proteins among the three P...... requires a complex array of TCS proteins to cope with diverse plant hosts, host responses, and environmental conditions. Results: Based on the genomic data, pattern searches with Hidden Markov Model (HMM) profiles have been used to identify putative HKs and RRs. The genomes of Psy B728a, Pto DC3000 and Pph...... 1448A were found to contain a large number of genes encoding TCS proteins, and a core of complete TCS proteins were shared between these genomes: 30 putative TCS clusters, 11 orphan HKs, 33 orphan RRs, and 16 hybrid HKs. A close analysis of the distribution of genes encoding TCS proteins revealed...

  12. Analysis of transcription regulatory regions of embryonic chicken pepsinogen (ECPg) gene.

    Science.gov (United States)

    Watanuki, Kumiko; Yasugi, Sadao

    2003-09-01

    Genes encoding pepsinogens, zymogens of digestive enzyme pepsins, are expressed specifically in the gland epithelial cells of the vertebrate stomach, and their expression is also developmentally regulated, therefore providing a good model for the analysis of transcriptional regulation of genes. In the development of chicken embryonic stomach, the epithelium invaginates into the mesenchyme and forms glands and gland epithelial cells then begin to express embryonic chicken pepsinogen (ECPg) gene. It has been shown that cGATA5 binds directly GATA binding sites located within 1.1-kbp upstream of ECPg gene and activates its transcription. To find more precisely the sequences necessary for ECPg gene transcription, we carried out deletion and mutation analysis with 1.1-kbp upstream region. The results suggest that binding of GATA factor to three GATA binding sites within the upstream region -656 to -419 synergistically regulates ECPg expression in the gland epithelial cells.

  13. Techniques for analyzing the impacts of certain electric-utility ratemaking and regulatory-policy concepts. Glossary

    Energy Technology Data Exchange (ETDEWEB)

    None

    1980-08-01

    This document, Glossary, is the first in a series of reports to identify, describe, and apply techniques for analyzing the impacts of certain electric utility concepts. This report was developed with a focus on the currently evolving issues of ratemaking, especially as they might be expected to arise under Sections 101, 111, 113, 114, 131, 132, and 210 of the P.U.R.P.A. of 1978. Because the evolutionary process of ratemaking has led to multiple proceedings and changes of inference in some terms, the glossary attempts to delineate these changes where appropriate. Definitions not uniquely related to ratemaking are included if they are likely to be used in ratemaking proceedings. To avoid unnecessary duplication of effort and expense, the compilers relied heavily on previously developed, publicly available glossaries and definitions developed by organizations such as Edison Electric Institute, the Electric Power Research Institute, and the Institute of Electrical and Electronics Engineers. Existing definitions were revised and new ones were developed as appropriate.

  14. A principal component analysis of 39 scientific impact measures

    CERN Document Server

    Bollen, Johan; Hagberg, Aric; Chute, Ryan

    2009-01-01

    The impact of scientific publications has traditionally been expressed in terms of citation counts. However, scientific activity has moved online over the past decade. To better capture scientific impact in the digital era, a variety of new impact measures has been proposed on the basis of social network analysis and usage log data. Here we investigate how these new measures relate to each other, and how accurately and completely they express scientific impact. We performed a principal component analysis of the rankings produced by 39 existing and proposed measures of scholarly impact that were calculated on the basis of both citation and usage log data. Our results indicate that the notion of scientific impact is a multi-dimensional construct that can not be adequately measured by any single indicator, although some measures are more suitable than others. The commonly used citation Impact Factor is not positioned at the core of this construct, but at its periphery, and should thus be used with caution.

  15. A principal component analysis of 39 scientific impact measures.

    Directory of Open Access Journals (Sweden)

    Johan Bollen

    Full Text Available BACKGROUND: The impact of scientific publications has traditionally been expressed in terms of citation counts. However, scientific activity has moved online over the past decade. To better capture scientific impact in the digital era, a variety of new impact measures has been proposed on the basis of social network analysis and usage log data. Here we investigate how these new measures relate to each other, and how accurately and completely they express scientific impact. METHODOLOGY: We performed a principal component analysis of the rankings produced by 39 existing and proposed measures of scholarly impact that were calculated on the basis of both citation and usage log data. CONCLUSIONS: Our results indicate that the notion of scientific impact is a multi-dimensional construct that can not be adequately measured by any single indicator, although some measures are more suitable than others. The commonly used citation Impact Factor is not positioned at the core of this construct, but at its periphery, and should thus be used with caution.

  16. Genome-wide Annotation, Identification, and Global Transcriptomic Analysis of Regulatory or Small RNA Gene Expression in Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Ronan K. Carroll

    2016-02-01

    Full Text Available In Staphylococcus aureus, hundreds of small regulatory or small RNAs (sRNAs have been identified, yet this class of molecule remains poorly understood and severely understudied. sRNA genes are typically absent from genome annotation files, and as a consequence, their existence is often overlooked, particularly in global transcriptomic studies. To facilitate improved detection and analysis of sRNAs in S. aureus, we generated updated GenBank files for three commonly used S. aureus strains (MRSA252, NCTC 8325, and USA300, in which we added annotations for >260 previously identified sRNAs. These files, the first to include genome-wide annotation of sRNAs in S. aureus, were then used as a foundation to identify novel sRNAs in the community-associated methicillin-resistant strain USA300. This analysis led to the discovery of 39 previously unidentified sRNAs. Investigating the genomic loci of the newly identified sRNAs revealed a surprising degree of inconsistency in genome annotation in S. aureus, which may be hindering the analysis and functional exploration of these elements. Finally, using our newly created annotation files as a reference, we perform a global analysis of sRNA gene expression in S. aureus and demonstrate that the newly identified tsr25 is the most highly upregulated sRNA in human serum. This study provides an invaluable resource to the S. aureus research community in the form of our newly generated annotation files, while at the same time presenting the first examination of differential sRNA expression in pathophysiologically relevant conditions.

  17. The Impact of Photobleaching on Microarray Analysis

    Directory of Open Access Journals (Sweden)

    Marcel von der Haar

    2015-09-01

    Full Text Available DNA-Microarrays have become a potent technology for high-throughput analysis of genetic regulation. However, the wide dynamic range of signal intensities of fluorophore-based microarrays exceeds the dynamic range of a single array scan by far, thus limiting the key benefit of microarray technology: parallelization. The implementation of multi-scan techniques represents a promising approach to overcome these limitations. These techniques are, in turn, limited by the fluorophores’ susceptibility to photobleaching when exposed to the scanner’s laser light. In this paper the photobleaching characteristics of cyanine-3 and cyanine-5 as part of solid state DNA microarrays are studied. The effects of initial fluorophore intensity as well as laser scanner dependent variables such as the photomultiplier tube’s voltage on bleaching and imaging are investigated. The resulting data is used to develop a model capable of simulating the expected degree of signal intensity reduction caused by photobleaching for each fluorophore individually, allowing for the removal of photobleaching-induced, systematic bias in multi-scan procedures. Single-scan applications also benefit as they rely on pre-scans to determine the optimal scanner settings. These findings constitute a step towards standardization of microarray experiments and analysis and may help to increase the lab-to-lab comparability of microarray experiment results.

  18. Meta-Analysis of Multiple Sclerosis Microarray Data Reveals Dysregulation in RNA Splicing Regulatory Genes.

    Science.gov (United States)

    Paraboschi, Elvezia Maria; Cardamone, Giulia; Rimoldi, Valeria; Gemmati, Donato; Spreafico, Marta; Duga, Stefano; Soldà, Giulia; Asselta, Rosanna

    2015-09-30

    Abnormalities in RNA metabolism and alternative splicing (AS) are emerging as important players in complex disease phenotypes. In particular, accumulating evidence suggests the existence of pathogenic links between multiple sclerosis (MS) and altered AS, including functional studies showing that an imbalance in alternatively-spliced isoforms may contribute to disease etiology. Here, we tested whether the altered expression of AS-related genes represents a MS-specific signature. A comprehensive comparative analysis of gene expression profiles of publicly-available microarray datasets (190 MS cases, 182 controls), followed by gene-ontology enrichment analysis, highlighted a significant enrichment for differentially-expressed genes involved in RNA metabolism/AS. In detail, a total of 17 genes were found to be differentially expressed in MS in multiple datasets, with CELF1 being dysregulated in five out of seven studies. We confirmed CELF1 downregulation in MS (p=0.0015) by real-time RT-PCRs on RNA extracted from blood cells of 30 cases and 30 controls. As a proof of concept, we experimentally verified the unbalance in alternatively-spliced isoforms in MS of the NFAT5 gene, a putative CELF1 target. In conclusion, for the first time we provide evidence of a consistent dysregulation of splicing-related genes in MS and we discuss its possible implications in modulating specific AS events in MS susceptibility genes.

  19. Determining important regulatory relations of amino acids from dynamic network analysis of plasma amino acids.

    Science.gov (United States)

    Shikata, Nahoko; Maki, Yukihiro; Nakatsui, Masahiko; Mori, Masato; Noguchi, Yasushi; Yoshida, Shintaro; Takahashi, Michio; Kondo, Nobuo; Okamoto, Masahiro

    2010-01-01

    The changes in the concentrations of plasma amino acids do not always follow the flow-based metabolic pathway network. We have previously shown that there is a control-based network structure among plasma amino acids besides the metabolic pathway map. Based on this network structure, in this study, we performed dynamic analysis using time-course data of the plasma samples of rats fed single essential amino acid deficient diet. Using S-system model (conceptual mathematical model represented by power-law formalism), we inferred the dynamic network structure which reproduces the actual time-courses within the error allowance of 13.17%. By performing sensitivity analysis, three of the most dominant relations in this network were selected; the control paths from leucine to valine, from methionine to threonine, and from leucine to isoleucine. This result is in good agreement with the biological knowledge regarding branched-chain amino acids, and suggests the biological importance of the effect from methionine to threonine.

  20. Foxp3+ regulatory T cells among tuberculosis patients: impact on prognosis and restoration of antigen specific IFN-γ producing T cells.

    Directory of Open Access Journals (Sweden)

    Amar Singh

    Full Text Available CD4(+CD25(+Foxp3(+ regulatory T cells (Treg and programmed death-1 (PD-1 molecules have emerged as pivotal players in immune suppression of chronic diseases. However, their impact on the disease severity, therapeutic response and restoration of immune response in human tuberculosis remains unclear. Here, we describe the possible role of Treg cells, their M. tuberculosis driven expansion and contribution of PD-1 pathway to the suppressive function of Treg cells among pulmonary tuberculosis (PTB patients. Multicolor flow cytometry, cell culture, cells sorting and ELISA were employed to execute the study. Our results showed significant increase in frequency of antigen-reactive Treg cells, which gradually declined during successful therapy and paralleled with decline of M. tuberculosis-specific IL-10 along with elevation of IFN-γ production, and raising the IFN-γ/IL-4 ratio. Interestingly, persistence of Treg cells tightly correlated with MDR tuberculosis. Also, we show that blocking PD-1/PD-L1 pathway abrogates Treg-mediated suppression, suggesting that the PD-1/PD-L1 pathway is required for Treg-mediated suppression of the antigen-specific T cells. Treg cells possibly play a role in dampening the effector immune response and abrogating PD-1 pathway on Treg cells significantly rescued protective T cell response, suggesting its importance in immune restoration among tuberculosis patients.

  1. RNA-seq analysis identifies an intricate regulatory network controlling cluster root development in white lupin

    Science.gov (United States)

    2014-01-01

    Background Highly adapted plant species are able to alter their root architecture to improve nutrient uptake and thrive in environments with limited nutrient supply. Cluster roots (CRs) are specialised structures of dense lateral roots formed by several plant species for the effective mining of nutrient rich soil patches through a combination of increased surface area and exudation of carboxylates. White lupin is becoming a model-species allowing for the discovery of gene networks involved in CR development. A greater understanding of the underlying molecular mechanisms driving these developmental processes is important for the generation of smarter plants for a world with diminishing resources to improve food security. Results RNA-seq analyses for three developmental stages of the CR formed under phosphorus-limited conditions and two of non-cluster roots have been performed for white lupin. In total 133,045,174 high-quality paired-end reads were used for a de novo assembly of the root transcriptome and merged with LAGI01 (Lupinus albus gene index) to generate an improved LAGI02 with 65,097 functionally annotated contigs. This was followed by comparative gene expression analysis. We show marked differences in the transcriptional response across the various cluster root stages to adjust to phosphate limitation by increasing uptake capacity and adjusting metabolic pathways. Several transcription factors such as PLT, SCR, PHB, PHV or AUX/IAA with a known role in the control of meristem activity and developmental processes show an increased expression in the tip of the CR. Genes involved in hormonal responses (PIN, LAX, YUC) and cell cycle control (CYCA/B, CDK) are also differentially expressed. In addition, we identify primary transcripts of miRNAs with established function in the root meristem. Conclusions Our gene expression analysis shows an intricate network of transcription factors and plant hormones controlling CR initiation and formation. In addition

  2. Contemporary Impact Analysis Methodology for Planetary Sample Return Missions

    Science.gov (United States)

    Perino, Scott V.; Bayandor, Javid; Samareh, Jamshid A.; Armand, Sasan C.

    2015-01-01

    Development of an Earth entry vehicle and the methodology created to evaluate the vehicle's impact landing response when returning to Earth is reported. NASA's future Mars Sample Return Mission requires a robust vehicle to return Martian samples back to Earth for analysis. The Earth entry vehicle is a proposed solution to this Mars mission requirement. During Earth reentry, the vehicle slows within the atmosphere and then impacts the ground at its terminal velocity. To protect the Martian samples, a spherical energy absorber called an impact sphere is under development. The impact sphere is composed of hybrid composite and crushable foam elements that endure large plastic deformations during impact and cause a highly nonlinear vehicle response. The developed analysis methodology captures a range of complex structural interactions and much of the failure physics that occurs during impact. Numerical models were created and benchmarked against experimental tests conducted at NASA Langley Research Center. The postimpact structural damage assessment showed close correlation between simulation predictions and experimental results. Acceleration, velocity, displacement, damage modes, and failure mechanisms were all effectively captured. These investigations demonstrate that the Earth entry vehicle has great potential in facilitating future sample return missions.

  3. Integrated analysis of the miRNA, gene and pathway regulatory network in gastric cancer.

    Science.gov (United States)

    Zhang, Haiyang; Qu, Yanjun; Duan, Jingjing; Deng, Ting; Liu, Rui; Zhang, Le; Bai, Ming; Li, Jialu; Zhou, Likun; Ning, Tao; Li, Hongli; Ge, Shaohua; Li, Hua; Ying, Guoguang; Huang, Dingzhi; Ba, Yi

    2016-02-01

    Gastric cancer is one of the most common malignant tumors worldwide; however, the efficacy of clinical treatment is limited. MicroRNAs (miRNAs) are a class of small non-coding RNAs that have been reported to play a key role in the development of cancer. They also provide novel candidates for targeted therapy. To date, in-depth studies on the molecular mechanisms of gastric cancer involving miRNAs are still absent. We previously reported that 5 miRNAs were identified as being significantly increased in gastric cancer, and the role of these miRNAs was investigated in the present study. By using bioinformatics tools, we found that more than 4,000 unique genes are potential downstream targets of gastric cancer miRNAs, and these targets belong to the protein class of nucleic acid binding, transcription factor, enzyme modulator, transferase and receptor. Pathway mapping showed that the targets of gastric cancer miRNAs are involved in the MAPK signaling pathway, pathways in cancer, the PI3K-Akt signaling pathway, the HTLV-1 signaling pathway and Ras signaling pathway, thus regulating cell growth, differentiation, apoptosis and metastasis. Analysis of the pathways related to miRNAs may provides potential drug targets for future therapy of gastric cancer.

  4. Genome-wide analysis of the p53 gene regulatory network in the developing mouse kidney.

    Science.gov (United States)

    Li, Yuwen; Liu, Jiao; McLaughlin, Nathan; Bachvarov, Dimcho; Saifudeen, Zubaida; El-Dahr, Samir S

    2013-10-16

    Despite mounting evidence that p53 senses and responds to physiological cues in vivo, existing knowledge regarding p53 function and target genes is largely derived from studies in cancer or stressed cells. Herein we utilize p53 transcriptome and ChIP-Seq (chromatin immunoprecipitation-high throughput sequencing) analyses to identify p53 regulated pathways in the embryonic kidney, an organ that develops via mesenchymal-epithelial interactions. This integrated approach allowed identification of novel genes that are possible direct p53 targets during kidney development. We find the p53-regulated transcriptome in the embryonic kidney is largely composed of genes regulating developmental, morphogenesis, and metabolic pathways. Surprisingly, genes in cell cycle and apoptosis pathways account for kidney lie within proximal promoters of annotated genes compared with 7% in a representative cancer cell line; 25% of the differentially expressed p53-bound genes are present in nephron progenitors and nascent nephrons, including key transcriptional regulators, components of Fgf, Wnt, Bmp, and Notch pathways, and ciliogenesis genes. The results indicate widespread p53 binding to the genome in vivo and context-dependent differences in the p53 regulon between cancer, stress, and development. To our knowledge, this is the first comprehensive analysis of the p53 transcriptome and cistrome in a developing mammalian organ, substantiating the role of p53 as a bona fide developmental regulator. We conclude p53 targets transcriptional networks regulating nephrogenesis and cellular metabolism during kidney development.

  5. Genome-Wide Analysis Revealed the Complex Regulatory Network of Brassinosteroid Effects in Photomorphogenesis

    Institute of Scientific and Technical Information of China (English)

    Li Song; Xiao-Yi Zhou; Li Li; Liang-Jiao Xue; Xi Yang; Hong-Wei Xue

    2009-01-01

    Light and brassinosteroids (BRs) have been proved to be crucial in regulating plant growth and development;however,the mechanism of how they synergistically function is still largely unknown.To explore the underlying mechanisms in photomorphogenesis,genome-wide analyses were carried out through examining the gene expressions of the dark-grown WT or BR biosynthesis-defective mutant det2 seedlings in the presence of light stimuli or exogenous Brassinolide (BL).Results showed that BR deficiency stimulates,while BL treatment suppresses,the expressions of lightresponsive genes and photomorphogenesis,confirming the negative effects of BR in photomorphogenesis.This is consistent with the specific effects of BR on the expression of genes involved in cell wall modification,cellular metabolism and energy utilization during dark-light transition.Further analysis revealed that hormone biosynthesis and signaling-related genes,especially those of auxin,were altered under BL treatment or light stimuli,indicating that BR may modulate photomorphogenesis through synergetic regulation with other hormones.Additionally,suppressed ubiquitin-cycle pathway during light-dark transition hinted the presence of a complicated network among light,hormone,and protein degradation.The study provides the direct evidence of BR effects in photomorphogenesis and identified the genes involved in BR and light signaling pathway,which will help to elucidate the molecular mechanism of plant photomorphogenesis.

  6. Genome-wide DNA methylation analysis identifies hypomethylated genes regulated by FOXP3 in human regulatory T cells.

    Science.gov (United States)

    Zhang, Yuxia; Maksimovic, Jovana; Naselli, Gaetano; Qian, Junyan; Chopin, Michael; Blewitt, Marnie E; Oshlack, Alicia; Harrison, Leonard C

    2013-10-17

    Regulatory T cells (Treg) prevent the emergence of autoimmune disease. Prototypic natural Treg (nTreg) can be reliably identified by demethylation at the Forkhead-box P3 (FOXP3) locus. To explore the methylation landscape of nTreg, we analyzed genome-wide methylation in human naive nTreg (rTreg) and conventional naive CD4(+) T cells (Naive). We detected 2315 differentially methylated cytosine-guanosine dinucleotides (CpGs) between these 2 cell types, many of which clustered into 127 regions of differential methylation (RDMs). Activation changed the methylation status of 466 CpGs and 18 RDMs in Naive but did not alter DNA methylation in rTreg. Gene-set testing of the 127 RDMs showed that promoter methylation and gene expression were reciprocally related. RDMs were enriched for putative FOXP3-binding motifs. Moreover, CpGs within known FOXP3-binding regions in the genome were hypomethylated. In support of the view that methylation limits access of FOXP3 to its DNA targets, we showed that increased expression of the immune suppressive receptor T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT), which delineated Treg from activated effector T cells, was associated with hypomethylation and FOXP3 binding at the TIGIT locus. Differential methylation analysis provides insight into previously undefined human Treg signature genes and their mode of regulation.

  7. Comprehensive analysis of clinical development and regulatory submission promotion schemes for oncologic drugs as the Japanese national projects.

    Science.gov (United States)

    Nagai, Sumimasa; Ozawa, Keiya

    2016-12-01

    To reduce the delay in marketing authorization of drugs in Japan, four Japanese national projects were instituted. We examined all oncologic drugs for adult patients approved or discussed through these schemes, for the first time. All the data are publicly available. In total, 197 applications/demands (181 indications and 16 dosages/uses) were collected. As of December 31, 2015, 64 indications and 10 dosages/uses were approved as off-label drugs through these schemes without conducting additional registration trials in Japan. Furthermore, 46 indications and two dosages/uses were approved after registration trials in Japan requested by the national scheme councils. Regarding the following 23 indications of the 197 applications/demands, registration trials in Japan were commenced after the national scheme council's request: 17 hematological malignancies and six orphan solid tumors. Moreover, 54 indications and three dosages/uses, for which demands were submitted, were regarded as not a high medical priority by the national scheme council. Regarding two hematological malignancy indications, the dosage approved in foreign countries was intolerable for the Japanese patients in Japanese registration trials and this stopped the clinical development in Japan. Our analysis showed that 110 indications and 12 dosages/uses were approved in Japan through these schemes. These national projects have provided numerous therapeutic options for Japanese patients and may be meaningful for promoting clinical development and regulatory approval especially in orphan diseases in countries other than Japan.

  8. Proteomics analysis of global regulatory cascades involved in clavulanic acid production and morphological development in Streptomyces clavuligerus.

    Science.gov (United States)

    Ferguson, Nicole L; Peña-Castillo, Lourdes; Moore, Marcus A; Bignell, Dawn R D; Tahlan, Kapil

    2016-04-01

    The genus Streptomyces comprises bacteria that undergo a complex developmental life cycle and produce many metabolites of importance to industry and medicine. Streptomyces clavuligerus produces the β-lactamase inhibitor clavulanic acid, which is used in combination with β-lactam antibiotics to treat certain β-lactam resistant bacterial infections. Many aspects of how clavulanic acid production is globally regulated in S. clavuligerus still remains unknown. We conducted comparative proteomics analysis using the wild type strain of S. clavuligerus and two mutants (ΔbldA and ΔbldG), which are defective in global regulators and vary in their ability to produce clavulanic acid. Approximately 33.5 % of the predicted S. clavuligerus proteome was detected and 192 known or putative regulatory proteins showed statistically differential expression levels in pairwise comparisons. Interestingly, the expression of many proteins whose corresponding genes contain TTA codons (predicted to require the bldA tRNA for translation) was unaffected in the bldA mutant.

  9. Analysis of Two Putative Candida albicans Phosphopantothenoylcysteine Decarboxylase / Protein Phosphatase Z Regulatory Subunits Reveals an Unexpected Distribution of Functional Roles

    Science.gov (United States)

    Petrényi, Katalin; Molero, Cristina; Kónya, Zoltán; Erdődi, Ferenc; Ariño, Joaquin; Dombrádi, Viktor

    2016-01-01

    Protein phosphatase Z (Ppz) is a fungus specific enzyme that regulates cell wall integrity, cation homeostasis and oxidative stress response. Work on Saccharomyces cerevisiae has shown that the enzyme is inhibited by Hal3/Vhs3 moonlighting proteins that together with Cab3 constitute the essential phosphopantothenoylcysteine decarboxylase (PPCDC) enzyme. In Candida albicans CaPpz1 is also involved in the morphological changes and infectiveness of this opportunistic human pathogen. To reveal the CaPpz1 regulatory context we searched the C. albicans database and identified two genes that, based on the structure of their S. cerevisiae counterparts, were termed CaHal3 and CaCab3. By pull down analysis and phosphatase assays we demonstrated that both of the bacterially expressed recombinant proteins were able to bind and inhibit CaPpz1 as well as its C-terminal catalytic domain (CaPpz1-Cter) with comparable efficiency. The binding and inhibition were always more pronounced with CaPpz1-Cter, indicating a protective effect against inhibition by the N-terminal domain in the full length protein. The functions of the C. albicans proteins were tested by their overexpression in S. cerevisiae. Contrary to expectations we found that only CaCab3 and not CaHal3 rescued the phenotypic traits that are related to phosphatase inhibition by ScHal3, such as tolerance to LiCl or hygromycin B, requirement for external K+ concentrations, or growth in a MAP kinase deficient slt2 background. On the other hand, both of the Candida proteins turned out to be essential PPCDC components and behaved as their S. cerevisiae counterparts: expression of CaCab3 and CaHal3 rescued the cab3 and hal3 vhs3 S. cerevisiae mutations, respectively. Thus, both CaHal3 and CaCab3 retained the PPCDC related functions and have the potential for CaPpz1 inhibition in vitro. The fact that only CaCab3 exhibits its phosphatase regulatory potential in vivo suggests that in C. albicans CaCab3, but not CaHal3, acts as a

  10. Molecular Analysis of the Clavulanic Acid Regulatory Gene Isolated from an Iranian Strain of Streptomyces Clavuligerus , PTCC 1709

    Science.gov (United States)

    Hojati, Zohreh; Salehi, Zahra; Motovali-Bashi, Majid; Korbekandi, Hasan; Jami, Saeed

    2011-01-01

    Objective: The clavulanic acid regulatory gene (claR) is in the clavulanic acid biosynthetic gene cluster that encodes ClaR. This protein is a putative regulator of the late steps of clavulanic acid biosynthesis. The aim of this research is the molecular cloning of claR, isolated from the Iranian strain of Streptomyces clavuligerus (S. clavuligerus). Materials and Methods: In this experimental study, two different strains of S. clavuligerus were used (PTCC 1705 and DSM 738), of which there is no claR sequence record for strain PTCC 1705 in all three main gene banks. The specific designed primers were subjected to a few base modifications for introduction of the recognition sites of BamHI and ClaI. The claR gene was amplified by polymerase chain reaction (PCR) using DNA isolated from S. clavuligerus PTCC 1705. Nested-PCR, restriction fragment length polymorphism (PCR-RFLP), and sequencing were used for molecular analysis of the claR gene. The confirmed claR was subjected to double digestion with BamHI and ClaI. The cut claR was ligated into a pBluescript (pBs) vector and transformed into E. coli. Results: The entire sequence of the isolated claR (Iranian strain) was identified. The presence of the recombinant vector in the transformed colonies was confirmed by the colony-PCR procedure. The correct structure of the recombinant vector, isolated from the transformed E. coli, was confirmed using gel electrophoresis, PCR, and double digestion with restriction enzymes. Conclusion: The constructed recombinant cassette, named pZSclaR, can be regarded as an appropriate tool for site directed mutagenesis and sub-cloning. At this time, claR has been cloned accompanied with its precisely selected promoter so it could be used in expression vectors. Hence the ClaR is known as a putative regulatory protein. The overproduced protein could also be used for other related investigations, such as a mobility shift assay. PMID:23508694

  11. Extending Impact Analysis in Government Social Media Research

    DEFF Research Database (Denmark)

    Medaglia, Rony; Zheng, Lei

    2017-01-01

    of this phenomenon, and falls short of investigating the impacts that these dimensions have on each other. Drawing on a revised framework for classifying existing social media research foci in the categories of management, context, user behavior, user characteristics, platform properties, and effects, we present......The use of social media by governments is a complex phenomenon that touches upon multiple dimensions, and that involves a wide array of relationships between these dimensions. Existing empirical research on government social media, however, is still mostly focusing on describing isolated aspects...... five empirical cases to illustrate impacts between dimensions of government social media. The empirical findings from the cases extend impact analysis beyond the existing foci, and enable us to propose a research agenda for future research on impacts in government social media....

  12. Analysis of High Plains Resource Risk and Economic Impacts

    Energy Technology Data Exchange (ETDEWEB)

    Tidwell, Vincent C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Vargas, Vanessa N [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Jones, Shannon M [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Dealy, Bern Caudill [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Shaneyfelt, Calvin [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Smith, Braeton James [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Moreland, Barbara Denise [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2016-04-01

    The importance of the High Plains Aquifer is broadly recognized as is its vulnerability to continued overuse. T his study e xplore s how continued depletions of the High Plains Aquifer might impact both critical infrastructure and the economy at the local, r egional , and national scale. This analysis is conducted at the county level over a broad geographic region within the states of Kansas and Nebraska. In total , 140 counties that overlie the High Plains Aquifer in these two states are analyzed. The analysis utilizes future climate projections to estimate crop production. Current water use and management practices are projected into the future to explore their related impact on the High Plains Aquifer , barring any changes in water management practices, regulat ion, or policy. Finally, the impact of declining water levels and even exhaustion of groundwater resources are projected for specific sectors of the economy as well as particular elements of the region's critical infrastructure.

  13. Refinery effluent analysis methodologies for relevant parameters from EU-regulatory regimes

    Energy Technology Data Exchange (ETDEWEB)

    Westwood, D.; Ward, T. [Beta Technology Ltd, Heavens Walk, Doncaster, South Yorkshire DN4 5HZ (United Kingdom); Prescott, N.; Rippin, I. [Environment Agency, National Laboratory Service, PO Box 544 Rotherham S60 1BY (United Kingdom); Comber, M.; Den Haan, K.

    2013-08-15

    This report provides guidance to CONCAWE members on the analytical methods that might be used to monitor oil refinery effluents for those refinery-specific parameters covered by relevant European legislation and a comparison of the methods that are used today, as reported in the last Effluent Survey. A method assessment programme is presented whereby the performance of methods of analysis (used to monitor oil refinery effluents) can be compared and prioritised in order of their analytical performance capabilities. Methods for a specific parameter, which is clearly and unambiguously defined, are compared with each other and then prioritised in terms of their overall quality. The quality of these methods is based on an assessment of a combination of characteristic features, namely, precision, bias or recovery, limit of detection (where appropriate), indicative costs, and ease of use. Ranking scores for each feature are assigned to various ranges of each feature, and then added together to give an overall ranking value. The method exhibiting the lowest overall ranking value is deemed the most appropriate method for analysing that parameter. Within this report, several recommendations are made in terms of comparing results of analyses or their associated uses. Where data are to be compared for a particular parameter, then, all CONCAWE members involved in this comparison should agree common objectives, in advance. These include defining a common definition for the: (1) Parameter being analysed and compared; (2) Limit of detection, and how this concentration value should be calculated; (3) Limit of quantification, and how this concentration value should be calculated and how it is to be applied for selective reporting purposes; and (4) Uncertainty of measurement and how it should be calculated. It is further recommended that these involved members should agree on the range of values and ranking scores chosen to reflect the performance characteristic features used in the

  14. Proteome-wide analysis of lysine acetylation suggests its broad regulatory scope in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Henriksen, Peter; Wagner, Sebastian Alexander; Weinert, Brian Tate;

    2012-01-01

    Post-translational modification of proteins by lysine acetylation plays important regulatory roles in living cells. The budding yeast Saccharomyces cerevisiae is a widely used unicellular eukaryotic model organism in biomedical research. S. cerevisiae contains several evolutionary conserved lysin...

  15. Structural Damage Prediction and Analysis for Hypervelocity Impact: Consulting

    Science.gov (United States)

    1995-01-01

    A portion of the contract NAS8-38856, 'Structural Damage Prediction and Analysis for Hypervelocity Impacts,' from NASA Marshall Space Flight Center (MSFC), included consulting which was to be documented in the final report. This attachment to the final report contains memos produced as part of that consulting.

  16. Expanded Polystyrene Re-Expansion Analysis Following Impact Compression

    Science.gov (United States)

    2015-03-04

    USAARL Report No. 2015-08 Expanded Polystyrene Re-Expansion Analysis Following Impact Compression By Mark S. Adams Frederick Brozoski Katie...13 iv This page is intentionally left blank. 1 Introduction Expanded bead polystyrene (EPS) is widely...EPS energy attenuating liners typically have complex geometric shapes. However, the use of flat sheets of polystyrene facilitated the sample

  17. Transport Energy Impact Analysis; NREL (National Renewable Energy Laboratory)

    Energy Technology Data Exchange (ETDEWEB)

    Gonder, J.

    2015-05-13

    Presented at the Sustainable Transportation Energy Pathways Spring 2015 Symposium on May 13, 2015, this presentation by Jeff Gonder of the National Renewable Energy Laboratory (NREL) provides information about NREL's transportation energy impact analysis of connected and automated vehicles.

  18. PCR analysis of the upstream regulatory region of human papillomavirus genomes in cervical intraepithelial neoplasia and cervical carcinoma.

    OpenAIRE

    Donaldson, Y K; Arends, M. J.; Duvall, E.; Bird, C C

    1993-01-01

    AIMS--To test whether human papillomavirus (HPV) variants with large scale sequence alterations to the upstream regulatory region are present in cervical intraepithelial neoplasias (CIN) and cervical carcinomas. METHODS--New PCR based assays were designed specifically to detect large scale insertion/deletion alterations in the upstream regulatory region of HPV 16 and 18. The assays were applied to 24 cases of CIN and 34 cases of cervical carcinoma previously shown to contain these two high ri...

  19. Global and robust stability analysis of genetic regulatory networks with time-varying delays and parameter uncertainties.

    Science.gov (United States)

    Fang-Xiang Wu

    2011-08-01

    The study of stability is essential for designing or controlling genetic regulatory networks. This paper addresses global and robust stability of genetic regulatory networks with time delays and parameter uncertainties. Most existing results on this issue are based on the linear matrix inequalities (LMIs) approach, which results in checking the existence of a feasible solution to high dimensional LMIs. Based on M-matrix theory, we will present several novel global stability conditions for genetic regulatory networks with time-varying and time-invariant delays. All of these stability conditions are given in terms of M-matrices, for which there are many and very easy ways to be verified. Then, we extend these results to genetic regulatory networks with time delays and parameter uncertainties. To illustrate the effectiveness of our theoretical results, several genetic regulatory networks are analyzed. Compared with existing results in the literature, we also show that our results are less conservative than existing ones with these illustrative genetic regulatory networks.

  20. [Environmental impacts of sewage treatment system based on emergy analysis].

    Science.gov (United States)

    Li, Min; Zhang, Xiao-Hong; Li, Yuan-Wei; Zhang, Hong; Zhao, Min; Deng, Shi-Huai

    2013-02-01

    "Integrated sewage treatment system" (ISTS) consists of sewage treatment plant system and their products (treated water and dewatered sludge) disposal facilities, which gives a holistic view of the whole sewage treatment process. During its construction and operation, ISTS has two main impacts on the environment, i.e., the consumption of resources and the damage of discharged pollutants on the environment, while the latter was usually ignored by the previous researchers when they assessed the impacts of wastewater treatment system. In order to more comprehensively understanding the impacts of sewage treatment on the environment, an analysis was made on the ISTS based on the theories of emergy analysis, and, in combining with ecological footprint theory, the sustainability of the ISTS was also analyzed. The results showed that the emergy of the impacts of water pollutants on the environment was far larger than that of the impacts of air pollutants, and NH3-N was the main responsible cause. The emergy consumption of ISTS mainly came from the emergy of wastewater and of local renewable resources. The "sewage treatment plant system + landfill system" had the highest emergy utilization efficiency, while the "sewage treatment plant system + reclaimed water reuse system + incineration system" had the lowest one. From the aspect of environmental sustainability, the "sewage treatment plant system + reclaimed water reuse system + landfill system" was the best ISTS, while the "sewage treatment plant system + incineration system" was the worst one.

  1. The impact of soil compaction on runoff - a meta analysis

    Science.gov (United States)

    Rogger, Magdalena; Blöschl, Günter

    2016-04-01

    Soil compaction caused by intensive agricultural practices is known to influence runoff processes at the local scale and is often speculated to have an impact on flood events at much larger scales. Due to the complex and diverse mechanisms related to soil compaction, the key processes influencing runoff at different scales are still poorly understood. The impacts of soil compaction are, however, not only investigated by hydrologists, but also by agricultural scientists since changes in the soil structure and water availability have a direct impact on agricultural yield. Results from these studies are also of interest to hydrologists. This study presents a meta analysis of such agricultural studies with the aim to analyse and bring together the results related to runoff processes. The study identifies the most important parameters used to describe soil compaction effects and compares the observed impacts under different climatic and soil conditions. The specific type of agricultural practice causing the soil compaction is also taken into account. In a further step the results of this study shall be used to derive a toy model for scenario analysis in order to identify the potential impacts of soil compaction on runoff processes at larger scales then the plot scale.

  2. Impact Cratering Theory and Modeling for the Deep Impact Mission: From Mission Planning to Data Analysis

    Science.gov (United States)

    Richardson, James E.; Melosh, H. Jay; Artemeiva, Natasha A.; Pierazzo, Elisabetta

    2005-03-01

    The cratering event produced by the Deep Impact mission is a unique experimental opportunity, beyond the capability of Earth-based laboratories with regard to the impacting energy, target material, space environment, and extremely low-gravity field. Consequently, impact cratering theory and modeling play an important role in this mission, from initial inception to final data analysis. Experimentally derived impact cratering scaling laws provide us with our best estimates for the crater diameter, depth, and formation time: critical in the mission planning stage for producing the flight plan and instrument specifications. Cratering theory has strongly influenced the impactor design, producing a probe that should produce the largest possible crater on the surface of Tempel 1 under a wide range of scenarios. Numerical hydrocode modeling allows us to estimate the volume and thermodynamic characteristics of the material vaporized in the early stages of the impact. Hydrocode modeling will also aid us in understanding the observed crater excavation process, especially in the area of impacts into porous materials. Finally, experimentally derived ejecta scaling laws and modeling provide us with a means to predict and analyze the observed behavior of the material launched from the comet during crater excavation, and may provide us with a unique means of estimating the magnitude of the comet’s gravity field and by extension the mass and density of comet Tempel 1.

  3. A Review of the Environmental Impacts for Marine and Hydrokinetic Projects to Inform Regulatory Permitting: Summary Findings from the 2015 Workshop on Marine and Hydrokinetic Technologies, Washington, D.C.

    Energy Technology Data Exchange (ETDEWEB)

    Baring-Gould, E. Ian [National Renewable Energy Lab. (NREL), Golden, CO (United States); Christol, Corrie [National Renewable Energy Lab. (NREL), Golden, CO (United States); LiVecchi, Al [National Renewable Energy Lab. (NREL), Golden, CO (United States); Kramer, Sharon [H.T. Harvey and Associates, Los Gatos, CA (United States); West, Anna [Kearns & West, Inc., San Francisco, CA (United States)

    2016-07-01

    In 2014 and 2015, the U.S. Department of Energy initiated efforts to develop and implement technology- and application-focused marine and hydrokinetic (MHK) workshops to share the global experience and knowledge base on evolving MHK technologies, observed and not-observed impacts, monitoring and measurement methods, and regulatory needs. The resulting MHK Regulator Workshops engaged resource managers and other decision makers at key regulatory organizations, scientists, researchers, facilitators, and technical experts and provided an opportunity to examine the risks of single-device and small-scale deployments, explore what can be learned and observed from single devices and small-scale arrays, and consider requirements for projects at varying scales of deployment. Experts and stakeholders identified key remaining information gaps. Initial discussions focused on differentiating between monitoring required for single or small-scale deployments and MHK impact research that, although important, goes beyond what is feasible or should be needed to meet specific project regulatory requirements but is appropriate for broader research and development. Four areas of identified potential environmental impacts provided the focus for the workshop: acoustic output impacts, electromagnetic field (EMF) emissions, physical interactions, and environmental effects of MHK energy development on the physical environment. Discussions also focused on the regulatory process and experience, adaptive management, industry drivers, and lessons that can be learned from the wind energy industry. The discussion was set in the context of the types of MHK technologies that are currently proposed or planned in the United States. All presentations and the following discussions are summarized in this document.

  4. The Michigan regulatory incentives study for electric utilities. Phase 1, Final report

    Energy Technology Data Exchange (ETDEWEB)

    Reid, M.W.; Weaver, E.M. [Barakat and Chamberlin, Inc., Oakland, CA (United States)

    1991-06-17

    This is the final report of Phase I of the Michigan Regulatory Incentives Study for Electric Utilities, a three-phase review of Michigan`s regulatory system and its effects on resource selection by electric utilities. The goal of Phase I is to identify and analyze financial incentive mechanisms that encourage selection of resources in accord with the principles of integrated resource planning (IRP) or least-cost planning (LCP). Subsequent study phases will involve further analysis of options and possibly a collaborative formal effort to propose regulatory changes. The Phase I analysis proceeded in three steps: (1) identification and review of existing regulatory practices that affect utilities; selection of resources, particularly DSM; (2) preliminary analysis of ten financial mechanisms, and selection of three for further study; (3) detailed analysis of the three mechanisms, including consideration of how they could be implemented in Michigan and financial modeling of their likely impacts on utilities and ratepayers.

  5. MicroRNA profiling analysis throughout tomato fruit development and ripening reveals potential regulatory role of RIN on microRNAs accumulation.

    Science.gov (United States)

    Gao, Chao; Ju, Zheng; Cao, Dongyan; Zhai, Baiqiang; Qin, Guozheng; Zhu, Hongliang; Fu, Daqi; Luo, Yunbo; Zhu, Benzhong

    2015-04-01

    The development and ripening of tomato fruit are complex processes involving many gene regulatory pathways at the transcriptional and post-transcriptional level. Ripening inhibitor (RIN) is a vital transcription factor, which targets numerous ripening-related genes at the transcriptional level during tomato fruit ripening. MicroRNAs (miRNAs) are a class of short noncoding RNAs that play important roles in post-transcriptional gene regulation. To elucidate the potential regulatory relationship between rin and miRNAs during fruit development and ripening, we identified known miRNAs and profiled their expression in wild-type tomato and rin mutant using a deep sequencing approach combined with quantitative RT-PCR. A total of 33 known miRNA families were identified, of which 14 miRNA families were differently accumulated. Subsequent promoter analysis showed that possible RIN-binding motifs (CArG-box) tended to occur frequently in the promoter regions of partial differently expressed miRNAs. In addition, ethylene may participate in the regulation of miRNAs accumulation during tomato fruit ripening. Chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay confirmed the direct binding of RIN to the promoter of MIR172a. Collectively, these results showed a close correlation between miRNA expression and RIN as well as ethylene, which further elucidated the regulatory roles of miRNAs during fruit development and ripening and enriched the regulatory network of RIN in tomato fruit.

  6. Differentiation state-specific mitochondrial dynamic regulatory networks are revealed by global transcriptional analysis of the developing chicken lens.

    Science.gov (United States)

    Chauss, Daniel; Basu, Subhasree; Rajakaruna, Suren; Ma, Zhiwei; Gau, Victoria; Anastas, Sara; Brennan, Lisa A; Hejtmancik, J Fielding; Menko, A Sue; Kantorow, Marc

    2014-06-13

    The mature eye lens contains a surface layer of epithelial cells called the lens epithelium that requires a functional mitochondrial population to maintain the homeostasis and transparency of the entire lens. The lens epithelium overlies a core of terminally differentiated fiber cells that must degrade their mitochondria to achieve lens transparency. These distinct mitochondrial populations make the lens a useful model system to identify those genes that regulate the balance between mitochondrial homeostasis and elimination. Here we used an RNA sequencing and bioinformatics approach to identify the transcript levels of all genes expressed by distinct regions of the lens epithelium and maturing fiber cells of the embryonic Gallus gallus (chicken) lens. Our analysis detected more than 15,000 unique transcripts expressed by the embryonic chicken lens. Of these, more than 3000 transcripts exhibited significant differences in expression between lens epithelial cells and fiber cells. Multiple transcripts coding for separate mitochondrial homeostatic and degradation mechanisms were identified to exhibit preferred patterns of expression in lens epithelial cells that require mitochondria relative to lens fiber cells that require mitochondrial elimination. These included differences in the expression levels of metabolic (DUT, PDK1, SNPH), autophagy (ATG3, ATG4B, BECN1, FYCO1, WIPI1), and mitophagy (BNIP3L/NIX, BNIP3, PARK2, p62/SQSTM1) transcripts between lens epithelial cells and lens fiber cells. These data provide a comprehensive window into all genes transcribed by the lens and those mitochondrial regulatory and degradation pathways that function to maintain mitochondrial populations in the lens epithelium and to eliminate mitochondria in maturing lens fiber cells.

  7. Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE analysis uncovers broad changes in chromatin structure resulting from hexavalent chromium exposure.

    Directory of Open Access Journals (Sweden)

    Jerald L Ovesen

    Full Text Available The ability of chromatin to switch back and forth from open euchromatin to closed heterochromatin is vital for transcriptional regulation and genomic stability, but its dynamic structure is subject to disruption by exposure to environmental agents such as hexavalent chromium. Cr(VI exposure disrupts chromatin remodeling mechanisms and causes chromosomal damage through formation of free radicals, Cr-DNA adducts, and DNA-Cr-protein cross-links. In addition, acute, high-concentration, and chronic, low-concentration exposures to Cr(VI lead to significantly different transcriptional and genomic stability outcomes. We used mouse hepatoma Hepa-1c1c7 cells to investigate how transcriptional responses to chromium treatment might correlate with structural chromatin changes. We used Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE analysis coupled with deep sequencing to identify regions of the genome that may switch between open and closed chromatin in response to exposure to varying Cr(VI concentrations. At either Cr(VI concentration, chromatin domains surrounding binding sites for AP-1 transcription factors become significantly open, whereas BACH2 and CTCF binding sites are open solely at the low and high concentrations, respectively. Parallel gene expression profiling using RNA-seq indicates that the structural chromatin changes caused by Cr(VI affect gene expression levels in the target areas that vary depending on Cr(VI concentration, but show no correlation between global changes in the overall transcriptional response and Cr(VI concentration. Our results suggest that FAIRE may be a useful technique to map chromatin elements targeted by DNA damaging agents for which there is no prior knowledge of their specificity, and to identify subsequent transcriptomic changes induced by those agents.

  8. Comparative Transcriptome Analysis between Gynoecious and Monoecious Plants Identifies Regulatory Networks Controlling Sex Determination in Jatropha curcas.

    Science.gov (United States)

    Chen, Mao-Sheng; Pan, Bang-Zhen; Fu, Qiantang; Tao, Yan-Bin; Martínez-Herrera, Jorge; Niu, Longjian; Ni, Jun; Dong, Yuling; Zhao, Mei-Li; Xu, Zeng-Fu

    2016-01-01

    Most germplasms of the biofuel plant Jatropha curcas are monoecious. A gynoecious genotype of J. curcas was found, whose male flowers are aborted at early stage of inflorescence development. To investigate the regulatory mechanism of transition from monoecious to gynoecious plants, a comparative transcriptome analysis between gynoecious and monoecious inflorescences were performed. A total of 3,749 genes differentially expressed in two developmental stages of inflorescences were identified. Among them, 32 genes were involved in floral development, and 70 in phytohormone biosynthesis and signaling pathways. Six genes homologous to KNOTTED1-LIKE HOMEOBOX GENE 6 (KNAT6), MYC2, SHI-RELATED SEQUENCE 5 (SRS5), SHORT VEGETATIVE PHASE (SVP), TERMINAL FLOWER 1 (TFL1), and TASSELSEED2 (TS2), which control floral development, were considered as candidate regulators that may be involved in sex differentiation in J. curcas. Abscisic acid, auxin, gibberellin, and jasmonate biosynthesis were lower, whereas cytokinin biosynthesis was higher in gynoecious than that in monoecious inflorescences. Moreover, the exogenous application of gibberellic acid (GA3) promoted perianth development in male flowers and partly prevented pistil development in female flowers to generate neutral flowers in gynoecious inflorescences. The arrest of stamen primordium at early development stage probably causes the abortion of male flowers to generate gynoecious individuals. These results suggest that some floral development genes and phytohormone signaling pathways orchestrate the process of sex determination in J. curcas. Our study provides a basic framework for the regulation networks of sex determination in J. curcas and will be helpful for elucidating the evolution of the plant reproductive system.

  9. Regulatory and Non-regulatory Responses to Hydraulic Fracturing in Local Communities

    Science.gov (United States)

    Phartiyal, P.

    2015-12-01

    The practice of extracting oil and gas from tight rock formations using advances in technology, such as hydraulic fracturing and directional drilling, has expanded exponentially in states and localities across the country. As the scientific data collection and analysis catches up on the many potential impacts of this unconventional oil and gas development, communities are turning to their local officials to make decisions on whether and how fracking should proceed. While most regulatory authority on the issue rests with the state agencies, local officials have experimented with a wide range of regulatory, non-regulatory, and fiscal tools to manage the impacts of fracking. These impacts can occur on the local air, water, seismicity, soil, roads, schools, and affect residents, on-site workers, emergency and social services. Local officials' approaches are often influenced by their prior experience with minerals extraction in their localities. The speaker will present examples of the kinds of information sources, tools and approaches communities across the country are using, from noise barriers to setback requirements to information sharing in order to be able to balance the promise and perils of oil and gas development in their jurisdictions.

  10. Impact Of Job Analysis On Job Performance: Analysis Of A Hypothesized Model

    Directory of Open Access Journals (Sweden)

    Rehman Safdar

    2011-01-01

    Full Text Available Researchers have developed a relationship between HRM practices and organizational performance, but the relationship between HRM practice like job analysis – employee Job performance remains unexplored. This paper, based on a study of employees of Pakistan Public sector regulatory authorities of telecommunication, oil and gas, power, media, security exchange, banking sector and organizations being regulated by these authorities is an attempt to develop and test a hypothesized model linking HR importance of job analysis with employee job performance. Survey results of 568 employees indicated that practice of job analysis was strongly related to employee job performance. The findings suggest that an organisation-wide policy of job analysis is an important source of competitive advantage in its own right, and requires due attention of HR professionals. The study extends the findings of the HR–employee job performance research pursued in Western countries to a non-Western context.

  11. Hydrodynamic impact analysis and testing of an unmanned aerial vehicle

    Science.gov (United States)

    Bird, Isabel

    Analysis and testing have been conducted to assess the feasibility of a small UAV that can be landed in the water and recovered for continued use. Water landings may be desirable in a number of situations, for example when testing UAVs outside of the territorial waters of the US to avoid violating FAA regulations. Water landings may also be desirable when conducting surveillance missions in marine environments. Although the goal in landing is to have the UAV lightly set down on the water, rough seas or gusty winds may result in a nose-in landing where the UAV essentially impacts the surface of the water. The tested UAV is a flying wing design constructed of expanded polypropylene foam wings with a hollowed out center-section for the avionics. Acceleration data was collected by means of LIS331 3-axis accelerometers positioned at five locations, including the wingtips. This allowed conclusions to be drawn with respect to the loads experienced on impact throughout the airframe. This data was also used to find loads corresponding to the maximum decelerations experienced during impact. These loads were input into a finite element analysis model of the wing spars to determine stress in the wing spars. Upon impact, the airframe experienced high-frequency oscillation. Surprisingly, peak accelerations at the wingtips were observed at up to 15g greater than corresponding accelerations at the center of the fuselage.

  12. Cross-Sector Impact Analysis of Industrial Efficiency Measures

    Energy Technology Data Exchange (ETDEWEB)

    Morrow, William [Lawrence Berkeley National Laboratory (LBNL); CreskoEngineering, Joe [Oak Ridge Institute for Science and Education (ORISE); Carpenter, Alberta [National Renewable Energy Laboratory (NREL); Masanet, Eric [Northwestern University, Evanston; Nimbalkar, Sachin U [ORNL; Shehabi, Arman [Lawrence Berkeley National Laboratory (LBNL)

    2013-01-01

    The industrial or manufacturing sector is a foundational component to all economic activity. In addition to being a large direct consumer of energy, the manufacturing sector also produces materials, products, and technologies that influence the energy use of other economic sectors. For example, the manufacturing of a lighter-weight vehicle component affects the energy required to ship that component as well as the fuel efficiency of the assembled vehicle. Many energy efficiency opportunities exist to improve manufacturing energy consumption, however comparisons of manufacturing sector energy efficiency investment opportunities tend to exclude any impacts that occur once the product leaves the factory. Expanding the scope of analysis to include energy impacts across different stages of product life-cycle can highlight less obvious opportunities and inform actions that create the greatest economy-wide benefits. We present a methodology and associated analysis tool (LIGHTEnUP Lifecycle Industry GHgas, Technology and Energy through the Use Phase) that aims to capture both the manufacturing sector energy consumption and product life-cycle energy consumption implications of manufacturing innovation measures. The tool architecture incorporates U.S. national energy use data associated with manufacturing, building operations, and transportation. Inputs for technology assessment, both direct energy saving to the manufacturing sector, and indirect energy impacts to additional sectors are estimated through extensive literature review and engineering methods. The result is a transparent and uniform system of comparing manufacturing and use-phase impacts of technologies.

  13. Cyber threat impact assessment and analysis for space vehicle architectures

    Science.gov (United States)

    McGraw, Robert M.; Fowler, Mark J.; Umphress, David; MacDonald, Richard A.

    2014-06-01

    This paper covers research into an assessment of potential impacts and techniques to detect and mitigate cyber attacks that affect the networks and control systems of space vehicles. Such systems, if subverted by malicious insiders, external hackers and/or supply chain threats, can be controlled in a manner to cause physical damage to the space platforms. Similar attacks on Earth-borne cyber physical systems include the Shamoon, Duqu, Flame and Stuxnet exploits. These have been used to bring down foreign power generation and refining systems. This paper discusses the potential impacts of similar cyber attacks on space-based platforms through the use of simulation models, including custom models developed in Python using SimPy and commercial SATCOM analysis tools, as an example STK/SOLIS. The paper discusses the architecture and fidelity of the simulation model that has been developed for performing the impact assessment. The paper walks through the application of an attack vector at the subsystem level and how it affects the control and orientation of the space vehicle. SimPy is used to model and extract raw impact data at the bus level, while STK/SOLIS is used to extract raw impact data at the subsystem level and to visually display the effect on the physical plant of the space vehicle.

  14. Analysis of accidental iceberg impacts with membrane tank LNG carriers

    OpenAIRE

    Myhre, Stine Aas

    2010-01-01

    The probability of ship-iceberg impacts are increasing due to increasing production and due to more transportation routes near arctic areas. The first part of this thesis is an introduction to Liquefied Natural Gas (LNG) and the LNG carriers, particularly LNG carriers with membrane type cargo containment system.Some theory regarding the principles of Non Linear Finite Element Analysis (NLFEA) and ship-iceberg collision is briefly described.A detailed finite element model of the cargo tank is ...

  15. Impact of replicate types on proteomic expression analysis.

    Science.gov (United States)

    Karp, Natasha A; Spencer, Matthew; Lindsay, Helen; O'Dell, Kevin; Lilley, Kathryn S

    2005-01-01

    In expression proteomics, the samples utilized within an experimental design may include technical, biological, or pooled replicates. This manuscript discusses various experimental designs and the conclusions that can be drawn from them. Specifically, it addresses the impact of mixing replicate types on the statistical analysis which can be performed. This study focuses on difference gel electrophoresis (DiGE), but the issues are equally applicable to all quantitative methodologies assessing relative changes in protein expression.

  16. An analysis of climatic impacts and adaptation strategies in Tanzania

    CSIR Research Space (South Africa)

    Ojoyi, MM

    2015-03-01

    Full Text Available International Journal of Climate Change Strategies and Management An analysis of climatic impacts and adaptation strategies in Tanzania Mercy M. Ojoyi School of Environmental Sciences, University of KwaZulu-Natal, Pietermaritzburg, South Africa... of climate change. Practical implications - The study suggests the need for leverage on resource use through education and good governance strategies to be employed by resource planners, leaders and policy makers. Social implications - This study links...

  17. Analysis of the behavior of sedimentary rocks under impact loading

    OpenAIRE

    Millon, O.; Ruiz Ripoll, M.L.; Hoerth, T.

    2016-01-01

    In multiple engineering fields such as rock drilling or building constructions or extreme events like earthquakes or impacts, the dynamic properties of rock play an important role. A way to model these events and define measures to minimize the damage derived from these events is created by means of numerical analysis. Hence, the knowledge of the dynamic material behavior is essential for studying the effects of such a loading scenario. Solid geological materials, from the family of the sedim...

  18. Comparative RNA-Seq Analysis Reveals That Regulatory Network of Maize Root Development Controls the Expression of Genes in Response to N Stress.

    Directory of Open Access Journals (Sweden)

    Xiujing He

    Full Text Available Nitrogen (N is an essential nutrient for plants, and it directly affects grain yield and protein content in cereal crops. Plant root systems are not only critical for anchorage in the soil, but also for N acquisition. Therefore, genes controlling root development might also affect N uptake by plants. In this study, the responses of nitrogen on root architecture of mutant rtcs and wild-type of maize were investigated by morphological and physiological analysis. Subsequently, we performed a comparative RNA-Seq analysis to compare gene expression profiles between mutant rtcs roots and wild-type roots under different N conditions. We identified 786 co-modulated differentially expressed genes (DEGs related to root development. These genes participated in various metabolic processes. A co-expression cluster analysis and a cis-regulatory motifs analysis revealed the importance of the AP2-EREBP transcription factor family in the rtcs-dependent regulatory network. Some genotype-specific DEGs contained at least one LBD motif in their promoter region. Further analyses of the differences in gene transcript levels between rtcs and wild-type under different N conditions revealed 403 co-modulated DEGs with distinct functions. A comparative analysis revealed that the regulatory network controlling root development also controlled gene expression in response to N-deficiency. Several AP2-EREBP family members involved in multiple hormone signaling pathways were among the DEGs. These transcription factors might play important roles in the rtcs-dependent regulatory network related to root development and the N-deficiency response. Genes encoding the nitrate transporters NRT2-1, NAR2.1, NAR2.2, and NAR2.3 showed much higher transcript levels in rtcs than in wild-type under normal-N conditions. This result indicated that the LBD gene family mainly functions as transcriptional repressors, as noted in other studies. In summary, using a comparative RNA-Seq-based approach

  19. Comparative RNA-Seq Analysis Reveals That Regulatory Network of Maize Root Development Controls the Expression of Genes in Response to N Stress.

    Science.gov (United States)

    He, Xiujing; Ma, Haixia; Zhao, Xiongwei; Nie, Shujun; Li, Yuhua; Zhang, Zhiming; Shen, Yaou; Chen, Qi; Lu, Yanli; Lan, Hai; Zhou, Shufeng; Gao, Shibin; Pan, Guangtang; Lin, Haijian

    2016-01-01

    Nitrogen (N) is an essential nutrient for plants, and it directly affects grain yield and protein content in cereal crops. Plant root systems are not only critical for anchorage in the soil, but also for N acquisition. Therefore, genes controlling root development might also affect N uptake by plants. In this study, the responses of nitrogen on root architecture of mutant rtcs and wild-type of maize were investigated by morphological and physiological analysis. Subsequently, we performed a comparative RNA-Seq analysis to compare gene expression profiles between mutant rtcs roots and wild-type roots under different N conditions. We identified 786 co-modulated differentially expressed genes (DEGs) related to root development. These genes participated in various metabolic processes. A co-expression cluster analysis and a cis-regulatory motifs analysis revealed the importance of the AP2-EREBP transcription factor family in the rtcs-dependent regulatory network. Some genotype-specific DEGs contained at least one LBD motif in their promoter region. Further analyses of the differences in gene transcript levels between rtcs and wild-type under different N conditions revealed 403 co-modulated DEGs with distinct functions. A comparative analysis revealed that the regulatory network controlling root development also controlled gene expression in response to N-deficiency. Several AP2-EREBP family members involved in multiple hormone signaling pathways were among the DEGs. These transcription factors might play important roles in the rtcs-dependent regulatory network related to root development and the N-deficiency response. Genes encoding the nitrate transporters NRT2-1, NAR2.1, NAR2.2, and NAR2.3 showed much higher transcript levels in rtcs than in wild-type under normal-N conditions. This result indicated that the LBD gene family mainly functions as transcriptional repressors, as noted in other studies. In summary, using a comparative RNA-Seq-based approach, we identified

  20. Türkiye’nin Avrupa Birliği’ne Sürdürülebilir Katılımı İçin Düzenleyici Etki Analizinin Gerekliliği(Regulatory Impact Assessment Indispensable for Turkey’s Sustainable Accession to the European Union

    Directory of Open Access Journals (Sweden)

    Sibel MEHTER AYKIN

    2010-01-01

    Full Text Available Despite the fact that regulatory impact assestment applications date back to 1990s in the OECD countries, it has not gained sufficient grounds in Turkey. Whereas, in the European Union, regulatory impact assessment is regarded as an important tool in decision making and policy formation process even in understanding the potential impacts of future accessions. In 2007, the Government declared Turkey’s acquis alignment programme in the framework of European Union and Turkish relations. The 2007-2013 programme requires a broad range of regulatory impact assesments to be done. By this way, sound grounds for transition period demands and derogations may be provided by Turkey. Furthermore, regulatory impact assessment enables all the stakeholders to manage the accession process effectively and efficiently on the basis of corporate responsibilty. Any acquis alignment programme, introduced without realizing relevant regulatory impact assessments, will be insufficient in achieving sustainability of Turkey’s accession to the EU. Thus, regulatory impact assessment as applied in the European Union should be studied in depth and realized.

  1. Pre-salt new regulatory mark and the economic order: constitutionality analysis; Novo marco regulatorio do pre-sal e a ordem economica: analise de constitucionalidade

    Energy Technology Data Exchange (ETDEWEB)

    Pinheiro, Marcela Brasil Pedrosa; Araujo, Mayara de Carvalho; Xavier, Yanko Marcius; Guimaraes, Patricia Borba Vilar [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil)

    2010-07-01

    The discovery of vast reserves of hydrocarbons in the pre-salt layer that extends from Espirito Santo to Santa Catarina, added with the economic and strategic value of oil and natural gas, has brought discussion about the reasonableness of the regulatory model adopted so far. Would be prudent to explore these resources through the concession model? From detailed analysis of the doctrinal and bills that aim to inaugurate the new regulatory bills, we sought to answer this question, based majorly on the principles of economic activity applied in our constitutional system. Motivated by the analysis of these constitutional principles proposed, the State is seen as a regulating agent of the economic activities, fulfilling its role to supervise, encourage and plan the direction of national economic system. The sharing model gives greater state involvement and is able to convert the wealth of pre-salt in citizenship, but only if well implemented. Thus, based on constitutional principles and the notion of development as freedom, the conclusion of this paperwork is for the constitutionality of the new regulatory bills. (author)

  2. PROACTIVE REGULATORY INTERVENTION IN EU COMMUNICATIONS SECTOR AND ITS FORESEEABLE FUTURE

    Directory of Open Access Journals (Sweden)

    Mantas Barčys

    2013-06-01

    Full Text Available Purpose – to review and provide insights on the issues concerning ex ante regulatory approach in EU telecommunications (hereinafter – electronic communications industry, identify and emphasise benefits, main challenges and further regulatory prospective. Design/methodology/approach – based on current regulatory framework and analysis of academic literature, author discusses problematic issues related to the needs and further perspectives of proactive regulatory regime in EU electronic communications sector. Findings – the author reviews special qualities for different regulatory regimes (ex ante, ex post and examines them in the context of sharp developments of the industry and EU regulatory policy. Research limitations/implications –the analysis aims to convey the main understanding on the regulatory specifics of the communications industry, the main features, distinguishing communications industry from the others and foreseeable regulatory perspectives Practical implications – the core aspect of the paper is to evaluate current regulatory approach of the EU electronic communications sector and assess potential regulatory approaches in the context of making self-sustaining pro-competitive market structure, technological development. Originality/Value – the paper highlights some significant changes between two regulatory approaches in the light of specific features in EU electronic communications. Author provides his insights on the status and perspectives on application for both regulatory methods. Apparently, these issues have so far been subjected too little academic analysis. As shown in this paper, regulatory policy can have the essential impact on the activities taken by other players. The decision to give an even bigger role to competition rules, do not mean to eliminate sector specifics itself. With this in mind, EU legislators are not able to eliminate proactive regulatory control, thus reducing ex ante rules progressively

  3. An analysis of the impacts of economic incentive programs on commercial nuclear power plant operations and maintenance costs

    Energy Technology Data Exchange (ETDEWEB)

    Kavanaugh, D.C.; Monroe, W.H. [Pacific Northwest Lab., Richland, WA (United States); Wood, R.S. [Nuclear Regulatory Commission, Washington, DC (United States)

    1996-02-01

    Operations and Maintenance (O and M) expenditures by nuclear power plant owner/operators possess a very logical and vital link in considerations relating to plant safety and reliability. Since the determinants of O and M outlays are considerable and varied, the potential linkages to plant safety, both directly and indirectly, can likewise be substantial. One significant issue before the US Nuclear Regulatory Commission is the impact, if any, on O and M spending from state programs that attempt to improve plant operating performance, and how and to what extent these programs may affect plant safety and pose public health risks. The purpose of this study is to examine the role and degree of impacts from state promulgated economic incentive programs (EIPs) on plant O and M spending. A multivariate regression framework is specified, and the model is estimated on industry data over a five-year period, 1986--1990. Explanatory variables for the O and M spending model include plant characteristics, regulatory effects, financial strength factors, replacement power costs, and the performance incentive programs. EIPs are found to have statistically significant effects on plant O and M outlays, albeit small in relation to other factors. Moreover, the results indicate that the relatively financially weaker firms are more sensitive in their O and M spending to the presence of such programs. Formulations for linking spending behavior and EIPs with plant safety performance remains for future analysis.

  4. Analysis of the impact of the regulation of toxic substances on Sandia

    Energy Technology Data Exchange (ETDEWEB)

    Arnold, C. Jr.; Pigg, J.

    1980-10-01

    In recent years, Congress has passed two regulatory acts, namely the Occupational Safety and Health Act (OSHA) and the Toxic Substance Control Act (TSCA) which seek to control the manufacture, use, and disposal of hazardous chemical substances. These acts can have a significant impact on Sandia's missions and will particularly affect those organizations involved in materials development and selection. The primary purpose of this report is to describe in some detail the impact of these acts on Sandia's corporate goals and make recommendations on what our response should be. Also described in this report is the present position of Sandia with respect to these regulatory acts and the policies and actions that Sandia has taken to date in an effort to minimize their impact.

  5. Transcriptional analysis of the jamaicamide gene cluster from the marine cyanobacterium Lyngbya majuscula and identification of possible regulatory proteins

    Directory of Open Access Journals (Sweden)

    Dorrestein Pieter C

    2009-12-01

    Full Text Available Abstract Background The marine cyanobacterium Lyngbya majuscula is a prolific producer of bioactive secondary metabolites. Although biosynthetic gene clusters encoding several of these compounds have been identified, little is known about how these clusters of genes are transcribed or regulated, and techniques targeting genetic manipulation in Lyngbya strains have not yet been developed. We conducted transcriptional analyses of the jamaicamide gene cluster from a Jamaican strain of Lyngbya majuscula, and isolated proteins that could be involved in jamaicamide regulation. Results An unusually long untranslated leader region of approximately 840 bp is located between the jamaicamide transcription start site (TSS and gene cluster start codon. All of the intergenic regions between the pathway ORFs were transcribed into RNA in RT-PCR experiments; however, a promoter prediction program indicated the possible presence of promoters in multiple intergenic regions. Because the functionality of these promoters could not be verified in vivo, we used a reporter gene assay in E. coli to show that several of these intergenic regions, as well as the primary promoter preceding the TSS, are capable of driving β-galactosidase production. A protein pulldown assay was also used to isolate proteins that may regulate the jamaicamide pathway. Pulldown experiments using the intergenic region upstream of jamA as a DNA probe isolated two proteins that were identified by LC-MS/MS. By BLAST analysis, one of these had close sequence identity to a regulatory protein in another cyanobacterial species. Protein comparisons suggest a possible correlation between secondary metabolism regulation and light dependent complementary chromatic adaptation. Electromobility shift assays were used to evaluate binding of the recombinant proteins to the jamaicamide promoter region. Conclusion Insights into natural product regulation in cyanobacteria are of significant value to drug discovery

  6. Impact of the Staphylococcus epidermidis LytSR two-component regulatory system on murein hydrolase activity, pyruvate utilization and global transcriptional profile

    Directory of Open Access Journals (Sweden)

    Yu Fangyou

    2010-11-01

    Full Text Available Abstract Background Staphylococcus epidermidis has emerged as one of the most important nosocomial pathogens, mainly because of its ability to colonize implanted biomaterials by forming a biofilm. Extensive studies are focused on the molecular mechanisms involved in biofilm formation. The LytSR two-component regulatory system regulates autolysis and biofilm formation in Staphylococcus aureus. However, the role of LytSR played in S. epidermidis remained unknown. Results In the present study, we demonstrated that lytSR knock-out in S. epidermidis did not alter susceptibility to Triton X-100 induced autolysis. Quantitative murein hydrolase assay indicated that disruption of lytSR in S. epidermidis resulted in decreased activities of extracellular murein hydrolases, although zymogram showed no apparent differences in murein hydrolase patterns between S. epidermidis strain 1457 and its lytSR mutant. Compared to the wild-type counterpart, 1457ΔlytSR produced slightly more biofilm, with significantly decreased dead cells inside. Microarray analysis showed that lytSR mutation affected the transcription of 164 genes (123 genes were upregulated and 41 genes were downregulated. Specifically, genes encoding proteins responsible for protein synthesis, energy metabolism were downregulated, while genes involved in amino acid and nucleotide biosynthesis, amino acid transporters were upregulated. Impaired ability to utilize pyruvate and reduced activity of arginine deiminase was observed in 1457ΔlytSR, which is consistent with the microarray data. Conclusions The preliminary results suggest that in S. epidermidis LytSR two-component system regulates extracellular murein hydrolase activity, bacterial cell death and pyruvate utilization. Based on the microarray data, it appears that lytSR inactivation induces a stringent response. In addition, LytSR may indirectly enhance biofilm formation by altering the metabolic status of the bacteria.

  7. Inferring polymorphism-induced regulatory gene networks active in human lymphocyte cell lines by weighted linear mixed model analysis of multiple RNA-Seq datasets.

    Directory of Open Access Journals (Sweden)

    Wensheng Zhang

    Full Text Available Single-nucleotide polymorphisms (SNPs contribute to the between-individual expression variation of many genes. A regulatory (trait-associated SNP is usually located near or within a (host gene, possibly influencing the gene's transcription or/and post-transcriptional modification. But its targets may also include genes that are physically farther away from it. A heuristic explanation of such multiple-target interferences is that the host gene transfers the SNP genotypic effects to the distant gene(s by a transcriptional or signaling cascade. These connections between the host genes (regulators and the distant genes (targets make the genetic analysis of gene expression traits a promising approach for identifying unknown regulatory relationships. In this study, through a mixed model analysis of multi-source digital expression profiling for 140 human lymphocyte cell lines (LCLs and the genotypes distributed by the international HapMap project, we identified 45 thousands of potential SNP-induced regulatory relationships among genes (the significance level for the underlying associations between expression traits and SNP genotypes was set at FDR < 0.01. We grouped the identified relationships into four classes (paradigms according to the two different mechanisms by which the regulatory SNPs affect their cis- and trans- regulated genes, modifying mRNA level or altering transcript splicing patterns. We further organized the relationships in each class into a set of network modules with the cis- regulated genes as hubs. We found that the target genes in a network module were often characterized by significant functional similarity, and the distributions of the target genes in three out of the four networks roughly resemble a power-law, a typical pattern of gene networks obtained from mutation experiments. By two case studies, we also demonstrated that significant biological insights can be inferred from the identified network modules.

  8. PlantPAN: Plant promoter analysis navigator, for identifying combinatorial cis-regulatory elements with distance constraint in plant gene groups

    Directory of Open Access Journals (Sweden)

    Huang Hsien-Da

    2008-11-01

    Full Text Available Abstract Background The elucidation of transcriptional regulation in plant genes is important area of research for plant scientists, following the mapping of various plant genomes, such as A. thaliana, O. sativa and Z. mays. A variety of bioinformatic servers or databases of plant promoters have been established, although most have been focused only on annotating transcription factor binding sites in a single gene and have neglected some important regulatory elements (tandem repeats and CpG/CpNpG islands in promoter regions. Additionally, the combinatorial interaction of transcription factors (TFs is important in regulating the gene group that is associated with the same expression pattern. Therefore, a tool for detecting the co-regulation of transcription factors in a group of gene promoters is required. Results This study develops a database-assisted system, PlantPAN (Plant Promoter Analysis Navigator, for recognizing combinatorial cis-regulatory elements with a distance constraint in sets of plant genes. The system collects the plant transcription factor binding profiles from PLACE, TRANSFAC (public release 7.0, AGRIS, and JASPER databases and allows users to input a group of gene IDs or promoter sequences, enabling the co-occurrence of combinatorial transcription factor binding sites (TFBSs within a defined distance (20 bp to 200 bp to be identified. Furthermore, the new resource enables other regulatory features in a plant promoter, such as CpG/CpNpG islands and tandem repeats, to be displayed. The regulatory elements in the conserved regions of the promoters across homologous genes are detected and presented. Conclusion In addition to providing a user-friendly input/output interface, PlantPAN has numerous advantages in the analysis of a plant promoter. Several case studies have established the effectiveness of PlantPAN. This novel analytical resource is now freely available at http://PlantPAN.mbc.nctu.edu.tw.

  9. a Study on Impact Analysis of Side Kick in Taekwondo

    Science.gov (United States)

    Lee, Jung-Hyun; Lee, Young-Shin; Han, Kyu-Hyun

    Taekwondo is a martial art form and sport that uses the hands and feet for attack and defense. Taekwondo basic motion is composed of the breaking, competition and poomsea motions. The side kick is one of the most important breaking motions. The side kick with the front foot can be made in two steps. In the first step, the front foot is extended forward from the back stance free-fighting position. For the second step, the rear foot is followed simultaneously. Then, the side kick is executed while the entire body weight rests on the rear foot. In this paper, the impact analysis on a human model for kicking posture was carried out. The ADAMS/LifeMOD used numerical modeling and simulation for the side kick. The numerical human models for assailant and opponent in competition motion were developed. The maximum impact force on the human body was obtained by experiment and was applied to impact simulation. As a result, the impact displacement and velocity of the numerical human model were investigated.

  10. A Decision Analysis Tool for Climate Impacts, Adaptations, and Vulnerabilities

    Energy Technology Data Exchange (ETDEWEB)

    Omitaomu, Olufemi A [ORNL; Parish, Esther S [ORNL; Nugent, Philip J [ORNL

    2016-01-01

    Climate change related extreme events (such as flooding, storms, and drought) are already impacting millions of people globally at a cost of billions of dollars annually. Hence, there are urgent needs for urban areas to develop adaptation strategies that will alleviate the impacts of these extreme events. However, lack of appropriate decision support tools that match local applications is limiting local planning efforts. In this paper, we present a quantitative analysis and optimization system with customized decision support modules built on geographic information system (GIS) platform to bridge this gap. This platform is called Urban Climate Adaptation Tool (Urban-CAT). For all Urban-CAT models, we divide a city into a grid with tens of thousands of cells; then compute a list of metrics for each cell from the GIS data. These metrics are used as independent variables to predict climate impacts, compute vulnerability score, and evaluate adaptation options. Overall, the Urban-CAT system has three layers: data layer (that contains spatial data, socio-economic and environmental data, and analytic data), middle layer (that handles data processing, model management, and GIS operation), and application layer (that provides climate impacts forecast, adaptation optimization, and site evaluation). The Urban-CAT platform can guide city and county governments in identifying and planning for effective climate change adaptation strategies.

  11. Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in Vermont. Preliminary background report

    Energy Technology Data Exchange (ETDEWEB)

    Feurer, D A; Weaver, C L; Gallagher, K C; Hejna, D; Rielley, K J

    1980-01-01

    The authority to regulate public utilities is vested generally in the Vermont Public Service Board (PSC). The PSB is comprised of three members appointed by the governor with the advice and consent of the senate. PSB members serve six year terms. Members must be free from any employment or pecuniary interests in any company subject to the supervision of the PSB. Local governments retain little regulatory authority over public utilities. Local governments are responsible for regulating the use of streets and other public property, but any person aggrieved by a local decision may appeal to the PSB within thirty days. The PSB is to review the local action at a public hearing and its decision is final. Public utility regulatory statutes, energy facility siting programs, and municipal franchising authority are examined to identify how they may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES.

  12. Coexpression network analysis in abdominal and gluteal adipose tissue reveals regulatory genetic loci for metabolic syndrome and related phenotypes

    DEFF Research Database (Denmark)

    Min, Josine L; Nicholson, George; Halgrimsdottir, Ingileif

    2012-01-01

    Metabolic Syndrome (MetS) is highly prevalent and has considerable public health impact, but its underlying genetic factors remain elusive. To identify gene networks involved in MetS, we conducted whole-genome expression and genotype profiling on abdominal (ABD) and gluteal (GLU) adipose tissue......, and whole blood (WB), from 29 MetS cases and 44 controls. Co-expression network analysis for each tissue independently identified nine, six, and zero MetS-associated modules of coexpressed genes in ABD, GLU, and WB, respectively. Of 8,992 probesets expressed in ABD or GLU, 685 (7.6%) were expressed in ABD...... and 51 (0.6%) in GLU only. Differential eigengene network analysis of 8,256 shared probesets detected 22 shared modules with high preservation across adipose depots (D(ABD-GLU) = 0.89), seven of which were associated with MetS (FDR P100,000 individuals; rs10282458, affecting expression of RARRES2...

  13. Evaluate the Impact of your Education and Outreach Program Using the Quantitative Collaborative Impact Analysis Method

    Science.gov (United States)

    Scalice, D.; Davis, H. B.

    2015-12-01

    The AGU scientific community has a strong motivation to improve the STEM knowledge and skills of today's youth, and we are dedicating increasing amounts of our time and energy to education and outreach work. Scientists and educational project leads can benefit from a deeper connection to the value of evaluation, how to work with an evaluator, and how to effectively integrate evaluation into projects to increase their impact. This talk will introduce a method for evaluating educational activities, including public talks, professional development workshops for educators, youth engagement programs, and more. We will discuss the impetus for developing this method--the Quantitative Collaborative Impact Analysis Method--how it works, and the successes we've had with it in the NASA Astrobiology education community.

  14. Normalising impacts in an environmental systems analysis of wastewater systems.

    Science.gov (United States)

    Kärrman, E; Jönsson, H

    2001-01-01

    In an environmental systems analysis of four wasterwater systems, the environmental aspects were prioritised by normalisation of predicted impacts from the studied systems to the total impacts from society. Priority Group 1 (highest priority) consisted of discharges (flows) of nitrogen, cadmium, lead and mercury to water, recycling of nitrogen and phosphorus to arable land and flows of heavy metals to arable land. A conventional wastewater system (A) was compared to irrigation of energy forest with biologically treated wastewater (B), liquid composting of toilet wastewater (C) and a conventional system supplemented with urine separation (D). Analysing the aspects in priority group one, systems B-D improved the management of plant nutrients and decreased the flow of heavy metals to water, while the flow to arable land increased, especially for system B. The suggested method is useful in municipal environmental planning and when choosing a wastewater system.

  15. The Impact of Technological Research Through an Analysis of Literature

    CERN Document Server

    Basaglia, Tullio; Dressendorfer, Paul; Pia, Maria Grazia

    2009-01-01

    A set of patterns related to the impact factor of technological journals has been analyzed, with emphasis on radiation instrumentation and medical physics publications. Attention was devoted in particular to two IEEE journals, IEEE Transactions on Nuclear Science and IEEE Transactions on Medical Imaging, representative of these categories. The results are compared to a similar survey of particle physics journals. The weight of citations coming from inside the same subject area has been evaluated with respect to the amount of citations deriving from publications in external domains. A preliminary analysis hints to a significant degree of correlation between a high impact factor of some journals and a large fraction of citations originating from the same field. The results highlight the cross-disciplinary role of technological journals.

  16. Advanced Reactor Technology -- Regulatory Technology Development Plan (RTDP)

    Energy Technology Data Exchange (ETDEWEB)

    Moe, Wayne Leland [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-05-01

    This DOE-NE Advanced Small Modular Reactor (AdvSMR) regulatory technology development plan (RTDP) will link critical DOE nuclear reactor technology development programs to important regulatory and policy-related issues likely to impact a “critical path” for establishing a viable commercial AdvSMR presence in the domestic energy market. Accordingly, the regulatory considerations that are set forth in the AdvSMR RTDP will not be limited to any one particular type or subset of advanced reactor technology(s) but rather broadly consider potential regulatory approaches and the licensing implications that accompany all DOE-sponsored research and technology development activity that deal with commercial non-light water reactors. However, it is also important to remember that certain “minimum” levels of design and safety approach knowledge concerning these technology(s) must be defined and available to an extent that supports appropriate pre-licensing regulatory analysis within the RTDP. Final resolution to advanced reactor licensing issues is most often predicated on the detailed design information and specific safety approach as documented in a facility license application and submitted for licensing review. Because the AdvSMR RTDP is focused on identifying and assessing the potential regulatory implications of DOE-sponsored reactor technology research very early in the pre-license application development phase, the information necessary to support a comprehensive regulatory analysis of a new reactor technology, and the resolution of resulting issues, will generally not be available. As such, the regulatory considerations documented in the RTDP should be considered an initial “first step” in the licensing process which will continue until a license is issued to build and operate the said nuclear facility. Because a facility license application relies heavily on the data and information generated by technology development studies, the anticipated regulatory

  17. Advanced Reactor Technologies - Regulatory Technology Development Plan (RTDP)

    Energy Technology Data Exchange (ETDEWEB)

    Moe, Wayne L.

    2017-08-23

    This DOE-NE Advanced Small Modular Reactor (AdvSMR) regulatory technology development plan (RTDP) will link critical DOE nuclear reactor technology development programs to important regulatory and policy-related issues likely to impact a “critical path” for establishing a viable commercial AdvSMR presence in the domestic energy market. Accordingly, the regulatory considerations that are set forth in the AdvSMR RTDP will not be limited to any one particular type or subset of advanced reactor technology(s) but rather broadly consider potential regulatory approaches and the licensing implications that accompany all DOE-sponsored research and technology development activity that deal with commercial non-light water reactors. However, it is also important to remember that certain “minimum” levels of design and safety approach knowledge concerning these technology(s) must be defined and available to an extent that supports appropriate pre-licensing regulatory analysis within the RTDP. Final resolution to advanced reactor licensing issues is most often predicated on the detailed design information and specific safety approach as documented in a facility license application and submitted for licensing review. Because the AdvSMR RTDP is focused on identifying and assessing the potential regulatory implications of DOE-sponsored reactor technology research very early in the pre-license application development phase, the information necessary to support a comprehensive regulatory analysis of a new reactor technology, and the resolution of resulting issues, will generally not be available. As such, the regulatory considerations documented in the RTDP should be considered an initial “first step” in the licensing process which will continue until a license is issued to build and operate the said nuclear facility. Because a facility license application relies heavily on the data and information generated by technology development studies, the anticipated regulatory

  18. Analysis Of The 2009 July Impact Debris In Jupiter'S Atmosphere

    Science.gov (United States)

    Sanchez-Lavega, Agustin; Hueso, R.; Legarreta, J.; Pérez-Hoyos, S.; García-Melendo, E.; Gómez, J. M.; Rojas, J. F.; Orton, G. S.; Wesley, A.; IOPW International Outer Planet Watch Team

    2009-09-01

    We report the analysis of images obtained by the contributors to the International Outer Planet Watch (IOPW) of the debris left in the atmosphere of Jupiter by the object that impacted the planet between 18 and 19 July 2009. The discovery images by Anthony Wesley in July 19.625 and the first two days of its tracking, shows a dark debris spot (continuum wavelength) located at planetocentric latitude -55.1 deg and 304.5 deg System III longitude. The imaging survey indicates that the spot was not present in July 18.375, so the impact occurred during a window between both dates. The main spot had a size of about 4,500 km and to its Northwest a thin debris halo of similar size was initially observed. Methane band images at a wavelength of 890 nm shows the spot to be bright indicating that the debris aerosols are highly placed in the atmosphere relative to surrounding clouds. At the central latitude of the impact, the Jovian flow has nearly zero speed but anticyclonic vorticity bounded by jets at -51.5 deg (directed westward with velocity -10 m/s) and at -57.5 deg (directed eastward with velocity 25 m/s). The morphology in the continuum and the spot brightness in the methane band strongly suggest that the feature was caused by a cometary or asteroidal impact, similar in behaviour to the SL9 impacts of 1994. This work has been funded by Spanish MEC AYA2006-07735 with FEDER support and Grupos Gobierno Vasco IT-464-07. RH acknowledges a "Ramón y Cajal” contract from MEC.

  19. Shape Effect Analysis of Aluminum Projectile Impact on Whipple Shields

    Science.gov (United States)

    Carrasquilla, Maria J.; Miller, Joshua E.

    2017-01-01

    The informed design with respect to hypervelocity collisions involving micrometeoroid and orbital debris (MMOD) is influential to the success of space missions. For an orbit comparable to that of the International Space Station, velocities for MMOD can range from 1 to 15 km/s, with an average velocity around 10 km/cu s. The high energy released during collisions at these speeds can result in damage to a spacecraft, or worst-case, loss of the spacecraft, thus outlining the importance of methods to predict the likelihood and extent of damage due to an impact. Through experimental testing and numerical simulations, substantial work has been conducted to better understand the effects of hypervelocity impacts (HVI) on spacecraft systems and shields; however, much of the work has been focused on spherical impacting particles. To improve environment models for the analysis of MMOD, a large-scale satellite break-up test was performed at the Arnold Engineering and Development Complex to better understand the varied impactor geometries that could be generated from a large impact. As a part of the post-experiment analysis, an undertaking to characterize the irregular fragments generated is currently being performed by the University of Florida under the management of NASA's Orbital Debris Program Office at Johnson Space Center (JSC). DebriSat was a representative, modern LEO satellite that was catastrophically broken up in a HVI test. The test chamber was lined with a soft-catch system of foam panels that captured the fragments after impact. Initial predictions put the number of fragments larger than 2mm generated from the HVI at roughly 85,000. The number of fragments thus far extracted from the foam panels has exceeded 100,000, with that number continuously increasing. The shapes of the fragments vary dependent upon the material. Carbon-fiber reinforced polymer pieces, for instance, are abundantly found as thin, flat slivers. The characterization of these fragments with

  20. 77 FR 47328 - Reducing Regulatory Burden

    Science.gov (United States)

    2012-08-08

    ... health and safety, and other advantages; distributive impacts; and equity). The regulatory process... businesses and the public. Agencies consider low-cost approaches that reduce burdens and maintain flexibility...-regulatory-system . The Department is committed to maintaining a consistent culture of retrospective...

  1. Mutational analysis of structural elements in a class-I cyclic di-GMP riboswitch to elucidate its regulatory mechanism.

    Science.gov (United States)

    Inuzuka, Saki; Nishimura, Kei-Ichiro; Kakizawa, Hitoshi; Fujita, Yuki; Furuta, Hiroyuki; Matsumura, Shigeyoshi; Ikawa, Yoshiya

    2016-09-01

    The Vc2 riboswitch possesses an aptamer domain belonging to the class-I c-di-GMP riboswitch family. This domain has been analysed and the molecular mechanism by which it recognizes the c-di-GMP ligand has been elucidated. On the other hand, the regulatory mechanism of the full-length Vc2 riboswitch to control its downstream open reading frame (ORF) remains largely unknown. In this study, we performed in vivo reporter assays and in vitro biochemical analyses of the full-length riboswitch and its aptamer domain. We evaluated the results of in vivo and in vitro analyses to elucidate the regulatory mechanism of the Vc2 riboswitch. The present results suggest that recognition of c-di-GMP ligand by the Vc2 riboswitch aptamer domain downregulates expression of its downstream ORF primarily at the translational level.

  2. Heimlich valve orientation error leading to radiographic tension pneumothorax: analysis of an error and a call for education, device redesign and regulatory action.

    Science.gov (United States)

    Broder, Joshua S; Fox, James W; Milne, Judy; Theiling, Brent Jason; White, Ann

    2016-04-01

    Medical errors are commonly multifactorial, with adverse clinical consequences often requiring the simultaneous failure of a series of protective layers, termed the Swiss Cheese model. Remedying and preventing future medical errors requires a series of steps, including detection, mitigation of patient harm, disclosure, reporting, root cause analysis, system modification, regulatory action, and engineering and manufacturing reforms. We describe this process applied to two cases of improper orientation of a Heimlich valve in a thoracostomy tube system, resulting in enlargement of an existing pneumothorax and the development of radiographic features of tension pneumothorax. We analyse elements contributing to the occurrence of the error and depict the implementation of reforms within our healthcare system and with regulatory authorities and the manufacturer. We identify features of the Heimlich valve promoting this error and suggest educational, design, and regulatory reforms for enhanced patient safety. 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/

  3. Functional analysis of a large set of BRCA2 exon 7 variants highlights the predictive value of hexamer scores in detecting alterations of exonic splicing regulatory elements.

    Science.gov (United States)

    Di Giacomo, Daniela; Gaildrat, Pascaline; Abuli, Anna; Abdat, Julie; Frébourg, Thierry; Tosi, Mario; Martins, Alexandra

    2013-11-01

    Exonic variants can alter pre-mRNA splicing either by changing splice sites or by modifying splicing regulatory elements. Often these effects are difficult to predict and are only detected by performing RNA analyses. Here, we analyzed, in a minigene assay, 26 variants identified in the exon 7 of BRCA2, a cancer predisposition gene. Our results revealed eight new exon skipping mutations in this exon: one directly altering the 5' splice site and seven affecting potential regulatory elements. This brings the number of splicing regulatory mutations detected in BRCA2 exon 7 to a total of 11, a remarkably high number considering the total number of variants reported in this exon (n = 36), all tested in our minigene assay. We then exploited this large set of splicing data to test the predictive value of splicing regulator hexamers' scores recently established by Ke et al. (). Comparisons of hexamer-based predictions with our experimental data revealed high sensitivity in detecting variants that increased exon skipping, an important feature for prescreening variants before RNA analysis. In conclusion, hexamer scores represent a promising tool for predicting the biological consequences of exonic variants and may have important applications for the interpretation of variants detected by high-throughput sequencing.

  4. MAGIA2: from miRNA and genes expression data integrative analysis to microRNA–transcription factor mixed regulatory circuits (2012 update)

    Science.gov (United States)

    Bisognin, Andrea; Sales, Gabriele; Coppe, Alessandro; Bortoluzzi, Stefania; Romualdi, Chiara

    2012-01-01

    MAGIA2 (http://gencomp.bio.unipd.it/magia2) is an update, extension and evolution of the MAGIA web tool. It is dedicated to the integrated analysis of in silico target prediction, microRNA (miRNA) and gene expression data for the reconstruction of post-transcriptional regulatory networks. miRNAs are fundamental post-transcriptional regulators of several key biological and pathological processes. As miRNAs act prevalently through target degradation, their expression profiles are expected to be inversely correlated to those of the target genes. Low specificity of target prediction algorithms makes integration approaches an interesting solution for target prediction refinement. MAGIA2 performs this integrative approach supporting different association measures, multiple organisms and almost all target predictions algorithms. Nevertheless, miRNAs activity should be viewed as part of a more complex scenario where regulatory elements and their interactors generate a highly connected network and where gene expression profiles are the result of different levels of regulation. The updated MAGIA2 tries to dissect this complexity by reconstructing mixed regulatory circuits involving either miRNA or transcription factor (TF) as regulators. Two types of circuits are identified: (i) a TF that regulates both a miRNA and its target and (ii) a miRNA that regulates both a TF and its target. PMID:22618880

  5. MAGIA²: from miRNA and genes expression data integrative analysis to microRNA-transcription factor mixed regulatory circuits (2012 update).

    Science.gov (United States)

    Bisognin, Andrea; Sales, Gabriele; Coppe, Alessandro; Bortoluzzi, Stefania; Romualdi, Chiara

    2012-07-01

    MAGIA(2) (http://gencomp.bio.unipd.it/magia2) is an update, extension and evolution of the MAGIA web tool. It is dedicated to the integrated analysis of in silico target prediction, microRNA (miRNA) and gene expression data for the reconstruction of post-transcriptional regulatory networks. miRNAs are fundamental post-transcriptional regulators of several key biological and pathological processes. As miRNAs act prevalently through target degradation, their expression profiles are expected to be inversely correlated to those of the target genes. Low specificity of target prediction algorithms makes integration approaches an interesting solution for target prediction refinement. MAGIA(2) performs this integrative approach supporting different association measures, multiple organisms and almost all target predictions algorithms. Nevertheless, miRNAs activity should be viewed as part of a more complex scenario where regulatory elements and their interactors generate a highly connected network and where gene expression profiles are the result of different levels of regulation. The updated MAGIA(2) tries to dissect this complexity by reconstructing mixed regulatory circuits involving either miRNA or transcription factor (TF) as regulators. Two types of circuits are identified: (i) a TF that regulates both a miRNA and its target and (ii) a miRNA that regulates both a TF and its target.

  6. myGRN: a database and visualisation system for the storage and analysis of developmental genetic regulatory networks

    Directory of Open Access Journals (Sweden)

    Bacha Jamil

    2009-06-01

    Full Text Available Abstract Background Biological processes are regulated by complex interactions between transcription factors and signalling molecules, collectively described as Genetic Regulatory Networks (GRNs. The characterisation of these networks to reveal regulatory mechanisms is a long-term goal of many laboratories. However compiling, visualising and interacting with such networks is non-trivial. Current tools and databases typically focus on GRNs within simple, single celled organisms. However, data is available within the literature describing regulatory interactions in multi-cellular organisms, although not in any systematic form. This is particularly true within the field of developmental biology, where regulatory interactions should also be tagged with information about the time and anatomical location of development in which they occur. Description We have developed myGRN (http://www.myGRN.org, a web application for storing and interrogating interaction data, with an emphasis on developmental processes. Users can submit interaction and gene expression data, either curated from published sources or derived from their own unpublished data. All interactions associated with publications are publicly visible, and unpublished interactions can only be shared between collaborating labs prior to publication. Users can group interactions into discrete networks based on specific biological processes. Various filters allow dynamic production of network diagrams based on a range of information including tissue location, developmental stage or basic topology. Individual networks can be viewed using myGRV, a tool focused on displaying developmental networks, or exported in a range of formats compatible with third party tools. Networks can also be analysed for the presence of common network motifs. We demonstrate the capabilities of myGRN using a network of zebrafish interactions integrated with expression data from the zebrafish database, ZFIN. Conclusion Here we

  7. An analysis of the impact of Renewable Portfolio Standards on residential electricity prices

    Science.gov (United States)

    Larson, Andrew James

    A Renewable Portfolio Standard (RPS) has become a popular policy for states seeking to increase the amount of renewable energy generated for consumers of electricity. The success of these state programs has prompted debate about the viability of a national RPS. The impact that these state level policies have had on the price consumers pay for electricity is the subject of some debate. Several federal organizations have conducted studies of the impact that a national RPS would have on electricity prices paid by consumers. NREL and US EIA utilize models that analyze the inputs in electricity generation to examine the future price impact of changes to electricity generation and show marginal increases in prices paid by end users. Other empirical research has produced similar results, showing that the existence of an RPS increases the price of electricity. These studies miss important aspects of RPS policies that may change how we view these price increases from RPS policies. By examining the previous empirical research on RPS policies, this study seeks to identify the controls necessary to build an effective model. These controls are utilized in a fixed effects model that seeks to show how the controls and variables of interest impact electricity prices paid by residential consumers of electricity. This study utilizes a panel data set from 1990 to 2014 to analyze the impact of these policies controlling for generating capacity, the regulatory status of utilities in each state, demographic characteristics of the states, and fuel prices. The results of the regressions indicate that prices are likely to be higher in states that have an RPS compared to states that do not have such a policy. Several of the characteristics mentioned above have price impacts, and so discussing RPS policies in the context of other factors that contribute to electricity prices is essential. In particular, the regulatory status of utilities in each state is an important determinate of price as

  8. Lightweight Solar Vehicle Impact Analysis Using ABAQUS/EXPLICIT

    Directory of Open Access Journals (Sweden)

    Rossi Passarella

    2012-12-01

    Full Text Available This paper described the Abaqus/Explicit 6.7 simulation work performed to study the frontal crash impact condition for an in-house designed and produced lightweight solar vehicle main structural body. The structural body was fabricated from aluminum hollow pipes welded together. The analysis is needed to safeguard the safety of the vehicle driver. The dynamic response of the vehicle structure when subjected to frontal impact condition was simulated, according to NASA best practice for crash test methodology. The simulated speed used was based on the NHTSA standard. Comparison of the analysis with the standard Head Injury Criteria (HIC and Chest Injury Criteria (CIC revealed that the driver of the designed vehicle would not be risk because the acceleration resultant was found to be lower than 20 G.  The analysis also proved that structural component was able to protect the driver during any frontal collision incident. However, to ensure the safety of the driver, safety precautions such as the use of seatbelt and helmet as well as driving below the speed limit are recommended.

  9. Evolutionary analysis and lateral gene transfer of two-component regulatory systems associated with heavy-metal tolerance in bacteria.

    Science.gov (United States)

    Bouzat, Juan L; Hoostal, Matthew J

    2013-05-01

    Microorganisms have adapted intricate signal transduction mechanisms to coordinate tolerance to toxic levels of metals, including two-component regulatory systems (TCRS). In particular, both cop and czc operons are regulated by TCRS; the cop operon plays a key role in bacterial tolerance to copper, whereas the czc operon is involved in the efflux of cadmium, zinc, and cobalt from the cell. Although the molecular physiology of heavy metal tolerance genes has been extensively studied, their evolutionary relationships are not well-understood. Phylogenetic relationships among heavy-metal efflux proteins and their corresponding two-component regulatory proteins revealed orthologous and paralogous relationships from species divergences and ancient gene duplications. The presence of heavy metal tolerance genes on bacterial plasmids suggests these genes may be prone to spread through horizontal gene transfer. Phylogenetic inferences revealed nine potential examples of lateral gene transfer associated with metal efflux proteins and two examples for regulatory proteins. Notably, four of the examples suggest lateral transfer across major evolutionary domains. In most cases, differences in GC content in metal tolerance genes and their corresponding host genomes confirmed lateral gene transfer events. Three-dimensional protein structures predicted for the response regulators encoded by cop and czc operons showed a high degree of structural similarity with other known proteins involved in TCRS signal transduction, which suggests common evolutionary origins of functional phenotypes and similar mechanisms of action for these response regulators.

  10. Deferred tax analysis and impact on firm's economic efficiency ratios

    Directory of Open Access Journals (Sweden)

    Hana Bohušová

    2005-01-01

    Full Text Available Category of deferred income tax is a complex topic including the whole accounting system and the income tax. Calculation method can be time-consuming and demanding a high quality system of analytical evidence and a system of valuation and demanding the high level of accountants' knowledge. The aim in the theoretical level was to analyze process of calculation and recording of deferred tax. Importance of recording of deferred tax and the impact on financial analysis ratios was analyzed. Fourteen business entities were examined. Deferred tax recording is a legal way to reduce retained earnings a to protect of its careless alocation.

  11. Differential impact of interferon regulatory factor 7 in the initiation of the type I interferon response in the LCMV infected CNS versus the periphery

    DEFF Research Database (Denmark)

    Christensen, Jeanette Erbo; Fenger, Christina; Issazadeh-Navikas, Shohreh

    2012-01-01

    Interferon (IFN) regulatory factors (IRFs) are a family of transcription factors involved in regulating type I IFN genes and other genes participating in the early antiviral host response. To better understand the mechanisms involved in virus-induced central nervous system (CNS) inflammation, we...

  12. Reducing the volume, exposure and negative impacts of advertising for foods high in fat, sugar and salt to children: A systematic review of the evidence from statutory and self-regulatory actions and educational measures.

    Science.gov (United States)

    Chambers, Stephanie A; Freeman, Ruth; Anderson, Annie S; MacGillivray, Steve

    2015-06-01

    To identify and review evidence on 1) the effectiveness of statutory and self-regulatory actions to reduce the volume, exposure or wider impact of advertising for foods high in fat, sugar and salt (HFSS) to children, and 2) the role of educational measures. A systematic review of three databases (Medline, CINAHL and PsycINFO) and grey literature was carried out. Relevant evidence included studies evaluating advertising bans and restrictions, advertising literacy programmes and parental communication styles. Relevant media included TV, internet, radio, magazines and newspaper advertising. No studies were excluded based on language or publication date. Forty-seven publications were included: 19 provided evidence for the results of statutory regulation, 25 for self-regulation, and six for educational approaches. Outcome measures varied in approach, quality and results. Findings suggested statutory regulation could reduce the volume of and children's exposure to advertising for foods HFSS, and had potential to impact more widely. Self-regulatory approaches showed varied results in reducing children's exposure. There was some limited support for educational measures. Consistency in measures from evaluations over time would assist the development and interpretation of the evidence base on successful actions and measures to reduce the volume, exposure and impact of advertising for foods HFSS to children. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Transient analysis techniques in performing impact and crash dynamic studies

    Science.gov (United States)

    Pifko, A. B.; Winter, R.

    1989-01-01

    Because of the emphasis being placed on crashworthiness as a design requirement, increasing demands are being made by various organizations to analyze a wide range of complex structures that must perform safely when subjected to severe impact loads, such as those generated in a crash event. The ultimate goal of crashworthiness design and analysis is to produce vehicles with the ability to reduce the dynamic forces experienced by the occupants to specified levels, while maintaining a survivable envelope around them during a specified crash event. DYCAST is a nonlinear structural dynamic finite element computer code that started from the plans systems of a finite element program for static nonlinear structural analysis. The essential features of DYCAST are outlined.

  14. Impact of misalignments on the analysis of $B$ decays

    CERN Document Server

    Gersabeck, M; Rodrigues, E

    2008-01-01

    This note investigates the effects of a misaligned tracking system on the analysis of $B$ decays. Misalignment effects of both the vertex locator and the inner and outer T-stations have been studied. $z$-scaling effects of the vertex locator are also considered. It is shown that misalignments of the order of one third of the detector single-hit resolutions have little or negligible effects on the quality of the reconstruction and of the analysis of B decays. The studies were performed with a sample of \\b2hh decays, but the impact of misalignments on the performance of the pattern recognition algorithms and on the primary vertex resolutions, assessed for the first time, are rather general and not restricted to $B^0_{(s)} \\to h^+h^{'-}$ decays.

  15. Analysis of the Behavior of Sedimentary Rocks Under Impact Loading

    Science.gov (United States)

    Millon, Oliver; Ruiz-Ripoll, Maria Luisa; Hoerth, Tobias

    2016-11-01

    In multiple engineering fields such as rock drilling or building constructions or extreme events like earthquakes or impacts, the dynamic properties of rock play an important role. A way to model these events and define measures to minimize the damage derived from these events is created by means of numerical analysis. Hence, the knowledge of the dynamic material behavior is essential for studying the effects of such a loading scenario. Solid geological materials, from the family of the sedimentary rocks, have been analyzed under quasi-static loads. However, there is a lack of knowledge when high strain rate loadings are involved. Within this context, the paper focuses on the experimental characterization of two sedimentary rocks, sandstone and limestone, under impact loading using the Hopkinson-Bar spallation and compression tests. The analysis encompasses the determination of the tensile and compressive properties as well as the comparison between the quasi-static and dynamic behavior (dynamic increase factors). The paper fills the gap of information existing about dynamic behavior of sedimentary rocks under strain rates between 100 and 5.2 × 102 s-1. Furthermore, the fragmentation under different strain rates is investigated and conclusions with respect to energy absorption capacity are drawn.

  16. A budget impact analysis of natalizumab use in Ireland.

    LENUS (Irish Health Repository)

    Dee, A

    2011-10-20

    BACKGROUND: Multiple sclerosis is the commonest cause of disability in young Irish adults. Natalizumab reduces disability progression in those patients with relapsing remitting multiple sclerosis who are suitable for it. First line disease modifying therapies are given in the community and are paid for by the hi-tech drug scheme. Natalizumab is given in hospital and is paid for from the hospital\\'s budget. Access to natalizumab has been problematic in some Irish hospitals. A budget impact analysis was performed to look at the overall cost to the Health Service Executive of giving natalizumab. METHODS: A budget impact analysis was performed from the perspective of the Health Service Executive comparing the use of natalizumab with first line disease modifying therapies for 2009-2011. RESULTS: The study showed that currently, the use of natalizumab is likely to be cost saving to the Health Service Executive overall, because some of the costs for natalizumab are borne by private insurers, whereas, all of the costs of disease modifying therapies are borne by the Health Service Executive. CONCLUSIONS: Although the use of natalizumab is cost saving, current funding arrangements in the Health Service Executive do not allow for the transfer of money saved from drugs paid for in the hi-tech scheme, to hospitals who are supplying alternative treatments.

  17. Exploratory factor analysis of the Oral Health Impact Profile.

    Science.gov (United States)

    John, M T; Reissmann, D R; Feuerstahler, L; Waller, N; Baba, K; Larsson, P; Celebić, A; Szabo, G; Rener-Sitar, K

    2014-09-01

    Although oral health-related quality of life (OHRQoL) as measured by the Oral Health Impact Profile (OHIP) is thought to be multidimensional, the nature of these dimensions is not known. The aim of this report was to explore the dimensionality of the OHIP using the Dimensions of OHRQoL (DOQ) Project, an international study of general population subjects and prosthodontic patients. Using the project's Learning Sample (n = 5173), we conducted an exploratory factor analysis on the 46 OHIP items not specifically referring to dentures for 5146 subjects with sufficiently complete data. The first eigenvalue (27·0) of the polychoric correlation matrix was more than ten times larger than the second eigenvalue (2·6), suggesting the presence of a dominant, higher-order general factor. Follow-up analyses with Horn's parallel analysis revealed a viable second-order, four-factor solution. An oblique rotation of this solution revealed four highly correlated factors that we named Oral Function, Oro-facial Pain, Oro-facial Appearance and Psychosocial Impact. These four dimensions and the strong general factor are two viable hypotheses for the factor structure of the OHIP.

  18. Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in California. Preliminary background report

    Energy Technology Data Exchange (ETDEWEB)

    Feurer, D.A.; Weaver, C.L.; Gallagher, K.C.; Hejna, D.; Rielley, K.J.

    1980-01-01

    The Constitution of the State of California grants to the Legislature control over persons and private corporations that own or operate a line, plant, or system for the production, generation, or transmission of heat, light, water, or power to be furnished either directly or indirectly to or for the public. The Constitution establishes the Public Utilities Commission and grants certain specific powers to the PUC, including the power to fix rates, establish rules and prescribe a uniform system of accounts. The Constitution also recognizes that the Legislature has plenary power to confer additional authority and jurisdiction upon the PUC. The Constitution prohibits regulation by a city, county, or other municipal body of matters over which the Legislature has granted regulatory power to the PUC. This provision does not, however, impair the right of any city to grant franchises for public utilities. The California legislature has enacted the California Public Utilities Code and has designated the PUC as the agency to implement the regulatory provisions of the Code. The Public Utilities Commission consists of five members appointed by the governor and approved by the senate, a majority of the membership concurring, for staggered 6-year terms. Certain limited powers over the conduct of public utilities may still be exercised by municipalities. Public utility regulatory statutes, energy facility siting programs, and municipal franchising authority are examined to identify how they may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES.

  19. Finite-Time Stability Analysis of Reaction-Diffusion Genetic Regulatory Networks with Time-Varying Delays.

    Science.gov (United States)

    Fan, Xiaofei; Zhang, Xian; Wu, Ligang; Shi, Michael

    2017-01-01

    This paper is concerned with the finite-time stability problem of the delayed genetic regulatory networks (GRNs) with reaction-diffusion terms under Dirichlet boundary conditions. By constructing a Lyapunov-Krasovskii functional including quad-slope integrations, we establish delay-dependent finite-time stability criteria by employing the Wirtinger-type integral inequality, Gronwall inequality, convex technique, and reciprocally convex technique. In addition, the obtained criteria are also reaction-diffusion-dependent. Finally, a numerical example is provided to illustrate the effectiveness of the theoretical results.

  20. A novel interferon-inducible domain: structural and functional analysis of the human interferon regulatory factor 1 gene promoter.

    OpenAIRE

    1993-01-01

    We have cloned and functionally characterized the human interferon regulatory factor 1 (IRF-1) gene promoter. The promoter contains a CpG island, with several GC boxes, a CAAT box, but no TATA box. IRF-1 mRNA is strongly induced by gamma interferon (IFN-gamma) but more weakly and transiently by IFN-alpha. There are several putative kappa B motifs and numerous AA(G/A)G(G/T)A and GAAANN motifs throughout the promoter. The IRF-1 promoter is not autoregulated by the IRF-1 gene product. IFN induci...

  1. ANALYSIS ON IMPACT RESPONSES OF UNRESTRAINED PLANAR FRAME STRUCTURE(Ⅱ)-NUMERICAL EXAMPLE ANALYSIS

    Institute of Scientific and Technical Information of China (English)

    CHEN Rong; ZHENG Hai-tao; XUE Song-tao; TANG He-sheng

    2005-01-01

    By using the formula derived in Part (Ⅰ), the instant response of an unrestrained planar frame structure subjected to the impact of a moving rigid-body are evaluated and analysed.The impact force-time history between the structure and the moving rigid-body, shear force and bending moment distribution along the beams, axial force distribution along the bars were calculated. The wave propagation phenomena of the longitudinal wave in the bars, the flexural and shear waves in the beams were also analysed. The numerical results show that the time duration of impact force is controlled by the flexural wave and the longitudinal wave; the shear effect in beams should not be neglected in the impact response analysis of structures.

  2. Comparative analysis of mutant plants impaired in the main regulatory mechanisms of photosynthetic light reactions - From biophysical measurements to molecular mechanisms.

    Science.gov (United States)

    Tikkanen, Mikko; Rantala, Sanna; Grieco, Michele; Aro, Eva-Mari

    2017-03-01

    Chlorophyll (chl) fluorescence emission by photosystem II (PSII) and light absorption by P700 reaction center chl a of photosystem I (PSI) provide easy means to probe the function of the photosynthetic machinery. The exact relationship between the measured optical variables and the molecular processes have, however, remained elusive. Today, the availability of mutants with distinct molecular characterization of photosynthesis regulatory processes should make it possible to gain further insights into this relationship, yet a systematic comparative analysis of such regulatory mutants has been missing. Here we have systematically compared the behavior of Dual-PAM fluorescence and P700 variables from well-characterized photosynthesis regulation mutants. The analysis revealed a very convincing relationship between the given molecular deficiency in the photosynthetic apparatus and the original fluorescence and P700 signals obtained by using varying intensities of actinic light and by applying a saturating pulse. Importantly, the specific information on the underlying molecular mechanism, present in these authentic signals of a given photosynthesis mutant, was largely nullified when using the commonly accepted parameters that are based on further treatment of the original signals. Understanding the unique relationship between the investigated molecular process of photosynthesis and the measured variable is an absolute prerequisite for comprehensive interpretation of fluorescence and P700 measurements. The data presented here elucidates the relationships between the main regulatory mechanisms controlling the photosynthetic light reactions and the variables obtained by fluorescence and P700 measurements. It is discussed how the full potential of optical photosynthesis measurements can be utilized in investigation of a given molecular mechanism. Copyright © 2017 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

  3. Language Assessment Impacts in China:a Tentative Analysis of TEM8

    Institute of Scientific and Technical Information of China (English)

    Cui; Yingqiong; Cheng; Hongying

    2015-01-01

    The paper aims to present a tentative analysis of language assessing impacts on relevant parties.It will start with discussing the connotation of test impacts and then the analysing the impacts of TEM8 on test takers,teachers and social level.The importance of such impacts will also be revealed in this paper.

  4. Development of the Level 1 PSA Model for PGSFR Regulatory

    Energy Technology Data Exchange (ETDEWEB)

    Na, Hyun Ju; Lee, Yong Suk [FNC Tech., Yongin (Korea, Republic of); Shin, Andong; Suh, Nam Duk [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2014-10-15

    SFR (sodium-cooled fast reactor) is Gen-IV nuclear energy system, which is designed for stability, sustainability and proliferation resistance. KALIMER-600 and PGSFR (Prototype Gen-IV SFR) are under development in Korea with enhanced passive safety concepts, e.g. passive reactor shutdown, passive residual heat removal, and etc. Risk analysis from a regulatory perspective is necessary for regulatory body to support the safety and licensing review of SFR. Safety issues should be identified in the early design phase in order to prevent the unexpected cost increase and the delay of PGSFR licensing schedule. In this respect, the preliminary PSA Model of KALIMER-600 had been developed for regulatory. In this study, the development of PSA Level 1 Model is presented. The important impact factors in the risk analysis for the PGSFR, such as Core Damage Frequency (CDF), have been identified and the related safety insights have been derived. The PSA level 1 model for PGSFR regulatory is developed and the risk analysis is conducted. Regarding CDF, LOISF frequency, uncertainty parameter for passive system CCF, loss of 125V DC control center bus and damper CCF are identified as the important factors. Sensitivity analyses show that the CDF would be differentiated (lowered) according to their values.

  5. Regulatory Snapshots: integrative mining of regulatory modules from expression time series and regulatory networks.

    Directory of Open Access Journals (Sweden)

    Joana P Gonçalves

    Full Text Available Explaining regulatory mechanisms is crucial to understand complex cellular responses leading to system perturbations. Some strategies reverse engineer regulatory interactions from experimental data, while others identify functional regulatory units (modules under the assumption that biological systems yield a modular organization. Most modular studies focus on network structure and static properties, ignoring that gene regulation is largely driven by stimulus-response behavior. Expression time series are key to gain insight into dynamics, but have been insufficiently explored by current methods, which often (1 apply generic algorithms unsuited for expression analysis over time, due to inability to maintain the chronology of events or incorporate time dependency; (2 ignore local patterns, abundant in most interesting cases of transcriptional activity; (3 neglect physical binding or lack automatic association of regulators, focusing mainly on expression patterns; or (4 limit the discovery to a predefined number of modules. We propose Regulatory Snapshots, an integrative mining approach to identify regulatory modules over time by combining transcriptional control with response, while overcoming the above challenges. Temporal biclustering is first used to reveal transcriptional modules composed of genes showing coherent expression profiles over time. Personalized ranking is then applied to prioritize prominent regulators targeting the modules at each time point using a network of documented regulatory associations and the expression data. Custom graphics are finally depicted to expose the regulatory activity in a module at consecutive time points (snapshots. Regulatory Snapshots successfully unraveled modules underlying yeast response to heat shock and human epithelial-to-mesenchymal transition, based on regulations documented in the YEASTRACT and JASPAR databases, respectively, and available expression data. Regulatory players involved in

  6. Incorporating operational flexibility into electric generation planning Impacts and methods for system design and policy analysis

    Science.gov (United States)

    Palmintier, Bryan S.

    This dissertation demonstrates how flexibility in hourly electricity operations can impact long-term planning and analysis for future power systems, particularly those with substantial variable renewables (e.g., wind) or strict carbon policies. Operational flexibility describes a power system's ability to respond to predictable and unexpected changes in generation or demand. Planning and policy models have traditionally not directly captured the technical operating constraints that determine operational flexibility. However, as demonstrated in this dissertation, this capability becomes increasingly important with the greater flexibility required by significant renewables (>= 20%) and the decreased flexibility inherent in some low-carbon generation technologies. Incorporating flexibility can significantly change optimal generation and energy mixes, lower system costs, improve policy impact estimates, and enable system designs capable of meeting strict regulatory targets. Methodologically, this work presents a new clustered formulation that tractably combines a range of normally distinct power system models, from hourly unit-commitment operations to long-term generation planning. This formulation groups similar generators into clusters to reduce problem size, while still retaining the individual unit constraints required to accurately capture operating reserves and other flexibility drivers. In comparisons against traditional unit commitment formulations, errors were generally less than 1% while run times decreased by several orders of magnitude (e.g., 5000x). Extensive numerical simulations, using a realistic Texas-based power system show that ignoring flexibility can underestimate carbon emissions by 50% or result in significant load and wind shedding to meet environmental regulations. Contributions of this dissertation include: 1. Demonstrating that operational flexibility can have an important impact on power system planning, and describing when and how these

  7. 78 FR 1646 - Semiannual Regulatory Agenda

    Science.gov (United States)

    2013-01-08

    ...; Organizational Conflicts of Interest. 416 FAR Case 2010-013, Privacy 9000-AM02 Training. 417 Federal Acquisition...: Action Date FR Cite NPRM 12/00/12 Regulatory Flexibility Analysis Required: Yes. Agency Contact: Edward.... L. 110-417). Timetable: Action Date FR Cite NPRM 04/00/13 Regulatory Flexibility Analysis Required...

  8. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false AF Form 813, Request for Environmental Impact... FORCE ENVIRONMENTAL PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.12 AF Form 813, Request for Environmental Impact Analysis. The Air Force uses AF Form 813 to document the need for...

  9. Computational modeling and impact analysis of textile composite structures

    Science.gov (United States)

    Hur, Hae-Kyu

    This study is devoted to the development of an integrated numerical modeling enabling one to investigate the static and the dynamic behaviors and failures of 2-D textile composite as well as 3-D orthogonal woven composite structures weakened by cracks and subjected to static-, impact- and ballistic-type loads. As more complicated modeling about textile composite structures is introduced, some of homogenization schemes, geometrical modeling and crack propagations become more difficult problems to solve. To overcome these problems, this study presents effective mesh-generation schemes, homogenization modeling based on a repeating unit cell and sinusoidal functions, and also a cohesive element to study micro-crack shapes. This proposed research has two: (1) studying behavior of textile composites under static loads, (2) studying dynamic responses of these textile composite structures subjected to the transient/ballistic loading. In the first part, efficient homogenization schemes are suggested to show the influence of textile architectures on mechanical characteristics considering the micro modeling of repeating unit cell. Furthermore, the structures of multi-layered or multi-phase composites combined with different laminar such as a sub-laminate, are considered to find the mechanical characteristics. A simple progressive failure mechanism for the textile composites is also presented. In the second part, this study focuses on three main phenomena to solve the dynamic problems: micro-crack shapes, textile architectures and textile effective moduli. To obtain a good solutions of the dynamic problems, this research attempts to use four approaches: (I) determination of governing equations via a three-level hierarchy: micro-mechanical unit cell analysis, layer-wise analysis accounting for transverse strains and stresses, and structural analysis based on anisotropic plate layers, (II) development of an efficient computational approach enabling one to perform transient

  10. Adequacy and verifiability of pharmaceutical mixtures and dose units by variographic analysis (Theory of Sampling) - A call for a regulatory paradigm shift.

    Science.gov (United States)

    Esbensen, Kim H; Román-Ospino, Andrés D; Sanchez, Adriluz; Romañach, Rodolfo J

    2016-02-29

    In spite of intense efforts in the last 20 years, the current state of affairs regarding evaluation of adequacy of pharmaceutical mixing is at an impressive standstill, characterized by two draft guidances, one withdrawn, and the other never approved. We here analyze the regulatory, scientific and technological situation and suggest a radical, but logical approach calling for a paradigm shift regarding sampling of pharmaceutical blends. In synergy with QbD/PAT efforts, blend uniformity testing should only be performed with properly designed sampling that can guarantee representativity-in contrast to the current deficient thief sampling. This is necessary for suitable in-process specifications and dosage units meeting desired specifications. The present exposé shows how process sampling based on the Theory of Sampling (TOS) constitutes a new asset for regulatory compliance, providing procedures that suppress hitherto adverse sampling errors. We identify that the optimal sampling location is after emptying the blender, guaranteeing complete characterisation of the residual heterogeneity. TOS includes variographic analysis that decomposes the effective total sampling and analysis error (TSE+TAE) from the variability of the manufacturing process itself. This approach provides reliable in-process characterization allowing independent approval or rejection by the Quality Control unit. The science-based sampling principles presented here will facilitate full control of blending processes, including whether post-blending segregation influences the material stream that reaches the tabletting feed-frame.

  11. Environmental Regulatory Update Table, January/February 1995

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Bock, R.E.; Mayer, S.J.; Salk, M.S.

    1995-03-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives impacting environmental, health, and safety management responsibilities. the table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  12. Molecular dynamics analysis on impact behavior of carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Seifoori, Sajjad, E-mail: sajjad.seifoori@vru.ac.ir

    2015-01-30

    Graphical abstract: - Highlights: • We present an analytical solution of impact based on two degree of freedom model. • The accuracy is verified by Molecular dynamics simulations. • The effects of the small-size effects on the dynamic deflections are investigated. • The relative motion is also accounted that is due to local indentation. - Abstract: Dynamic analysis of impact of a nanoparticle on carbon nanotubes is investigated based on two degree of freedom model. The accuracy and stability of the present methods are verified by molecular dynamics (MD) simulations. The effect of different types of boundary condition on the maximum dynamic deflections is studied for zigzag and armchair SWCNTs with various aspect ratios (length/diameter). Besides, the influences of velocity of impactor on the dynamic deflections are studied. It is shown that the dynamic behavior on the armchair and zigzag single-walled carbon nanotubes are almost similar. Finally, by making use of the above MD simulation and theoretical results some insight has been obtained about the dynamic characteristics of the impact problems of nanobeam structures. Nonlocal Timoshenko beam models TBT2 should be employed for an accurate prediction of the dynamic deflection rather than nonlocal Euler–Bernoulli beam models EBT2 which ignores the effects of transverse shear deformation and rotary inertia that is especially significant for short beams. The results from nonlocal EBT2 and TBT2 models demonstrated good agreement with MD simulation. The EBT2 and TBT2 models also account for the relative motion between the nanoparticle and the nanobeam that is due to local indentation as can be seen in MD simulation.

  13. HESS II Data Analysis with ImPACT

    CERN Document Server

    Parsons, R D; Murach, T

    2015-01-01

    The High Energy Stereoscopic System (H.E.S.S.) very high energy gamma-ray telescope array has added a fifth telescope of 600 m$^{2}$ mirror area to the centre of the 4 existing telescopes, lowering its energy threshold to the sub-100 GeV range and becoming the first operational IACT array using multiple telescope designs. In order to properly access this low-energy range however, some adaptation must be made to the existing event analysis. We present an adaptation of the high-performance event reconstruction algorithm, Image Pixelwise fit for Atmospheric Cherenkov Telescopes (ImPACT), for performing mono and stereo event reconstruction with the H.E.S.S. II array. The reconstruction algorithm is based around the likelihood fitting of camera pixel amplitudes to an expected image template, directly generated from Monte Carlo simulations. This advanced reconstruction is combined with a multi variate analysis based background rejection scheme to provide a sensitive and stable analysis scheme in the sub-100 GeV gam...

  14. Impact analysis of stainless steel spent fuel canisters

    Energy Technology Data Exchange (ETDEWEB)

    Aramayo, G.A. [Oak Ridge National Lab., TN (United States); Turner, D.W. [Lockheed Martin Energy Systems, Oak Ridge, TN (United States). Waste Management Organization

    1998-04-01

    This paper presents the results of the numerical analysis performed to asses the structural integrity of spent nuclear fuel (SNF) stainless steel canisters when subjected to impact loads associated with free gravity drops from heights not exceeding 20 ft. The SNF canisters are to be used for the Shipment of radioactive material from the Oak Ridge National Laboratory (ORNL) Site to the Idaho National Engineering and Environmental Laboratory (INEEL) for storage. The Idaho chemical Processing Plant Fuel Receipt Criteria Questionnaire requires that the vertical drop accidents from two heights be analyze. These heights are those that are considered to be critical at the time of unloading the canisters from the shipping cask. The configurations analyzed include a maximum payload of 90 lbs dropping from heights of 20 and 3 ft. The nominal weight of the canister is 23.3 lbs. The analysis has been performed using finite element methods. Innovative analysis techniques are used to capture the effects of failure and separation of canister components. The structural integrity is evaluated in terms of physical deformation and separation of the canister components that may result from failure of components at selected interfaces.

  15. Biological exposure models for oil spill impact analysis

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The oil spill impact analysis (OSIA) software system has been developed to supply a tool for comprehensive, quantitative environmental impact assessments resulting from oil spills. In the system, a biological component evaluates potential effects on exposed organisms based on results from a physico-chemieal fates component, including the extent and characteristics of the surface slick, and dissolved and total concentrations of hydrocarbons in the water column. The component includes a particle-based exposure model for migratory adult fish populations, a particle-based exposure model for spawning planktonic organisms (eggs and larvae), and an exposure model for wildlife species (sea birds or marine mammals). The exposure model for migratory adult fish populations simulates the migration behaviors of fish populations migrating to or staying in their feeding areas, over-wintering areas or spawning areas, and determines the acute effects (mortality) and chronic accumulation (body burdens) from the dissolved contaminant. The exposure model for spawning planktonic organisms simulates the release of eggs and larvae, also as particles, from specific spawning areas during the spawning period, and determines their potential exposure to contaminants in the water or sediment. The exposure model for wild species calculates the exposure to surrace oil of wildlife (bird and marine mammal ) categories inhabiting the contaminated area. Compared with the earlier models in which all kinds of organisms are assumed evenly and randomly distributed, the updated biological exposure models can more realistically estimate potential effects on marine ecological system from oil spill pollution events.

  16. WATER QUALITY ANALYSIS OF AGRICULTURALLY IMPACTED TIDAL BLACKBIRD CREEK, DELAWARE

    Directory of Open Access Journals (Sweden)

    Matthew Stone

    2016-11-01

    Full Text Available Blackbird Creek, Delaware is a small watershed in northern Delaware that has a significant proportion of land designated for agricultural land use. The Blackbird Creek water monitoring program was initiated in 2012 to assess the condition of the watershed’s habitats using multiple measures of water quality. Habitats were identified based on percent adjacent agricultural land use. Study sites varying from five to fourteen were sampled biweekly during April and November, 2012-2015. Data were analyzed using principal component analysis and generalized linear modeling. Results from these first four years of data documented no significant differences in water quality parameters (dissolved oxygen, pH, temperature, salinity, inorganic nitrate, nitrite, ammonia, orthophosphate, alkalinity, and turbidity between the two habitats, although both orthophosphate and turbidity were elevated beyond EPA-recommended values. There were statistically significant differences for all of the parameters between agriculture seasons. The lack of notable differences between habitats suggests that, while the watershed is generally impacted by agricultural land use practices, there appears to be no impact on the surface water chemistry. Because there were no differences between habitats, it was concluded that seasonal differences were likely due to basic seasonal variation and were not a function of agricultural land use practices.

  17. Small-scale wind power design, analysis, and environmental impacts

    CERN Document Server

    Abraham, John P

    2014-01-01

    In today's world, clean and robust energy sources are beingsought to provide power to residences, commercial operations,and manufacturing enterprises. Among the most appealingenergy sources is wind power-with its high reliability andlow environmental impact. Wind power's rapid penetrationinto markets throughout the world has taken many forms, andthis book discusses the types of wind power, as well as theappropriate decisions that need to be made regarding windpower design, testing, installation, and analysis.Inside, the authors detail the design of various small-windsystems including horizontal-axis wind turbines (HAWTs) andvertical-axis wind turbines (VAWTs). The design of wind turbinestakes advantage of many avenues of investigation, all of whichare included in the book. Analytical methods that have beendeveloped over the past few decades are major methods usedfor design. Alternatively, experimentation (typically using scaledmodels in wind tunnels) and numerical simulation (using moderncomputational fluid d...

  18. Sensitivity analysis for simulating pesticide impacts on honey bee colonies

    Science.gov (United States)

    Background/Question/Methods Regulatory agencies assess risks to honey bees from pesticides through a tiered process that includes predictive modeling with empirical toxicity and chemical data of pesticides as a line of evidence. We evaluate the Varroapop colony model, proposed by...

  19. Evaluating the impact of flexible alcohol trading hours on violence: an interrupted time series analysis.

    Science.gov (United States)

    Humphreys, David K; Eisner, Manuel P; Wiebe, Douglas J

    2013-01-01

    On November 24(th) 2005, the Government of England and Wales removed regulatory restrictions on the times at which licensed premises could sell alcohol. This study tests availability theory by treating the implementation of Licensing Act (2003) as a natural experiment in alcohol policy. An interrupted time series design was employed to estimate the Act's immediate and delayed impact on violence in the City of Manchester (Population 464,200). We collected police recorded rates of violence, robbery, and total crime between the 1st of February 2004 and the 31st of December 2007. Events were aggregated by week, yielding a total of 204 observations (95 pre-, and 109 post-intervention). Secondary analysis examined changes in daily patterns of violence. Pre- and post-intervention events were separated into four three-hour segments 18∶00-20∶59, 21∶00-23.59, 00∶00-02∶59, 03∶00-05∶59. Analysis found no evidence that the Licensing Act (2003) affected the overall volume of violence. However, analyses of night-time violence found a gradual and permanent shift of weekend violence into later parts of the night. The results estimated an initial increase of 27.5% between 03∶00 to 06∶00 (ω = 0.2433, 95% CI = 0.06, 0.42), which increased to 36% by the end of the study period (δ = -0.897, 95% CI = -1.02, -0.77). This study found no evidence that a national policy increasing the physical availability of alcohol affected the overall volume of violence. There was, however, evidence suggesting that the policy may be associated with changes to patterns of violence in the early morning (3 a.m. to 6 a.m.).

  20. Evaluating the impact of flexible alcohol trading hours on violence: an interrupted time series analysis.

    Directory of Open Access Journals (Sweden)

    David K Humphreys

    Full Text Available BACKGROUND: On November 24(th 2005, the Government of England and Wales removed regulatory restrictions on the times at which licensed premises could sell alcohol. This study tests availability theory by treating the implementation of Licensing Act (2003 as a natural experiment in alcohol policy. METHODS: An interrupted time series design was employed to estimate the Act's immediate and delayed impact on violence in the City of Manchester (Population 464,200. We collected police recorded rates of violence, robbery, and total crime between the 1st of February 2004 and the 31st of December 2007. Events were aggregated by week, yielding a total of 204 observations (95 pre-, and 109 post-intervention. Secondary analysis examined changes in daily patterns of violence. Pre- and post-intervention events were separated into four three-hour segments 18∶00-20∶59, 21∶00-23.59, 00∶00-02∶59, 03∶00-05∶59. RESULTS: Analysis found no evidence that the Licensing Act (2003 affected the overall volume of violence. However, analyses of night-time violence found a gradual and permanent shift of weekend violence into later parts of the night. The results estimated an initial increase of 27.5% between 03∶00 to 06∶00 (ω = 0.2433, 95% CI = 0.06, 0.42, which increased to 36% by the end of the study period (δ = -0.897, 95% CI = -1.02, -0.77. CONCLUSIONS: This study found no evidence that a national policy increasing the physical availability of alcohol affected the overall volume of violence. There was, however, evidence suggesting that the policy may be associated with changes to patterns of violence in the early morning (3 a.m. to 6 a.m..

  1. Multiobjective Policy Analysis to Evaluate Air Quality Impacts of Oil and Gas Regulations

    Science.gov (United States)

    Alongi, M.; Kasprzyk, J. R.; Milford, J.; Ryan, J. N.; Estep, M.

    2016-12-01

    Unconventional oil and gas development (UOGD) using hydraulic fracturing and horizontal drilling has recently fostered an unprecedented acceleration in energy development. Regulations seek to protect the public health of communities in proximity to UOGD and the environmental quality of these regions, while maintaining economic benefits. One such regulation is the setback distance, which dictates the minimum distance between an oil and gas well and an occupied structure, such as a residential or commercial building, or an area of special concern. This presentation discusses a new policy analysis framework for UOGD regulations, using the Borg multiobjective evolutionary algorithm (MOEA) coupled with AERMOD, a regulatory air dispersion model. The initial results explore how setback distance and well density regulations could impact the number of wells that can be drilled, based on a set of performance objectives that model potential increases in benzene, a hazardous air pollutant that has been linked to cancer and other detrimental health effects. The simulation calculates daily benzene averages using meteorological data from Greeley, CO. An important aspect of this work is to define representative quantitative objectives that accurately capture salient characteristics of the pollutant time series. For example, our framework will characterize the maximum concentration found over the entire spatial domain and over the duration of the simulation. Frequency-based objectives will also be explored, such as the number of exceedances of the benchmark annual average benzene concentration corresponding to a given level of cancer risk. The multiobjective analysis can also be expanded to integrate other objectives that represent performance-based outcomes on UOGD such as energy development profits, increases in noise pollution and decreases in property value. This research represents one application of how MOEAs can be used to inform policymaking for environmental regulations.

  2. The regulatory benefits of high levels of affect perception accuracy: a process analysis of reactions to stressors in daily life.

    Science.gov (United States)

    Robinson, Michael D; Moeller, Sara K; Buchholz, Maria M; Boyd, Ryan L; Troop-Gordon, Wendy

    2012-08-01

    Individuals attuned to affective signals from the environment may possess an advantage in the emotion-regulation realm. In two studies (total n = 151), individual differences in affective perception accuracy were assessed in an objective, performance-based manner. Subsequently, the same individuals completed daily diary protocols in which daily stressor levels were reported as well as problematic states shown to be stress-reactive in previous studies. In both studies, individual differences in affect perception accuracy interacted with daily stressor levels to predict the problematic outcomes. Daily stressors precipitated problematic reactions--whether depressive feelings (study 1) or somatic symptoms (study 2)--at low levels of affect perception accuracy, but did not do so at high levels of affect perception accuracy. The findings support a regulatory view of such perceptual abilities. Implications for understanding emotion regulation processes, emotional intelligence, and individual differences in reactivity are discussed.

  3. A DNA-binding-site landscape and regulatory network analysis for NAC transcription factors in Arabidopsis thaliana

    DEFF Research Database (Denmark)

    Lindemose, Søren; Jensen, Michael Krogh; de Velde, Jan Van

    2014-01-01

    regulatory networks of 12 NAC transcription factors. Our data offer specific single-base resolution fingerprints for most TFs studied and indicate that NAC DNA-binding specificities might be predicted from their DNA-binding domain's sequence. The developed methodology, including the application...... of complementary functional genomics filters, makes it possible to translate, for each TF, protein binding microarray data into a set of high-quality target genes. With this approach, we confirm NAC target genes reported from independent in vivo analyses. We emphasize that candidate target gene sets together......Target gene identification for transcription factors is a prerequisite for the systems wide understanding of organismal behaviour. NAM-ATAF1/2-CUC2 (NAC) transcription factors are amongst the largest transcription factor families in plants, yet limited data exist from unbiased approaches to resolve...

  4. 动机分析新视角:调节聚焦理论%The New Viewpoints on the Motivation Analysis:The Regulatory Focus Theory

    Institute of Scientific and Technical Information of China (English)

    何伊丽

    2015-01-01

    自Higgins提出调节聚焦理论以来,近年来此理论在国内外心理学界掀起了研究热潮,它从一个新的视角更深入地阐释和分析了人们行为的动机,并将这种行为动机进行了较为清晰的分类,使之更为广泛地应用于人们的生活实践之中。本文介绍了这一理论的具体内涵及其理论延伸———调节匹配理论,并对这一理论进行了综合分析,指出了该理论未来发展和可能的研究及应用方向。%Since Higgins proposed the Regulatory Focus Theory , this theory became the hotspot for the psychologists both at home and abroad in recent years .Regulatory Focus Theory deeply has interpreted and analyzed the motivation of human behavior from a new perspective .In addition, it classified the behavior motivation , which making it be more widely used in the practice of daily life.This paper introduced the concrete content of this theory and its extension , the regulatory fit theory .After comprehensive analysis, it pointed out that the potential application and possible future research .

  5. Comparative analysis of mRNA targets for human PUF-family proteins suggests extensive interaction with the miRNA regulatory system.

    Directory of Open Access Journals (Sweden)

    Alessia Galgano

    Full Text Available Genome-wide identification of mRNAs regulated by RNA-binding proteins is crucial to uncover post-transcriptional gene regulatory systems. The conserved PUF family RNA-binding proteins repress gene expression post-transcriptionally by binding to sequence elements in 3'-UTRs of mRNAs. Despite their well-studied implications for development and neurogenesis in metazoa, the mammalian PUF family members are only poorly characterized and mRNA targets are largely unknown. We have systematically identified the mRNAs associated with the two human PUF proteins, PUM1 and PUM2, by the recovery of endogenously formed ribonucleoprotein complexes and the analysis of associated RNAs with DNA microarrays. A largely overlapping set comprised of hundreds of mRNAs were reproducibly associated with the paralogous PUM proteins, many of them encoding functionally related proteins. A characteristic PUF-binding motif was highly enriched among PUM bound messages and validated with RNA pull-down experiments. Moreover, PUF motifs as well as surrounding sequences exhibit higher conservation in PUM bound messages as opposed to transcripts that were not found to be associated, suggesting that PUM function may be modulated by other factors that bind conserved elements. Strikingly, we found that PUF motifs are enriched around predicted miRNA binding sites and that high-confidence miRNA binding sites are significantly enriched in the 3'-UTRs of experimentally determined PUM1 and PUM2 targets, strongly suggesting an interaction of human PUM proteins with the miRNA regulatory system. Our work suggests extensive connections between the RBP and miRNA post-transcriptional regulatory systems and provides a framework for deciphering the molecular mechanism by which PUF proteins regulate their target mRNAs.

  6. Comparative analysis of mRNA targets for human PUF-family proteins suggests extensive interaction with the miRNA regulatory system.

    Science.gov (United States)

    Galgano, Alessia; Forrer, Michael; Jaskiewicz, Lukasz; Kanitz, Alexander; Zavolan, Mihaela; Gerber, André P

    2008-09-08

    Genome-wide identification of mRNAs regulated by RNA-binding proteins is crucial to uncover post-transcriptional gene regulatory systems. The conserved PUF family RNA-binding proteins repress gene expression post-transcriptionally by binding to sequence elements in 3'-UTRs of mRNAs. Despite their well-studied implications for development and neurogenesis in metazoa, the mammalian PUF family members are only poorly characterized and mRNA targets are largely unknown. We have systematically identified the mRNAs associated with the two human PUF proteins, PUM1 and PUM2, by the recovery of endogenously formed ribonucleoprotein complexes and the analysis of associated RNAs with DNA microarrays. A largely overlapping set comprised of hundreds of mRNAs were reproducibly associated with the paralogous PUM proteins, many of them encoding functionally related proteins. A characteristic PUF-binding motif was highly enriched among PUM bound messages and validated with RNA pull-down experiments. Moreover, PUF motifs as well as surrounding sequences exhibit higher conservation in PUM bound messages as opposed to transcripts that were not found to be associated, suggesting that PUM function may be modulated by other factors that bind conserved elements. Strikingly, we found that PUF motifs are enriched around predicted miRNA binding sites and that high-confidence miRNA binding sites are significantly enriched in the 3'-UTRs of experimentally determined PUM1 and PUM2 targets, strongly suggesting an interaction of human PUM proteins with the miRNA regulatory system. Our work suggests extensive connections between the RBP and miRNA post-transcriptional regulatory systems and provides a framework for deciphering the molecular mechanism by which PUF proteins regulate their target mRNAs.

  7. P2RP: a Web-based framework for the identification and analysis of regulatory proteins in prokaryotic genomes.

    Science.gov (United States)

    Barakat, Mohamed; Ortet, Philippe; Whitworth, David E

    2013-04-20

    Regulatory proteins (RPs) such as transcription factors (TFs) and two-component system (TCS) proteins control how prokaryotic cells respond to changes in their external and/or internal state. Identification and annotation of TFs and TCSs is non-trivial, and between-genome comparisons are often confounded by different standards in annotation. There is a need for user-friendly, fast and convenient tools to allow researchers to overcome the inherent variability in annotation between genome sequences. We have developed the web-server P2RP (Predicted Prokaryotic Regulatory Proteins), which enables users to identify and annotate TFs and TCS proteins within their sequences of interest. Users can input amino acid or genomic DNA sequences, and predicted proteins therein are scanned for the possession of DNA-binding domains and/or TCS domains. RPs identified in this manner are categorised into families, unambiguously annotated, and a detailed description of their features generated, using an integrated software pipeline. P2RP results can then be outputted in user-specified formats. Biologists have an increasing need for fast and intuitively usable tools, which is why P2RP has been developed as an interactive system. As well as assisting experimental biologists to interrogate novel sequence data, it is hoped that P2RP will be built into genome annotation pipelines and re-annotation processes, to increase the consistency of RP annotation in public genomic sequences. P2RP is the first publicly available tool for predicting and analysing RP proteins in users' sequences. The server is freely available and can be accessed along with documentation at http://www.p2rp.org.

  8. 次贷危机后美国金融监管制度改革及其影响%Reform of the U.S. Financial Regulatory System After the Subprime Mortgage Crisis and Its Impact

    Institute of Scientific and Technical Information of China (English)

    周南; 樊超

    2012-01-01

      本文通过对多德—弗兰克法案的主要内容介绍,立足于三个视角:一是基于系统性风险防范的金融监管安排;二是金融监管组织机构的改革;三是金融消费者权利的保护,来分析次贷危机后美国金融监管制度改革及其影响。金融业和金融监管措施的重大失误,是导致当前危机的根本原因。多德—弗兰克法案的出台,是美国重塑金融体系、防范系统性金融风险爆发的一项关键举措。该法案对美国的金融体系的运行规则和监管提出全新的思路,被称为美国金融监管改革的里程碑。%  In this paper, the main content of the Dodd-Frank Act introduced based on three perspectives:first, to prevent systemic risk financial regulatory arrangements;reform of the financial regulatory organizations;Third, the protection of the rights of financial consumersto analyze the subprime mortgage crisis, the U.S. financial regulatory system reform and its impact. The major mistakes of the financial sector and financial regulatory measures, the root causes that led to the current crisis. The introduction of the Dodd- Frank Act, to reshape the financial system in the United States, one of the key initiatives to prevent the outbreak of systemic financial risk. The bill proposed operating rules and supervision of the financial system in the United States, a new way of thinking, referred to as a milestone in the U.S. financial regulatory reform

  9. A meta-analysis of public microarray data identifies gene regulatory pathways deregulated in peripheral blood mononuclear cells from individuals with Systemic Lupus Erythematosus compared to those without.

    Science.gov (United States)

    Kröger, Wendy; Mapiye, Darlington; Entfellner, Jean-Baka Domelevo; Tiffin, Nicki

    2016-11-15

    Systemic Lupus Erythematosus (SLE) is a complex, multi-systemic, autoimmune disease for which the underlying aetiological mechanisms are poorly understood. The genetic and molecular processes underlying lupus have been extensively investigated using a variety of -omics approaches, including genome-wide association studies, candidate gene studies and microarray experiments of differential gene expression in lupus samples compared to controls. This study analyses a combination of existing microarray data sets to identify differentially regulated genetic pathways that are dysregulated in human peripheral blood mononuclear cells from SLE patients compared to unaffected controls. Two statistical approaches, quantile discretisation and scaling, are used to combine publicly available expression microarray datasets and perform a meta-analysis of differentially expressed genes. Differentially expressed genes implicated in interferon signaling were identified by the meta-analysis, in agreement with the findings of the individual studies that generated the datasets used. In contrast to the individual studies, however, the meta-analysis and subsequent pathway analysis additionally highlighted TLR signaling, oxidative phosphorylation and diapedesis and adhesion regulatory networks as being differentially regulated in peripheral blood mononuclear cells (PBMCs) from SLE patients compared to controls. Our analysis demonstrates that it is possible to derive additional information from publicly available expression data using meta-analysis techniques, which is particularly relevant to research into rare diseases where sample numbers can be limiting.

  10. Observer analysis and its impact on task performance modeling

    Science.gov (United States)

    Jacobs, Eddie L.; Brown, Jeremy B.

    2014-05-01

    Fire fighters use relatively low cost thermal imaging cameras to locate hot spots and fire hazards in buildings. This research describes the analyses performed to study the impact of thermal image quality on fire fighter fire hazard detection task performance. Using human perception data collected by the National Institute of Standards and Technology (NIST) for fire fighters detecting hazards in a thermal image, an observer analysis was performed to quantify the sensitivity and bias of each observer. Using this analysis, the subjects were divided into three groups representing three different levels of performance. The top-performing group was used for the remainder of the modeling. Models were developed which related image quality factors such as contrast, brightness, spatial resolution, and noise to task performance probabilities. The models were fitted to the human perception data using logistic regression, as well as probit regression. Probit regression was found to yield superior fits and showed that models with not only 2nd order parameter interactions, but also 3rd order parameter interactions performed the best.

  11. Impact of Instructional Decisions on the Effectiveness of Cooperative Learning in Chemistry through Meta-Analysis

    Science.gov (United States)

    Apugliese, Andrew; Lewis, Scott E.

    2017-01-01

    Meta-analysis can provide a robust description of the impact of educational reforms and also offer an opportunity to explore the conditions where such reforms are more or less effective. This article describes a meta-analysis on the impact of cooperative learning on students' chemistry understanding. Modifiers in the meta-analysis are purposefully…

  12. Impact of Instructional Decisions on the Effectiveness of Cooperative Learning in Chemistry through Meta-Analysis

    Science.gov (United States)

    Apugliese, Andrew; Lewis, Scott E.

    2017-01-01

    Meta-analysis can provide a robust description of the impact of educational reforms and also offer an opportunity to explore the conditions where such reforms are more or less effective. This article describes a meta-analysis on the impact of cooperative learning on students' chemistry understanding. Modifiers in the meta-analysis are purposefully…

  13. 23 CFR 772.9 - Analysis of traffic noise impacts and abatement measures.

    Science.gov (United States)

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Analysis of traffic noise impacts and abatement measures... Analysis of traffic noise impacts and abatement measures. (a) The highway agency shall determine and... environmental effects. (b) The traffic noise analysis shall include the following for each alternative...

  14. Identification of a new gene regulatory circuit involving B cell receptor activated signaling using a combined analysis of experimental, clinical and global gene expression data.

    Science.gov (United States)

    Schrader, Alexandra; Meyer, Katharina; Walther, Neele; Stolz, Ailine; Feist, Maren; Hand, Elisabeth; von Bonin, Frederike; Evers, Maurits; Kohler, Christian; Shirneshan, Katayoon; Vockerodt, Martina; Klapper, Wolfram; Szczepanowski, Monika; Murray, Paul G; Bastians, Holger; Trümper, Lorenz; Spang, Rainer; Kube, Dieter

    2016-07-26

    To discover new regulatory pathways in B lymphoma cells, we performed a combined analysis of experimental, clinical and global gene expression data. We identified a specific cluster of genes that was coherently expressed in primary lymphoma samples and suppressed by activation of the B cell receptor (BCR) through αIgM treatment of lymphoma cells in vitro. This gene cluster, which we called BCR.1, includes numerous cell cycle regulators. A reduced expression of BCR.1 genes after BCR activation was observed in different cell lines and also in CD10+ germinal center B cells. We found that BCR activation led to a delayed entry to and progression of mitosis and defects in metaphase. Cytogenetic changes were detected upon long-term αIgM treatment. Furthermore, an inverse correlation of BCR.1 genes with c-Myc co-regulated genes in distinct groups of lymphoma patients was observed. Finally, we showed that the BCR.1 index discriminates activated B cell-like and germinal centre B cell-like diffuse large B cell lymphoma supporting the functional relevance of this new regulatory circuit and the power of guided clustering for biomarker discovery.

  15. Sensitivity Analysis on the Impact Factors of the GSHP System Considering Energy Generation and Environmental Impact Using LCA

    Directory of Open Access Journals (Sweden)

    Taehoon Hong

    2016-04-01

    Full Text Available The world is facing a crisis due to energy depletion and environmental pollution. The ground source heat pump (GSHP system, the most efficient new/renewable energy (NRE system that can reduce the load of heating/cooling equipment in a building, can be used to address this crisis. Designers and contractors have implemented such systems depending on their experience, although there are many factors that affect the performance of the GSHP system. Therefore, this study aimed to conduct a sensitivity analysis on the impact factors in terms of energy generation and environmental impact. This study was conducted as follows: (i collecting the impact factors that affect the GSHP system’s performance; (ii establishing the GSHP system’s scenarios with the impact factors; (iii determining the methodology and calculation tool to be used for conducting sensitivity analysis; and (iv conducting sensitivity analysis on the impact factors of the GSHP system in terms of energy generation and environmental impact using life cycle assessment. The results of this study can be used: (i to establish the optimal design strategy for different application fields and different seasons; and (ii to conduct a feasibility study on energy generation and environmental impact at the level of the life cycle.

  16. Distance Based Root Cause Analysis and Change Impact Analysis of Performance Regressions

    Directory of Open Access Journals (Sweden)

    Junzan Zhou

    2015-01-01

    Full Text Available Performance regression testing is applied to uncover both performance and functional problems of software releases. A performance problem revealed by performance testing can be high response time, low throughput, or even being out of service. Mature performance testing process helps systematically detect software performance problems. However, it is difficult to identify the root cause and evaluate the potential change impact. In this paper, we present an approach leveraging server side logs for identifying root causes of performance problems. Firstly, server side logs are used to recover call tree of each business transaction. We define a novel distance based metric computed from call trees for root cause analysis and apply inverted index from methods to business transactions for change impact analysis. Empirical studies show that our approach can effectively and efficiently help developers diagnose root cause of performance problems.

  17. Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens.

    Directory of Open Access Journals (Sweden)

    Deborah Chasman

    2016-07-01

    Full Text Available Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.

  18. Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens.

    Science.gov (United States)

    Chasman, Deborah; Walters, Kevin B; Lopes, Tiago J S; Eisfeld, Amie J; Kawaoka, Yoshihiro; Roy, Sushmita

    2016-07-01

    Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.

  19. Regulatory mark; Marco regulatorio

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-10-15

    This chapter is based on a work performed in distinct phases. The first phase consisted in of the analysis regulatory legislation existent in Brazil for the sugar-alcohol sector since the beginning of the X X century. This analysis allowed the identification of non existent points and legal devices related to the studied aspects, and that were considered as problematic for the sector expansion. In the second phase, related treaties and international agreements was studied and possible obstacles for the brazilian bio ethanol exportation for the international market. Initiatives were examined at European Union, United States of America, Caribbean and countries of the sub-Saharan Africa. In this phase, policies were identified related to the incentives and adoption of use of bio fuels added to the gasoline in countries or group of countries considered as key for the consolidation of bio ethanol as a world commodity.

  20. Gene regulatory network inference and validation using relative change ratio analysis and time-delayed dynamic Bayesian network.

    Science.gov (United States)

    Li, Peng; Gong, Ping; Li, Haoni; Perkins, Edward J; Wang, Nan; Zhang, Chaoyang

    2014-12-01

    The Dialogue for Reverse Engineering Assessments and Methods (DREAM) project was initiated in 2006 as a community-wide effort for the development of network inference challenges for rigorous assessment of reverse engineering methods for biological networks. We participated in the in silico network inference challenge of DREAM3 in 2008. Here we report the details of our approach and its performance on the synthetic challenge datasets. In our methodology, we first developed a model called relative change ratio (RCR), which took advantage of the heterozygous knockdown data and null-mutant knockout data provided by the challenge, in order to identify the potential regulators for the genes. With this information, a time-delayed dynamic Bayesian network (TDBN) approach was then used to infer gene regulatory networks from time series trajectory datasets. Our approach considerably reduced the searching space of TDBN; hence, it gained a much higher efficiency and accuracy. The networks predicted using our approach were evaluated comparatively along with 29 other submissions by two metrics (area under the ROC curve and area under the precision-recall curve). The overall performance of our approach ranked the second among all participating teams.

  1. Transcriptome analysis reveals regulatory networks underlying differential susceptibility to Botrytis cinerea in response to nitrogen availability in Solanum lycopersicum.

    Directory of Open Access Journals (Sweden)

    Andrea eVega

    2015-11-01

    Full Text Available Nitrogen (N is one of the main limiting nutrients for plant growth and crop yield. It is well documented that changes in nitrate availability, the main N source found in agricultural soils, influences a myriad of developmental programs and processes including the plant defense response. Indeed, many agronomical reports indicate that the plant N nutritional status influences their ability to respond effectively when challenged by different pathogens. However, the molecular mechanisms involved in N-modulation of plant susceptibility to pathogens are poorly characterized. In this work, we show that Solanum lycopersicum defense response to the necrotrophic fungus Botrytis cinerea is affected by plant N availability, with higher susceptibility in nitrate-limiting conditions. Global gene expression responses of tomato against B. cinerea under contrasting nitrate conditions reveals that plant primary metabolism is affected by the fungal infection regardless of N regimes. This result suggests that differential susceptibility to pathogen attack under contrasting N conditions is not only explained by a metabolic alteration. We used a systems biology approach to identify the transcriptional regulatory network implicated in plant response to the fungus infection under contrasting nitrate conditions. Interestingly, hub genes in this network are known key transcription factors involved in ethylene and jasmonic acid signaling. This result positions these hormones as key integrators of nitrate and defense against B. cinerea in tomato plants. Our results provide insights into potential crosstalk mechanisms between necrotrophic defense response and N status in plants.

  2. Analysis of circulating regulatory T cells (CD4+CD25+CD127-) after cryosurgery in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Tong-Guo Si; Jun-Ping Wang; Zhi Guo

    2013-01-01

    This study was performed to assess the response of regulatory T cells (Tregs) following cryosurgery in prostate cancer (PCa) patients by measuring their frequency and immune function.Blood was collected prior to and at 4 and 8 weeks after treatment in 30 patients with high-risk PCa who underwent cryosurgery and from 15 healthy volunteers.Circulating CD4+CD25+CD127-Tregs were isolated.Their frequency was detected by flow cytometry,and immune suppressive function was evaluated by measuring the proliferation of CD4+CD25-T cells cocultured with Tregs.The results showed that the percentage of circulating CD4+CD25+CD127-Tregs was increased in PCa patients compared to healthy volunteers (7.6%±0.73% vs.5.8%±-0.54%,P<0.001).The frequency of circulating CD4+CD25+CD127-Tregs was reduced 4 weeks after cryosurgery compared to before surgery (6.3%±0.58% vs.7.6%±0.73%,P<0.001),and the decrease persisted for 8 weeks.However,the suppressive function of Tregs was increased in eight of 12 patients,which might contribute to cancer recurrence.Then the response of circulating rregs is complicated after cryosurgery for PCa,and further studies are warranted.

  3. Functional analysis of membrane-bound complement regulatory protein on T-cell immune response in ginbuna crucian carp.

    Science.gov (United States)

    Nur, Indriyani; Abdelkhalek, Nevien K; Motobe, Shiori; Nakamura, Ryota; Tsujikura, Masakazu; Somamoto, Tomonori; Nakao, Miki

    2016-02-01

    Complements have long been considered to be a pivotal component in innate immunity. Recent researches, however, highlight novel roles of complements in T-cell-mediated adaptive immunity. Membrane-bound complement regulatory protein CD46, a costimulatory protein for T cells, is a key molecule for T-cell immunomodulation. Teleost CD46-like molecule, termed Tecrem, has been newly identified in common carp and shown to function as a complement regulator. However, it remains unclear whether Tecrem is involved in T-cell immune response. We investigated Tecrem function related to T-cell responses in ginbuna crucian carp. Ginbuna Tecrem (gTecrem) proteins were detected by immunoprecipitation using anti-common carp Tecrem monoclonal antibody (mAb) and were ubiquitously expressed on blood cells including CD8α(+) and CD4(+) lymphocytes. gTecrem expression on leucocyte surface was enhanced after stimulation with the T-cell mitogen, phytohaemagglutinin (PHA). Coculture with the anti-Tecrem mAb significantly inhibited the proliferative activity of PHA-stimulated peripheral blood lymphocytes, suggesting that cross-linking of Tecrems on T-cells interferes with a signal transduction pathway for T-cell activation. These findings indicate that Tecrem may act as a T-cell moderator and imply that the complement system in teleost, as well as mammals, plays an important role for linking adaptive and innate immunity.

  4. The GacS-GacA two-component regulatory system of Pseudomonas fluorescens: a bacterial two-hybrid analysis.

    Science.gov (United States)

    Workentine, Matthew L; Chang, Limei; Ceri, Howard; Turner, Raymond J

    2009-03-01

    The two-component regulatory system comprised of the sensor kinase, GacS, and its response regulator, GacA, is involved in regulation of secondary metabolism and many other aspects of bacterial physiology. Although it is known that the sensor kinases RetS and LadS feed into the GacS/GacA system, the mechanism through which this occurs is unknown, as are the protein-protein interactions in this system. To characterize and define these interactions, we utilized a bacterial two-hybrid system to study the interactions of GacS and GacA from Pseudomonas fluorescens CHA0. Domains of GacA and GacS, identified through bioinformatics, were subcloned and their ability to interact in vivo was investigated. We found that the entire GacA molecule is required for GacA to interact with itself or GacS. Furthermore, the HisKA/HATPase/REC domains of GacS together are responsible for GacS interacting with GacA, while the HAMP domain of GacS is responsible for GacS interacting with itself. In addition, homologs of Pseudomonas aeruginosa hybrid sensor kinases, RetS and LadS, were identified in P. fluorescens, and shown to interact with GacS, but not GacA.

  5. 76 FR 37996 - West Virginia Regulatory Program

    Science.gov (United States)

    2011-06-29

    ... significant economic impact on a substantial number of small entities under the Regulatory Flexibility Act (5... making the determination as to whether this rule would have a significant economic impact, the Department... Virginia is amending its Code of State Regulations (CSR) to provide for the establishment of a minimum...

  6. Global Summit on Regulatory Science 2013.

    Science.gov (United States)

    Howard, Paul C; Tong, Weida; Weichold, Frank; Healy, Marion; Slikker, William

    2014-12-01

    Regulatory science has been defined as the science that is used to develop regulatory decisions by government bodies. Regulatory science encompasses many scientific disciplines that oversee many studies producing a wide array of data. These may include fundamental research into the cellular interaction or response to a particular chemical or substance, hazard-assessment and dose-response studies in animal species, neurophysiological or neurobehavioral studies, best practices for the generation and analysis of genomics data, bioinformatics approaches, and mathematical modeling of risk. The Global Summit on Regulatory Science is an international conference with a mission to explore emerging and innovative technologies, and provide a platform to enhance translation of basic science into regulatory applications. The Third Global Summit on Regulatory Science which focused on nanotechnology is discussed.

  7. Murine hyperglycemic vasculopathy and cardiomyopathy: whole-genome gene expression analysis predicts cellular targets and regulatory networks influenced by mannose binding lectin

    Directory of Open Access Journals (Sweden)

    Chenhui eZou

    2012-02-01

    Full Text Available Hyperglycemia, in the absence of type 1 or 2 diabetes, is an independent risk factor for cardiovascular disease. We have previously demonstrated a central role for mannose binding lectin (MBL-mediated cardiac dysfunction in acute hyperglycemic mice. In this study, we applied whole genome microarray data analysis to investigate MBL’s role in systematic gene expression changes. The data predict possible intracellular events taking place in multiple cellular compartments such as enhanced insulin signaling pathway sensitivity, promoted mitochondrial respiratory function, improved cellular energy expenditure and protein quality control, improved cytoskeleton structure and facilitated intracellular trafficking, all of which may contribute to the organismal health of MBL null mice against acute hyperglycemia. Our data show a tight association between gene expression profile and tissue function which might be a very useful tool in predicting cellular targets and regulatory networks connected with in vivo observations, providing clues for further mechanistic studies.

  8. 76 FR 40208 - Regulatory Flexibility Agenda

    Science.gov (United States)

    2011-07-07

    ... Comment Period End 04/04/05 Next Action Undetermined ......... Regulatory Flexibility Analysis Required... FR 10521 NPRM Comment Period End 04/04/05 Next Action Undetermined ......... Regulatory Flexibility... 70 FR 10521 NPRM Comment Period End 04/04/05 Next Action Undetermined ............

  9. On the Path to SunShot. Utility Regulatory and Business Model Reforms for Addressing the Financial Impacts of Distributed Solar on Utilities

    Energy Technology Data Exchange (ETDEWEB)

    Barbose, Galen [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Miller, John [National Renewable Energy Lab. (NREL), Golden, CO (United States); Sigrin, Ben [National Renewable Energy Lab. (NREL), Golden, CO (United States); Reiter, Emerson [National Renewable Energy Lab. (NREL), Golden, CO (United States); Cory, Karlynn [National Renewable Energy Lab. (NREL), Golden, CO (United States); McLaren, Joyce [National Renewable Energy Lab. (NREL), Golden, CO (United States); Seel, Joachim [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Mills, Andrew [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Darghouth, Naim [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Satchwell, Andrew [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2016-05-01

    Net-energy metering (NEM) has helped drive the rapid growth of distributed PV (DPV) but has raised concerns about electricity cost shifts, utility financial losses, and inefficient resource allocation. These concerns have motivated real and proposed reforms to utility regulatory and business models. This report explores the challenges and opportunities associated with such reforms in the context of the U.S. Department of Energy's SunShot Initiative. Most of the reforms to date address NEM concerns by reducing the benefits provided to DPV customers and thus constraining DPV deployment. Eliminating NEM nationwide, by compensating exports of PV electricity at wholesale rather than retail rates, could cut cumulative DPV deployment by 20% in 2050 compared with a continuation of current policies. This would slow the PV cost reductions that arise from larger scale and market certainty. It could also thwart achievement of the SunShot deployment goals even if the initiative's cost targets are achieved. This undesirable prospect is stimulating the development of alternative reform strategies that address concerns about distributed PV compensation without inordinately harming PV economics and growth. These alternatives fall into the categories of facilitating higher-value DPV deployment, broadening customer access to solar, and aligning utility profits and earnings with DPV. Specific strategies include utility ownership and financing of DPV, community solar, distribution network operators, services-driven utilities, performance-based incentives, enhanced utility system planning, pricing structures that incentivize high-value DPV configurations, and decoupling and other ratemaking reforms that reduce regulatory lag. These approaches represent near- and long-term solutions for preserving the legacy of the SunShot Initiative.

  10. The Financial Impact of the Internet on the Analysis of Commercial Banking

    Institute of Scientific and Technical Information of China (English)

    刘诺涯

    2014-01-01

    As we all know, the development of Internet-based financial model of commercial banks have impacted the traditional banking business, but this much impact in the end, whether commercial banks caused a fatal impact, this article will focus on the analysis.

  11. Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in Maryland. Preliminary background report

    Energy Technology Data Exchange (ETDEWEB)

    Feurer, D A; Weaver, C L; Gallagher, K C; Hejna, D; Rielley, K J

    1980-01-01

    The authority to regulate public utilities in Maryland is vested in the Public Service Commission under the authority of the Public Service Commission Law. The Commission consists of five commissioners who are appointed by the governor with the advice and consent of the Senate. Commissioners must be or become citizens of Maryland, at least three are to serve full time, and one of the commissioners is to be nominated as chairman. The tenure of each commissioner is six years and their terms are on a staggered schedule. Commissioners are eligible for reappointment. The Public Service Commission Law provides that the Commission's powers an jurisdiction shall extend to the full extent permitted by the Constitution and laws of the United States. Local governments in Maryland are not given regulatory power over public service companies. The only power that local governments have over the operations of utilities is the power to grant franchises. Public utility regulatory statutes, energy facility siting programs, and municipal franchising authority are examined to identify how they may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES.

  12. Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in Maine. Preliminary background report

    Energy Technology Data Exchange (ETDEWEB)

    Feurer, D A; Weaver, C L; Gallagher, K C; Hejna, D; Rielley, K J

    1980-01-01

    The Maine Supreme Court holds that the regulation of the operations of public utilities is an exercise of the police powers of the state. The legislature has delegated such regulatory authority to the Maine Public Utilities Commission (PUC). The statutes provide no role for local government in the regulation of public utilities. The PUC consists of three full time members, appointed by the Governor subject to review by the Joint Standing Committee on Public Utilities and to confirmation by the Legislature. They each serve seven year terms. One member is designated by the Governor as chairman. The Commission appoints a secretary, assistant secretary, director of transportation, and, with the approval of the Attorney General, a general counsel. A member of the PUC cannot have any official or professional connection or relation with or hold any stock or securities in any public utility. Public utility regulatory statutes, energy facility siting programs, and municipal franchising authority are examined to identify how they may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES.

  13. Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in Iowa. Preliminary background report

    Energy Technology Data Exchange (ETDEWEB)

    Feurer, D A; Weaver, C L; Gallagher, K C; Hejna, D; Rielley, K J

    1980-01-01

    The authority to regulate public utilities is vested generally in the Iowa State Commerce Commission. The Commission is comprised of three members appointed by the governor with the approval of two-thirds of the senate. Commissioners are appointed for six-year terms. They must be free from employment or pecuniary interests in any public utility. Although the right to grant franchises is specifically reserved for municipalities, local governments exercise no regulatory authority over the provision of utility services by public utilities. Municipally-owned utilities, however, are specifically excepted from rate regulation by the Commission. The regulation of rates charged by municipally-owned utilities is the responsibility of local governments. The Commission is given no authority to review decisions of local governments with respect to rates. Public utility regulatory statutes, energy facility siting programs, and municipal franchising authority are examined to identify how they may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES.

  14. Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in South Carolina. Preliminary background report

    Energy Technology Data Exchange (ETDEWEB)

    Feurer, D A; Weaver, C L; Gallagher, K C; Hejna, D; Rielley, K J

    1980-01-01

    Pursuant to constitutional South Carolina mandate the General Assembly has created the Public Service Commission. The Commission is composed of seven members elected to four year terms by the General Assembly. One commissioner is elected from each of seven districts corresponding to the congressional districts as they existed as of January 1, 1930. The commissioners elect one of their members as chairman. The South Carolina statutes contain separate chapters dealing with the regulation of public utilities and electric utilities. Public utility includes the furnishing of gas or heat (other than by means of electricity) to the public. While the Commission is granted general supervisory and regulatory powers over public utilities and electric utilities, total governments retain some control over electrical utilities. All municipality's have the power to grant exclusive franchises to such utilities for the furnishing of light to the municipality and its inhabitants. Public utility regulatory statutes, energy facility siting programs, and municipal franchising authority are examined to identify how they may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES.

  15. Droplet Impact on Inclined Surfaces for Forensic Bloodstain Analysis

    Science.gov (United States)

    Smith, Marc; Lockard, Michael; Neitzel, G. Paul

    2015-11-01

    During a crime scene investigation, bloodstains are used to infer the size, impact angle, and velocity of the blood droplet that produced the stain. This droplet impact process was explored using experiments and numerical simulations of droplets impacting planar, inclined surfaces with different roughness and wetting properties over a range of Reynolds numbers (1,000 - 5,500) and Weber numbers (200 - 2,000) typical of some forensics applications. Results will be presented showing how the size and shape of the final elliptical bloodstain varies with impact angle and surface roughness. The common forensics practice to predict the impact angle is fairly accurate for near-normal impacts, but it under-predicts the angle for oblique impacts less than about 40° and this effect worsens for rougher surfaces. The spreading of the droplet normal to the impact plane is shown to follow that of a droplet under normal impact as the impact velocity increases. This effect is also lessened by increased surface roughness. The reasons for these effects will be explored using a new GPU-based wavelet-adaptive flow simulation, which can resolve the flows near the solid surface and near the moving contact line of these droplets for the large Reynolds and Weber numbers of these experiments. Supported by the National Institute of Justice.

  16. Wavelet analysis in ecology and epidemiology: impact of statistical tests.

    Science.gov (United States)

    Cazelles, Bernard; Cazelles, Kévin; Chavez, Mario

    2014-02-06

    Wavelet analysis is now frequently used to extract information from ecological and epidemiological time series. Statistical hypothesis tests are conducted on associated wavelet quantities to assess the likelihood that they are due to a random process. Such random processes represent null models and are generally based on synthetic data that share some statistical characteristics with the original time series. This allows the comparison of null statistics with those obtained from original time series. When creating synthetic datasets, different techniques of resampling result in different characteristics shared by the synthetic time series. Therefore, it becomes crucial to consider the impact of the resampling method on the results.